Conclusion

Since the identification of the BRCA1 tumor suppressor gene more than a decade ago, intense research in the field has implicated BRCA1 in a disparate array of cellular processes. Despite the explosive knowledge of BRCA1 in the literature, there exists a disconnect between the universal nature of BRCA1 functions and the highly tissue-specific impact of the BRCA1 mutations on tumorigenesis. Although BRCA1 mutation carriers have a high risk of developing breast cancer, the genetic and nongenetic modifiers that influence the penetrance of BRCA1 mutations remain largely unexplored. Furthermore, the atypical clinicopathological features of BRCA1 -associated cancer suggests an involvement of BRCA1 in suppressing specific metastatic routes for cancer progression, although a direct role of BRCA1 mutations in metastasis remains to be discerned. A comprehensive understanding of these outstanding issues on BRCA1-related cancer biology will go a long way to help develop more targeted and effective prevention and treatment of the disease. A careful examination of the current literature has led us to the proposal of an integrative study of BRCA1 in the context of the unique mammary gland/tumor microenvironment. Historically, studies of BRCA1 have been conducted in breast epithelial/carcinoma cell lines. By looking "outside the box" of epithelial cells and interrogating the impact of BRCA1 in both mammary epithelial and stromal cells, we may be able to understand the etiology of BRCA1 mutation-associated tumors in a systemic way. Given the loss of BRCA1 expression in many sporadic breast cancer cases, continued work in this direction also promises to have a broad application to breast cancer therapies.

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