Breast Cancer Risk and Management Chemoprevention Surgery and Surveillance

MASSIMO CRISTOFANILLI, MD LISA NEWMAN, MD, FACS GABRIEL N. HORTOBAGYI, MD

In the past decade, the systematic use of mammography as part of diagnostic screening programs and the extensive use of stereotactic fine-needle biopsy techniques have greatly improved our ability to detect pre-invasive as well as microinvasive breast carcinomas. The consequent earlier detection of breast lesions is considered the most important factor explaining the recent decline in overall mortality from breast cancer observed in the United States.1 This progress has translated into many efforts to gain insight into the biologic mechanisms responsible for cancer development and progression and to identify potential areas of intervention for prevention studies.2

About 20 percent of women diagnosed with proliferative breast disease display atypical hyperplasia, a condition associated with increased risk of breast cancer and probably a precursor to the disease.3 The recognition of the importance of these benign breast lesions as risk factors and the identification of genetic alterations (BRCA1, BRCA2, p53) associated with genetic predisposition to breast cancer have spurred investigation in the areas of prophylactic surgery and chemo-prevention in the management of women at high risk of breast cancer and directed attention to specific interventions and to the design of comprehensive surveillance programs.4-6

The development of effective chemoprevention strategies requires a systematic approach focusing on multiple investigational aspects of the problem including (1) a clear description of the specific risk factors that may be used in selecting cohorts of women at increased risk and as end points for chemoprevention studies; (2) the identification and preclinical evaluation of cancer chemoprevention agents and subsequent development of definitive, large-scale clinical trials; and (3) the identification and characterization of specific molecular biomarkers that may be quantitatively assessed and used as surrogate end-point biomarkers (SEBs) in future trials.

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