Neoadjuvant chemotherapy in hormone receptor-positive/HER2-negative early breast cancer: When, why and what?

Indication for neoadjuvant chemotherapy (NACT) in HR+/HER2-negative tumors is controversial. Pathological complete response (pCR) rates range from 0 to 18 % while breast-conserving surgery (BCS) is achievable in up to 60 % of tumors. No pathological feature definitely predicts pCR; lobular and molecular luminal A tumors are less likely to achieve pCR although experiencing better outcomes. Luminal B subtype, high proliferation, lack of progesterone receptor, high tumor-infiltrating lymphocytes are positively associated with increased pCR rates but worse outcomes and the prognostic role of pCR is inconsistent across studies. Molecular intrinsic subtyping and genomic signatures appear as more accurate predictors of benefit from NACT, but larger studies are needed. Anthracycline and taxane-based chemotherapy remains the standard NACT; however, CDK 4/6 inhibitors and immune checkpoint inhibitors are under evaluation. In conclusion, NACT may be proposed for luminal tumors requiring downsizing for BCS after multidisciplinary evaluation, provided that other contraindications to BCS are excluded.