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Updated: Aug 24, 2026
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Published on: March 9, 2017
Leveraging endocrine sensitivity in ER-positive DCIS: Neoadjuvant therapy and nonoperative management
Ryoko Semba1, Sarah Childs2, Kate Saw3
1Garvan Institute of Medical Research, NSW, Australia; Department of Breast Oncology, Juntendo University School of Medicine, Tokyo, Japan.
Purpose:
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.
Methods:
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.
Results:
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.
Conclusion:
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.
Insights
Neoadjuvant endocrine therapy (NET) shows biological activity in oestrogen receptor-positive ductal carcinoma in situ (DCIS), but its therapeutic role and long-term efficacy require further study before non-surgical approaches are adopted.
Area of Science:
- Oncology
- Breast Cancer Research
- Endocrine Therapy
Background:
- Ductal carcinoma in situ (DCIS) is a non-invasive precursor to breast cancer, often oestrogen receptor (ER)-positive.
- Screening detects most DCIS cases, prompting investigation into less invasive management strategies.
- Neoadjuvant endocrine therapy (NET) is explored for ER-positive DCIS as a biological model and potential non-surgical treatment.
Purpose of the Study:
- To review current clinical and biological evidence on NET in ER-positive DCIS.
- To identify knowledge gaps and future research directions for NET in DCIS management.
Main Methods:
- Systematic literature search of PubMed/MEDLINE, Cochrane CENTRAL, and Embase.
- Inclusion of prospective and retrospective studies evaluating NET in DCIS.
- Narrative synthesis of data due to heterogeneity, focusing on biological (Ki-67, PR) and radiological outcomes.
Main Results:
- NET consistently demonstrated biological activity in ER-positive DCIS, including Ki-67/PR suppression and regression.
- Aromatase inhibitors showed measurable tumor downsizing, but clinical significance remains uncertain.
- Pathologic complete response was rare; occult invasive disease highlights the need for careful patient selection.
Conclusions:
- NET shows biological activity in ER-positive DCIS, useful for tumor biology assessment.
- Further prospective trials are needed to establish safety, efficacy, and long-term outcomes for endocrine-inclusive strategies.
- Robust validation is required before non-operative endocrine approaches can be integrated into clinical practice.
