Journal of Clinical Oncology & Advanced Therapy

Abstract

This article applies the Evidence-Selective Medicine (ESM) framework to trace how E3N and synthetic-dominated meta-analyses crystallized MHT breast cancer dogma, then reanalyzes those signals through formulation-stratified cohort evidence and mechanistic pharmacology, and concludes by proposing an ecological clinical paradigm that integrates competing risks, bioidentical MHT and structured shared decision-making tools for frontline clinicians.

The FDA's November 2025 announcement initiated the removal of black-box warnings for breast cancer, CVD and dementia from "menopausal hormone therapy (MHT)" or "hormone replacement therapy (HRT)” products. One exception, "systemic estrogen-alone products", left intact the boxed warning for endometrial cancer risk with systemic estrogen-only products in women with a uterus. In February 2026, the FDA issued label approvals for six leading MHT formulations (Prometrium, Divigel, Cenestin, Enjuvia, Estring, Bijuva), with black box warnings removed as well as “lowest effective dose for the shortest amount of time” language.21 These regulatory actions mark an institutional inflection point.