Anthracylines (A) were more commonly used in the adjuvant and metastatic treatment of breast cancer than any other agents. A large randomized NSABP study compared CMF with AC regimens in node-positive patients and found similar treatment outcomes among both groups. The AC regimen was preferred because of its shorter duration (four cycles for 3 months vs. six cycles for 6 months) and better tolerance (101).
Several landmark trials showed that taxanes such as paclitaxel and docetaxel in combination with anthracyclines have significant efficacy and are the new standard adjuvant therapy for node-positive breast cancer. The Cancer and Leukemia Group B was the first to show a 17% improvement in the rate of recurrence and 18% reduction in the rate of death with the addition of paclitaxel to cyclophosphamide (102). Given concerns over the cardiotoxicity of anthracyclines as well as the 0.21% risk of leukemia after the AC regimen at 5 years, a US oncology trial randomized stage I, II, and III patients to AC or docetaxel and cyclophosphamide (TC) every 3 weeks for four cycles and found that after 7 years’ follow-up disease-free survival and overall survival statistically favored the TC group (103). This was the first trial to compare a taxane-based regimen to an anthracycline-based regimen. Concerns remain because multiple trials demonstrate that the duration of therapy is significant and the TC regimen used was a short-duration treatment of four cycles (104). Until results of an ongoing US oncology trial designed to assess whether an incremental benefit exists for adding an anthracycline to TC-based therapy for six cycles on a 3-week dosing schedule for Her-2/neu negative patients, oncologists will need to decide whether to add anthracycline to taxane-based chemotherapy guided by their clinical judgment.
The use of neoadjuvant chemotherapy traditionally was limited to those individuals with either inoperable locally advanced or inﬂammatory breast cancers. The goal of preoperative systemic therapy was to convert inoperable patients into resectable candidates on the basis of pathologic and clinical responses (105). Indications for neoadjuvant chemotherapy were broadened to include individuals presenting with large operable tumors and wanting to undergo breast preservation instead of mastectomy. Reports indicate that breast conservation therapy is possible and that low rates of in-breast or local–regional recurrences occur when neoadjuvant chemotherapy results in clinical and pathological tumor downstaging (106). In addition to large, operable tumors, neoadjuvant therapy continues to have a role in the treatment of inﬂammatory breast cancers and those presenting in a locally advanced state.
Hormonal Therapy Hormonal manipulation with tamoxifen or an aromatase inhibitor, used alone or in combination with a cytotoxic regimen, is beneficial in select groups of women. Tamoxifen,an estrogen analogue, offers substantial benefits in both premenopausal and postmenopausal women. Taken at a dose of 20 mg per day for 5 years, tamoxifen reduces the annual risk of recurrence by about 50% and the annual risk of death by about 25%. These benefits occur in women with estrogen receptor–positive disease regardless of chemotherapy treatment (107).