Expression of Cyclin D1 protein in residual tumor after neoadjuvant chemotherapy for breast cancer

S L Villegas1, S Darb-Esfahani1,2, G von Minckwitz3

  • 1Institute of Pathology, Charité Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.

Abstract

Insights

Cyclin D1 is overexpressed in some hormone receptor-positive breast cancers after neoadjuvant chemotherapy. While not prognostic for disease-free survival, this marker can help stratify tumors for targeted post-chemotherapy treatments.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Hormone receptor (HR)-positive breast cancer (BC) often responds poorly to neoadjuvant chemotherapy (NACT).
  • The Cyclin D1-CDK4/CDK6 complex represents a potential therapeutic target for adjuvant or post-neoadjuvant treatment strategies.
  • Identifying patients with Cyclin D1 overexpression in residual tumors could guide personalized treatment decisions.

Purpose of the Study:

  • To determine Cyclin D1 expression levels in residual breast cancer tissue following NACT.
  • To correlate Cyclin D1 expression with clinicopathological parameters in breast cancer patients.
  • To evaluate the prognostic value of Cyclin D1 expression for disease-free survival (DFS) after NACT.

Main Methods:

  • Retrospective analysis of nuclear Cyclin D1 expression using tissue microarrays from 284 patients in the GeparTrio and GeparQuattro neoadjuvant trials.
  • Standardized immunoreactive score (IRS) was used for evaluation after defining a cut-off value.

Main Results:

  • High Cyclin D1 expression (IRS ≥ 6) was detected in 37.3% of specimens.
  • Increased Cyclin D1 expression was significantly associated with HR-positive tumors (p=0.02).
  • Low Cyclin D1 levels correlated with early clinical tumor stages (1-3) (p=0.03).

Conclusions:

  • Measurable nuclear Cyclin D1 expression exists in post-NACT residual tumor tissue of HR-positive breast cancer.
  • Cyclin D1 expression was not found to be prognostic for DFS after NACT in this cohort.
  • The study defined a cut-off for Cyclin D1 expression, enabling tumor stratification for potential targeted therapies, with ongoing prospective evaluation in the Penelope-B trial.

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