Edith A. Perez, MD

Worldwide, breast cancer is by far the most frequent cancer affecting women, with over 1 million new cases each year, and the leading cause of female cancer-related deaths. During the past decade, substantial progress has been made in the treatment of breast cancer, due to focused collaborative efforts in education, practice, and research.

The aromatase inhibitors (AIs) anastrozole (Arimidex), letrozole (Femara), and exemestane (Aromasin) are significantly more effective than the selective estrogen-receptor modulator (SERM) tamoxifen in preventing recurrence in estrogen receptor-positive early breast cancer. Aromatase inhibitors are likely to replace SERMs as first-line adjuvant therapy for many patients. However, AIs are associated with significantly more osteoporotic fractures and greater bone mineral loss. As antiresorptive agents, oral and intravenous bisphosphonates such as alendronate (Fosamax), risedronate (Actonel), ibandronate (Boniva), pamidronate (Aredia), and zoledronic acid (Zometa) have efficacy in preventing postmenopausal osteoporosis, cancer treatment-related bone loss, or skeletal complications of metastatic disease. Clinical practice guidelines recommend baseline and annual follow-up bone density monitoring for all patients initiating AI therapy. Bisphosphonate therapy should be prescribed for patients with osteoporosis (T score < -2.5) and considered on an individual basis for those with osteopenia (T score < -1). Modifiable lifestyle behaviors including adequate calcium and vitamin D intake, weight-bearing exercise, and smoking cessation should be addressed. Adverse events associated with bisphosphonates include gastrointestinal toxicity, renal toxicity, and osteonecrosis of the jaw. These safety concerns should be balanced with the potential of bisphosphonates to minimize or prevent the debilitating effects of AI-associated bone loss in patients with early, hormone receptor-positive breast cancer.

Mortality in breast cancer has declined in the past decade, owing toadvances in diagnosis, surgery, radiotherapy, and systemic treatments.Adjuvant chemotherapy has had a major effect on increasing survivalin women with locoregional breast cancer. Like all treatments, adjuvantchemotherapy is a work in progress, and it has evolved from singleoral agents to complex multidrug regimens. The choice of regimens isnot without controversy, however, and several have been shown to bemore effective than others, especially in patients who are at high riskfor recurrence. The taxanes paclitaxel and docetaxel (Taxotere) havebeen shown to be effective in the adjuvant setting, and they have alsobeen shown to improve the outcomes in node-positive disease. Bothdisease-free and overall survival are greater with doxorubicin,paclitaxel, and cyclophosphamide given in a dose-dense, every-2-weekschedule with growth factor support than with the same agents givenin an every-3-week schedule. Disease-free and overall survival in patientswith node-positive disease are greater with docetaxel, doxorubicin(Adriamycin), and cyclophosphamide (TAC) than with fluorouracil,doxorubicin, and cyclophosphamide (FAC). Febrile neutropenia iscommon with the TAC regimen, but it can be minimized with growthfactor support. Based on these findings, dose-dense therapy and TAC arethe current adjuvant treatments of choice in patients with node-positivedisease; other, less-intense regimens may be appropriate in patientswith lower-risk disease. Ongoing trials are investigating the efficacy ofcommonly used regimens, new chemotherapeutic and biologic agents,and novel doses and schedules of currently available agents.

The treatment of breast cancer has progressed substantially overthe past 15 years. Data from randomized adjuvant trials have shownthat the risk of disease recurrence and death is significantly reducedwhen adjuvant chemotherapy and/or hormonal therapy is added to treatment.As new strategies are incorporated, one of the continued controversiesin patient management is whether adjuvant anthracyclinesshould be the preferred treatment for all patients. Data from randomizedand translational clinical trials have become available and arehelping to elucidate the proper role of anthracyclines, as well as their acuteand long-term toxicities. In most situations, an anthracycline is currentlypreferred, but other single and combination chemotherapies arecurrently under evaluation and appear promising for use in the adjuvantsetting. Continued breast cancer research using molecular markers(such as topoisomerase II–alpha and gene clusters) as predictors oftreatment response, could help individualize decisions regardingwhether to incorporate anthracyclines into adjuvant therapy regimens.

Multimodality therapy-ie, surgical excision followed by appropriate systemic therapy and radiotherapy-has an established role in managing patients with locally