Abstract B62: Perturbed myoepithelial cell differentiation in BRCA mutation carriers and in DCIS (ductal carcinoma in situ)

Purpose The current literature suggests that ductal carcinoma in situ (DCIS) of the breast is infrequently diagnosed in patients with BRCA germline mutations. We studied women at high risk of hereditary breast cancer syndromes who underwent testing for BRCA1 and BRCA2 to estimate DCIS prevalence and incidence in known BRCA-positive women compared with high-risk women who were mutation negative. Methods We analyzed breast event outcomes in a retrospective cohort of 129 BRCA-positive and 269 BRCA-negative women undergoing genetic testing for a BRCA mutation between September 1996 and December 2003 at University of California, San Francisco. We estimated the frequency of DCIS and invasive cancer and time to breast events from birth using a Cox proportional hazard model for competing risks. Histologic grade of DCIS was also compared between groups. Results Among BRCA carriers, 48 (37%) had DCIS (with or without invasive cancer) compared with 92 noncarriers (34%). Univariate analysis showed that both DCIS and invasive cancer had an earlier onset in mutation carriers than in noncarriers, although on a per-woman basis, this difference was not statistically significant. High-grade DCIS was more common in BRCA1 mutation carriers than in patients without a mutation (P = .02). Conclusion DCIS is equally as prevalent in patients who carry deleterious BRCA mutations as in high familial-risk women who are noncarriers, but occurs at an earlier age. Our results argue for the consideration of DCIS as a criterion for BRCA risk assessments with appropriate weighting in prediction models such as BRCAPRO.

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Myoepithelial Cell Differentiation Markers in Ductal Carcinoma in Situ Progression

American Journal Of Pathology ◽

10.1016/j.ajpath.2015.07.004 ◽

2015 ◽

Vol 185 (11) ◽

pp. 3076-3089 ◽

Cited By ~ 24

Author(s):

Tanya D. Russell ◽

Sonali Jindal ◽

Samiat Agunbiade ◽

Dexiang Gao ◽

Megan Troxell ◽

...

Keyword(s):

Cell Differentiation ◽

Ductal Carcinoma In Situ ◽

Carcinoma In Situ ◽

Myoepithelial Cell ◽

Ductal Carcinoma ◽

Differentiation Markers

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Is it ductal carcinoma in situ with microinvasion or “Ductogenesis”? The role of myoepithelial cell markers

The Breast Journal ◽

10.1111/tbj.13897 ◽

2020 ◽

Vol 26 (6) ◽

pp. 1138-1147

Author(s):

Shahla Masood

Keyword(s):

Ductal Carcinoma In Situ ◽

Carcinoma In Situ ◽

Myoepithelial Cell ◽

Ductal Carcinoma ◽

Cell Markers

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Perturbed myoepithelial cell differentiation in BRCA mutation carriers and in ductal carcinoma in situ

Nature Communications ◽

10.1038/s41467-019-12125-5 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 5

Author(s):

Lina Ding ◽

Ying Su ◽

Anne Fassl ◽

Kunihiko Hinohara ◽

Xintao Qiu ◽

...

Keyword(s):

Germline Mutation ◽

Ductal Carcinoma In Situ ◽

Carcinoma In Situ ◽

Ductal Carcinoma ◽

Myoepithelial Cells ◽

Normal Breast ◽

Normal Mammary Gland ◽

Mutation Carriers ◽

Breast Tissues

Abstract Myoepithelial cells play key roles in normal mammary gland development and in limiting pre-invasive to invasive breast tumor progression, yet their differentiation and perturbation in ductal carcinoma in situ (DCIS) are poorly understood. Here, we investigated myoepithelial cells in normal breast tissues of BRCA1 and BRCA2 germline mutation carriers and in non-carrier controls, and in sporadic DCIS. We found that in the normal breast of non-carriers, myoepithelial cells frequently co-express the p63 and TCF7 transcription factors and that p63 and TCF7 show overlapping chromatin peaks associated with differentiated myoepithelium-specific genes. In contrast, in normal breast tissues of BRCA1 mutation carriers the frequency of p63+TCF7+ myoepithelial cells is significantly decreased and p63 and TCF7 chromatin peaks do not overlap. These myoepithelial perturbations in normal breast tissues of BRCA1 germline mutation carriers may play a role in their higher risk of breast cancer. The fraction of p63+TCF7+ myoepithelial cells is also significantly decreased in DCIS, which may be associated with invasive progression.

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