A very heterogeneous disease
Breast cancers include a large number of morphologically and molecularly heterogeneous diseases. This biological diversity explains very different clinical results.
We talk about two types of cancer: in situ cancer is when the tumor remains localized in the original tissue within the mammary gland. Invasive cancer is when tumor cells pass through the basal membrane. The classification of breast cancers is based first and foremost on histological analysis. More than 20 different histological types, each associated with molecular specificities that are being characterized, have been described following the 2012 OMS classification (currently being revised). The expression of key receptors is also part of the classification: estrogen receptors (ER), progesterone (PR) and HER2 which is a member of the EGFR family (Epithelial Growth Factor Receptor) which is involved in the regulation of cell proliferation and survival.
Despite the growing understanding of biological specificities of breast cancer subtypes, clinical decisions are still fundamentally based on these receptors and on cell proliferation capacity measured using the proliferation marker Ki-67.
Five different subtypes are defined for clinical care:
- Luminal A – ER positive, HER2 negative, low Ki-67 and high PR
- Luminal B – ER positive, HER2 negative and high Ki-67 or low PR
- Luminal B-like – ER positive, HER positive (overexpressed or amplified), all Ki-67 and all PR
- HER2 positive – HER2 positive (overexpressed or amplified), ER and PR absent
- Triple negative (TN) – HER2 negative and absent ER and PR
The management of these tumors in clinical routine involves surgery, chemotherapy, radiotherapy but also targeted therapies. In particular, this is the case with anti-estrogen therapies which have improved the management of luminal A tumors as well as anti-HER2 therapies which have considerably improved the outcome for HER2-postitive breast cancers. Recently patients with mutated tumors for the BRCA1/2 gene (involved in DNA repair) also benefit from a targeted therapy via PARP inhibitors (Poly (ADP-ribose) polymerase).
On the other hand patients with triple negative and luminal B cancers don’t have access to an efficient targeted treatment and show poorer results. These diseases, as well as metastatic diseases, are a major clinical challenge.
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Coordinators: Anne Vincent Salomon and Francois-Clement Bidard