Rethinking the combination treatment of fulvestrant and anastrozole for metastatic breast cancer: an integrated reanalysis of aromatase–estrogen receptor axis

Aberrant expression or hyperactivation of aromatase (CYP19A1)–estrogen receptor (ESR) axis is well identified as one of the major causes of breast cancer. Lots of drugs have been developed for targeting CYP19A1 or ESR respectively, such as anastrozole and fulvestrant. Recently, Mehta et al. reported in NEJM that the combined treatment of anastrozole and fulvestrant increased long-term survival of patients with metastatic breast cancer, especially for those without receiving endocrine therapy. However, the integrated prognostic analyses of CYP19A1 and ESR1/ESR2 indicated some contradictory outcomes to the recent clinical trial. Moreover, immunological investigation further revealed that targeting the whole CYP19A1–ESR axis might cause the inactivation of anti-tumor immune response, which largely attenuated its application prospects in breast cancer. Considered the pathophysiologic functions of CYP19A1 and ESR1/ESR2-mediated signaling pathway in breast cancer seem as more complicated than what we have already known, more precise evaluation will be needed in urgent.