# Germline BRCA1 mutations and a basal epithelial phenotype in breast cancer

Source: https://onco.cc/key-papers/paper-foulkes-brca1-basal-phenotype-jnci-2003/  
OnCo record `paper-foulkes-brca1-basal-phenotype-jnci-2003` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A 2003 study using an ordinary pathology stain, cytokeratin 5/6, to show that breast cancers in women with an inherited BRCA1 fault are nine times more likely to have the basal pattern; it brought the basal-like idea from the microarray to the pathology bench.

## Summary

Foulkes, Stefansson, Chappuis, Bégin and colleagues tested whether BRCA1-related breast cancers are more likely than non-BRCA1/2 cancers to express a basal epithelial phenotype, found in at most 15 percent of invasive breast cancers and associated with oestrogen receptor- and HER2-negative tumours. Among 292 specimens previously analysed for oestrogen receptor, HER2, p53 and germline BRCA1 and BRCA2 mutations, 76 were negative for both receptors; of 72 with sufficient material, 40 expressed cytokeratin 5 and/or 6. Cytokeratin 5/6 expression was significantly associated with BRCA1-related cancer (odds ratio 9.0, 95 percent confidence interval 1.9 to 43; p=0.002).

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Tags: tnbc-evidence
- Journal: Journal of the National Cancer Institute
- Year: 2003
- DOI: 10.1093/jnci/djg050
- Authors: Foulkes WD, Stefansson IM, Chappuis PO, et al.
- Findings: Among 72 oestrogen receptor- and HER2-negative tumours, cytokeratin 5/6 expression was associated with germline BRCA1 mutation: odds ratio 9.0 (95 percent CI 1.9 to 43), p=0.002.
- What it means: Confirmed the BRCA1 to basal link with a stain any laboratory could run, which is how the basal-like concept reached clinical pathology and how the Carolina Breast Cancer Study defined its subtypes three years later.
- Caveats: Small numbers and a wide confidence interval.; Cytokeratin 5/6 is a surrogate; the immunohistochemical definition of basal-like was never standardised.

## Sources

- J Natl Cancer Inst 2003: https://doi.org/10.1093/jnci/djg050
- PubMed: https://pubmed.ncbi.nlm.nih.gov/14519755/

## Connected records

- key papers: [Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study](https://onco.cc/key-papers/paper-carey-race-breast-cancer-subtypes-cbcs-jama-2006/), [Repeated observation of breast tumor subtypes in independent gene expression data sets](https://onco.cc/key-papers/paper-sorlie-repeated-observation-subtypes-brca1-basal-pnas-2003/)
- cancers: [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- targets: [BRCA1 / BRCA2 (HRD)](https://onco.cc/targets/brca/)
- terms: [Immunohistochemistry (IHC)](https://onco.cc/terms/ihc/)
- technologies: [Germline (hereditary) testing](https://onco.cc/technologies/germline-testing/)
- journals: [JNCI: Journal of the National Cancer Institute](https://onco.cc/journals/jnci/)
- roadmaps: [Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem](https://onco.cc/roadmaps/tnbc-roadmap/)

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