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respond initially to a SERM or AI but later manifest progressive disease may be crossed over to cytotoxic drugs Androgens have many toxicities and should rarely be used As in premenopausal patients, neither hypophysectomy nor adrenalectomy is being performed
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Cytotoxic drugs should be considered for the treatment of metastatic breast cancer (1) if visceral metastases are present (especially brain or lymphangitic pulmonary), (2) if hormonal treatment is unsuccessful or the disease has progressed after an initial response to hormonal manipulation, or (3) if the tumor is ER-negative Prior adjuvant chemotherapy does not seem to alter response rates in patients who relapse The most useful chemotherapeutic agent to date is doxorubicin, with a response rate of 40 50% Combination chemotherapy with multiple agents has proved to be more effective, with objectively observed favorable responses achieved in 60 80% of patients with stage IV disease (see Tables 40 3 and 40 4) Doxorubicin (40 mg/m2 intravenously on day 1) and cyclophosphamide (200 mg/m2 orally on days 3 6) produce an objective response in about 85% of patients so treated Various combinations of drugs have been used, and clinical trials are always ongoing to identify a combination to increase survival and reduce side effects Other chemotherapeutic regimens have consisted of various combinations of drugs, including cyclophosphamide, vincristine, methotrexate, fluorouracil, and taxanes with response rates ranging up to 60 70% Researchers continue to study new drugs and combinations of chemotherapy agents, such as capecitabine, mitoxantrone, vinorelbine, gemcitabine, irinotecan, cisplatin, and carboplatin Many of these agents or combinations are available to patients in a clinical trial setting or by physician s choice For patients whose tumors have progressed after many therapies and who are considering additional therapy, clinical trial participation with experimental drugs in phase I, II, or III testing should be encouraged Although infrequent, single agent use with taxanes (paclitaxel and docetaxel) has been shown to be very effective for patients with metastatic breast cancer, with a response rate of 30 40% They have usually been given after failure of combination chemotherapy for metastatic disease or relapse shortly after completion of adjuvant chemotherapy They may be especially valuable in treating anthracycline-resistant tumors High-dose chemotherapy and autologous bone marrow or stem cell transplantation aroused widespread interest for the treatment of metastatic breast cancer With this technique, the patient receives high doses of cytotoxic agents, eradicating the marrow, for which the patient subsequently undergoes autologous bone marrow or stem cell transplantation Most randomized trials, however, comparing high-dose chemotherapy with stem cell support showed no improvement in survival over conventional chemotherapy Enthusiasm for high-dose chemotherapy with stem cell support has waned, but additional studies continue and recently showed a beneficial effect in some high-risk women The technique is extremely costly, and the treatment itself is associated with a mortality rate of about 3 7%
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tant prognostic variables, but no markers are as significant as lymph node metastases in predicting outcome (see Biomarkers) The histologic subtype of breast cancer (eg, medullary, lobular, colloid) seems to have little significance in prognosis of invasive carcinomas Flow cytometry of tumor cells to analyze DNA index and S-phase frequency aid in prognosis Tumors with marked aneuploidy have a poor prognosis (see Table 16 4) The mortality rate of breast cancer patients exceeds that of age-matched normal controls for nearly 20 years Thereafter, the mortality rates are equal, though deaths that occur among breast cancer patients are often directly the result of tumor Five-year statistics do not accurately reflect the final outcome of therapy When cancer is localized to the breast, with no evidence of regional spread after pathologic examination, the clinical cure rate with most accepted methods of therapy is 75% to greater than 90% Variations to this generalization may be related to the hormonal receptor content of the tumor, tumor size, host resistance, or associated illness Patients with small mammographically detected biologically favorable tumors and no evidence of axillary spread have a 5year survival rate greater than 95% When the axillary lymph nodes are involved with tumor, the survival rate drops to 50 70% at 5 years and probably around 25 40% at 10 years In general, breast cancer appears to be somewhat more malignant in younger than in older women, and this may be related to the fact that fewer younger women have ER-positive tumors For those patients whose disease progresses despite treatment, studies suggest supportive group therapy may improve survival As they approach the end of life, such patients will require meticulous efforts at palliative care (see 5)
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Hayes DF Prognostic and predictive factors for breast cancer: translating technology to oncology J Clin Oncol 2005 Mar 10;23(8):1596 7 [PMID: 15755959]
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Bhatnagar AS Review of the development of letrozole and its use in advanced breast cancer and in the neoadjuvant setting Breast 2006 Feb;15 Suppl 1:S3 13 [PMID: 16500235] Gould RE et al Update on aromatase inhibitors in breast cancer Curr Opin Obstet Gynecol 2006 Feb;18(1):41 46 [PMID: 16493259] Howell A et al; ATAC Trialists Group Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years adjuvant treatment for breast cancer Lancet 2005 Jan 1 7;365(9453):60 2 [PMID: 15639680] Ingle JN et al; North Central Cancer Treatment Group Trial N0032 Fulvestrant in women with advanced breast cancer after progression on prior aromatase inhibitor therapy: North Central Cancer Treatment Group Trial N0032 J Clin Oncol 2006 Mar 1;24(7):1052 6 [PMID: 16505423] Joensuu H et al; FinHer Study Investigators Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer N Engl J Med 2006 Feb 23;354(8):809 20 [PMID: 16495393] Kaasa S et al Prospective randomised multicenter trial on single fraction radiotherapy (8 Gy x 1) versus multiple fractions (3 Gy x 10) in the treatment of painful bone metastases Radiother Oncol 2006 Jun;79(3):278 84 [PMID: 16793154] Kim T et al Lymphatic mapping and sentinel lymph node biopsy in early-stage breast carcinoma: a metaanalysis Cancer 2006 Jan 1;106(1):4 16 [PMID: 16329134] Leonard C et al Prospective trial of accelerated partial breast intensity-modulated radiotherapy Int J Radiat Oncol Biol Phys 2007 Jan 16; [Epub ahead of print] [PMID: 17234359] Mamounas EP et al Sentinel node biopsy after neoadjuvant chemotherapy in breast cancer: results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27 J Clin Oncol 2005 Apr 20;23(12):2694 702 [PMID: 15837984] Slamon DJ et al Advances in adjuvant therapy for breast cancer Clin Adv Hematol Oncol 2006 Mar;4(3) Suppl 1:4-9 [PMID: 16736568] Smith I Goals of treatment for patients with metastatic breast cancer Semin Oncol 2006 Feb;33(1 Suppl 2):S2 5 [PMID: 16472711] Smith I et al 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial Lancet 2007 Jan 6;369(9555):29 36 [PMID: 17208639] Stolier AJ et al Postlumpectomy insertion of the MammoSite brachytherapy device using the scar entry technique: initial experience and technical considerations Breast J 2005 May Jun;11(3):199 203 [PMID: 15871706] Vinh-Hung V et al Breast-conserving surgery with or without radiotherapy: pooled-analysis for risks of ipsilateral breast tumor recurrence and mortality J Natl Cancer Inst 2004 Jan 21;96(2):115 21 [PMID: 14734701] Voogd AC et al Prognosis of patients with locally recurrent breast cancer Am J Surg 2007 Jan;193(1):138 [PMID: 17188110]
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