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Effects of short-course preoperative endocrine therapy on tumour morphology and immunohistochemical profile in oestrogen receptor-positive, HER2-negative breast cancer.

Claudia Grosse·Alexandra Grosse·Petar Noack·Caroline Ines Preuss·Heike Kathleen Schwarz·Bruno Schneeweiss·Thomas Gitter·Peter Schrenk·Rupert Langer
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Abstract

AIMS: Short-term preoperative endocrine therapy (ET) is increasingly used in oestrogen receptor (ER)-positive, HER2-negative breast cancer as a functional test of endocrine sensitivity. We aimed to characterise histomorphological and immunophenotypic changes following preoperative ET and to identify predictors of endocrine response, defined as post-treatment Ki67&#x2009;&#x2264;&#x2009;10%. METHODS AND RESULTS: In this retrospective single-centre study, 180 patients treated with short-course preoperative ET (median duration 29&#x2009;days) were compared with 151 patients undergoing primary surgery without ET. Paired biopsy and resection specimens were assessed for histological features, stromal proportion, stromal tumour-infiltrating lymphocytes (strTILs) and expression of ER, progesterone receptor (PR), HER2 and Ki67. Genomic risk was determined using the MammaPrint assay. Preoperative ET was associated with a significant reduction in tumour proliferation, with 73.9% of cases showing post-treatment Ki67&#x2009;&#x2264;&#x2009;10% compared with none in controls (P&#x2009;<&#x2009;0.001). Histological grade decreased in 36.7% of ET-treated tumours versus 7.9% of controls (P&#x2009;<&#x2009;0.001), predominantly reflecting reduced mitotic activity. ER expression remained stable, whereas PR expression decreased more frequently following ET (P&#x2009;<&#x2009;0.001) and was independently associated with Ki67-defined response.&#xa0;HER2-low status was more frequently observed after ET (P&#x2009;<&#x2009;0.001), but HER2 expression and microenvironmental parameters, including strTILs, were not associated with response. High genomic risk was independently associated with a lower likelihood of achieving post-treatment Ki67&#x2009;&#x2264;&#x2009;10% (P&#x2009;<&#x2009;0.001). CONCLUSIONS: Short-course preoperative ET induces rapid and reproducible morphological and immunophenotypic changes in ER-positive, HER2-negative breast cancer. Ki67-defined response is associated with genomic risk and PR expression, whereas microenvironmental features appear to have limited predictive value.

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HumansFemaleBreast NeoplasmsErb-b2 Receptor Tyrosine KinasesReceptors, EstrogenMiddle AgedRetrospective StudiesAdultAgedAntineoplastic Agents, HormonalKi-67 AntigenImmunohistochemistryNeoadjuvant TherapyReceptors, ProgesteroneBiomarkers, TumorAged, 80 and overKi67MammaPrintbreast cancerpreoperative endocrine therapyprogesterone receptortumour gradingJournal Article

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Claudia Grosse, Alexandra Grosse, Petar Noack, Caroline Ines Preuss, Heike Kathleen Schwarz, Bruno Schneeweiss, Thomas Gitter, Peter Schrenk, Rupert Langer. 2026-06-18. Effects of short-course preoperative endocrine therapy on tumour morphology and immunohistochemical profile in oestrogen receptor-positive, HER2-negative breast cancer.. https://doi.org/10.1111/his.70203

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