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Poster Discussion - Breast cancer, early stage

4332 - Impact of chemotherapy-induced ovarian failure (CIOF) on disease-free survival (DFS) and overall survival (OS) in young women with early breast cancer (EBC)

Date

28 Sep 2019

Session

Poster Discussion - Breast cancer, early stage

Presenters

Jenny Furlanetto

Citation

Annals of Oncology (2019) 30 (suppl_5): v55-v98. 10.1093/annonc/mdz240

Authors

J. Furlanetto1, V. Nekljudova1, A. Schneeweiss2, C. Thode3, C. Denkert4, M. Untch5, M. Bassy3, T. Karn6, P.A. Fasching7, E. Stickeler8, C. Schem9, F. Marmé10, E. Grischke11, M. van Mackelenbergh12, D. Strik13, S. Schmatloch14, V. Müller15, S. Loibl1

Author affiliations

  • 1 Department Of Medicine And Research, German Breast Group (GBG) Forschungs GmbH, 63263 - Neu-Isenburg/DE
  • 2 Gynecologic Oncology, Nationales Centrum für Tumorerkrankungen Heidelberg, 69115 - Heidelberg/DE
  • 3 Laboratoriumsmedizin, Med. Mikrobiologie Und Immunologie, amedes MVZ wagnerstibbe für Laboratoriumsmedizin, medizinische Mikrobiologie und Immunologie, Göttingen/DE
  • 4 Institut Für Pathologie Ukgm, , Universitätsklinikum Marburg, 35037 - Marburg/DE
  • 5 Clinic For Gynecology, Gynecologic Oncology And Obstetrics, Helios Klinikum Berlin Buch, 13125 - Berlin/DE
  • 6 Labor Für Translationale Forschung, Universitätsklinikum Frankfurt, Frankfurt am Main/DE
  • 7 Department Of Gynecology And Obstetrics, Universitätsklinik Erlangen, 91054 - Erlangen/DE
  • 8 Klinik Für Gynäkologie Und Geburtsmedizin, Uniklinik RWTH Aachen, Aachen/DE
  • 9 Mammazentrum/op. Therapie Und Onkologie, Krankenhaus Jerusalem, 20357 - Hamburg/DE
  • 10 Gynecologic Oncology, University Hospital Mannheim, 68167 - Mannheim/DE
  • 11 Dept. Für Frauengesundheit, Universitӓts Frauenklinik Tubingen, Eberhard Karls University, 72072 - Tübingen/DE
  • 12 Klinik Für Gynäkologie Und Geburtshilfe, Schleswig-holstein, Universitätsklinikum Schleswig-Holstein, Kiel/DE
  • 13 Frauenheilkunde Und Geburtshilfe, Endokrinologikum Berlin, Berlin/DE
  • 14 Brustzentrum, Elisabeth Krankenhaus Kassel, Kassel/DE
  • 15 Department Of Gynecology, Hamburg-Eppendorf University Medical Center, 20246 - Hamburg/DE

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Abstract 4332

Background

Previous data has shown that chemotherapy (CT)-induced amenorrhea was associated with a better DFS and OS in premenopausal patients with EBC, regardless of the hormone-receptor status (Swain et al. NEJM 2010 ).

Methods

740 patients (pts) aged ≤45yrs treated with anthracycline/taxane-based CT for EBC from 4 German neo-/adjuvant trials were included. Centrally assessed estradiol and follicle-stimulating hormone (FSH) in paired blood samples collected at baseline and 4 weeks after the last therapy infusion were considered. CIOF was defined as estradiol <52.2 ng/L and FSH >12.4IU/l after CT for those pts with premenopausal hormone levels at baseline. 4-year DFS and OS (rate, hazard ratio (HR) and 95% confidence interval (CI)) overall and in subgroups by hormone-receptor status (positive, negative) and age (≤30, 31-35, 36-40, >40yrs) are presented.

Results

Median follow-up was 49.6 (range 48.8-50.3) months. 4-year DFS and OS rates as well as HR overall and in subgroups are presented in the Table below. Pts with CIOF had a better DFS compared to pts without CIOF (HR = 0.47, 95%CI 0.31-0.71). The DFS advantage was significant in pts with hormone-receptor positive (HR = 0.38, 95%CI 0.22-0.64) EBC. A trend towards a better OS was observed only for pts with hormone-receptor positive EBC (HR = 0.45, 95%CI 0.19-1.05). Within age groups, CIOF showed a statistically significant improvement in DFS only in women ≤30yrs (HR = 0.21, 95%CI 0.05-0.97). No statistically significant OS benefit was observed in any of the age groups. Only pts >40yrs showed a trend towards a better OS (HR = 0.35, 95%CI 0.11-1.16).Table:

180PD

DFSOS
4-year ratelog rank p-valueHR [95% CI]4-year ratelog rank p-valueHR [95% CI]
CIOFno CIOFCIOFno CIOF
overall (n = 740)84.465.0<0.0010.47 [0.31-0.71]92.688.70.1800.64 [0.33-1.23]
hormone-receptor status
negative (n = 315)79.969.70.1470.62 [0.32-1.19]88.989.30.8790.92 [0.32-2.62]
positive (n = 425)87.862.6<0.0010.38 [0.22-0.64]95.588.70.0590.45 [0.19-1.05]
age (years)
≤30 (n = 62)92.869.50.0270.21 [0.05-0.97]95.790.80.2860.31 [0.03-3.00]
31-35 (n = 100)80.459.90.0990.49 [0.21-1.16]92.296.30.9451.06 [0.22-5.15]
36-40 (n = 205)81.863.50.1190.54 [0.25-1.18]92.784.90.4310.61 [0.17-2.13]
>40 (n = 373)85.765.00.2070.53 [0.19-1.45]92.481.30.0720.35 [0.11-1.16]

Conclusions

Pts with CIOF after anthracycline/taxane-based CT for EBC show a better DFS, especially in women with hormone-receptor positive EBC or younger than 30 years. The improvement in DFS translates in a survival advantage in pts with hormone-receptor positive EBC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

German Breast Group (GBG).

Funding

The study was supported by Walter Schulz Stiftung.

Disclosure

A. Schneeweiss: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Celgene; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Molecular Partner; Honoraria (self), Speaker Bureau / Expert testimony: AstraZeneca; Honoraria (self): Pfizer; Honoraria (self): Novartis; Honoraria (self): MSD Oncology; Honoraria (self): Tesaro; Honoraria (self), Travel / Accommodation / Expenses: Lilly. C. Denkert: Shareholder / Stockholder / Stock options: Sividon Diagnostics; Honoraria (self): Teva; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Roche; Honoraria (self), Advisory / Consultancy: Amgen; Advisory / Consultancy: MSD Oncology; Advisory / Consultancy: Daiichi Sankyo; Licensing / Royalties: VMScope digital pathology software; Licensing / Royalties: Patent application: EP18209672 - cancer immunotherapy; Licensing / Royalties: Patent application EP20150702464 - therapy response; Licensing / Royalties: Patent application EP20150702464 - therapy response. M. Untch: Honoraria (institution), Non-remunerated activity/ies: Abbvie; Honoraria (institution), Non-remunerated activity/ies: Amgen GmbH; Honoraria (institution), Non-remunerated activity/ies: AstraZeneca; Honoraria (institution): BMS; Honoraria (institution), Non-remunerated activity/ies: Celgene GmbH; Honoraria (institution), Non-remunerated activity/ies: Daiji Sankyo; Honoraria (institution), Non-remunerated activity/ies: Eisai GmbH; Honoraria (institution), Non-remunerated activity/ies: Janssen Cilag; Honoraria (institution), Non-remunerated activity/ies: Lilly; Honoraria (institution), Non-remunerated activity/ies: MSD Merck; Honoraria (institution), Non-remunerated activity/ies: Mundipharma; Honoraria (institution), Non-remunerated activity/ies: Myriad Genetics; Honoraria (institution), Non-remunerated activity/ies: Odonate; Honoraria (institution), Non-remunerated activity/ies: Pfizer GmbH; Honoraria (institution): PUMA Biotechnology; Honoraria (institution), Non-remunerated activity/ies: Roche Pharma AG; Honoraria (institution), Non-remunerated activity/ies: Sanofi Aventis Deutschland GmbH; Honoraria (institution), Non-remunerated activity/ies: Sividon Diagnostics; Honoraria (institution), Non-remunerated activity/ies: TEVA Pharmaceuticals Ind Ltd; Honoraria (institution), Non-remunerated activity/ies: Novartis. P.A. Fasching: Honoraria (self), Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Biontech; Honoraria (self): Roche; Honoraria (self): Pfizer; Honoraria (self): Celgene; Honoraria (self): Daiichi-Sankyo; Honoraria (self): TEVA; Honoraria (self): AstraZeneca; Honoraria (self): Merck Sharp & Dohme; Honoraria (self): Myelo Therapeutics; Honoraria (self): Macrogenics; Honoraria (self): Eisai; Honoraria (self): PUMA; Research grant / Funding (institution): Cepheid. F. Marmé: Honoraria (self): Roche; Honoraria (self): AstraZeneca; Honoraria (self): Pfizer; Honoraria (self): Tesaro; Honoraria (self): Novartis; Honoraria (self): Amgen; Honoraria (self): PharmaMar; Honoraria (self): GenomicHealth; Honoraria (self): CureVac; Honoraria (self): EISAI; Honoraria (self): Clovis; Honoraria (self): Celgene. M. van Mackelenbergh: Honoraria (self): AstraZeneca; Honoraria (self): Novartis; Honoraria (self): Amgen. V. Müller: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgem; Honoraria (self), Speaker Bureau / Expert testimony: AstraZeneca; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Diichi-Sankyo; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Eisai; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Honoraria (self), Speaker Bureau / Expert testimony: Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Roche; Honoraria (self), Speaker Bureau / Expert testimony: Celgene; Honoraria (self), Speaker Bureau / Expert testimony: Teva; Honoraria (self), Speaker Bureau / Expert testimony: Janssen-Cilag; Honoraria (self), Advisory / Consultancy: Genomic Health; Honoraria (self), Advisory / Consultancy: Hexal; Honoraria (self), Advisory / Consultancy: Pierre Fabre; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: Tesaro; Honoraria (self), Advisory / Consultancy: Nektar; Research grant / Funding (institution): Seattle Genetics. S. Loibl: Research grant / Funding (institution): Roche; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Seattle Genetics; Research grant / Funding (institution): Teva; Research grant / Funding (institution): Vifor; Research grant / Funding (institution): PRIME; Research grant / Funding (institution): Daiichi; Licensing / Royalties: EP14153692.0 pending. All other authors have declared no conflicts of interest.

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