Stage I, II, IIIA, and Operable IIIC Breast Cancer
Chemotherapy and tamoxifen risks
Adjuvant combinations of tamoxifen and chemotherapy administered concurrently to enhance efficacy may also have enhanced toxic effects. A single study randomly assigned postmenopausal women with node-positive, ER-positive tumors to receive tamoxifen (30 mg/day for 2 years) plus CMF (intravenously for 6 months) (n = 353) or tamoxifen alone (n = 352). Of the women receiving combined chemohormonal therapy, 13.6% developed one or more thromboembolic events compared with 2.6% in the tamoxifen-alone group (P < .001). Also, statistically significantly more women were on combined treatment who developed severe thromboembolic events (grade 3-5), most of which (39 of 54) occurred while the women were actually receiving chemotherapy. Not all studies that compared concurrent chemotherapy plus tamoxifen with tamoxifen alone, however, have reported such high rates. In the NSABP-B-16 study that compared tamoxifen (20 mg/day for 5 years) plus chemotherapy with doxorubicin plus cyclophosphamide (four cycles) with tamoxifen alone, 4.9% of the women on combined treatment had thromboembolic events versus 2.1% of women on tamoxifen alone. Whether tamoxifen should be given concurrently or after the completion of chemotherapy has been addressed in an Intergroup trial (INT-0100), published in abstract form only, that compared the concurrent and sequential administration of CAF and tamoxifen in postmenopausal hormone receptor-positive patients. Sequential administration resulted in superior DFS that was significant at 8 years (67% vs. 62%; P = .045).[Level of evidence: 1iiDii]
Candidates for whom adjuvant therapy may not be necessary include individuals with small primary tumors (<1 cm) and negative axillary nodes who have an excellent prognosis, with nearly 90% of patients alive and free of disease at 20 years in one series. A U.S. Intergroup study (SWOG-8897) observed patients off treatment with tumors of low-risk (tumors too small for biochemical ER/PR assay) and uncertain-risk (tumors <2 cm, ER-positive and PR-positive, and low S-phase fractions). This low-risk and uncertain-risk subset had a 96% 5-year survival rate without adjuvant therapy. Whether this group of patients would derive long-term benefit from tamoxifen for either its adjuvant or preventive effects remains uncertain. Clearly, this group has a risk of developing a new breast cancer that would meet the eligibility criteria that were used in the Breast Cancer Prevention Trial that demonstrated a benefit with tamoxifen.
Proposals have been made to treat elderly patients with tamoxifen alone and without surgery. This approach has unacceptably high local failure rates and, outside of a clinical trial setting, should be used only for patients who are not candidates for mastectomy or breast-conserving surgery plus radiation therapy, or for those who refuse these options.[235,236,237]
- Breast-conserving therapy (lumpectomy, breast radiation, and surgical staging of the axilla).
- Modified radical mastectomy (removal of the entire breast with level I-II axillary dissection) with or without breast reconstruction.
- Sentinel node biopsy.