Prevalence and Predictors of Loss of Wild Type BRCA1 in Estrogen Receptor Positive and Negative BRCA1-Associated Breast Cancers

Prevalence and Predictors of Loss of Wild Type BRCA1 in Estrogen Receptor Positive and Negative BRCA1-Associated Breast Cancers

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Prevalence and Predictors of Loss of Wild Type BRCA1 in Estrogen Receptor Positive and Negative BRCA1-Associated Breast Cancers

dc.contributor.author	Fetten, Katharina
dc.contributor.author	Yassin, Yosuf
dc.contributor.author	Buraimoh, Ayodele
dc.contributor.author	Kim, Ji-Young
dc.contributor.author	Legare, Robert D
dc.contributor.author	Tung, Nadine Muskatel
dc.contributor.author	Miron, Alexander
dc.contributor.author	Schnitt, Stuart Jay
dc.contributor.author	Gautam, Shiva Prasad
dc.contributor.author	Kaplan, Jennifer
dc.contributor.author	Szasz, Attila M.
dc.contributor.author	Tian, Ruiyang
dc.contributor.author	Wang, Zhigang C.
dc.contributor.author	Collins, Laura Christine
dc.contributor.author	Brock, Jane Elizabeth
dc.contributor.author	Krag, Karen
dc.contributor.author	Sgroi, Dennis Charles
dc.contributor.author	Ryan, Paula D.
dc.contributor.author	Silver, Daniel P.
dc.contributor.author	Garber, Judy Ellen
dc.contributor.author	Richardson, Andrea Lynn
dc.date.accessioned	2012-03-01T01:18:16Z
dc.date.issued	2010
dc.identifier.citation	Tung, Nadine, Alexander Miron, Stuart J. Schnitt, Shiva Gautam, Katharina Fetten, Jennifer Kaplan, Yosuf Yassin, et al. 2010. Prevalence and predictors of loss of wild type BRCA1 in estrogen receptor positive and negative BRCA1-associated breast cancers. Breast Cancer Research 12(6): R95.	en_US
dc.identifier.issn	1465-5411	en_US
dc.identifier.uri	http://nrs.harvard.edu/urn-3:HUL.InstRepos:8296043
dc.description.abstract	Introduction: The majority of breast cancers that occur in BRCA1 mutation carriers (BRCA1 carriers) are estrogen receptor-negative (ER-). Therefore, it has been suggested that ER negativity is intrinsic to BRCA1 cancers and reflects the cell of origin of these tumors. However, approximately 20% of breast cancers that develop in BRCA1 carriers are ER-positive (ER+); these cancers are more likely to develop as BRCA1 carriers age, suggesting that they may be incidental and unrelated to BRCA1 deficiency. The purpose of this study was to compare the prevalence of loss of heterozygosity due to loss of wild type (wt) BRCA1 in ER+ and ER- breast cancers that have occurred in BRCA1 carriers and to determine whether age at diagnosis or any pathologic features or biomarkers predict for loss of wt BRCA1 in these breast cancers. Methods: Relative amounts of mutated and wt BRCA1 DNA were measured by quantitative polymerase chain reaction performed on laser capture microdissected cancer cells from 42 ER+ and 35 ER- invasive breast cancers that developed in BRCA1 carriers. BRCA1 gene methylation was determined on all cancers in which sufficient DNA was available. Immunostains for cytokeratins (CK) 5/6, 14, 8 and 18, epidermal growth factor receptor and p53 were performed on paraffin sections from tissue microarrays containing these cancers. Results: Loss of wt BRCA1 was equally frequent in ER+ and ER- BRCA1-associated cancers (81.0% vs 88.6%, respectively; P = 0.53). One of nine cancers tested that retained wt BRCA1 demonstrated BRCA1 gene methylation. Age at diagnosis was not significantly different between first invasive ER+ BRCA1 breast cancers with and without loss of wt BRCA1 (mean age 45.2 years vs 50.1 years, respectively; P = 0.51). ER+ BRCA1 cancers that retained wt BRCA1 were significantly more likely than those that lost wt BRCA1 to have a low mitotic rate (odds ratio (OR), 5.16; 95% CI, 1.91 to ∞). BRCA1 cancers with loss of wt BRCA1 were more likely to express basal cytokeratins CK 5/6 or 14 (OR 4.7; 95% CI, 1.85 to ∞). Conclusions: We found no difference in the prevalence of loss of wt BRCA1 between ER+ and ER- invasive BRCA1-associated breast cancers. Our findings suggest that many of the newer therapies for BRCA1 breast cancers designed to exploit the BRCA1 deficiency in these cancers may also be effective in ER+ cancers that develop in this population.	en_US
dc.language.iso	en_US	en_US
dc.publisher	BioMed Central	en_US
dc.relation.isversionof	doi:10.1186/bcr2776	en_US
dc.relation.hasversion	http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3046438/pdf/	en_US
dash.license	LAA
dc.title	Prevalence and Predictors of Loss of Wild Type BRCA1 in Estrogen Receptor Positive and Negative BRCA1-Associated Breast Cancers	en_US
dc.type	Journal Article	en_US
dc.description.version	Version of Record	en_US
dc.relation.journal	Breast Cancer Research	en_US
dash.depositing.author	Schnitt, Stuart Jay
dc.date.available	2012-03-01T01:18:16Z
dash.affiliation.other	HMS^Pathology	en_US
dash.affiliation.other	HMS^Pathology	en_US
dash.affiliation.other	HMS^Medicine-Brigham and Women's Hospital	en_US