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Updated: Feb 18, 2026

Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
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.
Purpose:
Hormone receptor (HR)-positive breast cancer (BC) shows a poor response to neoadjuvant chemotherapy (NACT). New treatment targets like the Cyclin D1-CDK4/CDK6 complex are promising adjuvant/post-neoadjuvant therapeutic strategies. Evaluating Cyclin D1 overexpression in residual tumor could recognize those patients that benefit most from such post-neoadjuvant treatment. In this study, we determined Cyclin D1 expression in residual BC after NACT. Secondary aims were to correlate Cyclin D1 expression levels with clinicopathological parameters and to assess its prognostic value after NACT.
Methods:
We retrospectively assessed the nuclear expression of Cyclin D1 on tissue microarrays with residual tumor from 284 patients treated in the neoadjuvant GeparTrio (n = 186) and GeparQuattro (n = 98) trials. Evaluation was performed with a standardized immunoreactive score (IRS) after selecting a cut-off value.
Results:
A high expression level (IRS ≥ 6) of Cyclin D1 was found in 37.3% of the assessed specimens. An increased Cyclin D1 expression was observed in HR-positive tumors, compared to HR-negative tumors (p = 0.02). Low Cyclin D1 levels correlated with clinical tumor stage 1-3 (p = 0.03). Among patients with HR-positive/Her2-negative tumors and high Cyclin D1 expression, a better disease-free survival (DFS) was graphically suggested, but not significant (p = 0.21).
Conclusion:
Our study demonstrates a measurable nuclear expression of Cyclin D1 in post-neoadjuvant residual tumor tissue of HR-positive BC. Cyclin D1 expression was not prognostic for DFS after NACT. Our results and defined cut-off suggest that the marker can be used to stratify tumors according to protein expression levels. Based on this, a prospective evaluation is currently performed in the ongoing Penelope-B trial.
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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