Editorial: Adjuvant systemic treatment strategy for early breast cancer

Breast cancer (BC) is a common malignancy among women, with approximately 1,670,000 new BC cases each year worldwide. Different genotypic and phenotypic features characterize BC, and gene expression patterns of cancer tissue derived from cDNA microarrays distinguish different subclasses of invasive breast carcinomas. Considering the cytokeratin 5/6 (CK5/6) and the epidermal growth factor receptor (EGFR) protein expression in addition to ER and HER2 expression, another BC stratification was proposed, based on the following four subtypes: (i) luminal (ER+/HER2-), (ii) HER2 enriched (any ER expression/HER2 overexpression), (iii) basal-like (ER-/HER2-/EGFR+ and/or CK5/6+), and (iv) unclassified (ER-/HER2-/EGFR-/CK5/6-) subtype. Adjuvant treatment of early BC requires both traditional and novel pharmacologic tools, especially in patients with TNBC who do not respond to endocrine therapy (ET). Selective estrogen receptor modulators (SERMs) block the effects of estrogens on ERs and also act as estrogen agonists in other tissues, such as bone and endometrium. Other drugs are available as adjuvant therapy in early BC. In premenopausal patients with luminal-type BC, tamoxifen alone or in combination with a gonadotropin-releasing hormone (GnRH) agonist is still the drug of choice. Postmenopausal women can be treated with either tamoxifen or other SERMs initially (usually for 5 years before being optionally switched to AIs); they can alternatively be treated with AIs alone upfront. Bisphosphonates are drugs typically used to prevent and treat postmenopausal bone loss consequences (e.g., osteopenia, osteoporosis, and pathologic fractures) and hypercalcemia. Triple-negative BC is a heterogeneous group of aggressive breast carcinomas that are unresponsive to ET, and requires individualized chemotherapeutic regimens. In TNBC, the potential therapeutic targets are also MET (a receptor tyrosine kinase), EGFR (epidermal growth factor receptor), and SphK1 (sphingosine kinase-1). Further studies could eventually demonstrate the potential usefulness of such new therapies in early BC in the adjuvant setting.