Breast-Conserving Therapy for Breast Cancer: Targets for Investigation to Improve Results

Abstract

Molecular characteristics of breast tumors are linked to their clinical behavior, with estrogen and progesterone receptor (ER/PR) expressing tumors, showing a less aggressive pattern of growth and metastasis, while ER/PR negative tumors behave in a more aggressive biologic fashion [1]. Expression of the EGF receptor-like moiety HER2-neu is also associated with adverse clinical behavior. The definition of tumor molecular signatures and clinical phenotype is undergoing redefinition with the description of luminal and basal-like categories [2]. Characteristic clinical behaviors and responsiveness to hormonal and chemotherapeutic definitions is predictable based on these features and continued definition of molecular targets for therapy is an important ongoing area of investigation. As the molecular pathways that govern tumor initiation, growth and metastasis are defined, it is certain that new effective targeted therapies will be developed to fundamentally direct our methods for treating breast cancer.

At the present time, the management of breast cancer is based on the coordinated therapeutic modalities of surgery, anti-tumor medications, and radiation therapy. The goals of each modality are based on the current biological hypothesis of breast cancer as a systemic disease. This hypothesis states that breast cancer is a systemic disease at the time of tumor initiation. It is presumed that circulating tumor cells are shed by the primary tumor, modulated by specific molecular characteristics of the malignancy, from the time when the tumor first develops [3]. Initially cleared by immunologic mechanisms, occult systemic metastases develop by entrapment and implantation of circulating tumor cells in remote organs. Cellular features of the tumor, including high cytological grade and rapid proliferative rate, are predictive of greater risk for metastasis, but the most reliable predictor of metastatic disease is the amount of tumor that has spread to the primary regional lymph node basin of the breast, the axillary nodal basin [4]. Breast cancer is graded by stage based on the American Joint Commission on Cancer staging system (AJCC) [5]. The disease of each patient with breast cancer is graded according to the tumor size (T), the presence and degree of node metastasis (N), and the presence or absence of detectable metastases (M). The TNM grades are then summated to establish a Stage for each patient with breast cancer. Stage I and II are considered early stage breast cancers, with 5-year survival rates of 98 and 85% respectively, while Stage III disease carries a 5-year survival rate of 55–65%. Stage IV is characterized by the presence of metastatic disease and survival rates are 20–30% at 5 years. Hence early detection and effective treatment of early stage breast cancer offers excellent opportunities for long-term survival and “cure.”