Adjuvant systemic therapies by subtypes: Guidelines

Abstract

Adjuvant systemic treatment aims to reduce the risk of breast cancer relapse and to prolong survival. It should be tailored according to tumor burden and biological behavior of cancer. Four molecular groups were described with the first genomic studies: luminal A, luminal B, HER2 enriched, and basal-like. A surrogate subtype classification using conventional clinicopathological factors was developed for clinical purposes. The luminal-like subtypes are characterized by tumors clinically described as estrogen receptor (ER) positive. A major biological difference between luminal A and B is the proliferation signature, which has higher expression in luminal B tumors. The luminal A subtype of breast cancer has the best prognosis among all subtypes. All luminal cancers should be treated with endocrine therapy (ET). Most luminal A tumors, except those with the highest risk of relapse (extensive nodal involvement), might benefit less from some chemotherapy regimens, whereas luminal B HER2-negative cancers constitute a population of highest uncertainty regarding chemotherapy indications and guidelines. HER2 (non-luminal) cancers are treated with chemotherapy plus trastuzumab, apart from selected cases with very low risk, such as small tumors (pT1a pN0). Luminal B HER2-positive tumors are treated with chemotherapy, ET, and trastuzumab, and no randomized data exist to support omission of chemotherapy in this group. Triple-negative breast cancer showed a lack of ER and most of the other genes that were usually co-expressed with ER. In the absence of a specific therapeutic target, conventional chemotherapy is the mainstay of triple-negative breast cancer treatment according to the majority of international guidelines.