Speciality
Spotlight

 




 


Oncology


 

 





Breast
Cancer

       

  • Efficacy
    of Bilateral Prophylactic Mastectomy in Women with a
    Family History of Breast Cancer
    .

    LC Hartmann, DJ Schaid, et al (Mayo Clinic and Mayo
    Found, Rochester, Minn; St Vincent’s Hosp, Dublin)

    N Engl J Med 340:77-84, 1999.

        

    Methods
    : Retrospective chart review between 1960 and 1993
    identified 639 women with a family history of breast who
    underwent a  bilateral
    prophylactic mastectomy (median age at mastectomy, 42
    years).  Most
    of the patients (66%) were at moderate risk of breast
    cancer, but one third were at high risk. 
    Breast cancer incidence and deaths were compared
    between the high-risk patients and a group of 403 of
    their sisters who had not undergone prophylactic
    mastectomy.  Patients
    were followed up for a median of 14 years.

        

    Findings
    :The Gail model estimated that 37.4 breast cancers would
    be expected to have occurred in moderate-risk group. 
    Prophylactic mastectomy significantly reduced the
    risk of breast cancer by 90% to 94% in the patients at
    high risk and it also reduced the risk of death from
    breast cancer by 81% to 94% in the patients at high
    risk.  At
    the last visit, ovarian cancer had developed in 2
    patients in the high-risk group.

         

    Conclusions
    : Drawn from the study: Prophylactic mastectomy is
    superior to surveillance for women with a moderate to
    high risk of breast cancer, significantly reducing not
    only the occurrence of this disease but also deaths
    caused by breast cancer. 
    The development of ovarian cancer in 2 patients
    underscores the need to follow up these patients to
    identify subsequent ovarian and other cancers.

         

  • MJ Silverstein, MD Lagios, S Groshen, et al (Univ of Southern California, Los Angeles; Harold E and Henrietta C Lee Breast Ctr of Kenneth NorrisJr Comprehensive Cancer Ctr, Los Angeles; St Mary’s Hosp, San Francisco; et al)

    The influence of Margin Width on Local Control of Ductal Carcinoma In Situ of the Breast.

    N Engl J Med 340: 1455-1461, 1999

      


    Ductal carcinoma in situ is a noninvasive cancer. It does not metastasis but is prone to local recurrence after excision. To prevent local recurrence. The usual distance or perimeter included in the complete excision is 10mm. 

         


    Postoperative radiation therapy is of value for patients where the width of excision is less than 1mm.


       

  • Braun
    S, Pantel K, Muller P, et al [Ludwig Maximilians Univ,
    Munich, Germany; Universitatsklinikum Eppendorf,
    Hamburg, Germany; Zentralklinikum Augsburg, Germany]


    Cytokeratin-Positive
    Cells in the Bone Marrow and Survival of Patients With
    Stage I, II, or III Breast Cancer

    N
    Engl J Med 342: 525-533, 2000

       

    The
    cytokeratin present on the ectopic epithelial
    cells can be detected by an antibody to cytokeratin.

     

    This
    study of 552 patients of completely resected stage I, II
    and III breast cancer as well as 191 control subjects
    without cancer were evaluated for an antibody [
    A45-B/B3] against cytokeratin in bone marrow. The
    patients with cytokeratin
    positive cells in bone marrow was 36% versus 1% for
    control subjects. Patients positive to bone marrow
    micrometastasis had more likelihood of distant
    metastasis. There was no difference in locoregional
    relapse.

       

  • Krawczyk
    JJ, Engel B [Allan Blair Cancer Centre, Regina,
    Saskatchewan, Canada]


    The
    importance of Surgical Clips for Adequate Tangential
    Beam Planning in Breast Conserving Surgery and
    Irradiation

    Int
    J Radiat Oncol Biol Phys 43: 347-350, 1999

      

    The
    breast conserving surgery demarcates the border of the
    lumpectomy and surgical clips implantation avoid
    geographic miss during radiation.

      

    This
    study of 25 patients with early stage breast cancer had
    surgical clips following lumpectomy 
    revealed adequate postoperative radiation was
    feasible by visualizing accurately where the surgeon has
    been.

         

  • Silverstein
    MJ, Lagios MD, Groshen S, et al [Univ of Southern
    California, Los Angeles; Harold E and Henrietta C Lee
    Breast Ctr of Kenneth Norris Jr Comprehensive Cancer Ctr,
    Los Angeles; St Mary’s Hosp, San Francisco; et al]


    The
    Influence of Margin Width on Local Control of Ductal
    Carcinoma in Situ of the Breast

    N
    Engl J Med 340 : 1455-1461, 1999

        

    Ductal
    carcinoma in situ [ DCIS ] is a noninvasive cancer and
    its
    management
    has always been controversial.

      

    This study of 469 specimens of DCIS who had breast
    conserving surgery were analyzed for the margin width
    and its role for planning local radiotherapy.

      

    Those patients with confirmed margins of 10mm or more
    did not benefit from postoperative radiation therapy is
    important for patients whose tumor margin widths are
    less than 1 mm after excision.

        

  • Simmons
    RM, Fish SK, Gayle L, et al [Strang-Cornell Breast Ctr,
    New York; New York Presbyterian Hosp; Cornell Univ Med
    College, New York; et al]


    Local
    and Distant Recurrence Rates In Skin-Sparing
    Mastectomies Compared with Non-Skin-Sparing Mastectomies

    Ann
    Surg Oncol 6: 676-681, 1999

     

    Skin-sparing
    mastectomies [SSMs] are increasingly being used for a
    better cosmetic outcome by maximum skin preservations
    and immediate reconstruction.

      

    This
    study of 75 patients with SSM and 154 with nonSSM had a
    local  5
    year recurrence free survival, 95.3 
    and 95.2 respectively.
    SSM do not increase the risk of local or distant
    recurrence.

      

  • Ratanawichitrasin
    A, Biscotti CV, Levy L, et al [ Cleveland Clinic Found,
    Ohio]


    Touch
    Imprint Cytological Analysis of Sentinel Lymph Nodes for
    Detecting Axillary Metastases in Patients with a Breast
    Cancer

    Br
    J Surg 86: 1346-1349, 1999

      

    Sentinel Lymph Node [SLN] biopsy, the first tumor
    draining lymph node is examined.
    This study of 55 patients with breast cancer in
    whom touch imprint slides were prepared.
    When compared with paraffin 
    block touch imprint analysis of SLN had a 95%
    concordance, it has 82% sensitivity 
    and a 100% specificity. This procedure is easy to
    perform and accurate and it is suitable for
    immunohistochemical staining.

      

  • Klimberg
    VS, Rubio IT, Henry R, et al [ Univ of Arkansas, Little
    Rock]


    Subareolar
    Versus Peritumoral Injection for Location of the
    Sentinel Lymph Node

    Ann
    Surg 229: 860-865, 1999

      

    The
    sentinel lymph node [SLN] biopsy is a popular approach
    of finding the metastatic status of axillary lymph node.
    The mapping of SLN by subareolar versus peritumoral
    injection were compared in this study. Among patient
    with invasive breast cancer subareolar injection is just
    as accurate in localizing SLN as peritumoral injection.
    In addition subareolar technique avoids the need
    for image-guided injections and problems with
    overlapping
    radioactivity, particularly in medial and
    upper-outer-quadrant 
    lesions and for multicentric disease
    when the drainage of breast and tumor bed
    coincide.

          

  • Veronesi
    U, for the Fenretinide Trial Investigators [ Istituto
    Europeo di Oncologia, Milan, Italy; et al]


    Randomized
    Trial of Fenretinide to Prevent Second Breast Malignancy
    in Women with Early Breast Cancer

    J
    Natl Cancer Inst 91: 1847-1856, 1999

      

    Fenretinide,
    a vitamin A analogue, inhibits the breast carcinogenesis.

       

    In
    this study 5 years of fenretinide in women with early
    breast cancer [Stage I or ductal carcinoma in situ ]
    does not appear to affect significantly the incidence of
    second breast cancer however it may be beneficial in
    premenopausal women, further studies in larger
    populations would be required for confirmation.

        

  • Miles
    DW, Harris WH, Gillett CE, et al [Guy’s Hosp, London]


    Effect
    of c-erbB2 and Estrogen Receptor Status on
    Survival of Women With Primary Breast Cancer Treated
    with Adjuvant Cyclophosphamide / Methotrexate /
    Fluorouracil

    Int
    J Cancer 84: 354-359, 1999

      

    This study a trial of clyclophosphamide /
    methotrexate / fluorouracil
    [CMF] in patients of breast cancer with node
    –positive operable breast cancer were evaluated, for
    C-erbB2, ER status. Among women with node
    positive breast cancer the survival benefit of adjuvant
    CMF is greater for those with ER negative tumor.
    The effect of CMF may also vary with c-erbB2
    status,being greater for patients with c-erbB2
    negative tumor.

      

  • Krag
    D, Weaver  D, Ashikaga T, et al [ Univ of Vermont, Burlington : Sylvester Cancer Ctr, Miami,
    Fla; Arcansas Cancer Research Ctr Little Rock, et al]

    The Sentinal Node in Breast Cancer : A Multicenter
    Validation Study 

    N Engl J Med 339: 941-946 , 1998

          

    Sentinal node resection (SLN) reflects the status of
    axillary lymphadenectomy and there by may reduce the
    complication including psychologic disturbances
    associated with axillary lymph node rsection .

       


    This is  multicenter study  4432 women with
    invasive breast cancer with negative axillary
    lymphadenectomy on examination. Prior to surgery a
    radioactive tracers [ 99 M Tc  sulfur colloid, 37 MBq] was injected on to the breast around the tumor
    a biopsy cavity. Hot spot on Gamma probe identified SLN
    in 93% of the patients & in 97 % accurately
    predicting the axillary lymph node status. However this
    procedure is technically complex and has many variables.
    False negative results are more likely for lesions in
    lateral half of the breast .

         

  • Andrulis
    IL, for the Toronto Breast Cancer Study Group [ Mount
    sinai Hosp, Toronto; Toronto Sunnybrook Health science
    Ctr; omen’s college Hospital, Toronto; et al] 

    Nu/erb B-2 Amplificatio Identifies a Poor – Prognosis
    Group of Women with node negative Breast Cancer

    J Clin Oncol 16 : 1340-1349 , 1998




    Prognostic factors for node positive breast
    cancer  patient include tumor size, steroid
    hormone receptor status, menopausal status and
    histological grade. Women with node negative
    breast cancer usually have a better prognosis but still
    20% have recurrence and die of metastasis. This study
    of 580 women with node negative breast cancer patients
    revealed 34 breast cancer recurrence and neu/erb 
    B-2 amplification increased the risk of recurrence.
    This was  confirmed to be an independent prognostic
    factor in multivariate analysis.

        

  • Clarke M, and the Early Breast Cancer Trialists’ Collaborative Group [Radcliffe Infirmary, Oxford, England]

    Tamoxifen for Early Breast Cancer: An Overview of the Randomized Trials

    Lancet 351: 1451-1467, 1998

        

    Treatment with adjuvant tamoxifen yielded notable
    improvement in 10-year survival rates in women with
    ER-positive tumours and in women with tumours of unknown
    ER status. These women also have proportional reductions
    in breast cancer recurrence and mortality that seem to
    be unaffected by other patient characteristics or
    treatments.

      

    This study has information collected and analyzed for 37,000 women in 55 trials on adjuvant tamoxifen.

      

    The proportion reduction in the rate of recurrence among ER positive tumor was significant with more prolonged treatment i.e. at 1,2 and approximately 5 years of adjuvant tamoxifen were 21%, 29%, & 47%. Corresponding decreases in proportional mortality rates were 12%, 17% & 26% respectively. 

      

    Improvement in survival rates became steadily better throughout the first 10 years.

      

    Absolute mortality decreases were greater in node-negative. The contralateral breast also benefited with reduction in breast cancer by 13%, 27% & 47% in trials of 1,2 and 5 years of adjuvant tamoxifen.

      

    The incidence of endometrial cancer also increased with the increasing duration of tamoxifen usage.

        

  • Clough KB, Bourgeois D, Falcou M-C, et al [Institut Curie, Paris]


    Immediate Breast Reconstruction by Prosthesis : A Safe Technique for Extensive Intraductal and Microinvasive Carcinomas


    Ann Surg Oncol 3: 212-218, 1998

       

    Breast implant following mastectomy is commonly advocated. However its indication remains controversial due to its morbidity and high removal rates.

       


    This study of one hundred forty one patients with extensive intraductal or microinvasive carcinomas underwent immediate breast reconstruction [IBR] with saline or gel-filled implants. The rate of prosthesis removal within two months of procedure was 0.7%. Only 2.1% of breasts required early surgical revision.

      


    Thus with appropriate selection of patients i.e. importance of skin spari ng mastectomy, in patients with noninvasive or microinvasive breast cancer immediate reconstruction could be performed.

        

  • DiBiase
    SJ, Komarnicky LT, Schwartz GF, et al [ Thomas Jefferson Univ, Philadelphia]


    The Number of Positive Margins Influences the Outcome of Women Treated with Breast Preservation for Early Stage Breast Carcinoma


    Cancer 82: 2212-2220, 1998

       


    The increase rate of recurrence following a positive margin at breast resection is well known. This study of 453 patients who had breast preservation surgery 19% had microscopically position margin. The local tumor control rate for patients with negative margins was 94% at 5 years and 87% at 10 year. The disease free survival & over all survivals were all better in patients with negative margins. Women with at least 2 positive margins had significantly inferior local tumor control. There is a clear indication that negative margins assure the best long-term disease control in women who have breast-conserving surgery.

       

  • Cox CE, Pendas S, Cox JM, et al [ Univ of South Florida, Tampa; Maimonides Med Ctr, Brooklyn, NY]


    Guidelines for Sentinel Node Biopsy and Lymphatic Mapping of Patients with Breast Cancer


    Ann Surg 227: 645-653, 1998

      

    Lymphatic mapping is a technique that can predict individual tumor behavior. In this study 466 consecutive breast cancer patients underwent intraoperative lymph node mapping with the use of lymphazurin blue dye and filtered technetium-labeled sulfur colloid. A sentinel lymph node [SLN] could be accurately identified as any blue, or hot node with a 10: ex vivo gamma probe ratio of SLN to non-SLN. This technique was found to be useful for smaller tumors. A ductal carcinoma in situ where nodal positivity is less likely and, therefore most patients don’t need full lymphadenectomy. In patients with positive SLN would even require adjuvant chemotherapy, whereas false negative rates would lead to inadequate therapy.

       

  • Fisher B, for the National Surgical Adjuvant Breast and Bowel Project Investigators [ Allegheny Univ of the Health Sciences, Pittsburgh, Pa; et al]


    Tamoxifen for Prevention of Breast Cancer : Report of the National Surgical Adjuvant Breast and Bowel Project p-1 Study


    J Natl Cancer Inst 90: 1371-1388, 1998

      

    Adjuvant tamoxifen therapy reduced contralateral breast cancer. The National surgical Adjuvant Breast and Bowel Project [ NSABP] has tested the role of tamoxifen in preventing breast cancer. A total of 13, 388 women at increased risk of breast cancer were studied. Tamoxifen decreased the risk of invasive breast cancer by 49%. The risk reduction occurred in women aged 49 years or younger [44%], 50 to 59 years [ 51%], and 60 years or older [55%]. The risk also decreased in women with histories of lobular carcinoma in situ and atypical hyperplasia and in women with any category of predicted 5-year risk. Tamoxifen increases the risk of endometrial cancer, strokes, pulmonary embolisms, and deep-vein thrombosis in the recipients above 50 years of age.

       

  • Clarke M, for the Early Breast Cancer Trialists’ Collaborative Group [Radcliffe Infirmary, Oxford, England]

    Polychemotherapy for Early Breast Cancer: An Overview of the Randomized Trials

    Lancet 352: 930-942, 1998

       

    An overview of the many randomized studies on adjuvant prolonged polychemotherapy among women with early breast cancer have been reviewed in this article.

      

    Polychemotherapy resulted in highly significant proportional decreases in recurrence among women younger than 50 years and among those with 50-69 years. The reduction in recurrence was observed primarily in first 5 years of follow-up and survival differences increased during first 10 years and these were regardless of nodal status after standardization of age. Duration of polychemotherapy for more that 3-6 months had no advantage. Adjuvant polychemotherapy can be expected to improve 10 year survival by 7% to 11% in women younger than 50 years and by 2% to 3% among those aged 50-69 years at presentation with early breast cancer.

       

  • Thor AD, Berry DA, Budman DR, et al [Northwestern Univ, Evanston, III; Cancer and Leukemia Group B Statistical Office, Durham, NC; North Shore Univ, Manhasset, NY; et al]

    ErB-2, p53, and Efficacy of Adjuvant Therapy in Lymph Node-Positive Breast Cancer

    J Natl Cancer Inst 90: 1346-1360, 1998

       

    High expression of erb-b2 gene in breast cancer patients has been associated with response to dose-intensive cyclophosphamide, doxorubicin and 5-flurouracil [CAF] treatment.

      

    In this study of 595 patients from CALGB protocol erb-b2 and p53 protein expression by immunohistochemical analysis were studied. erb-b2 expression and dose intensive doxorubicin chemotherapy was associated with a significant improvement in disease from 2 overall survival. Interaction between erb-b2 overexpression,
    p53 expression, and CAF dose is complete and multiple interactions may confound outcomes.

        

  • Krag D, Weaver D, Ashikaga T, et al [Univ of Vermont, Burlington: Sylvester Cancer Ctr, Miami, Fla; Arkansas Cancer Research Ctr Little Rock, et al]

    The Sentinel Node in Breast Cancer : A Multicenter Validation Study

    N Engl J Med 339: 941-946, 1998

      

    This is multicenter study 4432 women with invasive breast cancer with negative axillary lymphadenectomy on examination. Prior to surgery a radioactive tracers [99M Tc sulfur colloid, 37 MBq] was injected into the breast around the tumor a biopsy cavity. Hot spot on gamma probe identified SLN in 93% of the patients & in
    97% accurately predicting the axillary lymph node status. However this procedure is technically complex and has many variables. False negative results are more likely for lesions in lateral half of breast.

        

  • Andrulis IL, for the Toronto Breast Cancer Study Group [Mount sinai Hosp, Toronto; Toronto Sunnybrook Health Science Ctr; Women’s College Hosp, Toronto; et al]

    Neu/erb B-2 Amplification Identifies a Poor-Prognosis Group of Women with Node-Negative Breast Cancer

    J Clin Oncol 16: 1340-1349, 1998

      

    Prognostic factors for node positive breast cancer patient include tumor size, steroid hormone receptor status, menopausal status, and histological grade. Women with node-negative breast cancer usually have a better prognosis but still 20% have recurrence and die of metastasis. This study of 580 women with node-negative breast cancer patients revealed 34 breast cancer recurrence and neu/erbB-2 amplification increased the risk of recurrence. This was confirmed to be an independent prognostic factor in multivariate analysis.

        

  • Mertz KR, Baddour LM, Bell JL, et al [Univ of Tennessee, Knoxville]

    Breast Cellulitis Following Breast Conservation Therapy : A Novel Complication of Medical Progress

    Clin Infect Dis 26: 481-486, 1998

       

    This study illustrates 13 episodes of breast cellulitis in 9 patients after breast conservation surgery. All patients had received radiation therapy within 6 weeks of surgery. Approximately 8.5% of the patients had breast cellulitis within a median duration of 4.9 months from the completion of radiation therapy. The cause of this is unclear however it is believed that seromas formed at the time of surgery or later in clinical course and due to lymphatic and vascular compromise related to surgery and radiation therapy, the bacteria could not be cleared from the skin and subcutaneous tissues.

       

  • A Randomized Trial on the Use of Ultrasonogrpahy or Office Hysteroscopy for Endometrial

    Assessment in Postmenopausal Patients with Breast Cancer who were Treated with
    Tamoxifen.


    D Timmerman, J Deprest, et al (Univ Hosps Leuven, Belgium)

    Am J Obstet Gynecol 179:62-70, 1998.

       

    The mortality rate in women with breast cancer has been reduced by tamoxifen and this drug is currently the hormonal treatment of choice. About 1 million women are taking tamoxifen in the United States currently. There is now an increased interest in the potential side effects of tamoxifen, particularly because it is used as a prophylactic agent against breast cancer.

       

    There were 53 postmenopausal women with breast cancer who had no vaginal bleeding and who had taken tamoxifen at 20 or 40 mg/day for at least 6 months.

       

    Results – Endometrial cancer was found in 2 women. In both patients, endometrial cancer was detected only by transvaginal. One woman had primary and other had breast secondary. At least 1 polyp was found in 26 women. All 47 polyps were benign. There was no significant difference among the women who had polyps with regard to their age, body mass, months of tamoxifen intake, or their cumulative dose. The sensitivity of transvaginal ultrasound was 90% and the specificity was 100%. For office hysteroscopy, the sensitivity was 77% and the specificity was 92%.

         

    Some patients could not have office hysteroscopy due to cervical stenosis i.e. 19% of patients in the study.

      

  • Elmore
    JG, Barton MB, Moceri VM, et al [ Univ of Washington, Seattle; Harvard Med School, Boston]

    Ten-year Risk of False Positive Screening Mammograms and Clinical Breast Examinations

    N Engl J Med 338: 1089-1096, 1998

         

    The current recommendation for breast cancer screening by a yearly mammography and clinical breast examination leads to ample opportunities for false positive tests. This 10-year retrospective study analyzed the cumulative risk of a false positive breast cancer screening result. After 10 tests [mammography]. The cumulative risks of a false positive mammograms was estimated to be 49% [ 95% confidence interval [CI], 40% to 64%]. For clinical breast examination the cumulative risk was 22%. Women in their 40’s were more likely to have false positive than those in their 50’s and 70’s. Each 100$ spent on screening carried an additional $ 33 for evaluation of false positive results. This study does not undermine the importance of breast screening but it would encourage dissemination of knowledge regarding the risks of false positive tests to minimize the patient’s anxiety.

      

  • Baselga J, Norton L, Albanell J, et al
    [Mem Sloan-Kettering Cancer Ctr, New York 

    Vall d’Hebron Univ Hosp, Barcelona]

    Recombinant Humanized Anti-HER2 Antibody [Herceptin] Enhances the Antitumor Activity of Paclitaxel and Doxorubicin Against HER2/neu Overexpressing Human Breast Cancer Xenografts

    Cancer Res 58: 2825-2831, 1998

      

    HER2 gene, a new biological prognostic marker in breast cancer has revealed 25-30% overexpression and is associated with worse prognosis.

      

    In this study on human breast cancer cell lines in nude mice have revealed that a recombinant humanized anti HER2 antibody [ rhuMAb HER2
    [Herceptin] enhanced the anti tumor activity of paclitaxel and
    doxorubicin, greater enhancement was seen with
    paclitaxel. This study obviously provides the rationale for clinical trials to evaluate rhuMAb in combination with these and other drugs in breast tumors and other erb-B2 positive tumors.

      

  • Rohan TE, Hartwick W, Miller AB, et al
    [Univ of Toronto; Mt. Sinai Hosp, Toronto]

    Immunohistochemical Detectio of c-erB-2 and p53 in Benign Breast Disease and Breast Cancer Risk

    J Natl Cancer Inst 90: 1262-1269, 1998

      

    The prognostic marker in breast cancer c-erbB-2 and p53 protein expression are also relevant to the progression of breast cancer. This study reveals an association of p53 accumulation but not c-erbB-2 overexpression with increased risk of
    progression of benign breast disease to breast cancer and hence a close follow up and earlier intervention may be warranted in women with benign breast disease and p53 accumulation.

       

  • Rubio
    IT, Korourian S, Cowan C, et al [Univ of Arkansas,
    Little Rock, Univ of Vermont, Burlington]

    Use of Touch Preps for Intraoperative Diagnosis of
    Sentinel Lymph Node Metastases in Breast Cancer


    Ann Surg 5: 689-694, 1998

       

    The status of sentinel lymph node [SLN] during surgery
    for breast cancer is important for planning axillary
    lymphadenectomy. The touch prep[ TP] diagnoses correctly
    in 99.2% of the nodes. The false positive rate are 0 and
    false negative 0.8 and hence TP is fast, accurate,
    simple technique for identifying metastasis SLN. The
    editor comments that this [TP] results in improvement in
    both cost and time. The obvious drawbacks are
    immunohistochemistry and polymerase chain reaction
    evaluations are not possible.

       

  • LC
    Hartmann, DJ Schaid, et al (Mayo Clinic and Mayo Found,
    Rochester, Minn; St Vincent’s Hosp, Dublin)

    Efficacy of Bilateral Prophylactic Mastectomy
    in Women with a Family History of Breast Cancer.


    N Engl J Med 340:77-84, 1999, Pg. 4

     

    This retrospective study have revised the date of more
    than 30 years as regards the importance of prophylactic
    bilateral mastectomy in patients with moderate high risk
    depending on family history criteria. Prophylactic
    mastectomy reduced the risk of breast cancer by 90% to
    94% in patients at high risk and 89.5% in patients at
    moderate risks. Thereby also decreasing the numbers of
    deaths resulting from breast cancer.

        

  • Diaz
    LK, Wiley EL, Venta LA [Northwestern Univ, Chicago]

    Are Malignant Cells Displaced by Large-Gauge Needle Core Biopsy of the Breast?

    AJR 173: 1303-1313, 1999



    This study of 352 patients of breast cancer who underwent excision following large gauge needle core biopsies were examined for tumor displacement. In this analysis 32% of patients had tumor cell displaced and the incidence and the amount of tumor displacement were inversely associated with their core biopsy to excision interval. This suggests that these dislodged cells do not survive in their new micro environment as these are unsuitable for their growth or being consumed at biopsy sites by inflammatory
    reaction.

       

  • Johnson
    JM, Dalton RR, Wester SM, et al [ Gundersen Lutheran Med Ctr, La Crosse, Wis]

    Histological Correlation of Microcalcifications in Breast Biopsy Specimens

    Arch Surg 134: 712-716, 1999

      

    Microcalcification is one of the earliest detectable changes in breast carcinoma.

       

    This study of 403 consecutive patients and biopsies done for indeterminant microcalcifications, were identified for nonpalpable lesion. The pathologic abnormality of atypical hyperplasia, carcinoma in situ, or invasive carcinoma were identified in 61 specimens of 167 patients. Correlation with microcalcification was identified in 52%. The authors recommend a close follow-up of patients whose pathologic findings are benign.

         

  • Walker RA, Dearing SJ, Brown LA [Univ of Leicester, England]

    Comparison of Pathological and Biological Features of Symptomatic and Mammographically Detected Ductal Carcinoma in Situ of the Breast

    Hum Pathol 30: 943-948, 1999

        

    The study of 79 patients with mammographically detected DCIS were compared with 59 patients with DCIS presented clinically. Most symptomatic patients had invasion, primarily with high-grade tumors, increased c-erbB2 micropapillary patterns. Only clinical follow up determines the impact of these differences.

       

  • Silver SA, Tavassoli FA [Armed Forces Inst of Pathology, Washington, DC]

    Osteosarcomatous Differentiation in Phyllodes Tumors

    Am J Surg Pathol 23: 815-821, 1999

       

    This study was undertaken to reveal the prognostic significant of osteosarcoma arising in phyllodes tumors.

        

    Osteosarcomatous differentiation resulted in potentially aggressive neoplasms, especially when the neoplasms are large or are associated with either an osteoclastic or osteoblastic osteosarcoma. Complete excision without axillary dissection is recommended.

       

  • Hatada T, Ishii H, Ichii S, et al [ Hyogo College of Medicine, Japan]

    Diagnostic Value of Ultrasound-Guided Fine-Needle Aspiration Biopsy, Core-Needle Biopsy, and Evaluation of Combined Use in the Diagnosis of Breast Lesions

    J Am Coll Surg 190: 299-303, 2000

      

    This study compared the diagnostic value of US-guided core-needle biopsy [US-CNB] with that US-guided fine-needle aspiration biopsy [US-FNAB] in patients with breast cancer. 

       

    US-guided FNAB demonstrated a sensitivity of 86.9%, a specificity of 78.6% and accuracy of 84%. The sensitivity of US-CNB was 86.2% but specificity and accuracy were higher 95.8% and 89% respectively. For the combined procedure, sensitivity, accuracy, and specificity were all higher than US-FNAB. 

        

  • Paterakos M, Watkin WG, Edgerton SM, et al [Northwestern Univ, Evanston, III, Univ of California, San Francisco]

    Invasive Micropapillary Carcinoma of the Breast: A Prognostic Study

    Hum Pathol 30: 1459-1463, 1999

        

    Invasive micropapillary carcinoma [IMC] of the breast, a rare variant of infiltrating ductal carcinoma is believed to have distinctive pathologic appearance, high incidence of axillary lymph node metastasis and possibly a poor outcome. This study of 1287 patient’s histologic review revealed 21 patients with IMC. In an analysis of all patients univariate analysis reviewed a strong association between IMC and shortened survival, however in multivariate analysis no prognostic significance could be identified.

       

  • Jimenez RE, Bongers S. Bouwman D, et al [ Wayne State Univ, Detroit]

    Clinicopathologic Significance of Ductal Carcinoma in Situ in Breast Core Needle Biopsies With Invasive Cancer

    Am J Surg Pathol 24: 123-128, 2000

    Extensive Intraductal component [EIC] in diagnostic core biopsy specimen and its margin are associated with an increased risk or recurrence.

       

    This study of 50 patients with invasive ductal carcinoma who underwent core needle biopsy [CNB] followed by lumpectomy, 20% had extensive intraductual carcinoma and this correlated significantly with the in situ disease at the margin. Thus, wider margins are required for patients with EIC in CNB patients.

       

  • Balsari A, Casalini P, Tagliabue E, et al [ Milan Univ, Italy]

    Fluctuation of HER2 Expression in Breast Carcinomas During the Menstrual Cycle

    Am J Pathol 155: 1543-1547, 1999

        

    This study was of 198 premenopausal patients who underwent surgery for breast cancer, [duct lobular or mixed] and the record of menstrual cycle was obtained from the patient. The specimen was studied for markers of tumor aggressiveness HER2, p53, bcl-2, cathepsin D and hormone receptors.

         

    In hormone receptor positive specimen, the expression of HER2 differed significantly according to the phase of menstrual cycle, 7% and 11% during luteal phase to 25% & 20% during follicular phase for progesterone receptor and estrogen receptor positive patients respectively. This was not associated with gene amplification. The importance of this fluctuation in HER2 expression would have therapeutic implications. 

         

  • G Cserni (Bacs-Kiskun County Teaching Hosp, Kecskemet, Hungary)

    Metastases in Axillary Sentinel Lymph Nodes in Breast Cancer as Detected by Intensive Histopathological Work Up 

    J Clin Pathol 52: 922-924, 1999

         


    The role of sentinel lymph node (SLN) in penile carcinoma, malignant melanoma of the skin, breast cancer, thyroid neoplasms, oral and colorectal cancer has been studied as the initial target of lymphogenic metastases.

         


    The SLN were initially removed and analyzed by serial sections to both cytokeratin and epithelial membrane antigen. These results were compared with results of central cross sections. 

          


    The results support the serial sectioning of SLN and immunohistochemistry for negative cases.

       

  • G
    Viale, S Bosari, G Mazzarol, et al (Univ of Milan, Italy; European Inst of Oncology, Milan, Italy)

    Intraoperative Examination of Axillary Sentinel Lymph Nodes (SLN) in Breast Carcinoma Patients

    Cancer 85: 2433-2438, 1999

         


    This study on SLN identification, biopsy along with intraoperative frozen section analysis could avoid a second surgical procedure of axillary dissection in SLN-positive patients, rapid immunostaining for cytokeratin could reconfirm the metastasis. 

          


    This exhaustive intraoperative evaluation was completed in 30-40 minutes.

       

  • TJ Miner, CD Shriver, DP Jaques, et al (Walter Reed Army Med Ctr, Washington, DC; Vermont Cancer Ctr, Burlington)

    Sentinel Lymph Node Biopsy for Breast Cancer: The
    Role of Previous Biopsy on Patient Eligibility


    Am Surg 65: 493-499, 1999

         


    Previous authors have stated that prior excisional biopsy is a contraindication of SLN biopsy due to lymphatic disruption.

         


    This study of 82 patients with newly diagnosed invasive breast cancer could effectively localize the SLN with technetium 99m sulfur colloid regardless of the extent of prior biopsy.

         

  • S
    Pendas, E Dauway, CE Cox, et al (H Lee Moffitt Cancer Ctr and Research Inst, Tampa, Fla)

    Sentinel Node Biopsy and Cytokeratin Staining for the Accurate Staging of 478 Breast Cancer Patients

    Am Surg 65: 500-506, 1999

        


    The staging of regional lymph node in breast cancer patients is by detection of sentinel lymph node (SLN) and its rate could be further improved by detecting micrometastases.

         


    This study of 478 patients with newly diagnosed breast cancer. The SLN was removed for gross examination, intraoperative imprint cytology, (H & E) histologic and immunohistochemical examination (cytokeratin).

          


    The rate of upstaging H & E negative patients on the basis of cytokeratin stain was 10.6%.

         


    Even a small aggregates of cytokeratin positive cells were considered evidence of metastases only if retrospective review of H & E revealed malignant cells. The authors comment that high quality immunostains such as cytokeratin if revealed metastases is enough evidence as it would be reasonable for micrometastases to be absent in other sections.

         

  • ML
    Prasad, MP Osborne, DD Giri, et al (New York Presbyterian Hosp-Weill Med College of Cornell Univ, New York)

    Microinvasive Carcinoma (T1mic) of the Breast: Clinicopathologic Profile of 21 Cases

    Am J Surg Pathol 24: 422-428, 2000

        


    The definition of microinvasive carcinoma of breast (MICB) is unclear as it varies from stromal invasion in ductal carcinoma in situ (DCIS) to those that specify invasion of 2mm. 

         


    In 1996 the Union Internationale Contra Cancer introduced T1mic defining as “microinvasion 0.1 cm or less in diameter”.

         


    This study of 21 patients with MICB was ductal in 18 patients, 1 tubular, and 3 lobular carcinomas. One positive axillary lymph node was found in 2 to 15 patients and in two patients with recurrences had comedo DCIS. In both of these circumstances there was associated wide spread DCIS with high nuclear grade and necrosis.

        

  • Jimmie Harvey, James Cantrell, Mark Campbell, Alan Cartmell, Walter Urba, Manuel Modiano, Michael Schuster, et al (Bruno Cancer Baptist Medical Center, Birmingham, Alabama; Bruno Cancer Center, St. Vincent’s Hospital, Birmingham, Alabama; Cancer and Hematology Center of West Michigan, Grand Rapids, Michigan, et al)

    Mitoxantrone and Paclitaxel Combination Chemotherapy in Metastatic Breast Cancer

    Cancer Investigation 2001 Vol. 19 (3) Pg. 225-233

      

    Paclitaxel and doxorubicin had been showing promising responses in metastatic breast cancer. The limitation of this combination is cardiotoxicity. In one study cumulative dose of doxorubicin was 369 mg/m2. Mitoxantrone a topoisomerase II inhibitor is less cardiotoxic and hence this combination was studied in 37 patients with metastatic carcinoma breast who had received at least one but no more than two prior chemotherapy regimens. The dose of paclitaxel 150 mg/m2 I.V. over 3 hours day 1 and mitoxantrone 14 mg/m2 I.V. day 1, 35% had an objective response, 5% had CR, 23% had partial response, and 41% had stable disease.

      

    The median time to progression and survival for all patients was 6 months to 12 months respectively. The most significant adverse event was grade IV neutropenia in 71% of patients. In the current study 34% of patients had received prior doxorubicin and the objective response rate in this subgroup was not different from overall response which means that this regimen was active even after doxorubicin therapy.

        

  • David
    Khayat, Eric-Charles Antoine, and David Coeffic (Department of Medical Oncology, Hopital de La Salpetriere, Paris, France)

    Taxol in the Management of Cancers of the Breast and the Ovary

    Cancer Investigation 2000 Vol. 18 (3) Pg. 242-260

       


    Paclitaxel is one of the most active agent in advanced breast cancer, 40-60% response rates.

        


    The optimum dose and schedule still remain to be determined, however most studies state the dose of 175 mg/m2 over 3 hours, at this dose the infusion duration will not result in any change in antitumoral activity. The dose dense weekly schedules would enhance both the therapeutic action and antiangiogenic and proapoptotic effects.

        


    The early phase I/II studies of paclitaxel and doxorubicin have reported response rate of 42 to 94%. This combination is however known to produce cardiomyopathy in up to 20% of the patients.

         


    The drug paclitaxel in combination with a nonanthracycline agent such as cyclophosphamide, vinorelbine, 5-fluorouracil and platinum compounds have been tried for anthracycline resistant metastases breast cancer.

           


    Paclitaxel and cyclophosphamide combination had various infusion duration and dosage schedules for paclitaxel administration. The hematologic toxicity occurred with 3 hours paclitaxel infusion as versus longer duration, the pharmacologic explanation for this effect was not available.

          


    Paclitaxel and vinorelbine have the same target, the tubuline but with opposite effects as vinorelbine inhibits polymerization of microtubules whereas paclitaxel enhances and stabilizes their polymerization.

          


    This combination had a response range of 40-50% in the various series so far reported. Grade 3 and 4 neutropenia was the main toxicity.

          


    Paclitaxel and 5-fluorouracil (5-FU) have been tried with very variable dosing schedule of 5-FU. The response rates range from 40-62%.

            


    Paclitaxel and platinum have been tried in metastatic breast cancer patients. The biweekly sequential combination has impressive response rate.

          


    Paclitaxel has been integrated in adjuvant programs for primary breast cancer. 

          


    CALGB 93-94 presented at ASCO 98 compared node-positive breast cancer patients to four cycles of cyclophosphamide (CA) + adriamycin followed by paclitaxel 175 mg/m2 four cycles or not. 

         


    At median follow-up of 18 months the sequential addition of Taxol to CA improved the disease free survival and overall survival. Similar encouraging results by Hudis who used intensive adjuvant chemotherapy with doxorubicin followed by paclitaxel and then cyclophosphamide 3 gm/m2 the preliminary results reveal 81% of patients relapse free at a median follow-up of more than 3 years.

          


    Paclitaxel and adriamycin have also been incorporated in neoadjuvant setting for breast cancer.

          


    Taxol in management of ovarian cancer:

         


    Paclitaxel 175 mg/m2 in a 3 hour infusion is now considered a standard regimen in most of Europe. The phase I-II weekly paclitaxel at 80 mg/m2 have also been reported equivalent results.

         


    Argentine group reported 39% response in advanced ovarian cancers after first-line failure.

         


    The efficacy of carboplatinum-paclitaxel combination seems to be similar to cisplatinum-paclitaxel combination in ovarian cancer.

           


    The three drug combination cyclophosphamide + paclitaxel + cisplatinum although has a good response but due to the toxicity whether they would really add any benefit in terms of activity to toxicity ratio is not clear.

          


    The GOG 111 and larger European Canadian intergroup have favored the use of paclitaxel with platinum in advanced ovarian cancer and naive of treatment whereas GOG 132 published contradictory results and revealed platinum as the main stay drug for ovarian cancer.

          

  • Point

    C. Lin Puckett (Division of Plastic and Reconstructive Surgery, University of Missouri Health Sciences Center, Columbia, Missouri, President, American Society of Plastic Surgeons)

    On the safety of silicone gel breast implants

    Cancer Investigation 2000 Vol. 18 (3) Pg. 278-280

      

    The 1990 sensational reporting of association of gel-filled breast implants being dangerous and it’s association with collagen diseases led to the ban by FDA for general use, except, reconstructive patients.

       

    Recent studies however failed to demonstrate this association and a fascinating corollary found in many studies was the decreased incidence of breast cancer in the implanted patients.

       

    The complication such as scar formation around the prosthesis or capsule contracture can result in excessive firmness, there are manufacturing flaws or effects of stress and time.

      

    The surgery of implanted patients reveals an overall satisfaction rate of > 95%.

       

  • Counterpoint

    Gary Solomon (Hospital for Joint Diseases, Orthopedic Institute, New York, New York)

    Are Silicon Gel Breast Implants Safe?

    Cancer Investigation 2000 Vol. 18 (3) Pg. 281-284

      

    Silicone gel breast implants have local complications including painful capsular contracture, implant rupture with spillage of silicone resulting into silicone granulomas, infection and axillary adenopathy. The rupture rates approximate 50% by year 15 after implantation and approach 100% over time.

      

    Older studies had associated silicon gel breast implant and systemic illness most notably an atypical connective tissue disease
    (ACTD).

       

    However recent epidemiologic studies could not verify this association.

          

  • Evangelia
    Razis, Athanassios-Meletios Dimopoulos, Dimitris Bafaloukos, Christos Papadimitriou, Anna Kalogera-Fountzila, Haralambos Kalofonos, Evangelos Briassoulis, Epaminontas Samantas, Antonios Keramopoulos, Nicholas Pavlidis, Paris Kosmidis, and George Fountzilas (Hygeia Hospital, Maroussi, Athens, Greece; Alexandra Hospital, Athens, Greece; Metaxa Cancer Hospital, Piraeus, Greece; University of Patras, Patras, Greece; University of Ioannina, Ioannina, Greece; Agii Anargyri Cancer Hospital, Athens, Greece; AHEPA Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece)

    Dose-Dense Sequential Chemotherapy with Epirubicin and Paclitaxel in Advanced Breast Cancer

    Cancer Investigation 2001 Vol. 19 (2) Pg. 137-144

         


    Dose dense chemotherapy is administration of anti cancer drugs sequentially at adequate dose as single agents in short intervals for increasing the dose intensity. 

          


    This study of 41 patients with recurrent or metastatic (stage IV) breast cancer, half of whom had received prior chemotherapy now received four cycles of epirubicin 100 mg/m2 every 2 weeks followed by four cycles of paclitaxel 225 mg/m2 every 2 weeks along with G-CSF.

           


    CR was possible in 19.5% and partial response 36.5%. These results are inferior to the combination of paclitaxel and doxorubicin. However the cardiac toxicity and febrile neutropenia were also less frequent in the present study and this was possible with better dose intensity (DI) of paclitaxel 112.5 mg/m2 per week and doxorubicin 55 mg/m2 per week compared to 66.6 mg/m2 per week and 30 mg/m2 per week respectively. 

            


    The reason of inferior response in this study could be due to lesser numbers of courses of each drug or may be due to inadequate length of therapy. 

          


    An ongoing randomized study of same sequential regimen with epirubicin and paclitaxel every 3 weeks for 6 courses will throw more light on the above issues.

              

  • Edith A. Perez (Mayo Foundation and Mayo Clinic Jacksonville, Jacksonville, Florida)

    Doxorubicin and Paclitaxel in the Treatment of Advanced Breast Cancer: Efficacy and Cardiac Considerations 


    Cancer Investigation 2001 Vol. 19 (2) Pg. 155-164

           


    Doxorubicin and paclitaxel are highly active agents in the treatment of breast cancer. The earlier trials of this combination yielded good response rates associated with high congestive heart failure depending on the dose of doxorubicin, approx 21% with median cumulative dose of 480 mg/m2 and was also associated with cardiac risk factors such as hypertension, obesity, radiation to the left side of chest wall or familial history of heart disease. The overall response rates ranged from 53 to 80%. The overall responses and median time to progression were statistically superior for combination compared to single agents, however there was no difference in overall survival. 

           


    In view of the congestive heart failure the cumulative doxorubicin dose was £360 mg/m2. The pharmacokinetic study has revealed that the clearance of doxorubicin is decreased by 30% when administered shortly before or after 3-hour infusion of paclitaxel.

          


    The doxorubicinol a major metabolite of doxorubicin was also increased more than two fold leading to increase cardiac toxicity. 

             

  • R.
    Colomer, L. A. Shamon, M. S. Tsai and R. Lupu (Hospital 12 de Octubre, Madrid, Spain; Ernest O. Lawrence Berkeley National Laboratory, University of California, Berkeley, California)

    Herceptin: From the Bench to the Clinic

    Cancer Investigation 2001 Vol. 19 (1) Pg. 49-56

            

    The erbB-2 oncogene product is expressed in 25-30% of breast patients. The tyrosine kinase transduction appears to play an important role in breast cancer progression and metastasis.

             

    The antibody 4D5 directed against the extracellular domain of erbB-2 overexpressing cells was identified for preclinical studies, it was found to downregulate erbB-2 protein levels and inhibit growth of erbB-2 overexpressing breast cancer cells. The humanization of murine monoclonal anti-erbB-2 antibody, 4D5 was termed herceptin. 

            

    This agent has been approved by FDA as a single agent for the treatment of patients with metastatic breast cancer whose tumor overexpress erbB-2 protein ++ expression (>10% of cells weakly positive) or +++ expression (>10% of cells strongly positive) and have failed previous chemotherapy regimens.

             

    Paclitaxel with herceptin has also been approved by FDA as first line in metastatic breast cancer. Herceptin as single agent in first line had 23% response rate and 31% clinical benefit (response plus stable disease longer than 6 months).

            

    Paclitaxel with herceptin had response rate of 57% vs 25% for paclitaxel alone. Herceptin and chemotherapy particularly paclitaxel yielded longer time to disease progression with median time to 8.6 months compared to 5.5 months.

            

    An increase in cardiac toxicity was observed in combination of herceptin with anthracycline. As a single agent herceptin, the cardiac dysfunction was 4% and could be worrisome.

           

  • Andrew W. Menzin, and David Gal (Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, et al)

    Point/Counterpoint Series

    Point: Should Women Receiving Tamoxifen Be Screened for Endometrical Cancer? An Argument for Screening 

    Cancer Investigation 2001 Vol. 18 (8) Pg. 793-795

         

    The Swedish and NSABP-14 trial support a propensity to develop endometrial cancer as a result of exposure to TMX (Tamoxifen). 

           

    The length of treatment and the cumulative dose of TMX were significantly associated with high risk of endometrial cancer. However NSABP-14 results do not support this statement and have clearly noted that quantitative benefits of TMX well outweigh the impact of endometrial cancer risk.

          

    Increasing age with personal history of breast cancer is generally accepted as high risk for development of endometrial cancer following TMX and this subgroup would benefit from screening.

           

    The efficient modality for screening of endometrial cancer is not clear. The sonographic thickening of the endometrial stripe is the absence of pathologic change is well known. The invasive technique of sonohysterography is believed to be more accurate screening technique.

           

    Endometrial sampling as the primary modality has been recommended by the authors with the ancient instrument being only few mm in diameter and flexible are well tolerated and have a high rate of successful sampling.

           

    Yearly gynecologic evaluation is the minimum, the NSABP-14 researches have recommended for women on adjuvant TMX.

           

  • Richard R. Barakat (Gynecology Service, Department of Surgery, et al)

    Counterpoint: Should Women Receiving Tamoxifen for Breast Cancer Be Screened for Endometrial Cancer?

    Cancer Investigation 2001 Vol. 18 (8) Pg. 796-797

           

    Screening procedure should detect cancer at earlier stage and thereby improve survival. To date no screening techniques for endometrial cancer following TMX have been identified.

          

    Endometrial sampling for symptomatic patients may be reasonable modality however post menopausal women with stenotic cervices would pose difficulty.

          

    Transvaginal sonography provides a noninvasive means of screening for endometrial pathology. An endometrial stipe of > 8 mm has a 100% predictive for an endometrial pathology (atypical hyperplasia or polyps).

           

    The authors recommend all women whether or not receiving Tamoxifen should undergo annual gynecologic evaluation, which would include endometrial sampling especially in the presence of abnormal vaginal bleeding or discharge.

           

  • Ian E. Smith and Lara Lipton (The Breast Unit, Royal Marsden NHS Trust, London, UK)

    Preoperative/Neoadjuvant Medical Therapy For Early Breast Cancer

    The Lancet Oncology September 2001 Vol. 2 (9) Pg. 561-570

       

    The aim of preoperative medical therapy in early breast cancer is to downstage the tumour so as to avoid mastectomy. Chemotherapy combination routinely used such as cyclophosphamide + adriamycin + 5-fluorouracil (CAF) or cyclophosphamide + methotrexate + 5-fluorouracil + (CMF) or CA, when used preoperatively had no survival advantage. The NSABP – B-18 used cyclophosphamide + adriamycin before or after surgery for early breast cancer and there was no survival benefit at 5 year follow-up for both groups.

      

    Newer chemotherapy schedules are also not likely to have any survival advantage. Studies from Bonadonna and colleagues have revealed that with tumors more than 5cms are difficult candidates for conservative mastectomy. Thus down staging the disease could lead to conservative mastectomy (lumpectomy).

      

    This beneficial trend of lumpectomy following preoperative chemotherapy may be associated with small increase in the risk of local recurrence but without any difference in survival. The potential predictive factors for preoperative chemotherapy are clinical tumor response, attainment of complete clinical response is an essential prerequisite for improved survival.

     

    Complete pathological response has also emerged as clear cut predictor of survival. Persistent involvement of pathological nodes is a predictor for poor response. The biological factor that predict favorable outcome are high apoptotic index, low Ki-67 antigen.

      

    Estrogen receptor expression and absence of cERB 2 had better outlook.

      

    Of the endocrine therapy letrozole for 4 months as preoperative therapy indicated 55% response rate as compared with 36% for tamoxifen. Whether this short term benefit is translated to improved survival is not clear at present.    

              

  • Carolyn I. Sartor (Department of Radiation Oncology and Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, USA)   

    Postmastectomy Radiotherapy in Women with Breast Cancer Metastatic to One to Three Axillary Lymph Nodes

    Current Oncology Reports Vol. 3(6) November 2001 Pg. 497-505   

                     

    Breast cancer progression is believed to be a hybrid of Halstedian and Fisher hypothesis i.e. it begins as a local disease and evolves to systemic disease. Thus a subset of population in whom local therapy could be curative and in whom local failure could lead to distant metastasis. 

                            

    A meta-analysis revealed randomized radiotherapy led to significant reduction in risk of death due to breast cancer improving the breast cancer specific survival from 48.6% to 53.4% at 20 years. 

                                       

    However non-breast cancer deaths were on the risk in patients with local radiotherapy. The Danish trial revealed benefit of post mastectomy chest wall radiotherapy (PMCWRT) to patients with 1-3 lymph nodes. High survival benefit in this subgroup was seen only in one trial. 

                                       

    The number of lymph node removed is again an important factor and under evaluation or lesser lymph node excised may contribute to high risk of LLR. Anthracycline based CT does not appear to decrease the indication for PMCWRT. Extracapsular extension involvement of skin, nipple and lymph node is a important predictor of locoregional recurrence (LRR). 

                                                           

    20-30% of patients with axillary lymph node has IMN and left ant-descending artery remain within the typical field of local RT if all 5 interspaces are treated. The 1998 American society for therapeutic radiology concluded that evidence for PMCWRT for T1- – T2 tumors and 1-3 involved lymph node is dismal and hence routine PMCWRT is not recommended in this subgroup.     

                                                          

  • Julie R. Gralow (Seattle Cancer Care Alliance, University of Washington School of Medicine, USA)  

    The Role of Bisphosphonates as Adjuvant Therapy for Breast Cancer  

    Current Oncology Reports Vol. 3(6) November 2001 Pg. 506-515  

                                                                    

    Bone is the most common site of distant recurrence in breast cancer. Patient with bone metastasis have a median survival of 3 years and 5 years survival rate 20%. This allows the bony metastasis for various skeletal related problems. 

                                                                 

    Bisphosphonates reduce the skeletal related events and symptoms by 30 to 40% in breast cancer patients. Etidronate is the first generation bisphosphonate and is the least potent inhibitor of bone resorption whereas zoledronate and ibandronate represent the third generation. Oral bisphosphonate are compromised by poor absorption and esophagitis. 

                                                                        

    In the treatment of bony metastasis from breast cancer bisphosphonates are commonly used in conjunction with anti neoplastic agents to reduce the skeletal related events. Ibandronate is a highly potent bisphosphonate. It improved the event free survival of the patient with metastatic breast cancer in a phase III placebo controlled trial. ASCO guidelines states the use of injection pamidronate 90mg IV over 1-2 hours every 3-4 weeks in patients with metastatic breast cancer along with chemotherapy or hormonal therapy. 

                                                                      

    Bone sialoprotein is a non collagenous matrix protein high levels have predicted bony metastasis. Elevated levels of collagen cross links, pyridinoline and deoxypyridinoline and N-telopeptide (NTX) are excreted in urine with intensified bony activpity. Suppression of osteoclastic activity correlates with normalization of NTX and hence NTX would be useful for monitoring bisphosphonates utility.                       

                                                                                                                                               

  • Edith A. Perez (Division of Hematology/Oncology, Mayo Clinic and Mayo Foundation, USA)

    The Role of Adjuvant Monoclonal Antibody Therapy for Breast Cancer: Rationale and New Studies 

    Current Oncology Reports Vol. 3(6) November 2001 Pg. 516-522  

                                                                                

    HER2 a member of epidermal growth factor receptor family of tyrosine kinases and is involved in the growth, invasion, metastasis, and prognosis of breast cancer. HER2-positive tumors are more likely to relapse and die from their disease, compared to those with HER2-negative breast tumors.                

                                                                              

    A meta-analysis revealed patients over expressing HER2 are more resistant to hormonal treatment. Some studies have indicated HER2 positive
    breast tumors receive more benefit from doxorubicin-based therapies.  

                                                            

    Anti HER2 therapy is a monoclonal antibody treatment directed specifically against the HER2 protein. This therapy was found to have approximately 25% response rates as a single agent in metastatic breast cancer. The response is best in patients with immunohistochemistry 3+ for HER2. The other method for evaluation of HER2 protein is FISH, which evaluates HER2 gene amplification.       

                                                                              

    The addition of anti HER2 to chemotherapy such as AC or paclitaxel showed an improvement in overall response rates. However when administered with adriamycin cardiotoxicity was a problem. Paclitaxel + anti HER2 was well tolerated. The other chemotherapy
    agent used with anti HER2 are the combinations of paclitaxel + carboplat or docetaxel + cisplat or single agent vinorelbine.  

                                          

    The newer studies have incorporated herceptin in adjuvant therapy for breast cancer. However the cumulative dose of adriamycin being limited to 240 mg/m2 and herceptin being given once every 3 weekly based on clinical and pharmacokinetic data.                                                                                  

                                         

  • Lawrence N. Shulman (Dana-Farber Cancer Institute/Brigham and Women’s Hospital, USA)

    What is the Ideal Duration of Adjuvant Therapy for Primary Breast Cancer: Are Four Cycles of Cyclophosphamide and Doxorubicin Enough?

    Current Oncology Reports Vol. 3(6) November 2001 Pg. 523-528

                  

    The adjuvant trials of breast cancer demonstrates a modest but significant survival advantage for chemotherapy over no postoperative treatment. Inspite of these studies the duration of adjuvant therapy are not known and this is due to many other variables such as choice of agents, intensity, number of courses rather than duration and the results of adjuvant trials take 7-10 years to give mature results. 

                          

    Bonadonna’s earlier study had revealed 12 cycles of CMF, was as efficacious as 6 cycles of CMF. The International Breast Cancer Study Group study demonstrated 3 cycles of CMF were inferior to 6 courses of CMF. 

                           

    The (NSABP) B-15 study of 1984 and reported in 1990, equal efficacy of four cycles of cyclophosphamide and doxorubicin once every 3 weeks for 3 months to 6 cycles of oral CMF. 

                         

    The NSABP B-23 also confirmed similar findings in women with node negative breast cancer. Studies have revealed further dose escalation of cyclophosphamide above 600 and adriamycin above 60 is not useful. 

                              

    The National Cancer Institute of Canada (NCIC) designed a trial for comparison of CMF v/s CEF. In this study women receiving CEF had superior disease free and overall survival.

                           

    A study by Piccart compared epirubicin and cyclophosphamide (EC), two dose levels v/s CMF. This study reports CF (low dose) to be inferior to CMF whereas high dose EC and CMF had equivalent results. The role of paclitaxel in adjuvant setting is still not clear.                                     

                                                        

  • Sharon E. Soule and Kathy D. Miller (Indiana University School of Medicine, USA)

    Adjuvant Chemotherapy for Tumors of One Centimeter or Less: The Law of Diminishing Returns

    Current Oncology Reports Vol. 3(6) November 2001 Pg. 529-535

                                              

    The NSABP B-19 randomly assigned women without lymph node metastases to CMF and MF. Those patients treated with CMF experienced an increase in overall survival and disease free survival. 

                                                     

    The most recent Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) analysis revealed combination chemotherapy produced a 23.5% relative reduction in the annual hazards of recurrence and a 15.3% relative reduction in annual hazards of death.

                                     

    Studies have revealed that this favorable group of patients (less than 1 cm tumor) had overall survival rate 90-99% and the absolute benefit of chemotherapy is most likely 1% or less.

                                           

    Adjuvant chemotherapy has some serious long term toxicities such as cardiac dysfunction, treatment related leukemia, premature ovarian failure and long term cognitive defects. 

                                         

    These results do not justify adjuvant chemotherapy for breast cancer patients with less than a cm tumor.           

       

  • Ruth M O’Regan and V Craig Jordan (Comprehensive Cancer Center, Northwestern University Medical School, Chicago, USA)

    The Evaluation of Tamoxifen Therapy in Breast Cancer: Selective Oestrogen-Receptor Modulators and Downregulators

    The Lancet Oncology April 2002; Vol. 3(4): 207-14

      

    The earlier studies on rats revealed that tamoxifen had antifertility activity and could prevent rat mammary carcinogenesis. It was subsequently found to block the estrogen binding to human estrogen receptor (ER). Studies on advanced breast cancer showed responses in approximately 40-60% patients with ER positive tumors.

      

    The Oxford overview analysis conclusively showed that 5 years of tamoxifen treatment not only reduces the rate of recurrence of early breast cancer but also improved the survival. Studies in a advanced breast cancer showed patients with ER/PR positive benefited from tamoxifen as adjuvant. The recent NSABP chemoprevential trial showed that tamoxifen significantly reduces the frequency of invasive breast cancer and ductal carcinoma in situ by about 50% in high risk women.

     

    The recognition of selective oestrogen receptor modulation (SERM) by tamoxifen and its related nonsteroidal compound, acting as antioestrogen on the breast and mammary gland while acting as partial antioestrogen on the uterus has captured the imagination of medical chemists to design new drugs for the host of oestrogen modulated diseases. The side effects associated with tamoxifen apart from increased incidences of thromboembolism is the drug resistance.

      

    The other endocrine agent in breast cancer are Raloxifene widely used for prevention of osteoporosis however its effectively in breast cancer vis a vis tamoxifen is studied in the STAR trial. The results of which would be available by 2005. The long acting raloxifene LY353, 381. HCL (arzoxifene) is being developed for breast cancer treatment and prevention.

      

    The other nonsteroidal antioestrogen ICI 164, 384 has antioestrogen effect in all target tissues. This is by premature destruction of the estrogen receptor.

     

    The aromatase inhibitors act by preventing the conversion of andcostenedione and testerone to oestrogen by inhibiting the aromatase-enzymes complex competitively (anastrazole and letrzole) or non competitively (exemestame) in peripheral tissues and tumors of postmenopausal women.

       

  • Rockhill B, Spiegelman D, et al (Harvard Med School, Boston)

    Validation of the Gail et al Model of Breast Cancer Risk Prediction and Implications for Chemoprevention

    J Natl Cancer Inst 93: 358-366, 2001

       

    The primary model by Gail et al (model 1) is a large case cohort subsample and provides an estimate of the probability that a woman who has annual breast cancer screening performance will develop invasive or in situ breast cancer over a defined age interval.

    The model 2 is a modification to predict the risk of invasive breast cancer based on data from the Surveillance, Epidemiology and End Results program. Data from 82,109 white women 45 to 71 who participated in the Nurses Health Study (NHS). During follow-up there were 1354 cases of invasive breast cancer in the NHS cohort. Model 2 predicted 1273 cases and hence the ratios of expected (E) : Observed (O) was 0.94. The goodness of fit was better for those undergoing screening, but was poor if the results were based on number of first degree relatives with invasive breast cancer.

      

    Thus, the discriminating accuracy of model 2 in NHS cohort was modest. In view of this modest discriminatory accuracy with only 3.3% of the 1354 cases of breast cancer occurring in the high risk group and hence the chemopreventive strategy of tamoxifen would not have major impact.

       

  • Colleoni M, for the International Breast Cancer Study Group (European Inst of Oncology, Milan, Italy; et al)

    Early Start of Adjuvant Chemotherapy May Improve Treatment Outcome for Premenopausal Breast Cancer Patients With Tumors Not Expressing Estrogen Receptors

    J Clin Oncol 18: 584-590, 2000

      

    This study based on data obtained on 1788 premenopausal node-positive women treated in International Breast Cancer Study Group (IBCSG) trials I, II, and VI. Among patients with estrogen receptor (ER)-negative tumors early adjuvant chemotherapy was associated with a 60%, 10-year disease-free survival compared with 34% for later chemotherapy (more than 3 week following surgery).

      

    However for ER positive tumors this difference was not significant. The authors express concern that in many current trials of adjuvant chemotherapy allowing up to 12 weeks between surgery and initiation of adjuvant therapy, may require to be redefined.

       

  • Kaufmann M, for the Exemestane Study Group (Universitatsklinik, Frankfurt, Germany; et al)

    Exemestane Is Superior to Megestrol Acetate After Tamoxifen Failure in Postmenopausal Women With Advanced Breast Cancer: Results of a Phase III Randomized Double-blind Trial

    J Clin Oncol 18: 1399-1411, 2000

      

    The novel aromatase inactivator exemestane was compared to megestrol acetate (MA) in postmenopausal women with progressive advanced breast cancer unresponsive to tamoxifen.

      

    Exemestane 25 mg/day could prolong survival time, time to tumor progression and time to treatment failure compared with MA 40 mg four times a day.

      

    These results suggest that an aromatase inhibitor should be hormonal treatment of choice after an antiestrogen in those who respond to antiestrogen and later relapse. The author’s concern in this study is a modest response and short time to progression (5 months or less) for both the hormonal therapy arms and thereby administering chemotherapy particularly for these chemonaive patients would be more beneficial.

       

  • Paridaens R, for the European Organization for Research and Treatment of Cancer-Investigational Drug Branch for Breast Cancer/Early Clinical Studies Group (Univ Hosp Gasthuisberg, Leuven, Belgium; et al)

    Paclitaxel Versus Doxorubicin as First-Line Single-Agent Chemotherapy for Metastatic Breast Cancer: A European Organization for Research and Treatment of Cancer Randomized Study With Cross-over

    J Clin Oncol 18: 724-733, 2000

       

    This study randomly assigned 331 patients with metastatic breast cancer to paclitaxel 200 mg/m2, 3 hours infusion every 3 weeks to doxorubicin 25 mg/m2 bolus every 3 weeks. The objective response in first line treatment was significantly better with doxorubicin than that with paclitaxel, 41% vs 25% respectively and longer median progression free survival 7.5 months vs 3.9 months respectively.

       

    In second line treatment when crossed over the response rates favoured doxorubicin. 30% compared to 16% with paclitaxel whereas median survival duration had a nonsignificant difference. These two agents are not completely cross-resistant, which suggests that the need for further research on these drugs in combination or in sequence would be worth while.

      

    The authors comment that the results of this study contrast with the results of intergroup study in the United States that did not reveal any significant difference between doxorubicin and paclitaxel although the dose and schedules were different.

       

  • Stadtmauer EA, and the Philadelphia Bone Marrow Transplant Group (Univ of Pennsylvania, Philadelphia; et al)

    Conventional-Dose Chemotherapy Compared With High-Dose Chemotherapy Plus Autologous Hematopoietic Stem-Cell Transplantation for Metastatic Breast Cancer

    N Engl J Med 342: 1069-1076, 2000

        

    This study by Philadelphia bone marrow transplant group had 553 patients with metastatic breast cancer, 18 to 60 years of age and who had a partial response to 4-6 courses of standard combination chemotherapy.

       

    These were randomised to single course of high dose carboplatinum, thiotepa, and cyclophosphamide followed by autologous hematopoietic stem cell transplantation and other group received conventional CMF up to 24 months.

       

    The 3-year overall survival was 32% in transplant group as compared to 38% in conventional chemotherapy neither there was a significant difference in median time to progression. The transplantation group had higher rate of serious adverse effects without any survival benefit.

       

  • Hortobagyi GN, Buzdar AU, et al (Univ of Texas MD Anderson Cancer Ctr, Houston; Yale Univ, New Haven, Conn)

    Randomized Trial of High-Dose Chemotherapy and Blood Cell Autografts for High-Risk Primary Breast Carcinoma

    J Natl Cancer Inst 92: 225-233, 2000

       

    This prospective randomized study enrolled 78 patients with 10 or more positive axillary lymph nodes after primary breast surgery or with 4 or more positive axillary lymph nodes after 4 cycles of primary chemotherapy.

       

    31 received 8 courses of 5-Fluorouracil, Adriamycin, and, Cyclophosphamide (FAC) and 39 were assigned to FAC followed by high-dose chemotherapy (HDC).

        

    The addition of HDC to FAC conferred no relapse free or overall survival advantage.

      



 

  

Speciality Spotlight

 

 

Breast Cancer
       

  • Efficacy of Bilateral Prophylactic Mastectomy in Women with a Family History of Breast Cancer.
    LC Hartmann, DJ Schaid, et al (Mayo Clinic and Mayo Found, Rochester, Minn; St Vincent’s Hosp, Dublin)
    N Engl J Med 340:77-84, 1999.
        
    Methods : Retrospective chart review between 1960 and 1993 identified 639 women with a family history of breast who underwent a  bilateral prophylactic mastectomy (median age at mastectomy, 42 years).  Most of the patients (66%) were at moderate risk of breast cancer, but one third were at high risk.  Breast cancer incidence and deaths were compared between the high-risk patients and a group of 403 of their sisters who had not undergone prophylactic mastectomy.  Patients were followed up for a median of 14 years.
        
    Findings :The Gail model estimated that 37.4 breast cancers would be expected to have occurred in moderate-risk group.  Prophylactic mastectomy significantly reduced the risk of breast cancer by 90% to 94% in the patients at high risk and it also reduced the risk of death from breast cancer by 81% to 94% in the patients at high risk.  At the last visit, ovarian cancer had developed in 2 patients in the high-risk group.
         
    Conclusions : Drawn from the study: Prophylactic mastectomy is superior to surveillance for women with a moderate to high risk of breast cancer, significantly reducing not only the occurrence of this disease but also deaths caused by breast cancer.  The development of ovarian cancer in 2 patients underscores the need to follow up these patients to identify subsequent ovarian and other cancers.
         

  • MJ Silverstein, MD Lagios, S Groshen, et al (Univ of Southern California, Los Angeles; Harold E and Henrietta C Lee Breast Ctr of Kenneth NorrisJr Comprehensive Cancer Ctr, Los Angeles; St Mary’s Hosp, San Francisco; et al)
    The influence of Margin Width on Local Control of Ductal Carcinoma In Situ of the Breast.
    N Engl J Med 340: 1455-1461, 1999
      
    Ductal carcinoma in situ is a noninvasive cancer. It does not metastasis but is prone to local recurrence after excision. To prevent local recurrence. The usual distance or perimeter included in the complete excision is 10mm. 
         
    Postoperative radiation therapy is of value for patients where the width of excision is less than 1mm.
       

  • Braun S, Pantel K, Muller P, et al [Ludwig Maximilians Univ, Munich, Germany; Universitatsklinikum Eppendorf, Hamburg, Germany; Zentralklinikum Augsburg, Germany]
    Cytokeratin-Positive Cells in the Bone Marrow and Survival of Patients With Stage I, II, or III Breast Cancer
    N Engl J Med 342: 525-533, 2000
       
    The cytokeratin present on the ectopic epithelial cells can be detected by an antibody to cytokeratin.
     
    This study of 552 patients of completely resected stage I, II and III breast cancer as well as 191 control subjects without cancer were evaluated for an antibody [ A45-B/B3] against cytokeratin in bone marrow. The patients with cytokeratin positive cells in bone marrow was 36% versus 1% for control subjects. Patients positive to bone marrow micrometastasis had more likelihood of distant metastasis. There was no difference in locoregional relapse.
       

  • Krawczyk JJ, Engel B [Allan Blair Cancer Centre, Regina, Saskatchewan, Canada]
    The importance of Surgical Clips for Adequate Tangential Beam Planning in Breast Conserving Surgery and Irradiation
    Int J Radiat Oncol Biol Phys 43: 347-350, 1999
      
    The breast conserving surgery demarcates the border of the lumpectomy and surgical clips implantation avoid geographic miss during radiation.
      
    This study of 25 patients with early stage breast cancer had surgical clips following lumpectomy  revealed adequate postoperative radiation was feasible by visualizing accurately where the surgeon has been.
         

  • Silverstein MJ, Lagios MD, Groshen S, et al [Univ of Southern California, Los Angeles; Harold E and Henrietta C Lee Breast Ctr of Kenneth Norris Jr Comprehensive Cancer Ctr, Los Angeles; St Mary’s Hosp, San Francisco; et al]
    The Influence of Margin Width on Local Control of Ductal Carcinoma in Situ of the Breast
    N Engl J Med 340 : 1455-1461, 1999
        
    Ductal carcinoma in situ [ DCIS ] is a noninvasive cancer and its management has always been controversial.
      
    This study of 469 specimens of DCIS who had breast conserving surgery were analyzed for the margin width and its role for planning local radiotherapy.
      
    Those patients with confirmed margins of 10mm or more did not benefit from postoperative radiation therapy is important for patients whose tumor margin widths are less than 1 mm after excision.
        

  • Simmons RM, Fish SK, Gayle L, et al [Strang-Cornell Breast Ctr, New York; New York Presbyterian Hosp; Cornell Univ Med College, New York; et al]
    Local and Distant Recurrence Rates In Skin-Sparing Mastectomies Compared with Non-Skin-Sparing Mastectomies
    Ann Surg Oncol 6: 676-681, 1999
     
    Skin-sparing mastectomies [SSMs] are increasingly being used for a better cosmetic outcome by maximum skin preservations and immediate reconstruction.
      
    This study of 75 patients with SSM and 154 with nonSSM had a local  5 year recurrence free survival, 95.3  and 95.2 respectively. SSM do not increase the risk of local or distant recurrence.
      

  • Ratanawichitrasin A, Biscotti CV, Levy L, et al [ Cleveland Clinic Found, Ohio]
    Touch Imprint Cytological Analysis of Sentinel Lymph Nodes for Detecting Axillary Metastases in Patients with a Breast Cancer
    Br J Surg 86: 1346-1349, 1999
      
    Sentinel Lymph Node [SLN] biopsy, the first tumor draining lymph node is examined. This study of 55 patients with breast cancer in whom touch imprint slides were prepared. When compared with paraffin  block touch imprint analysis of SLN had a 95% concordance, it has 82% sensitivity  and a 100% specificity. This procedure is easy to perform and accurate and it is suitable for immunohistochemical staining.
      

  • Klimberg VS, Rubio IT, Henry R, et al [ Univ of Arkansas, Little Rock]
    Subareolar Versus Peritumoral Injection for Location of the Sentinel Lymph Node
    Ann Surg 229: 860-865, 1999
      
    The sentinel lymph node [SLN] biopsy is a popular approach of finding the metastatic status of axillary lymph node. The mapping of SLN by subareolar versus peritumoral injection were compared in this study. Among patient with invasive breast cancer subareolar injection is just as accurate in localizing SLN as peritumoral injection. In addition subareolar technique avoids the need for image-guided injections and problems with overlapping radioactivity, particularly in medial and upper-outer-quadrant  lesions and for multicentric disease when the drainage of breast and tumor bed coincide.
          

  • Veronesi U, for the Fenretinide Trial Investigators [ Istituto Europeo di Oncologia, Milan, Italy; et al]
    Randomized Trial of Fenretinide to Prevent Second Breast Malignancy in Women with Early Breast Cancer
    J Natl Cancer Inst 91: 1847-1856, 1999
      
    Fenretinide, a vitamin A analogue, inhibits the breast carcinogenesis.
       
    In this study 5 years of fenretinide in women with early breast cancer [Stage I or ductal carcinoma in situ ] does not appear to affect significantly the incidence of second breast cancer however it may be beneficial in premenopausal women, further studies in larger populations would be required for confirmation.
        

  • Miles DW, Harris WH, Gillett CE, et al [Guy’s Hosp, London]
    Effect of c-erbB2 and Estrogen Receptor Status on Survival of Women With Primary Breast Cancer Treated with Adjuvant Cyclophosphamide / Methotrexate / Fluorouracil
    Int J Cancer 84: 354-359, 1999
      
    This study a trial of clyclophosphamide / methotrexate / fluorouracil [CMF] in patients of breast cancer with node –positive operable breast cancer were evaluated, for C-erbB2, ER status. Among women with node positive breast cancer the survival benefit of adjuvant CMF is greater for those with ER negative tumor. The effect of CMF may also vary with c-erbB2 status,being greater for patients with c-erbB2 negative tumor.
      

  • Krag D, Weaver  D, Ashikaga T, et al [ Univ of Vermont, Burlington : Sylvester Cancer Ctr, Miami, Fla; Arcansas Cancer Research Ctr Little Rock, et al]
    The Sentinal Node in Breast Cancer : A Multicenter Validation Study 
    N Engl J Med 339: 941-946 , 1998
          
    Sentinal node resection (SLN) reflects the status of axillary lymphadenectomy and there by may reduce the complication including psychologic disturbances associated with axillary lymph node rsection .
       
    This is  multicenter study  4432 women with invasive breast cancer with negative axillary lymphadenectomy on examination. Prior to surgery a radioactive tracers [ 99 M Tc  sulfur colloid, 37 MBq] was injected on to the breast around the tumor a biopsy cavity. Hot spot on Gamma probe identified SLN in 93% of the patients & in 97 % accurately predicting the axillary lymph node status. However this procedure is technically complex and has many variables. False negative results are more likely for lesions in lateral half of the breast .
         

  • Andrulis IL, for the Toronto Breast Cancer Study Group [ Mount sinai Hosp, Toronto; Toronto Sunnybrook Health science Ctr; omen’s college Hospital, Toronto; et al] 
    Nu/erb B-2 Amplificatio Identifies a Poor – Prognosis Group of Women with node negative Breast Cancer
    J Clin Oncol 16 : 1340-1349 , 1998

    Prognostic factors for node positive breast cancer  patient include tumor size, steroid hormone receptor status, menopausal status and histological grade. Women with node negative breast cancer usually have a better prognosis but still 20% have recurrence and die of metastasis. This study of 580 women with node negative breast cancer patients revealed 34 breast cancer recurrence and neu/erb  B-2 amplification increased the risk of recurrence. This was  confirmed to be an independent prognostic factor in multivariate analysis.
        

  • Clarke M, and the Early Breast Cancer Trialists’ Collaborative Group [Radcliffe Infirmary, Oxford, England]
    Tamoxifen for Early Breast Cancer: An Overview of the Randomized Trials
    Lancet 351: 1451-1467, 1998
        
    Treatment with adjuvant tamoxifen yielded notable improvement in 10-year survival rates in women with ER-positive tumours and in women with tumours of unknown ER status. These women also have proportional reductions in breast cancer recurrence and mortality that seem to be unaffected by other patient characteristics or treatments.
      
    This study has information collected and analyzed for 37,000 women in 55 trials on adjuvant tamoxifen.
      
    The proportion reduction in the rate of recurrence among ER positive tumor was significant with more prolonged treatment i.e. at 1,2 and approximately 5 years of adjuvant tamoxifen were 21%, 29%, & 47%. Corresponding decreases in proportional mortality rates were 12%, 17% & 26% respectively. 
      
    Improvement in survival rates became steadily better throughout the first 10 years.
      
    Absolute mortality decreases were greater in node-negative. The contralateral breast also benefited with reduction in breast cancer by 13%, 27% & 47% in trials of 1,2 and 5 years of adjuvant tamoxifen.
      
    The incidence of endometrial cancer also increased with the increasing duration of tamoxifen usage.
        

  • Clough KB, Bourgeois D, Falcou M-C, et al [Institut Curie, Paris]
    Immediate Breast Reconstruction by Prosthesis : A Safe Technique for Extensive Intraductal and Microinvasive Carcinomas
    Ann Surg Oncol 3: 212-218, 1998
       
    Breast implant following mastectomy is commonly advocated. However its indication remains controversial due to its morbidity and high removal rates.
       
    This study of one hundred forty one patients with extensive intraductal or microinvasive carcinomas underwent immediate breast reconstruction [IBR] with saline or gel-filled implants. The rate of prosthesis removal within two months of procedure was 0.7%. Only 2.1% of breasts required early surgical revision.
      
    Thus with appropriate selection of patients i.e. importance of skin spari ng mastectomy, in patients with noninvasive or microinvasive breast cancer immediate reconstruction could be performed.
        

  • DiBiase SJ, Komarnicky LT, Schwartz GF, et al [ Thomas Jefferson Univ, Philadelphia]
    The Number of Positive Margins Influences the Outcome of Women Treated with Breast Preservation for Early Stage Breast Carcinoma
    Cancer 82: 2212-2220, 1998
       
    The increase rate of recurrence following a positive margin at breast resection is well known. This study of 453 patients who had breast preservation surgery 19% had microscopically position margin. The local tumor control rate for patients with negative margins was 94% at 5 years and 87% at 10 year. The disease free survival & over all survivals were all better in patients with negative margins. Women with at least 2 positive margins had significantly inferior local tumor control. There is a clear indication that negative margins assure the best long-term disease control in women who have breast-conserving surgery.
       

  • Cox CE, Pendas S, Cox JM, et al [ Univ of South Florida, Tampa; Maimonides Med Ctr, Brooklyn, NY]
    Guidelines for Sentinel Node Biopsy and Lymphatic Mapping of Patients with Breast Cancer
    Ann Surg 227: 645-653, 1998
      
    Lymphatic mapping is a technique that can predict individual tumor behavior. In this study 466 consecutive breast cancer patients underwent intraoperative lymph node mapping with the use of lymphazurin blue dye and filtered technetium-labeled sulfur colloid. A sentinel lymph node [SLN] could be accurately identified as any blue, or hot node with a 10: ex vivo gamma probe ratio of SLN to non-SLN. This technique was found to be useful for smaller tumors. A ductal carcinoma in situ where nodal positivity is less likely and, therefore most patients don’t need full lymphadenectomy. In patients with positive SLN would even require adjuvant chemotherapy, whereas false negative rates would lead to inadequate therapy.
       

  • Fisher B, for the National Surgical Adjuvant Breast and Bowel Project Investigators [ Allegheny Univ of the Health Sciences, Pittsburgh, Pa; et al]
    Tamoxifen for Prevention of Breast Cancer : Report of the National Surgical Adjuvant Breast and Bowel Project p-1 Study
    J Natl Cancer Inst 90: 1371-1388, 1998
      
    Adjuvant tamoxifen therapy reduced contralateral breast cancer. The National surgical Adjuvant Breast and Bowel Project [ NSABP] has tested the role of tamoxifen in preventing breast cancer. A total of 13, 388 women at increased risk of breast cancer were studied. Tamoxifen decreased the risk of invasive breast cancer by 49%. The risk reduction occurred in women aged 49 years or younger [44%], 50 to 59 years [ 51%], and 60 years or older [55%]. The risk also decreased in women with histories of lobular carcinoma in situ and atypical hyperplasia and in women with any category of predicted 5-year risk. Tamoxifen increases the risk of endometrial cancer, strokes, pulmonary embolisms, and deep-vein thrombosis in the recipients above 50 years of age.
       

  • Clarke M, for the Early Breast Cancer Trialists’ Collaborative Group [Radcliffe Infirmary, Oxford, England]
    Polychemotherapy for Early Breast Cancer: An Overview of the Randomized Trials
    Lancet 352: 930-942, 1998
       
    An overview of the many randomized studies on adjuvant prolonged polychemotherapy among women with early breast cancer have been reviewed in this article.
      
    Polychemotherapy resulted in highly significant proportional decreases in recurrence among women younger than 50 years and among those with 50-69 years. The reduction in recurrence was observed primarily in first 5 years of follow-up and survival differences increased during first 10 years and these were regardless of nodal status after standardization of age. Duration of polychemotherapy for more that 3-6 months had no advantage. Adjuvant polychemotherapy can be expected to improve 10 year survival by 7% to 11% in women younger than 50 years and by 2% to 3% among those aged 50-69 years at presentation with early breast cancer.
       

  • Thor AD, Berry DA, Budman DR, et al [Northwestern Univ, Evanston, III; Cancer and Leukemia Group B Statistical Office, Durham, NC; North Shore Univ, Manhasset, NY; et al]
    ErB-2, p53, and Efficacy of Adjuvant Therapy in Lymph Node-Positive Breast Cancer
    J Natl Cancer Inst 90: 1346-1360, 1998
       
    High expression of erb-b2 gene in breast cancer patients has been associated with response to dose-intensive cyclophosphamide, doxorubicin and 5-flurouracil [CAF] treatment.
      
    In this study of 595 patients from CALGB protocol erb-b2 and p53 protein expression by immunohistochemical analysis were studied. erb-b2 expression and dose intensive doxorubicin chemotherapy was associated with a significant improvement in disease from 2 overall survival. Interaction between erb-b2 overexpression, p53 expression, and CAF dose is complete and multiple interactions may confound outcomes.
        

  • Krag D, Weaver D, Ashikaga T, et al [Univ of Vermont, Burlington: Sylvester Cancer Ctr, Miami, Fla; Arkansas Cancer Research Ctr Little Rock, et al]
    The Sentinel Node in Breast Cancer : A Multicenter Validation Study
    N Engl J Med 339: 941-946, 1998
      
    This is multicenter study 4432 women with invasive breast cancer with negative axillary lymphadenectomy on examination. Prior to surgery a radioactive tracers [99M Tc sulfur colloid, 37 MBq] was injected into the breast around the tumor a biopsy cavity. Hot spot on gamma probe identified SLN in 93% of the patients & in 97% accurately predicting the axillary lymph node status. However this procedure is technically complex and has many variables. False negative results are more likely for lesions in lateral half of breast.
        

  • Andrulis IL, for the Toronto Breast Cancer Study Group [Mount sinai Hosp, Toronto; Toronto Sunnybrook Health Science Ctr; Women’s College Hosp, Toronto; et al]
    Neu/erb B-2 Amplification Identifies a Poor-Prognosis Group of Women with Node-Negative Breast Cancer
    J Clin Oncol 16: 1340-1349, 1998
      
    Prognostic factors for node positive breast cancer patient include tumor size, steroid hormone receptor status, menopausal status, and histological grade. Women with node-negative breast cancer usually have a better prognosis but still 20% have recurrence and die of metastasis. This study of 580 women with node-negative breast cancer patients revealed 34 breast cancer recurrence and neu/erbB-2 amplification increased the risk of recurrence. This was confirmed to be an independent prognostic factor in multivariate analysis.
        

  • Mertz KR, Baddour LM, Bell JL, et al [Univ of Tennessee, Knoxville]
    Breast Cellulitis Following Breast Conservation Therapy : A Novel Complication of Medical Progress
    Clin Infect Dis 26: 481-486, 1998
       
    This study illustrates 13 episodes of breast cellulitis in 9 patients after breast conservation surgery. All patients had received radiation therapy within 6 weeks of surgery. Approximately 8.5% of the patients had breast cellulitis within a median duration of 4.9 months from the completion of radiation therapy. The cause of this is unclear however it is believed that seromas formed at the time of surgery or later in clinical course and due to lymphatic and vascular compromise related to surgery and radiation therapy, the bacteria could not be cleared from the skin and subcutaneous tissues.
       

  • A Randomized Trial on the Use of Ultrasonogrpahy or Office Hysteroscopy for Endometrial
    Assessment in Postmenopausal Patients with Breast Cancer who were Treated with Tamoxifen.

    D Timmerman, J Deprest, et al (Univ Hosps Leuven, Belgium)
    Am J Obstet Gynecol 179:62-70, 1998.
       
    The mortality rate in women with breast cancer has been reduced by tamoxifen and this drug is currently the hormonal treatment of choice. About 1 million women are taking tamoxifen in the United States currently. There is now an increased interest in the potential side effects of tamoxifen, particularly because it is used as a prophylactic agent against breast cancer.
       
    There were 53 postmenopausal women with breast cancer who had no vaginal bleeding and who had taken tamoxifen at 20 or 40 mg/day for at least 6 months.
       
    Results – Endometrial cancer was found in 2 women. In both patients, endometrial cancer was detected only by transvaginal. One woman had primary and other had breast secondary. At least 1 polyp was found in 26 women. All 47 polyps were benign. There was no significant difference among the women who had polyps with regard to their age, body mass, months of tamoxifen intake, or their cumulative dose. The sensitivity of transvaginal ultrasound was 90% and the specificity was 100%. For office hysteroscopy, the sensitivity was 77% and the specificity was 92%.
         
    Some patients could not have office hysteroscopy due to cervical stenosis i.e. 19% of patients in the study.
      

  • Elmore JG, Barton MB, Moceri VM, et al [ Univ of Washington, Seattle; Harvard Med School, Boston]
    Ten-year Risk of False Positive Screening Mammograms and Clinical Breast Examinations
    N Engl J Med 338: 1089-1096, 1998
         
    The current recommendation for breast cancer screening by a yearly mammography and clinical breast examination leads to ample opportunities for false positive tests. This 10-year retrospective study analyzed the cumulative risk of a false positive breast cancer screening result. After 10 tests [mammography]. The cumulative risks of a false positive mammograms was estimated to be 49% [ 95% confidence interval [CI], 40% to 64%]. For clinical breast examination the cumulative risk was 22%. Women in their 40’s were more likely to have false positive than those in their 50’s and 70’s. Each 100$ spent on screening carried an additional $ 33 for evaluation of false positive results. This study does not undermine the importance of breast screening but it would encourage dissemination of knowledge regarding the risks of false positive tests to minimize the patient’s anxiety.
      

  • Baselga J, Norton L, Albanell J, et al [Mem Sloan-Kettering Cancer Ctr, New York 
    Vall d’Hebron Univ Hosp, Barcelona]
    Recombinant Humanized Anti-HER2 Antibody [Herceptin] Enhances the Antitumor Activity of Paclitaxel and Doxorubicin Against HER2/neu Overexpressing Human Breast Cancer Xenografts
    Cancer Res 58: 2825-2831, 1998
      
    HER2 gene, a new biological prognostic marker in breast cancer has revealed 25-30% overexpression and is associated with worse prognosis.
      
    In this study on human breast cancer cell lines in nude mice have revealed that a recombinant humanized anti HER2 antibody [ rhuMAb HER2 [Herceptin] enhanced the anti tumor activity of paclitaxel and doxorubicin, greater enhancement was seen with paclitaxel. This study obviously provides the rationale for clinical trials to evaluate rhuMAb in combination with these and other drugs in breast tumors and other erb-B2 positive tumors.
      

  • Rohan TE, Hartwick W, Miller AB, et al [Univ of Toronto; Mt. Sinai Hosp, Toronto]
    Immunohistochemical Detectio of c-erB-2 and p53 in Benign Breast Disease and Breast Cancer Risk
    J Natl Cancer Inst 90: 1262-1269, 1998
      
    The prognostic marker in breast cancer c-erbB-2 and p53 protein expression are also relevant to the progression of breast cancer. This study reveals an association of p53 accumulation but not c-erbB-2 overexpression with increased risk of progression of benign breast disease to breast cancer and hence a close follow up and earlier intervention may be warranted in women with benign breast disease and p53 accumulation.
       

  • Rubio IT, Korourian S, Cowan C, et al [Univ of Arkansas, Little Rock, Univ of Vermont, Burlington]
    Use of Touch Preps for Intraoperative Diagnosis of Sentinel Lymph Node Metastases in Breast Cancer
    Ann Surg 5: 689-694, 1998
       
    The status of sentinel lymph node [SLN] during surgery for breast cancer is important for planning axillary lymphadenectomy. The touch prep[ TP] diagnoses correctly in 99.2% of the nodes. The false positive rate are 0 and false negative 0.8 and hence TP is fast, accurate, simple technique for identifying metastasis SLN. The editor comments that this [TP] results in improvement in both cost and time. The obvious drawbacks are immunohistochemistry and polymerase chain reaction evaluations are not possible.
       

  • LC Hartmann, DJ Schaid, et al (Mayo Clinic and Mayo Found, Rochester, Minn; St Vincent’s Hosp, Dublin)
    Efficacy of Bilateral Prophylactic Mastectomy in Women with a Family History of Breast Cancer.
    N Engl J Med 340:77-84, 1999, Pg. 4
     
    This retrospective study have revised the date of more than 30 years as regards the importance of prophylactic bilateral mastectomy in patients with moderate high risk depending on family history criteria. Prophylactic mastectomy reduced the risk of breast cancer by 90% to 94% in patients at high risk and 89.5% in patients at moderate risks. Thereby also decreasing the numbers of deaths resulting from breast cancer.
        

  • Diaz LK, Wiley EL, Venta LA [Northwestern Univ, Chicago]
    Are Malignant Cells Displaced by Large-Gauge Needle Core Biopsy of the Breast?
    AJR 173: 1303-1313, 1999

    This study of 352 patients of breast cancer who underwent excision following large gauge needle core biopsies were examined for tumor displacement. In this analysis 32% of patients had tumor cell displaced and the incidence and the amount of tumor displacement were inversely associated with their core biopsy to excision interval. This suggests that these dislodged cells do not survive in their new micro environment as these are unsuitable for their growth or being consumed at biopsy sites by inflammatory reaction.
       

  • Johnson JM, Dalton RR, Wester SM, et al [ Gundersen Lutheran Med Ctr, La Crosse, Wis]
    Histological Correlation of Microcalcifications in Breast Biopsy Specimens
    Arch Surg 134: 712-716, 1999
      
    Microcalcification is one of the earliest detectable changes in breast carcinoma.
       
    This study of 403 consecutive patients and biopsies done for indeterminant microcalcifications, were identified for nonpalpable lesion. The pathologic abnormality of atypical hyperplasia, carcinoma in situ, or invasive carcinoma were identified in 61 specimens of 167 patients. Correlation with microcalcification was identified in 52%. The authors recommend a close follow-up of patients whose pathologic findings are benign.
         

  • Walker RA, Dearing SJ, Brown LA [Univ of Leicester, England]
    Comparison of Pathological and Biological Features of Symptomatic and Mammographically Detected Ductal Carcinoma in Situ of the Breast
    Hum Pathol 30: 943-948, 1999
        
    The study of 79 patients with mammographically detected DCIS were compared with 59 patients with DCIS presented clinically. Most symptomatic patients had invasion, primarily with high-grade tumors, increased c-erbB2 micropapillary patterns. Only clinical follow up determines the impact of these differences.
       

  • Silver SA, Tavassoli FA [Armed Forces Inst of Pathology, Washington, DC]
    Osteosarcomatous Differentiation in Phyllodes Tumors
    Am J Surg Pathol 23: 815-821, 1999
       
    This study was undertaken to reveal the prognostic significant of osteosarcoma arising in phyllodes tumors.
        
    Osteosarcomatous differentiation resulted in potentially aggressive neoplasms, especially when the neoplasms are large or are associated with either an osteoclastic or osteoblastic osteosarcoma. Complete excision without axillary dissection is recommended.
       

  • Hatada T, Ishii H, Ichii S, et al [ Hyogo College of Medicine, Japan]
    Diagnostic Value of Ultrasound-Guided Fine-Needle Aspiration Biopsy, Core-Needle Biopsy, and Evaluation of Combined Use in the Diagnosis of Breast Lesions
    J Am Coll Surg 190: 299-303, 2000
      
    This study compared the diagnostic value of US-guided core-needle biopsy [US-CNB] with that US-guided fine-needle aspiration biopsy [US-FNAB] in patients with breast cancer. 
       
    US-guided FNAB demonstrated a sensitivity of 86.9%, a specificity of 78.6% and accuracy of 84%. The sensitivity of US-CNB was 86.2% but specificity and accuracy were higher 95.8% and 89% respectively. For the combined procedure, sensitivity, accuracy, and specificity were all higher than US-FNAB. 
        

  • Paterakos M, Watkin WG, Edgerton SM, et al [Northwestern Univ, Evanston, III, Univ of California, San Francisco]
    Invasive Micropapillary Carcinoma of the Breast: A Prognostic Study
    Hum Pathol 30: 1459-1463, 1999
        
    Invasive micropapillary carcinoma [IMC] of the breast, a rare variant of infiltrating ductal carcinoma is believed to have distinctive pathologic appearance, high incidence of axillary lymph node metastasis and possibly a poor outcome. This study of 1287 patient’s histologic review revealed 21 patients with IMC. In an analysis of all patients univariate analysis reviewed a strong association between IMC and shortened survival, however in multivariate analysis no prognostic significance could be identified.
       

  • Jimenez RE, Bongers S. Bouwman D, et al [ Wayne State Univ, Detroit]
    Clinicopathologic Significance of Ductal Carcinoma in Situ in Breast Core Needle Biopsies With Invasive Cancer
    Am J Surg Pathol 24: 123-128, 2000
    Extensive Intraductal component [EIC] in diagnostic core biopsy specimen and its margin are associated with an increased risk or recurrence.
       
    This study of 50 patients with invasive ductal carcinoma who underwent core needle biopsy [CNB] followed by lumpectomy, 20% had extensive intraductual carcinoma and this correlated significantly with the in situ disease at the margin. Thus, wider margins are required for patients with EIC in CNB patients.
       

  • Balsari A, Casalini P, Tagliabue E, et al [ Milan Univ, Italy]
    Fluctuation of HER2 Expression in Breast Carcinomas During the Menstrual Cycle
    Am J Pathol 155: 1543-1547, 1999
        
    This study was of 198 premenopausal patients who underwent surgery for breast cancer, [duct lobular or mixed] and the record of menstrual cycle was obtained from the patient. The specimen was studied for markers of tumor aggressiveness HER2, p53, bcl-2, cathepsin D and hormone receptors.
         
    In hormone receptor positive specimen, the expression of HER2 differed significantly according to the phase of menstrual cycle, 7% and 11% during luteal phase to 25% & 20% during follicular phase for progesterone receptor and estrogen receptor positive patients respectively. This was not associated with gene amplification. The importance of this fluctuation in HER2 expression would have therapeutic implications. 
         

  • G Cserni (Bacs-Kiskun County Teaching Hosp, Kecskemet, Hungary)
    Metastases in Axillary Sentinel Lymph Nodes in Breast Cancer as Detected by Intensive Histopathological Work Up 
    J Clin Pathol 52: 922-924, 1999
         
    The role of sentinel lymph node (SLN) in penile carcinoma, malignant melanoma of the skin, breast cancer, thyroid neoplasms, oral and colorectal cancer has been studied as the initial target of lymphogenic metastases.
         
    The SLN were initially removed and analyzed by serial sections to both cytokeratin and epithelial membrane antigen. These results were compared with results of central cross sections. 
          
    The results support the serial sectioning of SLN and immunohistochemistry for negative cases.
       

  • G Viale, S Bosari, G Mazzarol, et al (Univ of Milan, Italy; European Inst of Oncology, Milan, Italy)
    Intraoperative Examination of Axillary Sentinel Lymph Nodes (SLN) in Breast Carcinoma Patients
    Cancer 85: 2433-2438, 1999
         
    This study on SLN identification, biopsy along with intraoperative frozen section analysis could avoid a second surgical procedure of axillary dissection in SLN-positive patients, rapid immunostaining for cytokeratin could reconfirm the metastasis. 
          
    This exhaustive intraoperative evaluation was completed in 30-40 minutes.
       

  • TJ Miner, CD Shriver, DP Jaques, et al (Walter Reed Army Med Ctr, Washington, DC; Vermont Cancer Ctr, Burlington)
    Sentinel Lymph Node Biopsy for Breast Cancer: The Role of Previous Biopsy on Patient Eligibility
    Am Surg 65: 493-499, 1999
         
    Previous authors have stated that prior excisional biopsy is a contraindication of SLN biopsy due to lymphatic disruption.
         
    This study of 82 patients with newly diagnosed invasive breast cancer could effectively localize the SLN with technetium 99m sulfur colloid regardless of the extent of prior biopsy.
         

  • S Pendas, E Dauway, CE Cox, et al (H Lee Moffitt Cancer Ctr and Research Inst, Tampa, Fla)
    Sentinel Node Biopsy and Cytokeratin Staining for the Accurate Staging of 478 Breast Cancer Patients
    Am Surg 65: 500-506, 1999
        
    The staging of regional lymph node in breast cancer patients is by detection of sentinel lymph node (SLN) and its rate could be further improved by detecting micrometastases.
         
    This study of 478 patients with newly diagnosed breast cancer. The SLN was removed for gross examination, intraoperative imprint cytology, (H & E) histologic and immunohistochemical examination (cytokeratin).
          
    The rate of upstaging H & E negative patients on the basis of cytokeratin stain was 10.6%.
         
    Even a small aggregates of cytokeratin positive cells were considered evidence of metastases only if retrospective review of H & E revealed malignant cells. The authors comment that high quality immunostains such as cytokeratin if revealed metastases is enough evidence as it would be reasonable for micrometastases to be absent in other sections.
         

  • ML Prasad, MP Osborne, DD Giri, et al (New York Presbyterian Hosp-Weill Med College of Cornell Univ, New York)
    Microinvasive Carcinoma (T1mic) of the Breast: Clinicopathologic Profile of 21 Cases
    Am J Surg Pathol 24: 422-428, 2000
        
    The definition of microinvasive carcinoma of breast (MICB) is unclear as it varies from stromal invasion in ductal carcinoma in situ (DCIS) to those that specify invasion of 2mm. 
         
    In 1996 the Union Internationale Contra Cancer introduced T1mic defining as “microinvasion 0.1 cm or less in diameter”.
         
    This study of 21 patients with MICB was ductal in 18 patients, 1 tubular, and 3 lobular carcinomas. One positive axillary lymph node was found in 2 to 15 patients and in two patients with recurrences had comedo DCIS. In both of these circumstances there was associated wide spread DCIS with high nuclear grade and necrosis.
        

  • Jimmie Harvey, James Cantrell, Mark Campbell, Alan Cartmell, Walter Urba, Manuel Modiano, Michael Schuster, et al (Bruno Cancer Baptist Medical Center, Birmingham, Alabama; Bruno Cancer Center, St. Vincent’s Hospital, Birmingham, Alabama; Cancer and Hematology Center of West Michigan, Grand Rapids, Michigan, et al)
    Mitoxantrone and Paclitaxel Combination Chemotherapy in Metastatic Breast Cancer
    Cancer Investigation 2001 Vol. 19 (3) Pg. 225-233
      
    Paclitaxel and doxorubicin had been showing promising responses in metastatic breast cancer. The limitation of this combination is cardiotoxicity. In one study cumulative dose of doxorubicin was 369 mg/m2. Mitoxantrone a topoisomerase II inhibitor is less cardiotoxic and hence this combination was studied in 37 patients with metastatic carcinoma breast who had received at least one but no more than two prior chemotherapy regimens. The dose of paclitaxel 150 mg/m2 I.V. over 3 hours day 1 and mitoxantrone 14 mg/m2 I.V. day 1, 35% had an objective response, 5% had CR, 23% had partial response, and 41% had stable disease.
      
    The median time to progression and survival for all patients was 6 months to 12 months respectively. The most significant adverse event was grade IV neutropenia in 71% of patients. In the current study 34% of patients had received prior doxorubicin and the objective response rate in this subgroup was not different from overall response which means that this regimen was active even after doxorubicin therapy.
        

  • David Khayat, Eric-Charles Antoine, and David Coeffic (Department of Medical Oncology, Hopital de La Salpetriere, Paris, France)
    Taxol in the Management of Cancers of the Breast and the Ovary
    Cancer Investigation 2000 Vol. 18 (3) Pg. 242-260
       
    Paclitaxel is one of the most active agent in advanced breast cancer, 40-60% response rates.
        
    The optimum dose and schedule still remain to be determined, however most studies state the dose of 175 mg/m2 over 3 hours, at this dose the infusion duration will not result in any change in antitumoral activity. The dose dense weekly schedules would enhance both the therapeutic action and antiangiogenic and proapoptotic effects.
        
    The early phase I/II studies of paclitaxel and doxorubicin have reported response rate of 42 to 94%. This combination is however known to produce cardiomyopathy in up to 20% of the patients.
         
    The drug paclitaxel in combination with a nonanthracycline agent such as cyclophosphamide, vinorelbine, 5-fluorouracil and platinum compounds have been tried for anthracycline resistant metastases breast cancer.
           
    Paclitaxel and cyclophosphamide combination had various infusion duration and dosage schedules for paclitaxel administration. The hematologic toxicity occurred with 3 hours paclitaxel infusion as versus longer duration, the pharmacologic explanation for this effect was not available.
          
    Paclitaxel and vinorelbine have the same target, the tubuline but with opposite effects as vinorelbine inhibits polymerization of microtubules whereas paclitaxel enhances and stabilizes their polymerization.
          
    This combination had a response range of 40-50% in the various series so far reported. Grade 3 and 4 neutropenia was the main toxicity.
          
    Paclitaxel and 5-fluorouracil (5-FU) have been tried with very variable dosing schedule of 5-FU. The response rates range from 40-62%.
            
    Paclitaxel and platinum have been tried in metastatic breast cancer patients. The biweekly sequential combination has impressive response rate.
          
    Paclitaxel has been integrated in adjuvant programs for primary breast cancer. 
          
    CALGB 93-94 presented at ASCO 98 compared node-positive breast cancer patients to four cycles of cyclophosphamide (CA) + adriamycin followed by paclitaxel 175 mg/m2 four cycles or not. 
         
    At median follow-up of 18 months the sequential addition of Taxol to CA improved the disease free survival and overall survival. Similar encouraging results by Hudis who used intensive adjuvant chemotherapy with doxorubicin followed by paclitaxel and then cyclophosphamide 3 gm/m2 the preliminary results reveal 81% of patients relapse free at a median follow-up of more than 3 years.
          
    Paclitaxel and adriamycin have also been incorporated in neoadjuvant setting for breast cancer.
          
    Taxol in management of ovarian cancer:
         
    Paclitaxel 175 mg/m2 in a 3 hour infusion is now considered a standard regimen in most of Europe. The phase I-II weekly paclitaxel at 80 mg/m2 have also been reported equivalent results.
         
    Argentine group reported 39% response in advanced ovarian cancers after first-line failure.
         
    The efficacy of carboplatinum-paclitaxel combination seems to be similar to cisplatinum-paclitaxel combination in ovarian cancer.
           
    The three drug combination cyclophosphamide + paclitaxel + cisplatinum although has a good response but due to the toxicity whether they would really add any benefit in terms of activity to toxicity ratio is not clear.
          
    The GOG 111 and larger European Canadian intergroup have favored the use of paclitaxel with platinum in advanced ovarian cancer and naive of treatment whereas GOG 132 published contradictory results and revealed platinum as the main stay drug for ovarian cancer.
          

  • Point
    C. Lin Puckett (Division of Plastic and Reconstructive Surgery, University of Missouri Health Sciences Center, Columbia, Missouri, President, American Society of Plastic Surgeons)
    On the safety of silicone gel breast implants
    Cancer Investigation 2000 Vol. 18 (3) Pg. 278-280
      
    The 1990 sensational reporting of association of gel-filled breast implants being dangerous and it’s association with collagen diseases led to the ban by FDA for general use, except, reconstructive patients.
       
    Recent studies however failed to demonstrate this association and a fascinating corollary found in many studies was the decreased incidence of breast cancer in the implanted patients.
       
    The complication such as scar formation around the prosthesis or capsule contracture can result in excessive firmness, there are manufacturing flaws or effects of stress and time.
      
    The surgery of implanted patients reveals an overall satisfaction rate of > 95%.
       

  • Counterpoint
    Gary Solomon (Hospital for Joint Diseases, Orthopedic Institute, New York, New York)
    Are Silicon Gel Breast Implants Safe?
    Cancer Investigation 2000 Vol. 18 (3) Pg. 281-284
      
    Silicone gel breast implants have local complications including painful capsular contracture, implant rupture with spillage of silicone resulting into silicone granulomas, infection and axillary adenopathy. The rupture rates approximate 50% by year 15 after implantation and approach 100% over time.
      
    Older studies had associated silicon gel breast implant and systemic illness most notably an atypical connective tissue disease (ACTD).
       
    However recent epidemiologic studies could not verify this association.
          

  • Evangelia Razis, Athanassios-Meletios Dimopoulos, Dimitris Bafaloukos, Christos Papadimitriou, Anna Kalogera-Fountzila, Haralambos Kalofonos, Evangelos Briassoulis, Epaminontas Samantas, Antonios Keramopoulos, Nicholas Pavlidis, Paris Kosmidis, and George Fountzilas (Hygeia Hospital, Maroussi, Athens, Greece; Alexandra Hospital, Athens, Greece; Metaxa Cancer Hospital, Piraeus, Greece; University of Patras, Patras, Greece; University of Ioannina, Ioannina, Greece; Agii Anargyri Cancer Hospital, Athens, Greece; AHEPA Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece)
    Dose-Dense Sequential Chemotherapy with Epirubicin and Paclitaxel in Advanced Breast Cancer
    Cancer Investigation 2001 Vol. 19 (2) Pg. 137-144
         
    Dose dense chemotherapy is administration of anti cancer drugs sequentially at adequate dose as single agents in short intervals for increasing the dose intensity. 
          
    This study of 41 patients with recurrent or metastatic (stage IV) breast cancer, half of whom had received prior chemotherapy now received four cycles of epirubicin 100 mg/m2 every 2 weeks followed by four cycles of paclitaxel 225 mg/m2 every 2 weeks along with G-CSF.
           
    CR was possible in 19.5% and partial response 36.5%. These results are inferior to the combination of paclitaxel and doxorubicin. However the cardiac toxicity and febrile neutropenia were also less frequent in the present study and this was possible with better dose intensity (DI) of paclitaxel 112.5 mg/m2 per week and doxorubicin 55 mg/m2 per week compared to 66.6 mg/m2 per week and 30 mg/m2 per week respectively. 
            
    The reason of inferior response in this study could be due to lesser numbers of courses of each drug or may be due to inadequate length of therapy. 
          
    An ongoing randomized study of same sequential regimen with epirubicin and paclitaxel every 3 weeks for 6 courses will throw more light on the above issues.
              

  • Edith A. Perez (Mayo Foundation and Mayo Clinic Jacksonville, Jacksonville, Florida)
    Doxorubicin and Paclitaxel in the Treatment of Advanced Breast Cancer: Efficacy and Cardiac Considerations 
    Cancer Investigation 2001 Vol. 19 (2) Pg. 155-164
           
    Doxorubicin and paclitaxel are highly active agents in the treatment of breast cancer. The earlier trials of this combination yielded good response rates associated with high congestive heart failure depending on the dose of doxorubicin, approx 21% with median cumulative dose of 480 mg/m2 and was also associated with cardiac risk factors such as hypertension, obesity, radiation to the left side of chest wall or familial history of heart disease. The overall response rates ranged from 53 to 80%. The overall responses and median time to progression were statistically superior for combination compared to single agents, however there was no difference in overall survival. 
           
    In view of the congestive heart failure the cumulative doxorubicin dose was £360 mg/m2. The pharmacokinetic study has revealed that the clearance of doxorubicin is decreased by 30% when administered shortly before or after 3-hour infusion of paclitaxel.
          
    The doxorubicinol a major metabolite of doxorubicin was also increased more than two fold leading to increase cardiac toxicity. 
             

  • R. Colomer, L. A. Shamon, M. S. Tsai and R. Lupu (Hospital 12 de Octubre, Madrid, Spain; Ernest O. Lawrence Berkeley National Laboratory, University of California, Berkeley, California)
    Herceptin: From the Bench to the Clinic
    Cancer Investigation 2001 Vol. 19 (1) Pg. 49-56
            
    The erbB-2 oncogene product is expressed in 25-30% of breast patients. The tyrosine kinase transduction appears to play an important role in breast cancer progression and metastasis.
             
    The antibody 4D5 directed against the extracellular domain of erbB-2 overexpressing cells was identified for preclinical studies, it was found to downregulate erbB-2 protein levels and inhibit growth of erbB-2 overexpressing breast cancer cells. The humanization of murine monoclonal anti-erbB-2 antibody, 4D5 was termed herceptin. 
            
    This agent has been approved by FDA as a single agent for the treatment of patients with metastatic breast cancer whose tumor overexpress erbB-2 protein ++ expression (>10% of cells weakly positive) or +++ expression (>10% of cells strongly positive) and have failed previous chemotherapy regimens.
             
    Paclitaxel with herceptin has also been approved by FDA as first line in metastatic breast cancer. Herceptin as single agent in first line had 23% response rate and 31% clinical benefit (response plus stable disease longer than 6 months).
            
    Paclitaxel with herceptin had response rate of 57% vs 25% for paclitaxel alone. Herceptin and chemotherapy particularly paclitaxel yielded longer time to disease progression with median time to 8.6 months compared to 5.5 months.
            
    An increase in cardiac toxicity was observed in combination of herceptin with anthracycline. As a single agent herceptin, the cardiac dysfunction was 4% and could be worrisome.
           

  • Andrew W. Menzin, and David Gal (Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, et al)
    Point/Counterpoint Series
    Point: Should Women Receiving Tamoxifen Be Screened for Endometrical Cancer? An Argument for Screening 
    Cancer Investigation 2001 Vol. 18 (8) Pg. 793-795
         
    The Swedish and NSABP-14 trial support a propensity to develop endometrial cancer as a result of exposure to TMX (Tamoxifen). 
           
    The length of treatment and the cumulative dose of TMX were significantly associated with high risk of endometrial cancer. However NSABP-14 results do not support this statement and have clearly noted that quantitative benefits of TMX well outweigh the impact of endometrial cancer risk.
          
    Increasing age with personal history of breast cancer is generally accepted as high risk for development of endometrial cancer following TMX and this subgroup would benefit from screening.
           
    The efficient modality for screening of endometrial cancer is not clear. The sonographic thickening of the endometrial stripe is the absence of pathologic change is well known. The invasive technique of sonohysterography is believed to be more accurate screening technique.
           
    Endometrial sampling as the primary modality has been recommended by the authors with the ancient instrument being only few mm in diameter and flexible are well tolerated and have a high rate of successful sampling.
           
    Yearly gynecologic evaluation is the minimum, the NSABP-14 researches have recommended for women on adjuvant TMX.
           

  • Richard R. Barakat (Gynecology Service, Department of Surgery, et al)
    Counterpoint: Should Women Receiving Tamoxifen for Breast Cancer Be Screened for Endometrial Cancer?
    Cancer Investigation 2001 Vol. 18 (8) Pg. 796-797
           
    Screening procedure should detect cancer at earlier stage and thereby improve survival. To date no screening techniques for endometrial cancer following TMX have been identified.
          
    Endometrial sampling for symptomatic patients may be reasonable modality however post menopausal women with stenotic cervices would pose difficulty.
          
    Transvaginal sonography provides a noninvasive means of screening for endometrial pathology. An endometrial stipe of > 8 mm has a 100% predictive for an endometrial pathology (atypical hyperplasia or polyps).
           
    The authors recommend all women whether or not receiving Tamoxifen should undergo annual gynecologic evaluation, which would include endometrial sampling especially in the presence of abnormal vaginal bleeding or discharge.
           

  • Ian E. Smith and Lara Lipton (The Breast Unit, Royal Marsden NHS Trust, London, UK)
    Preoperative/Neoadjuvant Medical Therapy For Early Breast Cancer
    The Lancet Oncology September 2001 Vol. 2 (9) Pg. 561-570
       
    The aim of preoperative medical therapy in early breast cancer is to downstage the tumour so as to avoid mastectomy. Chemotherapy combination routinely used such as cyclophosphamide + adriamycin + 5-fluorouracil (CAF) or cyclophosphamide + methotrexate + 5-fluorouracil + (CMF) or CA, when used preoperatively had no survival advantage. The NSABP – B-18 used cyclophosphamide + adriamycin before or after surgery for early breast cancer and there was no survival benefit at 5 year follow-up for both groups.
      
    Newer chemotherapy schedules are also not likely to have any survival advantage. Studies from Bonadonna and colleagues have revealed that with tumors more than 5cms are difficult candidates for conservative mastectomy. Thus down staging the disease could lead to conservative mastectomy (lumpectomy).
      
    This beneficial trend of lumpectomy following preoperative chemotherapy may be associated with small increase in the risk of local recurrence but without any difference in survival. The potential predictive factors for preoperative chemotherapy are clinical tumor response, attainment of complete clinical response is an essential prerequisite for improved survival.
     
    Complete pathological response has also emerged as clear cut predictor of survival. Persistent involvement of pathological nodes is a predictor for poor response. The biological factor that predict favorable outcome are high apoptotic index, low Ki-67 antigen.
      
    Estrogen receptor expression and absence of cERB 2 had better outlook.
      
    Of the endocrine therapy letrozole for 4 months as preoperative therapy indicated 55% response rate as compared with 36% for tamoxifen. Whether this short term benefit is translated to improved survival is not clear at present.    
              

  • Carolyn I. Sartor (Department of Radiation Oncology and Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, USA)   
    Postmastectomy Radiotherapy in Women with Breast Cancer Metastatic to One to Three Axillary Lymph Nodes
    Current Oncology Reports Vol. 3(6) November 2001 Pg. 497-505   
                     
    Breast cancer progression is believed to be a hybrid of Halstedian and Fisher hypothesis i.e. it begins as a local disease and evolves to systemic disease. Thus a subset of population in whom local therapy could be curative and in whom local failure could lead to distant metastasis. 
                            
    A meta-analysis revealed randomized radiotherapy led to significant reduction in risk of death due to breast cancer improving the breast cancer specific survival from 48.6% to 53.4% at 20 years. 
                                       
    However non-breast cancer deaths were on the risk in patients with local radiotherapy. The Danish trial revealed benefit of post mastectomy chest wall radiotherapy (PMCWRT) to patients with 1-3 lymph nodes. High survival benefit in this subgroup was seen only in one trial. 
                                       
    The number of lymph node removed is again an important factor and under evaluation or lesser lymph node excised may contribute to high risk of LLR. Anthracycline based CT does not appear to decrease the indication for PMCWRT. Extracapsular extension involvement of skin, nipple and lymph node is a important predictor of locoregional recurrence (LRR). 
                                                           
    20-30% of patients with axillary lymph node has IMN and left ant-descending artery remain within the typical field of local RT if all 5 interspaces are treated. The 1998 American society for therapeutic radiology concluded that evidence for PMCWRT for T1- – T2 tumors and 1-3 involved lymph node is dismal and hence routine PMCWRT is not recommended in this subgroup.     
                                                          

  • Julie R. Gralow (Seattle Cancer Care Alliance, University of Washington School of Medicine, USA)  
    The Role of Bisphosphonates as Adjuvant Therapy for Breast Cancer  
    Current Oncology Reports Vol. 3(6) November 2001 Pg. 506-515  
                                                                    
    Bone is the most common site of distant recurrence in breast cancer. Patient with bone metastasis have a median survival of 3 years and 5 years survival rate 20%. This allows the bony metastasis for various skeletal related problems. 
                                                                 
    Bisphosphonates reduce the skeletal related events and symptoms by 30 to 40% in breast cancer patients. Etidronate is the first generation bisphosphonate and is the least potent inhibitor of bone resorption whereas zoledronate and ibandronate represent the third generation. Oral bisphosphonate are compromised by poor absorption and esophagitis. 
                                                                        
    In the treatment of bony metastasis from breast cancer bisphosphonates are commonly used in conjunction with anti neoplastic agents to reduce the skeletal related events. Ibandronate is a highly potent bisphosphonate. It improved the event free survival of the patient with metastatic breast cancer in a phase III placebo controlled trial. ASCO guidelines states the use of injection pamidronate 90mg IV over 1-2 hours every 3-4 weeks in patients with metastatic breast cancer along with chemotherapy or hormonal therapy. 
                                                                      
    Bone sialoprotein is a non collagenous matrix protein high levels have predicted bony metastasis. Elevated levels of collagen cross links, pyridinoline and deoxypyridinoline and N-telopeptide (NTX) are excreted in urine with intensified bony activpity. Suppression of osteoclastic activity correlates with normalization of NTX and hence NTX would be useful for monitoring bisphosphonates utility.                       
                                                                                                                                               

  • Edith A. Perez (Division of Hematology/Oncology, Mayo Clinic and Mayo Foundation, USA)
    The Role of Adjuvant Monoclonal Antibody Therapy for Breast Cancer: Rationale and New Studies 
    Current Oncology Reports Vol. 3(6) November 2001 Pg. 516-522  
                                                                                
    HER2 a member of epidermal growth factor receptor family of tyrosine kinases and is involved in the growth, invasion, metastasis, and prognosis of breast cancer. HER2-positive tumors are more likely to relapse and die from their disease, compared to those with HER2-negative breast tumors.                
                                                                              
    A meta-analysis revealed patients over expressing HER2 are more resistant to hormonal treatment. Some studies have indicated HER2 positive breast tumors receive more benefit from doxorubicin-based therapies.  
                                                            
    Anti HER2 therapy is a monoclonal antibody treatment directed specifically against the HER2 protein. This therapy was found to have approximately 25% response rates as a single agent in metastatic breast cancer. The response is best in patients with immunohistochemistry 3+ for HER2. The other method for evaluation of HER2 protein is FISH, which evaluates HER2 gene amplification.       
                                                                              
    The addition of anti HER2 to chemotherapy such as AC or paclitaxel showed an improvement in overall response rates. However when administered with adriamycin cardiotoxicity was a problem. Paclitaxel + anti HER2 was well tolerated. The other chemotherapy agent used with anti HER2 are the combinations of paclitaxel + carboplat or docetaxel + cisplat or single agent vinorelbine.  
                                          
    The newer studies have incorporated herceptin in adjuvant therapy for breast cancer. However the cumulative dose of adriamycin being limited to 240 mg/m2 and herceptin being given once every 3 weekly based on clinical and pharmacokinetic data.                                                                                  
                                         

  • Lawrence N. Shulman (Dana-Farber Cancer Institute/Brigham and Women’s Hospital, USA)
    What is the Ideal Duration of Adjuvant Therapy for Primary Breast Cancer: Are Four Cycles of Cyclophosphamide and Doxorubicin Enough?
    Current Oncology Reports Vol. 3(6) November 2001 Pg. 523-528
                  
    The adjuvant trials of breast cancer demonstrates a modest but significant survival advantage for chemotherapy over no postoperative treatment. Inspite of these studies the duration of adjuvant therapy are not known and this is due to many other variables such as choice of agents, intensity, number of courses rather than duration and the results of adjuvant trials take 7-10 years to give mature results. 
                          
    Bonadonna’s earlier study had revealed 12 cycles of CMF, was as efficacious as 6 cycles of CMF. The International Breast Cancer Study Group study demonstrated 3 cycles of CMF were inferior to 6 courses of CMF. 
                           
    The (NSABP) B-15 study of 1984 and reported in 1990, equal efficacy of four cycles of cyclophosphamide and doxorubicin once every 3 weeks for 3 months to 6 cycles of oral CMF. 
                         
    The NSABP B-23 also confirmed similar findings in women with node negative breast cancer. Studies have revealed further dose escalation of cyclophosphamide above 600 and adriamycin above 60 is not useful. 
                              
    The National Cancer Institute of Canada (NCIC) designed a trial for comparison of CMF v/s CEF. In this study women receiving CEF had superior disease free and overall survival.
                           
    A study by Piccart compared epirubicin and cyclophosphamide (EC), two dose levels v/s CMF. This study reports CF (low dose) to be inferior to CMF whereas high dose EC and CMF had equivalent results. The role of paclitaxel in adjuvant setting is still not clear.                                     
                                                        

  • Sharon E. Soule and Kathy D. Miller (Indiana University School of Medicine, USA)
    Adjuvant Chemotherapy for Tumors of One Centimeter or Less: The Law of Diminishing Returns
    Current Oncology Reports Vol. 3(6) November 2001 Pg. 529-535
                                              
    The NSABP B-19 randomly assigned women without lymph node metastases to CMF and MF. Those patients treated with CMF experienced an increase in overall survival and disease free survival. 
                                                     
    The most recent Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) analysis revealed combination chemotherapy produced a 23.5% relative reduction in the annual hazards of recurrence and a 15.3% relative reduction in annual hazards of death.
                                     
    Studies have revealed that this favorable group of patients (less than 1 cm tumor) had overall survival rate 90-99% and the absolute benefit of chemotherapy is most likely 1% or less.
                                           
    Adjuvant chemotherapy has some serious long term toxicities such as cardiac dysfunction, treatment related leukemia, premature ovarian failure and long term cognitive defects. 
                                         
    These results do not justify adjuvant chemotherapy for breast cancer patients with less than a cm tumor.           
       

  • Ruth M O’Regan and V Craig Jordan (Comprehensive Cancer Center, Northwestern University Medical School, Chicago, USA)
    The Evaluation of Tamoxifen Therapy in Breast Cancer: Selective Oestrogen-Receptor Modulators and Downregulators
    The Lancet Oncology April 2002; Vol. 3(4): 207-14
      
    The earlier studies on rats revealed that tamoxifen had antifertility activity and could prevent rat mammary carcinogenesis. It was subsequently found to block the estrogen binding to human estrogen receptor (ER). Studies on advanced breast cancer showed responses in approximately 40-60% patients with ER positive tumors.
      
    The Oxford overview analysis conclusively showed that 5 years of tamoxifen treatment not only reduces the rate of recurrence of early breast cancer but also improved the survival. Studies in a advanced breast cancer showed patients with ER/PR positive benefited from tamoxifen as adjuvant. The recent NSABP chemoprevential trial showed that tamoxifen significantly reduces the frequency of invasive breast cancer and ductal carcinoma in situ by about 50% in high risk women.
     
    The recognition of selective oestrogen receptor modulation (SERM) by tamoxifen and its related nonsteroidal compound, acting as antioestrogen on the breast and mammary gland while acting as partial antioestrogen on the uterus has captured the imagination of medical chemists to design new drugs for the host of oestrogen modulated diseases. The side effects associated with tamoxifen apart from increased incidences of thromboembolism is the drug resistance.
      
    The other endocrine agent in breast cancer are Raloxifene widely used for prevention of osteoporosis however its effectively in breast cancer vis a vis tamoxifen is studied in the STAR trial. The results of which would be available by 2005. The long acting raloxifene LY353, 381. HCL (arzoxifene) is being developed for breast cancer treatment and prevention.
      
    The other nonsteroidal antioestrogen ICI 164, 384 has antioestrogen effect in all target tissues. This is by premature destruction of the estrogen receptor.
     
    The aromatase inhibitors act by preventing the conversion of andcostenedione and testerone to oestrogen by inhibiting the aromatase-enzymes complex competitively (anastrazole and letrzole) or non competitively (exemestame) in peripheral tissues and tumors of postmenopausal women.
       

  • Rockhill B, Spiegelman D, et al (Harvard Med School, Boston)
    Validation of the Gail et al Model of Breast Cancer Risk Prediction and Implications for Chemoprevention
    J Natl Cancer Inst 93: 358-366, 2001
       
    The primary model by Gail et al (model 1) is a large case cohort subsample and provides an estimate of the probability that a woman who has annual breast cancer screening performance will develop invasive or in situ breast cancer over a defined age interval.
    The model 2 is a modification to predict the risk of invasive breast cancer based on data from the Surveillance, Epidemiology and End Results program. Data from 82,109 white women 45 to 71 who participated in the Nurses Health Study (NHS). During follow-up there were 1354 cases of invasive breast cancer in the NHS cohort. Model 2 predicted 1273 cases and hence the ratios of expected (E) : Observed (O) was 0.94. The goodness of fit was better for those undergoing screening, but was poor if the results were based on number of first degree relatives with invasive breast cancer.
      
    Thus, the discriminating accuracy of model 2 in NHS cohort was modest. In view of this modest discriminatory accuracy with only 3.3% of the 1354 cases of breast cancer occurring in the high risk group and hence the chemopreventive strategy of tamoxifen would not have major impact.
       

  • Colleoni M, for the International Breast Cancer Study Group (European Inst of Oncology, Milan, Italy; et al)
    Early Start of Adjuvant Chemotherapy May Improve Treatment Outcome for Premenopausal Breast Cancer Patients With Tumors Not Expressing Estrogen Receptors
    J Clin Oncol 18: 584-590, 2000
      
    This study based on data obtained on 1788 premenopausal node-positive women treated in International Breast Cancer Study Group (IBCSG) trials I, II, and VI. Among patients with estrogen receptor (ER)-negative tumors early adjuvant chemotherapy was associated with a 60%, 10-year disease-free survival compared with 34% for later chemotherapy (more than 3 week following surgery).
      
    However for ER positive tumors this difference was not significant. The authors express concern that in many current trials of adjuvant chemotherapy allowing up to 12 weeks between surgery and initiation of adjuvant therapy, may require to be redefined.
       

  • Kaufmann M, for the Exemestane Study Group (Universitatsklinik, Frankfurt, Germany; et al)
    Exemestane Is Superior to Megestrol Acetate After Tamoxifen Failure in Postmenopausal Women With Advanced Breast Cancer: Results of a Phase III Randomized Double-blind Trial
    J Clin Oncol 18: 1399-1411, 2000
      
    The novel aromatase inactivator exemestane was compared to megestrol acetate (MA) in postmenopausal women with progressive advanced breast cancer unresponsive to tamoxifen.
      
    Exemestane 25 mg/day could prolong survival time, time to tumor progression and time to treatment failure compared with MA 40 mg four times a day.
      
    These results suggest that an aromatase inhibitor should be hormonal treatment of choice after an antiestrogen in those who respond to antiestrogen and later relapse. The author’s concern in this study is a modest response and short time to progression (5 months or less) for both the hormonal therapy arms and thereby administering chemotherapy particularly for these chemonaive patients would be more beneficial.
       

  • Paridaens R, for the European Organization for Research and Treatment of Cancer-Investigational Drug Branch for Breast Cancer/Early Clinical Studies Group (Univ Hosp Gasthuisberg, Leuven, Belgium; et al)
    Paclitaxel Versus Doxorubicin as First-Line Single-Agent Chemotherapy for Metastatic Breast Cancer: A European Organization for Research and Treatment of Cancer Randomized Study With Cross-over
    J Clin Oncol 18: 724-733, 2000
       
    This study randomly assigned 331 patients with metastatic breast cancer to paclitaxel 200 mg/m2, 3 hours infusion every 3 weeks to doxorubicin 25 mg/m2 bolus every 3 weeks. The objective response in first line treatment was significantly better with doxorubicin than that with paclitaxel, 41% vs 25% respectively and longer median progression free survival 7.5 months vs 3.9 months respectively.
       
    In second line treatment when crossed over the response rates favoured doxorubicin. 30% compared to 16% with paclitaxel whereas median survival duration had a nonsignificant difference. These two agents are not completely cross-resistant, which suggests that the need for further research on these drugs in combination or in sequence would be worth while.
      
    The authors comment that the results of this study contrast with the results of intergroup study in the United States that did not reveal any significant difference between doxorubicin and paclitaxel although the dose and schedules were different.
       

  • Stadtmauer EA, and the Philadelphia Bone Marrow Transplant Group (Univ of Pennsylvania, Philadelphia; et al)
    Conventional-Dose Chemotherapy Compared With High-Dose Chemotherapy Plus Autologous Hematopoietic Stem-Cell Transplantation for Metastatic Breast Cancer
    N Engl J Med 342: 1069-1076, 2000
        
    This study by Philadelphia bone marrow transplant group had 553 patients with metastatic breast cancer, 18 to 60 years of age and who had a partial response to 4-6 courses of standard combination chemotherapy.
       
    These were randomised to single course of high dose carboplatinum, thiotepa, and cyclophosphamide followed by autologous hematopoietic stem cell transplantation and other group received conventional CMF up to 24 months.
       
    The 3-year overall survival was 32% in transplant group as compared to 38% in conventional chemotherapy neither there was a significant difference in median time to progression. The transplantation group had higher rate of serious adverse effects without any survival benefit.
       

  • Hortobagyi GN, Buzdar AU, et al (Univ of Texas MD Anderson Cancer Ctr, Houston; Yale Univ, New Haven, Conn)
    Randomized Trial of High-Dose Chemotherapy and Blood Cell Autografts for High-Risk Primary Breast Carcinoma
    J Natl Cancer Inst 92: 225-233, 2000
       
    This prospective randomized study enrolled 78 patients with 10 or more positive axillary lymph nodes after primary breast surgery or with 4 or more positive axillary lymph nodes after 4 cycles of primary chemotherapy.
       
    31 received 8 courses of 5-Fluorouracil, Adriamycin, and, Cyclophosphamide (FAC) and 39 were assigned to FAC followed by high-dose chemotherapy (HDC).
        
    The addition of HDC to FAC conferred no relapse free or overall survival advantage.
      

 

By |2022-07-20T16:44:05+00:00July 20, 2022|Uncategorized|Comments Off on Breast Cancer

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