Universität zu Köln

Pohl-Rescigno, Esther, Hauke, Jan, Loibl, Sibylle, Moebus, Volker, Denkert, Carsten, Fasching, Peter A., Kayali, Mohamad, Ernst, Corinna ORCID: 0000-0001-7756-8815, Weber-Lassalle, Nana, Hanusch, Claus, Tesch, Hans, Mueller, Volkmar, Altmueller, Janine, Thiele, Holger ORCID: 0000-0002-0169-998X, Untch, Michael, Luebbe, Kristina, Nuernberg, Peter, Rhiem, Kerstin, Furlanetto, Jenny, Lederer, Bianca, Jackisch, Christian, Nekljudova, Valentina, Schmutzler, Rita K., Schneeweiss, Andreas and Hahnen, Eric (2020). Association of Germline Variant Status With Therapy Response in High-risk Early-Stage Breast Cancer A Secondary Analysis of the GeparOcto Randomized Clinical Trial. JAMA Oncol., 6 (5). S. 744 - 749. CHICAGO: AMER MEDICAL ASSOC. ISSN 2374-2445

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Abstract

Importance The GeparOcto randomized clinical trial compared the efficacy of 2 neoadjuvant breast cancer (BC) treatment regimens: sequential intense dose-dense epirubicin, paclitaxel, and cyclophosphamide (iddEPC) vs weekly paclitaxel and nonpegylated liposomal doxorubicin (PM) in patients with different biological BC subtypes. Patients with triple-negative BC (TNBC) randomized to the PM arm received additional carboplatin (PMCb). Overall, no difference in pathologic complete response (pCR) rates was observed between study arms. It remained elusive whether the germline variant status of BRCA1/2 and further BC predisposition genes are associated with treatment outcome. Objective To determine treatment outcome for BC according to germline variant status. Design, Setting, and Participants This retrospective biomarker study is a secondary analysis of the GeparOcto multicenter prospective randomized clinical trial conducted between December 2014 and June 2016. Genetic analyses assessing for variants in BRCA1/2 and 16 other BC predisposition genes in 914 of 945 women were performed at the Center for Familial Breast and Ovarian Cancer, Cologne, Germany, from August 2017 through December 2018. Main Outcomes and Measures Proportion of patients who achieved pCR (ypT0/is ypN0 definition) after neoadjuvant treatment according to germline variant status. Results In the study sample of 914 women with different BC subtypes with a mean (range) age at BC diagnosis of 48 (21-76) years, overall higher pCR rates were observed in patients with BRCA1/2 variants than in patients without (60.4% vs 46.7%; odds ratio [OR], 1.74; 95% CI, 1.13-2.68; P = .01); variants in non-BRCA1/2 BC predisposition genes were not associated with therapy response. Patients with TNBC with BRCA1/2 variants achieved highest pCR rates. In the TNBC subgroup, a positive BRCA1/2 variant status was associated with therapy response in both the PMCb arm (74.3% vs 47.0% without BRCA1/2 variant; OR, 3.26; 95% CI, 1.44-7.39; P = .005) and the iddEPC arm (64.7% vs 45.0%; OR, 2.24; 95% CI, 1.04-4.84; P = .04). A positive BRCA1/2 variant status was also associated with elevated pCR rates in patients with ERBB2-negative, hormone receptor-positive BC (31.8% vs 11.9%; OR, 3.44; 95% CI, 1.22-9.72; P = .02). Conclusions and Relevance Effective chemotherapy for BRCA1/2-mutated TNBC is commonly suggested to be platinum based. With a pCR rate of 64.7%, iddEPC may also be effective in these patients, though further prospective studies are needed. The elevated pCR rate in BRCA1/2-mutated ERBB2-negative, hormone receptor-positive BC suggests that germline BRCA1/2 testing should be considered prior to treatment start. Question Is germline variant status of BRCA1/2 and non-BRCA1/2 breast cancer predisposition genes associated with higher response rates in patients enrolled in the GeparOcto trial? Findings In this secondary analysis of 914 patients included in a randomized clinical trial, women with triple-negative breast cancer with BRCA1/2 variants benefited most from both treatment regimens (paclitaxel and nonpegylated liposomal doxorubicin plus carboplatin, 74.3%; epirubicin, paclitaxel, and cyclophosphamide, 64.7%). A positive BRCA1/2 variant status also was associated with higher response rates in ERBB2-negative, hormone receptor-positive breast cancer. Meaning Effective chemotherapy for BRCA1/2-mutated triple-negative breast cancer is commonly suggested to be platinum based; sequential intense dose-dense epirubicin, paclitaxel, and cyclophosphamide appears to also be effective in these patients, though with a lower point estimate. Patients with ERBB2-negative, hormone receptor-positive breast cancer may benefit from BRCA1/2 testing prior to treatment. This secondary analysis of a randomized clinical trial assesses treatment outcomes in women with different biological types of breast cancer according to germline variant status of BRCA1/2 and non-BRCA1/2 breast cancer predisposition genes.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Pohl-Rescigno, Esther UNSPECIFIED UNSPECIFIED UNSPECIFIED Hauke, Jan UNSPECIFIED UNSPECIFIED UNSPECIFIED Loibl, Sibylle UNSPECIFIED UNSPECIFIED UNSPECIFIED Moebus, Volker UNSPECIFIED UNSPECIFIED UNSPECIFIED Denkert, Carsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Fasching, Peter A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kayali, Mohamad UNSPECIFIED UNSPECIFIED UNSPECIFIED Ernst, Corinna UNSPECIFIED orcid.org/0000-0001-7756-8815 UNSPECIFIED Weber-Lassalle, Nana UNSPECIFIED UNSPECIFIED UNSPECIFIED Hanusch, Claus UNSPECIFIED UNSPECIFIED UNSPECIFIED Tesch, Hans UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, Volkmar UNSPECIFIED UNSPECIFIED UNSPECIFIED Altmueller, Janine UNSPECIFIED UNSPECIFIED UNSPECIFIED Thiele, Holger UNSPECIFIED orcid.org/0000-0002-0169-998X UNSPECIFIED Untch, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Luebbe, Kristina UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuernberg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Rhiem, Kerstin UNSPECIFIED UNSPECIFIED UNSPECIFIED Furlanetto, Jenny UNSPECIFIED UNSPECIFIED UNSPECIFIED Lederer, Bianca UNSPECIFIED UNSPECIFIED UNSPECIFIED Jackisch, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Nekljudova, Valentina UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmutzler, Rita K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schneeweiss, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Hahnen, Eric UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-335126
DOI:	10.1001/jamaoncol.2020.0007
Journal or Publication Title:	JAMA Oncol.
Volume:	6
Number:	5
Page Range:	S. 744 - 749
Date:	2020
Publisher:	AMER MEDICAL ASSOC
Place of Publication:	CHICAGO
ISSN:	2374-2445
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PATHOLOGICAL COMPLETE RESPONSE; MUTATIONS; GENE Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/33512