Comparative microRNA profiling of sporadic and BRCA1 associated basal-like breast cancers

kConFab Investigators, kConFab

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Background: While a number of studies have examined miRNA profiles across the molecular subtypes of breast cancer, it is unclear whether BRCA1 basal-like cancers have a specific miRNA profile. This study aims to compare grade independent miRNA expression in luminal cancers, sporadic and BRCA1 basal-type breast cancers. It also aims to ascertain an immunohistochemical profile regulated by BRCA1 specific miRNAs for potential diagnostic use. Methods: miRNA expression was assessed in 11 BRCA1 basal, 16 sporadic basal, 17 luminal grade 3 cancers via microarrays. The expression of Cyclin D1, FOXP1, FIH-1, pan-ERβ, NRP1 and CD99, predicted to be regulated by BRCA1 specific miRNAs by computer prediction algorithms, was assessed via immunohistochemistry in a cohort of 35 BRCA1 and 52 sporadic basal-like cancers. Assessment of cyclin D1, FOXP1, NRP1 and CD99 expression was repeated on a validation cohort of 82 BRCA1 and 65 sporadic basal-like breast cancers. Results: Unsupervised clustering of basal cancers resulted in a "sporadic" cluster of 11 cancers, and a "BRCA1" cluster of 16 cancers, including a subgroup composed entirely of 10 BRCA1 cancers. Compared with sporadic basal cancers, BRCA1 cancers showed reduced positivity for proteins predicted to be regulated by miRNAs: FOXP1 (6/20[30%] vs. 37/49[76%], p<0.001), cyclin D1 (8/22[36%] vs. 30/46[65%], p=0.025), NRP1 (2/20[10%] vs. 23/46[50%], p=0.002). This was confirmed in the validation cohort (all p<0.001). Negative staining for 2 or more out of FOXP1, cyclin D1 and NRP1 predicts germline BRCA1 mutation with a sensitivity of 92%, specificity of 44%, positive predictive value of 38% and a negative predictive value of 94%. Conclusion: Sporadic and BRCA1 basal-like cancers have grade independent miRNA expression profiles. Furthermore miRNA driven differences in the expression of proteins in BRCA1 basal cancers may be detected via immunohistochemistry. These findings may have important diagnostic implications, as immunohistochemical assessment of basal cancers, in addition to the patient's family and clinical history, may potentially identify patients who may benefit from BRCA1 gene testing.

Original languageEnglish
Article number506
JournalBMC Cancer
Issue number1
StatePublished - 8 Jul 2015
Externally publishedYes

Bibliographical note

Funding Information:
We thank Heather Thorne, Eveline Niedermayr, the kConFab research nurses and staff, the staff of the Family Cancer Clinics, and the Clinical Follow Up Study (funded by NHMRC grants 145684, 288704, and 454508) for the collection of data and tissue specimens. kConFab is supported by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC), and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania, and South Australia, and the Cancer Foundation of Western Australia. This study was partly funded by the Victorian Breast Cancer Research Consortium, the NHMRC, the Cancer Council Victoria and the Victorian Cancer Biobank (MY, SD, SF).

Publisher Copyright:
© 2015 Yan et al.


  • BRCA1
  • Basal-like
  • Breast cancer
  • microRNA


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