Atlas of breast cancer early detection

IHC assessment of three molecular biomarkers – ER, PR, and HER2 – is standard practice and these are recognized as indispensable predictive and prognostic factors for invasive breast carcinoma. ER and PR receptor status are very important predictive markers to identify patients who may benefit from hormone therapy, and are minor favourable prognostic markers. HER2 status is an essential predictive marker to identify patients who may benefit from HER2-targeted therapies, such as trastuzumab or newer biological molecules, and also for anthracycline-based therapy. HER2 positivity is an independent prognostic marker of poor outcome in the absence of adjuvant treatment and decreased overall survival. In addition, a fourth IHC proliferation marker, Ki-67, is suggested for the classification of breast cancer at the molecular level in order to effectively tailor treatment.
Based on these surrogate IHC markers, the molecular subtypes of breast cancer are:

• Luminal A-like: ER positive, PR positive, HER2 negative, Ki-67 proliferation index low
• Luminal B-like (HER2 negative): ER positive, HER2 negative, at least one of the following: Ki-67 proliferation index high, PR negative or low
• Luminal B-like (HER2 positive): ER positive, HER2 overexpressed or amplified, Ki-67 proliferation index any, PR any
• HER2 positive (non-luminal): HER2 overexpressed or amplified, ER negative, PR negative
• Triple-negative: ER negative, PR negative, HER2 negative

Details of the steps of IHC are not within the scope of this manual. For further details see Tang P, Tse GM (2016). Immunohistochemical surrogates for molecular classification of breast carcinoma: a 2015 update. Arch Pathol Lab Med. 140(8):806–14.https://doi.org/10.5858/arpa.2015-0133-RA PMID:27472239.