Treatment of Breast Cancer in Countries with Limited Resources

Early and accurate diagnosis of breast cancer is important for optimizing treatment. Local treatment of early stage breast cancer involves either mastectomy or breast-conserving surgery followed by whole-breast irradiation. The pathologic and biologic properties of a woman's breast cancer may be used to estimate her probability for recurrence of and death from breast cancer, as well as the magnitude of benefit she is likely to receive from adjuvant endocrine therapy or cytotoxic chemotherapy. Ovarian ablation or suppression with or without tamoxifen is an effective endocrine therapy in the adjuvant treatment of breast cancer in premenopausal women with estrogen receptor (ER)-positive or ER-unknown breast cancer. In postmenopausal women with ER- and/or progesterone receptor (PR)-positive or PR-unknown breast cancer, the use of tamoxifen or anastrozole is effective adjuvant endocrine therapy. The benefit of tamoxifen is additive to that of chemotherapy. Cytotoxic chemotherapy also improves recurrence rates and survival, with the magnitude of benefit decreasing with increasing age. Substantial support systems are required to optimally and safely use breast-conserving approaches to local therapy or cytotoxic chemotherapy as systemic therapy. Locally advanced breast cancer (LABC) accounts for at least half of all breast cancers in countries with limited resources and has a poor prognosis. Initial treatment of LABC with anthracycline-based chemotherapy is standard and effective. Addition of a sequential, neoadjuvant taxane thereafter increases the rate of pathologic complete responses. Neoadjuvant endocrine therapy may benefit postmenopausal women with hormone receptor-positive LABC. After an initial response to neoadjuvant chemotherapy, the use of local-regional surgery is appropriate. Most women will require a radical or modified radical mastectomy. In those women in whom mastectomy is not possible after neoadjuvant chemotherapy, the use of whole-breast and regional lymph node irradiation alone is appropriate. In those women who cannot receive neoadjuvant chemotherapy because of resource constraints, mastectomy with node dissection, when feasible, may still be considered in an attempt to achieve local-regional control. After local-regional therapy, most women should receive additional systemic chemotherapy. Women with LABC that has a positive or unknown hormone receptor status benefit from endocrine therapy with tamoxifen. The treatment of LABC requires multiple disciplines and is resource intensive. Efforts to reduce the number of breast cancers diagnosed at an advanced stage thus have the potential to improve rates of survival while decreasing the use of limited resources

Extended adjuvant therapy with anastrozole among postmenopausal breast cancer patients: results from the randomized Austrian Breast and

Five years of adjuvant tamoxifen has been the standard endocrine treatment for early-stage breast cancer for several decades. Adjuvant endocrine therapy following primary surgery for breast cancer reduces the risk of recurrence and increases overall survival beyond the period of treatment for women with estrogen receptor (ER) -positive disease ( 1 ). Mature meta-analysis data on 15-year recurrence and breast cancer mortality probabilities demonstrate substantial and persistent benefits of receiving adjuvant tamoxifen compared with no adjuvant treatment ( 1 ). Most of the effect of adjuvant tamoxifen on recurrence is seen during the first 5 years after surgery, when tamoxifen is generally still administered, with gains in recurrence-free survival of 11.4%. However, many women who are treated with 5 years of adjuvant tamoxifen still develop recurrent disease, and most of the effect of adjuvant tamoxifen on breast cancer mortality occurs after the fifth year after surgery

Extended adjuvant therapy with anastrozole among postmenopausal breast cancer patients: results from the randomized Austrian Breast and

Five years of adjuvant tamoxifen has been the standard endocrine treatment for early-stage breast cancer for several decades. Adjuvant endocrine therapy following primary surgery for breast cancer reduces the risk of recurrence and increases overall survival beyond the period of treatment for women with estrogen receptor (ER) -positive disease ( 1 ). Mature meta-analysis data on 15-year recurrence and breast cancer mortality probabilities demonstrate substantial and persistent benefits of receiving adjuvant tamoxifen compared with no adjuvant treatment ( 1 ). Most of the effect of adjuvant tamoxifen on recurrence is seen during the first 5 years after surgery, when tamoxifen is generally still administered, with gains in recurrence-free survival of 11.4%. However, many women who are treated with 5 years of adjuvant tamoxifen still develop recurrent disease, and most of the effect of adjuvant tamoxifen on breast cancer mortality occurs after the fifth year after surgery

Adjuvant Chemotherapy With Sequential or Concurrent Anthracycline and Docetaxel: Breast International Group 02-98 Randomized Trial

Background Docetaxel is more effective than doxorubicin for patients with advanced breast cancer. The Breast International Group 02-98 randomized trial tested the effect of incorporating docetaxel into anthracycline-based adjuvant chemotherapy and compared sequential vs concurrent administration of doxorubicin and docetaxel. Methods Patients with lymph node-positive breast cancer (n = 2887) were randomly assigned to one of four treatments: 1) sequential control (four cycles of doxorubicin at 75 mg/m2, followed by three cycles of cyclophosphamide, methotrexate, and 5-fluorouracil [CMF]); 2) concurrent control (four cycles of doxorubicin at 60 mg/m2 plus cyclophosphamide at 600 mg/m2, followed by three cycles of CMF); 3) sequential docetaxel (three cycles of doxorubicin at 75 mg/m2, followed by three cycles of docetaxel at 100 mg/m2, followed by three cycles of CMF); 4) concurrent docetaxel (four cycles of doxorubicin at 50 mg/m2 plus docetaxel at 75 mg/m2, followed by three cycles of CMF). The primary comparison evaluated the efficacy of including docetaxel regardless of schedule and was planned after 1215 disease-free survival (DFS) events (ie, relapse, second primary cancer, or death from any cause). Docetaxel and control treatment groups were compared by log-rank tests, and hazard ratios (HR) of DFS events were calculated by Cox modeling. All statistical tests were two-sided. Results Due to a lower-than-anticipated rate of relapse, this analysis was performed after 5 years with 732 events. Patients in control arms had a 5-year DFS of 73% (95% confidence interval [CI] = 70% to 75%). Docetaxel treatment resulted in an improvement in DFS of borderline statistical significance compared with control treatment (HR = 0.86, 95% CI = 0.74 to 1.00; P = .05). However, DFS in the sequential docetaxel arm was better than that in the concurrent docetaxel arm (HR = 0.83, 95% CI = 0.69 to 1.00) and in the sequential control arm (HR = 0.79, 95% CI = 0.64 to 0.98). Conclusions Incorporating docetaxel into anthracycline-based therapy resulted in an improvement in DFS that was of borderline statistical significance. However, important differences may be related to doxorubicin and docetaxel scheduling, with sequential but not concurrent administration, appearing to produce better DFS than anthracycline-based chemotherap