Abstract
The purpose of this study is to evaluate the efficacy and safety of neoadjuvant treatment with carboplatin and eribulin in patients with early-stage triple negative breast cancer (TNBC), and to explore biomarkers based on DNA and protein expression profiles as predictors of response. Patients with histologically confirmed early-stage TNBC received carboplatin AUC 6 iv every 21 days, and eribulin 1.4 mg/m2 day 1 and day 8 every 21 days for four cycles. The primary endpoint of the study was pathologic complete response (pCR), with secondary endpoints including clinical response and safety of the combination. Exploratory studies assessed DNA-based biomarkers [homologous recombination deficiency (HRD) score, and HR deficiency status (HRD score + BRCA1/BRCA2 mutation status)], protein-based biomarkers (Ki67, TP53, androgen receptor, Cyclin E, CDK2, Cyclin D, CDK4, Pin1 and Smad3), and clinical pretreatment factors as predictors of pCR. 13/30 (43.3 %) patients enrolled in the study achieved pCR. 24 (80.0 %) had a clinical complete or partial response. The combination was safe with mostly grade 1 and 2 toxicities. HRD score (P = 0.0024) and HR deficiency status (P = 0.0012) significantly predicted pCR. Pretreatment cytoplasmic CDK2 was also associated with pCR (P = 0.021). Significant differences in pre- versus post-treatment expression levels of nuclear Cyclin D (P = 0.020), nuclear CDK4 (P = 0.0030), and nuclear Smad3 (P = 0.015) were detected. The combination of carboplatin and eribulin is safe and efficacious in the treatment of early-stage TNBC. HRD score, HR deficiency status, and cytoplasmic CDK2 predicted pCR in this patient population.
Original language | English (US) |
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Pages (from-to) | 629-638 |
Number of pages | 10 |
Journal | Breast Cancer Research and Treatment |
Volume | 151 |
Issue number | 3 |
DOIs | |
State | Published - Jun 4 2015 |
Funding
VGK was financially supported by Dolores Knes Fund, Lynn Sage Foundation, and Harris Family Fund, and JSJ was financially supported by Central Surgical Association, Society of Surgical Oncology, Saslow Family and A Sister’s Hope (JSJ) under the grant nos. NIH K22 CA138776 and R01GM097220. This work was specifically funded by the Society of Surgical Oncology/Susan G. Komen of the Cure Clinical Investigator Award (JSJ). This clinical trial was supported by EISAI. Genomic assays were performed at Myriad Genetics, Inc.
Keywords
- BRCA1
- BRCA2
- Biomarker studies
- Breast cancer
- Homologous recombination deficiency
- Phase II Trials
ASJC Scopus subject areas
- Oncology
- Cancer Research