Hormone replacement therapy after oophorectomy and breast cancer risk among BRCA1 mutation carriers

Hereditary Breast Cancer Clinical Study Group

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

IMPORTANCE Prophylactic bilateral salpingo-oophorectomy is recommended for BRCA1 mutation carriers to prevent ovarian cancer. Whether or not hormone replacement therapy (HRT) initiated after oophorectomy is associated with an increased risk of breast cancer has not been evaluated in a prospective study. OBJECTIVE To determine the association between HRT use and BRCA1-associated breast cancer. DESIGN, SETTING, AND PARTICIPANTS A prospective, longitudinal cohort study of BRCA1 and BRCA2 mutation carriers from 80 participating centers in 17 countries was conducted between 1995 and 2017 with a mean follow-up of 7.6 years. Participants had sought genetic testing for a BRCA1 or BRCA2 mutation because of a personal or family history of breast and/or ovarian cancer. Carriers of BRCA1 mutation with no personal medical history of cancer who underwent bilateral oophorectomy following enrollment were eligible for the cohort study. EXPOSURES A follow-up questionnaire was administered every 2 years to obtain detailed information on HRT use. A left-truncated Cox proportional hazard analysis was used to estimate the hazard ratios (HRs) and 95% CIs associated with the initiation of HRT use postoophorectomy. MAIN OUTCOMES AND MEASURES Incident breast cancer. RESULTS A total of 872 BRCA1 mutation carriers with a mean postoophorectomy follow-up period of 7.6 years (range, 0.4-22.1) were included in this study. Mean (SD) age of participants was 43.4 (8.5) years. Among these, 92 (10.6%) incident breast cancers were diagnosed. Overall, HRT use after oophorectomy was not associated with an increased risk of breast cancer. The HR was 0.97 (95% CI, 0.62-1.52; P = .89) for ever use of any type of HRT vs no use; however, the effects of estrogen alone and combination hormonal therapy were different. After 10 years of follow-up, the cumulative incidence of breast cancer among women who used estrogen-alone HRT was 12% compared with 22% among women who used estrogen plus progesterone HRT (absolute difference, 10%; log rank P = .04). CONCLUSIONS AND RELEVANCE These findings suggest that use of estrogen after oophorectomy does not increase the risk of breast cancer among women with a BRCA1 mutation and should reassure BRCA1 mutation carriers considering preventive surgery that HRT is safe. The possible adverse effect of progesterone-containing HRT warrants further study.

Original languageEnglish (US)
Pages (from-to)1059-1065
Number of pages7
JournalJAMA oncology
Volume4
Issue number8
DOIs
StatePublished - Aug 1 2018

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Hormone Replacement Therapy
Ovariectomy
Breast Neoplasms
Mutation
Estrogens
Ovarian Neoplasms
Progesterone
Cohort Studies
Genetic Testing
Longitudinal Studies
Prospective Studies
Incidence

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Hormone replacement therapy after oophorectomy and breast cancer risk among BRCA1 mutation carriers. / Hereditary Breast Cancer Clinical Study Group.

In: JAMA oncology, Vol. 4, No. 8, 01.08.2018, p. 1059-1065.

Research output: Contribution to journalArticle

Hereditary Breast Cancer Clinical Study Group. / Hormone replacement therapy after oophorectomy and breast cancer risk among BRCA1 mutation carriers. In: JAMA oncology. 2018 ; Vol. 4, No. 8. pp. 1059-1065.
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abstract = "IMPORTANCE Prophylactic bilateral salpingo-oophorectomy is recommended for BRCA1 mutation carriers to prevent ovarian cancer. Whether or not hormone replacement therapy (HRT) initiated after oophorectomy is associated with an increased risk of breast cancer has not been evaluated in a prospective study. OBJECTIVE To determine the association between HRT use and BRCA1-associated breast cancer. DESIGN, SETTING, AND PARTICIPANTS A prospective, longitudinal cohort study of BRCA1 and BRCA2 mutation carriers from 80 participating centers in 17 countries was conducted between 1995 and 2017 with a mean follow-up of 7.6 years. Participants had sought genetic testing for a BRCA1 or BRCA2 mutation because of a personal or family history of breast and/or ovarian cancer. Carriers of BRCA1 mutation with no personal medical history of cancer who underwent bilateral oophorectomy following enrollment were eligible for the cohort study. EXPOSURES A follow-up questionnaire was administered every 2 years to obtain detailed information on HRT use. A left-truncated Cox proportional hazard analysis was used to estimate the hazard ratios (HRs) and 95{\%} CIs associated with the initiation of HRT use postoophorectomy. MAIN OUTCOMES AND MEASURES Incident breast cancer. RESULTS A total of 872 BRCA1 mutation carriers with a mean postoophorectomy follow-up period of 7.6 years (range, 0.4-22.1) were included in this study. Mean (SD) age of participants was 43.4 (8.5) years. Among these, 92 (10.6{\%}) incident breast cancers were diagnosed. Overall, HRT use after oophorectomy was not associated with an increased risk of breast cancer. The HR was 0.97 (95{\%} CI, 0.62-1.52; P = .89) for ever use of any type of HRT vs no use; however, the effects of estrogen alone and combination hormonal therapy were different. After 10 years of follow-up, the cumulative incidence of breast cancer among women who used estrogen-alone HRT was 12{\%} compared with 22{\%} among women who used estrogen plus progesterone HRT (absolute difference, 10{\%}; log rank P = .04). CONCLUSIONS AND RELEVANCE These findings suggest that use of estrogen after oophorectomy does not increase the risk of breast cancer among women with a BRCA1 mutation and should reassure BRCA1 mutation carriers considering preventive surgery that HRT is safe. The possible adverse effect of progesterone-containing HRT warrants further study.",
author = "{Hereditary Breast Cancer Clinical Study Group} and Joanne Kotsopoulos and Jacek Gronwald and Karlan, {Beth Y.} and Tomasz Huzarski and Nadine Tung and Pal Moller and Susan Armel and Lynch, {Henry T.} and Leigha Senter and Andrea Eisen and Singer, {Christian F.} and Foulkes, {William D.} and Jacobson, {Michelle R.} and Ping Sun and Jan Lubinski and Narod, {Steven A.} and Tuya Pal and Georgia Wiesner and Charis Eng and Neuhausen, {Susan L.} and Peter Ainsworth and Louise Bordeleau and Eitan Friedman and Wendy Meschino and Carrie Snyder and Kelly Metcalfe and Aletta Poll and Nicole Gojska and Ellen Warner and Barry Rosen and Rochelle Demsky and Weitzel, {Jeffrey N.} and Karen Panabaker and Melanie Taylor and Fergus Couch and Siranoush Manoukian and Barbara Pasini and Daly, {Mary B.} and Linda Steele and Howard Saal and Taya Fallen and Marie Wood and Wendy McKinnon and Edmond Lemire and Chudley, {Albert E.} and Kim Serfas and Kevin Sweet and Seema Panchal and Christine Elser and Ophira Ginsburg",
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T1 - Hormone replacement therapy after oophorectomy and breast cancer risk among BRCA1 mutation carriers

AU - Hereditary Breast Cancer Clinical Study Group

AU - Kotsopoulos, Joanne

AU - Gronwald, Jacek

AU - Karlan, Beth Y.

AU - Huzarski, Tomasz

AU - Tung, Nadine

AU - Moller, Pal

AU - Armel, Susan

AU - Lynch, Henry T.

AU - Senter, Leigha

AU - Eisen, Andrea

AU - Singer, Christian F.

AU - Foulkes, William D.

AU - Jacobson, Michelle R.

AU - Sun, Ping

AU - Lubinski, Jan

AU - Narod, Steven A.

AU - Pal, Tuya

AU - Wiesner, Georgia

AU - Eng, Charis

AU - Neuhausen, Susan L.

AU - Ainsworth, Peter

AU - Bordeleau, Louise

AU - Friedman, Eitan

AU - Meschino, Wendy

AU - Snyder, Carrie

AU - Metcalfe, Kelly

AU - Poll, Aletta

AU - Gojska, Nicole

AU - Warner, Ellen

AU - Rosen, Barry

AU - Demsky, Rochelle

AU - Weitzel, Jeffrey N.

AU - Panabaker, Karen

AU - Taylor, Melanie

AU - Couch, Fergus

AU - Manoukian, Siranoush

AU - Pasini, Barbara

AU - Daly, Mary B.

AU - Steele, Linda

AU - Saal, Howard

AU - Fallen, Taya

AU - Wood, Marie

AU - McKinnon, Wendy

AU - Lemire, Edmond

AU - Chudley, Albert E.

AU - Serfas, Kim

AU - Sweet, Kevin

AU - Panchal, Seema

AU - Elser, Christine

AU - Ginsburg, Ophira

PY - 2018/8/1

Y1 - 2018/8/1

N2 - IMPORTANCE Prophylactic bilateral salpingo-oophorectomy is recommended for BRCA1 mutation carriers to prevent ovarian cancer. Whether or not hormone replacement therapy (HRT) initiated after oophorectomy is associated with an increased risk of breast cancer has not been evaluated in a prospective study. OBJECTIVE To determine the association between HRT use and BRCA1-associated breast cancer. DESIGN, SETTING, AND PARTICIPANTS A prospective, longitudinal cohort study of BRCA1 and BRCA2 mutation carriers from 80 participating centers in 17 countries was conducted between 1995 and 2017 with a mean follow-up of 7.6 years. Participants had sought genetic testing for a BRCA1 or BRCA2 mutation because of a personal or family history of breast and/or ovarian cancer. Carriers of BRCA1 mutation with no personal medical history of cancer who underwent bilateral oophorectomy following enrollment were eligible for the cohort study. EXPOSURES A follow-up questionnaire was administered every 2 years to obtain detailed information on HRT use. A left-truncated Cox proportional hazard analysis was used to estimate the hazard ratios (HRs) and 95% CIs associated with the initiation of HRT use postoophorectomy. MAIN OUTCOMES AND MEASURES Incident breast cancer. RESULTS A total of 872 BRCA1 mutation carriers with a mean postoophorectomy follow-up period of 7.6 years (range, 0.4-22.1) were included in this study. Mean (SD) age of participants was 43.4 (8.5) years. Among these, 92 (10.6%) incident breast cancers were diagnosed. Overall, HRT use after oophorectomy was not associated with an increased risk of breast cancer. The HR was 0.97 (95% CI, 0.62-1.52; P = .89) for ever use of any type of HRT vs no use; however, the effects of estrogen alone and combination hormonal therapy were different. After 10 years of follow-up, the cumulative incidence of breast cancer among women who used estrogen-alone HRT was 12% compared with 22% among women who used estrogen plus progesterone HRT (absolute difference, 10%; log rank P = .04). CONCLUSIONS AND RELEVANCE These findings suggest that use of estrogen after oophorectomy does not increase the risk of breast cancer among women with a BRCA1 mutation and should reassure BRCA1 mutation carriers considering preventive surgery that HRT is safe. The possible adverse effect of progesterone-containing HRT warrants further study.

AB - IMPORTANCE Prophylactic bilateral salpingo-oophorectomy is recommended for BRCA1 mutation carriers to prevent ovarian cancer. Whether or not hormone replacement therapy (HRT) initiated after oophorectomy is associated with an increased risk of breast cancer has not been evaluated in a prospective study. OBJECTIVE To determine the association between HRT use and BRCA1-associated breast cancer. DESIGN, SETTING, AND PARTICIPANTS A prospective, longitudinal cohort study of BRCA1 and BRCA2 mutation carriers from 80 participating centers in 17 countries was conducted between 1995 and 2017 with a mean follow-up of 7.6 years. Participants had sought genetic testing for a BRCA1 or BRCA2 mutation because of a personal or family history of breast and/or ovarian cancer. Carriers of BRCA1 mutation with no personal medical history of cancer who underwent bilateral oophorectomy following enrollment were eligible for the cohort study. EXPOSURES A follow-up questionnaire was administered every 2 years to obtain detailed information on HRT use. A left-truncated Cox proportional hazard analysis was used to estimate the hazard ratios (HRs) and 95% CIs associated with the initiation of HRT use postoophorectomy. MAIN OUTCOMES AND MEASURES Incident breast cancer. RESULTS A total of 872 BRCA1 mutation carriers with a mean postoophorectomy follow-up period of 7.6 years (range, 0.4-22.1) were included in this study. Mean (SD) age of participants was 43.4 (8.5) years. Among these, 92 (10.6%) incident breast cancers were diagnosed. Overall, HRT use after oophorectomy was not associated with an increased risk of breast cancer. The HR was 0.97 (95% CI, 0.62-1.52; P = .89) for ever use of any type of HRT vs no use; however, the effects of estrogen alone and combination hormonal therapy were different. After 10 years of follow-up, the cumulative incidence of breast cancer among women who used estrogen-alone HRT was 12% compared with 22% among women who used estrogen plus progesterone HRT (absolute difference, 10%; log rank P = .04). CONCLUSIONS AND RELEVANCE These findings suggest that use of estrogen after oophorectomy does not increase the risk of breast cancer among women with a BRCA1 mutation and should reassure BRCA1 mutation carriers considering preventive surgery that HRT is safe. The possible adverse effect of progesterone-containing HRT warrants further study.

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