International Journal of Clinical Oncology

, Volume 13, Issue 5, pp 395–400

Basal-like subtype and BRCA1 dysfunction in breast cancers

Review Article

DOI: 10.1007/s10147-008-0831-x

Cite this article as:
Miyoshi, Y., Murase, K. & Oh, K. Int J Clin Oncol (2008) 13: 395. doi:10.1007/s10147-008-0831-x

Abstract

Basal-like breast cancers are characterized by their unique expression profile, with the frequent loss of BRCA1, caused by such mechanisms as promoter methylation and the overexpression of high-mobility group proteins of the A type 1 or inhibitor of differentiation 4. Clinicopathologically, basal-like cancers are estrogen receptor-, progesterone receptor-, and human epidermal growth factor receptor type 2 (HER2)-negative; they are of high grade and have a poor prognosis. The fundamental similarity between BRCA1-mutated and basal-like cancers indicates that disruption of BRCA1 may be an essential common initial pathogenic event. Furthermore, p53 mutation and EGFR overexpression occur similarly in BRCA1-mutated and basal-like cancers; these shared alterations provide very important information for understanding not only the genetic and epigenetic carcinogenic pathways in these tumors but also therapeutic strategies. Despite the limited available clinical data about response to chemotherapy, anthracycline-based chemotherapy seems to be effective in a distinct subset of basal-like cancers. Both disrupted BRCA1 and overexpressed topoisomerase II-α possibly found in basal-like cancers are speculated to be associated with their increased sensitivity to anthracyclines. If these tumors respond to this chemotherapy, a favorable prognosis might be expected; however, in patients who do not respond, the prognosis is poor. Currently, the sensitivity of basal-like cancers to taxanes is not clear, but considering that these tumors have disrupted mitotic checkpoint function, a poor response may be suggested. On the basis of in vitro studies, BRCA1-disrupted basal-like cancers may be sensitive to DNA-damaging agents including platinum-based compounds, topoisomerase I and II inhibitors, and alkylating agents. In future, new therapeutic approaches for patients with basal-like cancers that are unlikely to respond to chemotherapy should focus on molecules that are involved in the pathogenic pathways of this disease.

Key words

Breast cancerBasal-likeBRCA1Triple-negativeChemotherapy

Copyright information

© Japan Society of Clinical Oncology 2008

Authors and Affiliations

  1. 1.Department of Breast and Endocrine SurgeryHyogo College of MedicineHyogoJapan