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the tumors overexpress HER-2/neu The use of anthracyclines is superior to combinations without anthracyclines Tamoxifen should be used as a systemic agent in all women whose tumors are hormone receptor positive regardless of age, menopausal status, or other prognostic factors HER-2/neu status should not affect the choice of cytotoxic agents or the use of hormone therapy Ovarian ablation in premenopausal patients with ER-positive tumors may produce a benefit similar to that of adjuvant systemic chemotherapy Taxanes have demonstrated benefit in patients with metastatic cancer and are being used in node-negative patients Adjuvant systemic therapy should not be given to women who have small node-negative breast cancers with favorable histologic findings and tumor markers such as mucinous or tubular carcinoma, ER-positive, low grade In practice, most medical oncologists are currently using systemic adjuvant therapy for patients with either node-negative or node-positive breast cancer Prognostic factors other than nodal status being used to determine the patient s risks are tumor size, ER and PR status, nuclear grade, histologic type, proliferative rate, and oncogene expression (Table 16 4) The assumption is made that all patients with node-negative aggressive tumors should receive adjuvant therapy except those who have serious coexistent medical problems In general, systemic chemotherapy decreases the chance of recurrence by about 30% Most patients tolerate at least tamoxifen
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adjuvant chemotherapy but is certainly no worse There was considerable concern as to the timing of sentinel lymph node biopsy (SLNB), since the chemotherapy may affect any cancer present in the lymph nodes After several studies, it is still unclear as to the appropriate timing of the procedure A large multicenter study, NSABP B-27, demonstrated a false-negative rate was as high as 107%, well above the false-negative rate outside the neoadjuvant setting (< 1 5%) Many physicians recommend performing SLNB before administering the chemotherapy in order to avoid a false-negative result If a complete dissection is necessary, this can be completed at the time of the definitive surgery Important questions remaining to be answered are the timing and duration of adjuvant and neoadjuvant chemotherapy, which chemotherapeutic agents should be applied for which subgroups of patients, the use of combinations of hormonal therapy and chemotherapy, and the value of prognostic factors other than hormone receptors in predicting response to therapy Adjuvant systemic therapy is not generally used in patients with small tumors and those with negative lymph nodes who have favorable tumor markers However, a small disease-free survival benefit, even in patients with small favorable tumors, has been suggested It appears that adjuvant systemic therapy benefits all breast cancer patients, but the clinician and patient must decide if the benefits outweigh the risks, complications, and expense
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E Neoadjuvant Therapy
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The use of chemotherapy or hormonal therapy prior to resection of the primary tumor (neoadjuvant) is gaining popularity This enables the assessment of in vivo chemosensitivity A complete tumor response in vivo prior to operation appears to be associated with improvement in survival Neoadjuvant chemotherapy also permits breast conservation by shrinking the primary tumor in women who would otherwise need mastectomy for local control Survival after neoadjuvant chemotherapy has not been shown to be superior to that seen with postoperative
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A Radiotherapy
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Palliative radiotherapy may be advised for primary treatment of locally advanced cancers with distant metastases to control ulceration, pain, and other manifestations in the breast and regional nodes Irradiation of the breast and chest wall and the axillary, internal mammary, and supraclavicular nodes should be undertaken in an attempt to cure locally advanced and inoperable lesions when there is no evidence of distant metastases A small number of patients in this group are cured in spite of extensive breast and regional node involvement Palliative irradiation is of value also in the treatment of certain bone or soft-tissue metastases to control pain or avoid fracture Radiotherapy is especially useful in the treatment of isolated bony metastases, chest wall recurrences, brain metastases, and acute spinal cord compression
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