T. Link (Dresden, Germany)

Background

Several trials confirmed a survival benefit from temporary menopause during or after chemotherapy (CT) for patients with estrogen receptor-negative early BC. We investigated the impact of menopause on TNBC outcome after neoadjuvant CT (NACT).

Methods

GeparSixto evaluated the addition of carboplatin to anthracycline-taxane-based NACT. We aimed to determine the impact of menopausal status on continuous Ki-67 and TILs from baseline biopsies in all patients, and according to germline (g)BRCA1 status. TILs and gBRCA status were centrally assessed. Secondary objectives were the impact of age (≤40 vs >40 years) on baseline Ki-67 and TILs in all patients and according to gBRCA1 status, baseline menopausal status and age on pathological complete response (pCR, ypT0 ypN0), disease-free survival (DFS) and distant disease-free survival (DDFS) according to pCR.

Results

43/315 included patients had a gBRCA1 mutation (14.8%); mean Ki-67 was higher in ≤40 compared to >40 years (63.9 vs 57.9%, p=0.045) and in pre- compared to postmenopausal patients (63.1 vs 53.9%, t-test p=0.001). Mean TILs did not differ according to age (38.4 vs 33.5%, p=0.126) or menopausal status (35.9 vs 33.0%, p=0.311). There was no difference in Ki-67 or TILs according to age and menopausal status in gBRCA1 carriers. pCR rate was higher in women ≤40 years (55.4 vs 44.4%) and premenopausal (50.5 vs 36.6%). For multivariate analysis for DFS refer to the below table. Neither young age nor premenopausal status at baseline predicted for DFS. In non-pCR patients, premenopausal status at baseline but not age ≤40 years was associated with a higher relapse risk (Table). Similar results were obtained for DDFS. Table: 66P

	pCR (ypT0 ypN0)	OR (95% CI)*	p-value	5-year DFS rate (N=315)	HR (95% CI)*	p-value	5-year DFS rate in non-pCR (N=173)	HR (95% CI)*	p-value	5-year DFS rate in pCR (N=142)	HR (95% CI)*	p-value
Age
>40 years (N=232)	41.4%	1		74.9%	1		62.7%	1		91.7%	1
≤40 years (N=83)	55.4%	1.47 (0.85-2.55)	0.167	81.2%	0.87 (0.48-1.55)	0.631	68.8%	0.83 (0.43-1.61)	0.583	91.6%	1.11 (0.26-4.68)	0.890
Menopausal status
Postmenopausal (N=123)	36.6%	1		78.4%	1		70.2%	1		92.3%	1
Premenopausal (N=192)	50.5%	1.54 (0.92-2.57)	0.101	75.3%	1.49 (0.88-2.52)	0.137	58.8%	1.79 (1.01-3.18)	0.046	91.4%	1.16 (0.26-5.20)	0.849

* adjusted for tumor stage, nodal status, tumor grade, Ki67, TILs and carboplatin use.

Conclusions

In patients with early TNBC, premenopausal compared to postmenopausal status is associated with a higher cancer cell proliferation at baseline and a higher risk of relapse in case of no pCR.

Legal entity responsible for the study

GBG.

Funding

Has not received any funding.

Disclosure

S.I. Labidi-Galy: Honoraria (self): AstraZeneca; Honoraria (institution): Novimmune. A. Schneeweiss: Honoraria (self), Honoraria (institution), Travel/Accommodation/Expenses, Research Grant, Travel expenses, Medical writing grant: Celgene; Honoraria (self), Honoraria (institution), Travel/Accommodation/Expenses, Expert testimony, Research Grant, Travel expenses: Roche; Honoraria (institution), Research Grant: AbbVie; Honoraria (self), Expert testimony, Honoraria: AstraZeneca; Honoraria (self), Travel/Accommodation/Expenses, Honoraria, Travel expenses: Pfizer; Honoraria (self), Honoraria: Novartis; Honoraria (self), Honoraria: MSD; Honoraria (self), Honoraria: Tesaro; Honoraria (self), Honoraria: Lilly. J-U. Blohmer: Honoraria (self): Amgen; Honoraria (self): AstraZeneca; Honoraria (self): Lilly; Honoraria (self): MSD; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self), Honoraria (institution): Sysmex; Honoraria (self): Roche; Honoraria (self): Pierre Fabre. J. Huober: Honoraria (self): Lilly; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): AbbVie; Honoraria (self): AstraZeneca; Honoraria (self): MSD; Honoraria (self): Celgene; Honoraria (self): Roche; Travel/Accommodation/Expenses: Daiichi; Travel/Accommodation/Expenses: Roche; Travel/Accommodation/Expenses: Pfizer; Honoraria (institution): Novartis; Honoraria (institution): Hexal. T. Link: Honoraria (self): Teva; Honoraria (self): Tesaro; Honoraria (self): MSD; Honoraria (self): Roche; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Amgen; Honoraria (self): Clovis; Honoraria (self): Celgene; Honoraria (self): Lilly; Honoraria (self): Myriad. C. Hanusch: Honoraria (self): Roche; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): AstraZeneca; Honoraria (self): Lilly. C. Jackisch: Honoraria (self): Celgene. P.A. Fasching: Honoraria (self): Novartis; Honoraria (institution): Biontech; Honoraria (self): Pfizer; Honoraria (self): Daiichi Sankyo; Honoraria (self): AstraZeneca; Honoraria (self): Eisai; Honoraria (self): Merck Sharp & Dohme; Honoraria (institution): Cepheid; Honoraria (self): Lilly; Honoraria (self): Pierre Fabre; Honoraria (self): Seattle Genetics; Honoraria (self): Roche; Honoraria (self): Hexal. K.E. Rhiem: Honoraria (self): AstraZeneca; Honoraria (self): Pfizer; Honoraria (self): MSD. C. Denkert: Honoraria (institution), Oncobiome project: European Commission H2020; Honoraria (institution), INTEGRATE-TN project: German Cancer Aid Translational Oncology; Honoraria (self): Novartis; Honoraria (self): Roche; Honoraria (self): MSD Oncology; Honoraria (self): Daiichi Sankyo; Honoraria (self): AstraZeneca; Honoraria (self): Molecular Health; Honoraria (institution): Myriad; Honoraria (self): Merck; Shareholder/Stockholder/Stock options, Cofounder/shareholder until 2016: Sividon diagnostics; Licensing/Royalties: VMScope digital pathology software; Licensing/Royalties: WO2020109570A1 - cancer immunotherapy; Licensing/Royalties: WO2015114146A1 and WO2010076322A1- therapy response. M. Untch: Honoraria (institution), All fees to the institution/employer: AbbVie; Honoraria (institution), All fees to the institution/employer: Amgen GmbH; Honoraria (institution), All fees to the institution/employer: AstraZeneca; Honoraria (institution), All fees to the institution/employer: BMS; Honoraria (institution), All fees to the institution/employer: Celgene GmbH; Honoraria (institution), All fees to the institution/employer: Daiichi Sankyo; Honoraria (institution), All fees to the institution/employer: Eisai GmbH; Honoraria (institution), All fees to the institution/employer: Lilly Deutschland; Honoraria (institution), All fees to the institution/employer: Lilly Int.; Honoraria (institution), All fees to the institution/employer: MSD Merck; Honoraria (institution), All fees to the institution/employer: Mundipharma; Honoraria (institution), All fees to the institution/employer: Myriad Genetics; Honoraria (institution): Odonate; Honoraria (institution), All fees to the institution/employer: Pfizer GmbH; Honoraria (institution): PUMA Biotechnology; Honoraria (institution), All fees to the institution/employer: Roche Pharma AG; Honoraria (institution), All fees to the institution/employer: Sanofi Aventis Deutschland GmbH; Honoraria (institution), All fees to the institution/employer: TEVA Pharmaceuticals Ind Ltd.; Honoraria (institution), All fees to the institution/employer: Novartis; Honoraria (institution), All fees to the institution/employer: Pierre Fabre, Clovis Oncology, Seatlle Genetics. S. Loibl: Honoraria (institution), honorario for lectures and ad boards paid to institute: AbbVie; Honoraria (institution), honorario for lectures and ad boards paid to institute: Celgene; Honoraria (institution), honorarium for lectures paid to institute: PriME/Medscape; Honoraria (self), lecture: Chugai; Honoraria (self), Honoraria (institution), honorario paid to institute: Daiichi Sankyo; Honoraria (institution), honorarium for ad boards paid to institute: Lilly; Honoraria (institution), advisor honorarium paid to institute: BMS; Honoraria (institution), advisor honorarium paid to institute: Puma; Honoraria (institution), paid to institute: Immunomedics; Honoraria (institution), honorarium for lectures and ad boards paid to institute: AstraZeneca; Honoraria (institution), honorarium for lectures and ad boards paid to institute: Pierre Fabre; Honoraria (institution), honorarium for lectures and ad boards paid to institute: Merck; Honoraria (institution), advisor honorarium paid to institute: EirGenix; Honoraria (institution), honorarium for lectures and ad boards paid to institute: Amgen; Honoraria (institution), honorarium for lectures and ad boards paid to institute: Novartis; Honoraria (institution), honorarium for lectures and ad boards paid to institute: Pfizer; Honoraria (institution), grant and honorarium paid to institute: Roche; Honoraria (institution), paid to institute: Seagen; Licensing/Royalties, Immunsignature in TNBC: EP14153692.0. All other authors have declared no conflicts of interest.