Leveraging endocrine sensitivity in ER-positive DCIS: Neoadjuvant therapy and nonoperative management

Ductal carcinoma in situ (DCIS) is a non-invasive precursor to breast cancer, frequently oestrogen receptor (ER)-positive and detected through screening. Neoadjuvant endocrine therapy (NET), established in ER-positive invasive breast cancer, is being investigated in DCIS both as a short-term biological response model and as a potential component of emerging non-surgical or active-surveillance strategies. This review synthesises current clinical and biological evidence on NET in ER-positive DCIS and identifies knowledge gaps and future directions.

A systematic search (PubMed/MEDLINE, the Cochrane CENTRAL, Embase) was performed to identify prospective and retrospective studies evaluating NET in DCIS. Eligible studies included those assessing biological (Ki-67, PR expression) or radiological (lesion volume reduction) outcomes. Data were narratively synthesised due to study heterogeneity.

Four early-phase trials demonstrated consistent biological responsiveness of ER-positive DCIS to NET, with suppression of Ki-67 and PR expression, and occasional histologic regression. Aromatase inhibitors produced measurable radiologic downsizing in selected cohorts, although the clinical significance of these changes in DCIS remains uncertain. Pathologic complete response was uncommon, and a small proportion of cases were found to have occult invasive disease at surgery, underscoring the need for careful patient selection and cautious interpretation of early NET studies. Furthermore, the validity of short-term surrogate endpoints, such as Ki-67 suppression and radiological volume reduction, remains unproven regarding long-term prevention of invasive transformation.

NET demonstrates consistent biological activity in ER-positive DCIS, supporting its use as a tool for tumour biology assessment rather than as a therapeutic alternative to surgery. Further prospective studies (COMET, LORETTA, RECAST, HORNEO01) are required to determine the safety, efficacy, appropriate patient population, and long-term outcomes of endocrine-inclusive personalised strategies. Given the exploratory nature and limitations of current data, these findings offer a conceptual framework that mandates robust, long-term prospective validation before any non-operative endocrine approach can be integrated into routine clinical practice.