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.
Subject(s)
BRCA1 Protein/metabolism , BRCA2 Protein/metabolism , Carcinoma, Ductal, Breast/metabolism , Mutation/genetics , Animals , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Carcinoma, Ductal, Breast/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Cell Proliferation/physiology , Female , Fluorescent Antibody Technique , Germ-Line Mutation/genetics , Humans , Immunohistochemistry , Mice , T Cell Transcription Factor 1/genetics , T Cell Transcription Factor 1/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Tumor Suppressor Proteins/genetics , Tumor Suppressor Proteins/metabolismABSTRACT
PURPOSE: Radial scar and radial sclerosis (RS) are considered benign breast lesions with proliferative features. There is sparse literature on frequency of cancer upgrade in these patients without atypical features found on image-guided needle biopsy. This study retrospectively reviews cases of isolated RS diagnosed on needle biopsy and evaluates the cancer upgrade after subsequent surgical excision. METHODS: We conducted a retrospective cross-sectional study of cases with an isolated RS diagnosis based on needle biopsy and subsequent surgical pathology among all patients between January 1, 2009 and December 31, 2013. Patients with concomitant atypia, lobular carcinoma in situ on core biopsy, complete excision of very small RS with needle biopsy, and radiology-pathology discordance were excluded. An upgrade from the needle biopsy of RS was defined as surgical excision pathology that revealed ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC), and/or invasive lobular carcinoma (ILC). RESULTS: 10,921 image-guided needle biopsy pathology reports were collected and 88 patients (0.81 %) were identified as having isolated RS. Of these 88 patients, 63 (72 %) underwent excision. The upgrade rate to cancer on subsequent surgical excision was 1.59 % (1/63) for DCIS; 0 % (0/63) for IDC; and 0 % (0/63) ILC. Twenty-five patients who did not undergo surgical excision had stable imaging studies with mean (±SD) 26 (±20) months follow up. CONCLUSIONS: Isolated radial scar on needle biopsy may not warrant routine surgical excision given relatively low cancer upgrade rates. Advancement in breast imaging, pathology and multidisciplinary approaches to care may effectively guide non-surgical management of RS.
