TY - JOUR
T1 - Optimal adjuvant endocrine treatment of ER+/HER2+ breast cancer patients by age at diagnosis
T2 - A population-based cohort study
AU - Dackus, G. M.H.E.
AU - Jóźwiak, Katarzyna
AU - Sonke, Gabe S
AU - van der Wall, E.
AU - van Diest, P. J.
AU - Hauptmann, M.
AU - Siesling, S.
AU - Linn, S. C.
N1 - Funding Information:
The authors would like to thank the Netherlands Comprehensive Cancer Organization for maintaining and collecting information in the Netherlands Cancer Registry and in particular all NCR registrars for the collection and completion of any additional and missing variables for the Netherlands Breast Cancer Project. In addition, we would like to thank The Netherlands Organization for Health Research and Development (ZonMW), A Sisters Hope and De Vrienden van UMC Utrecht for their financial support in conducting this study.
Funding Information:
This work was supported by grants from The Netherlands Organization for Health Research and Development [project number 836021019 ], A Sisters Hope and De Vrienden van UMC Utrecht . None of the funders had any influence on study design; data collection; and/or project management; data analysis, interpretation; or manuscript preparation, review or approval.
Publisher Copyright:
© 2017 The Authors
PY - 2018/2/1
Y1 - 2018/2/1
N2 - Background Prior randomised controlled trials on adjuvant hormonal therapy included HER2any patients; however, a differential effect of aromatase inhibitors (AIs) versus tamoxifen (TAM) may have been missed in ER+/HER2+ patients that comprise 7–15% of all breast cancer patients. In addition, a woman's hormonal microenvironment may influence sensitivity to TAM and AIs in the adjuvant setting, which changes during menopausal transition, a process that takes years. We studied the efficacy of AIs versus TAM in ER+/HER2+ breast cancer patients grouped by age at diagnosis as a proxy for menopausal status using treatment and outcome data from the nationwide population-based Netherlands Cancer Registry (NCR). Patients and methods All women diagnosed between 2005 and 2007 with endocrine-treated, TanyNanyM0, ER+/HER2+ breast cancer were identified through the NCR (n = 1155). Patients were divided by age at diagnosis: premenopausal (≤45 years; n = 326), perimenopausal (4555 years; n = 525). A time-dependent variable, indicating whether AI or TAM was received for >50% of endocrine treatment duration, was applied to subdivide groups by predominant treatment received. Recurrence-free survival (RFS) and overall survival (OS) were assessed using Kaplan–Meier survival estimation and Cox regression. Hazard ratios (HRs) were adjusted for chemotherapy, trastuzumab, age at diagnosis, N-status, grade, pT-stage and ovarian ablation. Results During follow-up, 237 recurrences and 182 deaths occurred. Perimenopausal women derived significant RFS and OS benefit from AI compared with TAM, HR 0.47 (95% CI 0.25–0.91; P = 0.03) and HR 0.37 (95% CI 0.18–0.79; P = 0.01), respectively, whereas premenopausal women derived no benefit from AI compared with TAM. Treatment effects differed significantly between these age groups (interaction P = 0.03 and P = 0.02, respectively). Among postmenopausal women a small but non-significant AI benefit was observed. Conclusion AI treatment, preferably without any TAM treatment, was associated with the best RFS and OS outcome in ER+/HER2+ perimenopausal breast cancer patients.
AB - Background Prior randomised controlled trials on adjuvant hormonal therapy included HER2any patients; however, a differential effect of aromatase inhibitors (AIs) versus tamoxifen (TAM) may have been missed in ER+/HER2+ patients that comprise 7–15% of all breast cancer patients. In addition, a woman's hormonal microenvironment may influence sensitivity to TAM and AIs in the adjuvant setting, which changes during menopausal transition, a process that takes years. We studied the efficacy of AIs versus TAM in ER+/HER2+ breast cancer patients grouped by age at diagnosis as a proxy for menopausal status using treatment and outcome data from the nationwide population-based Netherlands Cancer Registry (NCR). Patients and methods All women diagnosed between 2005 and 2007 with endocrine-treated, TanyNanyM0, ER+/HER2+ breast cancer were identified through the NCR (n = 1155). Patients were divided by age at diagnosis: premenopausal (≤45 years; n = 326), perimenopausal (4555 years; n = 525). A time-dependent variable, indicating whether AI or TAM was received for >50% of endocrine treatment duration, was applied to subdivide groups by predominant treatment received. Recurrence-free survival (RFS) and overall survival (OS) were assessed using Kaplan–Meier survival estimation and Cox regression. Hazard ratios (HRs) were adjusted for chemotherapy, trastuzumab, age at diagnosis, N-status, grade, pT-stage and ovarian ablation. Results During follow-up, 237 recurrences and 182 deaths occurred. Perimenopausal women derived significant RFS and OS benefit from AI compared with TAM, HR 0.47 (95% CI 0.25–0.91; P = 0.03) and HR 0.37 (95% CI 0.18–0.79; P = 0.01), respectively, whereas premenopausal women derived no benefit from AI compared with TAM. Treatment effects differed significantly between these age groups (interaction P = 0.03 and P = 0.02, respectively). Among postmenopausal women a small but non-significant AI benefit was observed. Conclusion AI treatment, preferably without any TAM treatment, was associated with the best RFS and OS outcome in ER+/HER2+ perimenopausal breast cancer patients.
KW - Breast cancer
KW - Endocrine treatment
KW - ER
KW - HER2
KW - Survival analysis
KW - Time-dependent analysis
UR - http://www.scopus.com/inward/record.url?scp=85038869653&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2017.11.010
DO - 10.1016/j.ejca.2017.11.010
M3 - Article
C2 - 29274928
AN - SCOPUS:85038869653
SN - 0959-8049
VL - 90
SP - 92
EP - 101
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -