Denkert, Carsten, Seither, Fenja, Schneeweiss, Andreas, Link, Theresa, Blohmer, Jens-Uwe, Just, Marianne, Wimberger, Pauline, Forberger, Almuth, Tesch, Hans, Jackisch, Christian, Schmatloch, Sabine, Reinisch, Mattea, Solomayer, Erich F., Schmitt, Wolfgang D., Hanusch, Claus, Fasching, Peter A., Luebbe, Kristina, Solbach, Christine, Huober, Jens, Rhiem, Kerstin, Marme, Frederik, Reimer, Toralf, Schmidt, Marcus ORCID: 0000-0003-1365-2414, Sinn, Bruno, V, Janni, Wolfgang, Stickeler, Elmar, Michel, Laura, Stoetzer, Oliver, Hahnen, Eric, Furlanetto, Jenny, Seiler, Sabine, Nekljudova, Valentina, Untch, Michael and Loibl, Sibylle (2021). Clinical and molecular characteristics of HER2-low-positive breast cancer: pooled analysis of individual patient data from four prospective, neoadjuvant clinical trials. Lancet Oncol., 22 (8). S. 1151 - 1162. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1474-5488

Full text not available from this repository.

Abstract

Background The development of anti-HER2 antibody-drug conjugates opens new therapeutic options for patients with breast cancer, including patients with low expression of HER2. To characterise this new breast cancer subtype, we have compared the clinical and molecular characteristics of HER2-low-positive and HER2-zero breast cancer, including response to neoadjuvant chemotherapy and prognosis. Methods In this pooled analysis of individual patient data, we evaluated a cohort of 2310 patients with HER2non-amplified primary breast cancer that were treated with neoadjuvant combination chemotherapy in four prospective neoadjuvant clinical trials (GeparSepto, NCT01583426; GeparOcto, NCT02125344; GeparX, NCT02682693; Gain-2 neoadjuvant, NCT01690702) between July 30, 2012, and March 20, 2019. Central HER2 testing was done prospectively before random assignment of participants in all trials. HER2-low-positive status was defined as immunohistochemistry (IHC) 1+ or IHC2+/in-situ hybridisation negative and HER2-zero was defined as IHC0, based on the American Society of Clinical Oncology/College of American Pathologists guidelines. Disease-free survival and overall survival data were available for 1694 patients (from all trials except GeparX) with a median followup of 46.6 months (IQR 35.0-52.3). Bivariable and multivariable logistic regression models and Cox-proportional hazards models were performed based on a predefined statistical analysis plan for analysis of the endpoints pathological complete response, disease-free survival, and overall survival. Findings A total of 1098 (47.5%) of 2310 tumours were HER2-low-positive and 1212 (52.5%) were HER2-zero. 703 (64.0%) of 1098 patients with HER2-low-positive tumours were hormone receptor positive, compared with 445 (36.7%) of 1212 patients with HER2-zero tumours (p<0.0001). HER2-low-positive tumours had a significantly lower pathological complete response rate than HER2-zero tumours (321 [29.2%] of 1098 vs 473 [39.0%] of 1212, p=0.0002). Pathological complete response was also significantly lower in HER2-low-positive tumours versus HER2-zero tumours in the hormone receptor-positive subgroup (123 [17.5%] of 703 vs 105 [23.6%] of 445, p=0.024), but not in the hormone receptor-negative subgroup (198 [50.1%] of 395 vs 368 [48.0%] of 767, p=0.21). Patients with HER2-low-positive tumours had significantly longer survival than did patients with HER2-zero tumours (3-year disease-free survival: 83.4% [95% CI 80.5-85.9] vs 76.1% [72.9-79.0]; stratified log-rank test p=0.0084; 3-year overall survival: 91.6% [84.9-93.4] vs 85.8% [83.0-88.1]; stratified log-rank test p=0.0016). Survival differences were also seen in patients with hormone receptor-negative tumours (3-year disease free survival: 84.5% [95% CI 79.5-88.3] vs 74.4% [70.2-78.0]; stratified log-rank test p=0.0076; 3-year overall survival: 90.2% [86.0-93.2] vs 84.3% [80.7-87.3], stratified log-rank test p=0.016), but not in patients with hormone receptor-positive tumours (3-year disease-free survival 82.8% [79.1-85.9] vs 79.3% [73.9-83.7]; stratified log-rank test p=0.39; 3-year overall survival 92.3% [89.6-94.4] vs 88.4% [83.8-91.8]; stratified log-rank test p=0.13). Interpretation Our results show that HER2-low-positive tumours can be identified as new subgroup of breast cancer by standardised IHC, distinct from HER2-zero tumours. HER2-low-positive tumours have a specific biology and show differences in response to therapy and prognosis, which is particularly relevant in therapy-resistant, hormone receptor-negative tumours. Our results provide a basis for a better understanding of the biology of breast cancer subtypes and the refinement of future diagnostic and therapeutic strategies. Funding German Cancer Aid (Deutsche Krebshilfe). Copyright (c) 2021 Elsevier Ltd. All rights reserved.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Denkert, CarstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Seither, FenjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schneeweiss, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Link, TheresaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blohmer, Jens-UweUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Just, MarianneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wimberger, PaulineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Forberger, AlmuthUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tesch, HansUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jackisch, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmatloch, SabineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reinisch, MatteaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Solomayer, Erich F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmitt, Wolfgang D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hanusch, ClausUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fasching, Peter A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Luebbe, KristinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Solbach, ChristineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Huober, JensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rhiem, KerstinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Marme, FrederikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reimer, ToralfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmidt, MarcusUNSPECIFIEDorcid.org/0000-0003-1365-2414UNSPECIFIED
Sinn, Bruno, VUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Janni, WolfgangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stickeler, ElmarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Michel, LauraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stoetzer, OliverUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hahnen, EricUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Furlanetto, JennyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Seiler, SabineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nekljudova, ValentinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Untch, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Loibl, SibylleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-606259
DOI: 10.1016/S1470-2045(21)00301-6
Journal or Publication Title: Lancet Oncol.
Volume: 22
Number: 8
Page Range: S. 1151 - 1162
Date: 2021
Publisher: ELSEVIER SCIENCE INC
Place of Publication: NEW YORK
ISSN: 1474-5488
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
AMERICAN-SOCIETY; HER2 EXPRESSION; RECOMMENDATIONS; PACLITAXELMultiple languages
OncologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/60625

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item