Adjuvant Aromatase Inhibitors or Tamoxifen Following Chemotherapy for Perimenopausal Breast Cancer Patients

Gwen M H E Dackus; Katarzyna Jóźwiak; Gabe S Sonke; Elsken van der Wall; Paul J van Diest; Sabine Siesling; Michael Hauptmann; Sabine C Linn

doi:10.1093/jnci/djab091

Adjuvant Aromatase Inhibitors or Tamoxifen Following Chemotherapy for Perimenopausal Breast Cancer Patients

Gwen M H E Dackus, Katarzyna Jóźwiak, Gabe S Sonke, Elsken van der Wall, Paul J van Diest, Sabine Siesling, Michael Hauptmann, Sabine C Linn

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Abstract

BACKGROUND: The benefit of adjuvant aromatase inhibitors (AI) vs tamoxifen has been investigated in randomized clinical trials for premenopausal and postmenopausal patients with early, estrogen receptor-positive (ER+) breast cancer. The optimal endocrine treatment for chemotherapy-treated perimenopausal women, who generally develop chemotherapy-induced amenorrhea, is uncertain.

METHODS: All Dutch women who received adjuvant chemotherapy and endocrine treatment for stage I-III, ER+ (>10% positive cells), invasive breast cancer diagnosed between 2004 and 2007 were identified through the Netherlands Cancer Registry. Included women were considered perimenopausal based on an age at diagnosis of 45 to 50 years (n = 2295). For each patient, AI treatment duration relative to total endocrine treatment duration was calculated. Predominantly tamoxifen-treated patients (AI < 25%) were compared with those receiving AI and tamoxifen for a similar duration (AI 25%-75%) and those mostly using AI (AI > 75%). Adjusted hazard ratios (HRs) for recurrence-free survival (RFS) and overall survival were calculated using time-dependent Cox regression.

RESULTS: After an average follow-up of 7.6 years, 377 RFS events occurred. Women mostly receiving AI (AI > 75%) had the best RFS (adjusted HR = 0.63, 95% confidence interval = 0.46 to 0.86) followed by those receiving AI 25% to 75% (adjusted HR = 0.85, 95% confidence interval = 0.65 to 1.12) compared with predominantly tamoxifen-treated women. Trend analyses showed that every 10% increase in AI-endocrine treatment ratio reduced RFS event risk by 5% (2-sided Ptrend = .002). In total, 236 deaths occurred; hazard ratios for overall survival showed similar trends.

CONCLUSIONS: These results suggest that the best adjuvant endocrine treatment for chemotherapy-treated, ER+ breast cancer patients diagnosed aged 45-50 years consists of mainly AI followed by a switch strategy and mainly tamoxifen.

Original language	English
Pages (from-to)	1506-1514
Number of pages	9
Journal	Journal of the National Cancer Institute
Volume	113
Issue number	11
DOIs	https://doi.org/10.1093/jnci/djab091
Publication status	Published - 2 Nov 2021

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@article{81a62b737748475088e02bfa28975c83,

title = "Adjuvant Aromatase Inhibitors or Tamoxifen Following Chemotherapy for Perimenopausal Breast Cancer Patients",

abstract = "BACKGROUND: The benefit of adjuvant aromatase inhibitors (AI) vs tamoxifen has been investigated in randomized clinical trials for premenopausal and postmenopausal patients with early, estrogen receptor-positive (ER+) breast cancer. The optimal endocrine treatment for chemotherapy-treated perimenopausal women, who generally develop chemotherapy-induced amenorrhea, is uncertain.METHODS: All Dutch women who received adjuvant chemotherapy and endocrine treatment for stage I-III, ER+ (>10% positive cells), invasive breast cancer diagnosed between 2004 and 2007 were identified through the Netherlands Cancer Registry. Included women were considered perimenopausal based on an age at diagnosis of 45 to 50 years (n = 2295). For each patient, AI treatment duration relative to total endocrine treatment duration was calculated. Predominantly tamoxifen-treated patients (AI < 25%) were compared with those receiving AI and tamoxifen for a similar duration (AI 25%-75%) and those mostly using AI (AI > 75%). Adjusted hazard ratios (HRs) for recurrence-free survival (RFS) and overall survival were calculated using time-dependent Cox regression.RESULTS: After an average follow-up of 7.6 years, 377 RFS events occurred. Women mostly receiving AI (AI > 75%) had the best RFS (adjusted HR = 0.63, 95% confidence interval = 0.46 to 0.86) followed by those receiving AI 25% to 75% (adjusted HR = 0.85, 95% confidence interval = 0.65 to 1.12) compared with predominantly tamoxifen-treated women. Trend analyses showed that every 10% increase in AI-endocrine treatment ratio reduced RFS event risk by 5% (2-sided Ptrend = .002). In total, 236 deaths occurred; hazard ratios for overall survival showed similar trends.CONCLUSIONS: These results suggest that the best adjuvant endocrine treatment for chemotherapy-treated, ER+ breast cancer patients diagnosed aged 45-50 years consists of mainly AI followed by a switch strategy and mainly tamoxifen.",

author = "Dackus, {Gwen M H E} and Katarzyna J{\'o}{\'z}wiak and Sonke, {Gabe S} and {van der Wall}, Elsken and {van Diest}, {Paul J} and Sabine Siesling and Michael Hauptmann and Linn, {Sabine C}",

note = "Publisher Copyright: {\textcopyright} 2021 The Author(s). Published by Oxford University Press.",

year = "2021",

month = nov,

day = "2",

doi = "10.1093/jnci/djab091",

language = "English",

volume = "113",

pages = "1506--1514",

journal = "Journal of the National Cancer Institute",

issn = "0027-8874",

publisher = "Oxford University Press",

number = "11",

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T1 - Adjuvant Aromatase Inhibitors or Tamoxifen Following Chemotherapy for Perimenopausal Breast Cancer Patients

AU - Dackus, Gwen M H E

AU - Jóźwiak, Katarzyna

AU - Sonke, Gabe S

AU - van der Wall, Elsken

AU - van Diest, Paul J

AU - Siesling, Sabine

AU - Hauptmann, Michael

AU - Linn, Sabine C

PY - 2021/11/2

Y1 - 2021/11/2

N2 - BACKGROUND: The benefit of adjuvant aromatase inhibitors (AI) vs tamoxifen has been investigated in randomized clinical trials for premenopausal and postmenopausal patients with early, estrogen receptor-positive (ER+) breast cancer. The optimal endocrine treatment for chemotherapy-treated perimenopausal women, who generally develop chemotherapy-induced amenorrhea, is uncertain.METHODS: All Dutch women who received adjuvant chemotherapy and endocrine treatment for stage I-III, ER+ (>10% positive cells), invasive breast cancer diagnosed between 2004 and 2007 were identified through the Netherlands Cancer Registry. Included women were considered perimenopausal based on an age at diagnosis of 45 to 50 years (n = 2295). For each patient, AI treatment duration relative to total endocrine treatment duration was calculated. Predominantly tamoxifen-treated patients (AI < 25%) were compared with those receiving AI and tamoxifen for a similar duration (AI 25%-75%) and those mostly using AI (AI > 75%). Adjusted hazard ratios (HRs) for recurrence-free survival (RFS) and overall survival were calculated using time-dependent Cox regression.RESULTS: After an average follow-up of 7.6 years, 377 RFS events occurred. Women mostly receiving AI (AI > 75%) had the best RFS (adjusted HR = 0.63, 95% confidence interval = 0.46 to 0.86) followed by those receiving AI 25% to 75% (adjusted HR = 0.85, 95% confidence interval = 0.65 to 1.12) compared with predominantly tamoxifen-treated women. Trend analyses showed that every 10% increase in AI-endocrine treatment ratio reduced RFS event risk by 5% (2-sided Ptrend = .002). In total, 236 deaths occurred; hazard ratios for overall survival showed similar trends.CONCLUSIONS: These results suggest that the best adjuvant endocrine treatment for chemotherapy-treated, ER+ breast cancer patients diagnosed aged 45-50 years consists of mainly AI followed by a switch strategy and mainly tamoxifen.

AB - BACKGROUND: The benefit of adjuvant aromatase inhibitors (AI) vs tamoxifen has been investigated in randomized clinical trials for premenopausal and postmenopausal patients with early, estrogen receptor-positive (ER+) breast cancer. The optimal endocrine treatment for chemotherapy-treated perimenopausal women, who generally develop chemotherapy-induced amenorrhea, is uncertain.METHODS: All Dutch women who received adjuvant chemotherapy and endocrine treatment for stage I-III, ER+ (>10% positive cells), invasive breast cancer diagnosed between 2004 and 2007 were identified through the Netherlands Cancer Registry. Included women were considered perimenopausal based on an age at diagnosis of 45 to 50 years (n = 2295). For each patient, AI treatment duration relative to total endocrine treatment duration was calculated. Predominantly tamoxifen-treated patients (AI < 25%) were compared with those receiving AI and tamoxifen for a similar duration (AI 25%-75%) and those mostly using AI (AI > 75%). Adjusted hazard ratios (HRs) for recurrence-free survival (RFS) and overall survival were calculated using time-dependent Cox regression.RESULTS: After an average follow-up of 7.6 years, 377 RFS events occurred. Women mostly receiving AI (AI > 75%) had the best RFS (adjusted HR = 0.63, 95% confidence interval = 0.46 to 0.86) followed by those receiving AI 25% to 75% (adjusted HR = 0.85, 95% confidence interval = 0.65 to 1.12) compared with predominantly tamoxifen-treated women. Trend analyses showed that every 10% increase in AI-endocrine treatment ratio reduced RFS event risk by 5% (2-sided Ptrend = .002). In total, 236 deaths occurred; hazard ratios for overall survival showed similar trends.CONCLUSIONS: These results suggest that the best adjuvant endocrine treatment for chemotherapy-treated, ER+ breast cancer patients diagnosed aged 45-50 years consists of mainly AI followed by a switch strategy and mainly tamoxifen.

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U2 - 10.1093/jnci/djab091

DO - 10.1093/jnci/djab091

M3 - Article

C2 - 34101806

SN - 0027-8874

VL - 113

SP - 1506

EP - 1514

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

IS - 11

ER -

Adjuvant Aromatase Inhibitors or Tamoxifen Following Chemotherapy for Perimenopausal Breast Cancer Patients

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