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

• Published in: Breast cancer research and treatment Vol. 168; no. 1; pp. 179 - 187
• Main Authors: Villegas, S. L., Darb-Esfahani, S., von Minckwitz, G., Huober, J., Weber, K., Marmé, F., Furlanetto, J., Schem, C., Pfitzner, B. M., Lederer, B., Engels, K., Kümmel, S., Müller, V., Mehta, K., Denkert, C., Loibl, S.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.02.2018; Springer; Springer Nature B.V
• Subjects: Adjuvant chemotherapy; Adult; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomarkers, Tumor - analysis; Biomarkers, Tumor - metabolism; Breast - cytology; Breast - pathology; Breast - surgery; Breast cancer; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Breast Neoplasms - therapy; Cancer research; Care and treatment; Cell Nucleus - metabolism; Chemotherapy; Clinical Trial; Clinical trials; Cyclin D1; Cyclin D1 - analysis; Cyclin D1 - metabolism; Cyclin-dependent kinase 4; D1 protein; Disease-Free Survival; ErbB-2 protein; Female; Gene Expression Profiling - methods; Health aspects; Humans; Mastectomy; Medicine; Medicine & Public Health; Middle Aged; Neoadjuvant Therapy - methods; Neoplasm, Residual; Oncology; Prognosis; Receptor, ErbB-2 - metabolism; Receptors, Estrogen - metabolism; Receptors, Progesterone - metabolism; Retrospective Studies; Tissue Array Analysis - methods; Tumors; Neoadjuvant chemotherapy; Cyclin D1 TMA; Breast cancer; Cyclin D1; Prognose Cyclin D1; Cyclin D-CDK4/CDK6; Cyclin D1 overexpression
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-017-4581-1

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.