Medical therapy of locally advanced breast cancer

The term "locally advanced breast cancer" (LABC) encompasses a heterogeneous group of clinical scenarios. Historically, this has included patients with tumors larger than 5 cm in size and/or tumors that involve the skin or chest wall. Advanced nodal involvement also is included in this definition; patients with matted axillary lymph nodes, involvement of the ipsilateral supraclavicular, infraclavicular, or internal mammary lymph nodes are also included in this group description. The American Joint Committee on Cancer (AJCC) TNM staging system includes all patients with clinical and pathologic stage III disease as well as a subgroup of stage IIB (T3N0) patients in this locally advanced group [1]. Inflammatory breast cancer has often been included in this group; however, this disease has distinct biologic behavior and clinical presentation that separates it into a distinct category from patients described as being advanced purely by tumor size or nodal status. With improved public awareness about breast cancer, including the increasing use of screening mammography, proportionally fewer patients are being diagnosed with LABC. The American College of Surgeons National Cancer Data Base describes 9% of women newly diagnosed with invasive breast cancer in the USA having stage III disease [2]. In many parts of the world, however (e.g., Latin America, Asia, Africa, the Middle East), about half or more of newly diagnosed breast cancers are stages III and IV [3]. As with earlier stages of breast cancer, the majority (44%) of patients diagnosed with LABC in the USA are between 40 and 59 years of age, with an additional 19% of patients being between the ages of 60 and 69 years. The poor outcome observed for patients with advanced disease is reflected in historical data that describe a 5-year disease-free survival (DFS) of 41% for surgery alone and 29% for primary radiation therapy [4]. More contemporary survival data obtained from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) program finds that median survival for women with stage III breast cancer is 4.9 years [5].