Bilateral Oophorectomy and Breast Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

Joanne Kotsopoulos; Tomasz Huzarski; Jacek Gronwald; Christian F Singer; Pal Moller; Henry T Lynch; Susan Armel; Beth Karlan; William D Foulkes; Susan L Neuhausen; Leigha Senter; Nadine Tung; Jeffrey N Weitzel; Andrea Eisen; Kelly Metcalfe; Charis Eng; Tuya Pal; Gareth Evans; Ping Sun; Jan Lubinski; Steven A Narod; The Hereditary Breast Cancer Clinical Study Group

doi:10.1093/jnci/djw177

Bilateral Oophorectomy and Breast Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

Joanne Kotsopoulos, Tomasz Huzarski, Jacek Gronwald, Christian F Singer, Pal Moller, Henry T Lynch, Susan Armel, Beth Karlan, William D Foulkes, Susan L Neuhausen, Leigha Senter, Nadine Tung, Jeffrey N Weitzel, Andrea Eisen, Kelly Metcalfe, Charis Eng, Tuya Pal, Gareth Evans, Ping Sun, Jan LubinskiSteven A Narod, The Hereditary Breast Cancer Clinical Study Group

Division of Evolution, Infection and Genomics

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Abstract

BACKGROUND: Whether oophorectomy reduces breast cancer risk among BRCA mutation carriers is a matter of debate. We undertook a prospective analysis of bilateral oophorectomy and breast cancer risk in BRCA mutation carriers.

METHODS: Subjects had no history of cancer, had both breasts intact, and had information on oophorectomy status (n = 3722). Women were followed until breast cancer diagnosis, prophylactic bilateral mastectomy, or death. A Cox regression model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of breast cancer associated with oophorectomy (coded as a time-dependent variable). All statistical tests were two-sided.

RESULTS: Over a mean follow-up of 5.6 years, 350 new breast cancers were diagnosed. Among women with a BRCA1 or BRCA2 mutation, oophorectomy was not associated with breast cancer risk compared with women who did not undergo an oophorectomy. The age-adjusted hazard ratio associated with oophorectomy was 0.96 (95% CI = 0.73 to 1.26, P = 76) for BRCA1 and was 0.65 (95% CI = 0.37 to 1.16, P = 14) for BRCA2 mutation carriers. In stratified analyses, the effect of oophorectomy was statistically significant for breast cancer in BRCA2 mutation carriers diagnosed prior to age 50 years (age-adjusted HR = 0.18, 95% CI = 0.05 to 0.63, P = 007). Oophorectomy was not associated with risk of breast cancer prior to age 50 years among BRCA1 mutation carriers (age-adjusted HR = 0.79, 95% CI = 0.55 to 1.13, P = 51).

CONCLUSIONS: Findings from this large prospective study support a role of oophorectomy for the prevention of premenopausal breast cancer in BRCA2, but not BRCA1 mutation carriers. These findings warrant further evaluation.

Original language	English
Journal	Journal of the National Cancer Institute
Volume	109
Issue number	1
Early online date	6 Sept 2016
DOIs	https://doi.org/10.1093/jnci/djw177
Publication status	Published - Jan 2017

Keywords

Journal Article

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Kotsopoulos, J., Huzarski, T., Gronwald, J., Singer, C. F., Moller, P., Lynch, H. T., Armel, S., Karlan, B., Foulkes, W. D., Neuhausen, S. L., Senter, L., Tung, N., Weitzel, J. N., Eisen, A., Metcalfe, K., Eng, C., Pal, T., Evans, G., Sun, P., ... The Hereditary Breast Cancer Clinical Study Group (2017). Bilateral Oophorectomy and Breast Cancer Risk in BRCA1 and BRCA2 Mutation Carriers. Journal of the National Cancer Institute, 109(1). https://doi.org/10.1093/jnci/djw177

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abstract = "BACKGROUND: Whether oophorectomy reduces breast cancer risk among BRCA mutation carriers is a matter of debate. We undertook a prospective analysis of bilateral oophorectomy and breast cancer risk in BRCA mutation carriers.METHODS: Subjects had no history of cancer, had both breasts intact, and had information on oophorectomy status (n = 3722). Women were followed until breast cancer diagnosis, prophylactic bilateral mastectomy, or death. A Cox regression model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of breast cancer associated with oophorectomy (coded as a time-dependent variable). All statistical tests were two-sided.RESULTS: Over a mean follow-up of 5.6 years, 350 new breast cancers were diagnosed. Among women with a BRCA1 or BRCA2 mutation, oophorectomy was not associated with breast cancer risk compared with women who did not undergo an oophorectomy. The age-adjusted hazard ratio associated with oophorectomy was 0.96 (95% CI = 0.73 to 1.26, P = 76) for BRCA1 and was 0.65 (95% CI = 0.37 to 1.16, P = 14) for BRCA2 mutation carriers. In stratified analyses, the effect of oophorectomy was statistically significant for breast cancer in BRCA2 mutation carriers diagnosed prior to age 50 years (age-adjusted HR = 0.18, 95% CI = 0.05 to 0.63, P = 007). Oophorectomy was not associated with risk of breast cancer prior to age 50 years among BRCA1 mutation carriers (age-adjusted HR = 0.79, 95% CI = 0.55 to 1.13, P = 51).CONCLUSIONS: Findings from this large prospective study support a role of oophorectomy for the prevention of premenopausal breast cancer in BRCA2, but not BRCA1 mutation carriers. These findings warrant further evaluation.",

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author = "Joanne Kotsopoulos and Tomasz Huzarski and Jacek Gronwald and Singer, {Christian F} and Pal Moller and Lynch, {Henry T} and Susan Armel and Beth Karlan and Foulkes, {William D} and Neuhausen, {Susan L} and Leigha Senter and Nadine Tung and Weitzel, {Jeffrey N} and Andrea Eisen and Kelly Metcalfe and Charis Eng and Tuya Pal and Gareth Evans and Ping Sun and Jan Lubinski and Narod, {Steven A} and {The Hereditary Breast Cancer Clinical Study Group}",

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doi = "10.1093/jnci/djw177",

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Kotsopoulos, J, Huzarski, T, Gronwald, J, Singer, CF, Moller, P, Lynch, HT, Armel, S, Karlan, B, Foulkes, WD, Neuhausen, SL, Senter, L, Tung, N, Weitzel, JN, Eisen, A, Metcalfe, K, Eng, C, Pal, T, Evans, G, Sun, P, Lubinski, J, Narod, SA & The Hereditary Breast Cancer Clinical Study Group 2017, 'Bilateral Oophorectomy and Breast Cancer Risk in BRCA1 and BRCA2 Mutation Carriers', Journal of the National Cancer Institute, vol. 109, no. 1. https://doi.org/10.1093/jnci/djw177

TY - JOUR

T1 - Bilateral Oophorectomy and Breast Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

AU - Kotsopoulos, Joanne

AU - Huzarski, Tomasz

AU - Gronwald, Jacek

AU - Singer, Christian F

AU - Moller, Pal

AU - Lynch, Henry T

AU - Armel, Susan

AU - Karlan, Beth

AU - Foulkes, William D

AU - Neuhausen, Susan L

AU - Senter, Leigha

AU - Tung, Nadine

AU - Weitzel, Jeffrey N

AU - Eisen, Andrea

AU - Metcalfe, Kelly

AU - Eng, Charis

AU - Pal, Tuya

AU - Evans, Gareth

AU - Sun, Ping

AU - Lubinski, Jan

AU - Narod, Steven A

AU - The Hereditary Breast Cancer Clinical Study Group

PY - 2017/1

Y1 - 2017/1

N2 - BACKGROUND: Whether oophorectomy reduces breast cancer risk among BRCA mutation carriers is a matter of debate. We undertook a prospective analysis of bilateral oophorectomy and breast cancer risk in BRCA mutation carriers.METHODS: Subjects had no history of cancer, had both breasts intact, and had information on oophorectomy status (n = 3722). Women were followed until breast cancer diagnosis, prophylactic bilateral mastectomy, or death. A Cox regression model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of breast cancer associated with oophorectomy (coded as a time-dependent variable). All statistical tests were two-sided.RESULTS: Over a mean follow-up of 5.6 years, 350 new breast cancers were diagnosed. Among women with a BRCA1 or BRCA2 mutation, oophorectomy was not associated with breast cancer risk compared with women who did not undergo an oophorectomy. The age-adjusted hazard ratio associated with oophorectomy was 0.96 (95% CI = 0.73 to 1.26, P = 76) for BRCA1 and was 0.65 (95% CI = 0.37 to 1.16, P = 14) for BRCA2 mutation carriers. In stratified analyses, the effect of oophorectomy was statistically significant for breast cancer in BRCA2 mutation carriers diagnosed prior to age 50 years (age-adjusted HR = 0.18, 95% CI = 0.05 to 0.63, P = 007). Oophorectomy was not associated with risk of breast cancer prior to age 50 years among BRCA1 mutation carriers (age-adjusted HR = 0.79, 95% CI = 0.55 to 1.13, P = 51).CONCLUSIONS: Findings from this large prospective study support a role of oophorectomy for the prevention of premenopausal breast cancer in BRCA2, but not BRCA1 mutation carriers. These findings warrant further evaluation.

AB - BACKGROUND: Whether oophorectomy reduces breast cancer risk among BRCA mutation carriers is a matter of debate. We undertook a prospective analysis of bilateral oophorectomy and breast cancer risk in BRCA mutation carriers.METHODS: Subjects had no history of cancer, had both breasts intact, and had information on oophorectomy status (n = 3722). Women were followed until breast cancer diagnosis, prophylactic bilateral mastectomy, or death. A Cox regression model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of breast cancer associated with oophorectomy (coded as a time-dependent variable). All statistical tests were two-sided.RESULTS: Over a mean follow-up of 5.6 years, 350 new breast cancers were diagnosed. Among women with a BRCA1 or BRCA2 mutation, oophorectomy was not associated with breast cancer risk compared with women who did not undergo an oophorectomy. The age-adjusted hazard ratio associated with oophorectomy was 0.96 (95% CI = 0.73 to 1.26, P = 76) for BRCA1 and was 0.65 (95% CI = 0.37 to 1.16, P = 14) for BRCA2 mutation carriers. In stratified analyses, the effect of oophorectomy was statistically significant for breast cancer in BRCA2 mutation carriers diagnosed prior to age 50 years (age-adjusted HR = 0.18, 95% CI = 0.05 to 0.63, P = 007). Oophorectomy was not associated with risk of breast cancer prior to age 50 years among BRCA1 mutation carriers (age-adjusted HR = 0.79, 95% CI = 0.55 to 1.13, P = 51).CONCLUSIONS: Findings from this large prospective study support a role of oophorectomy for the prevention of premenopausal breast cancer in BRCA2, but not BRCA1 mutation carriers. These findings warrant further evaluation.

KW - Journal Article

U2 - 10.1093/jnci/djw177

DO - 10.1093/jnci/djw177

M3 - Article

C2 - 27601060

SN - 0027-8874

VL - 109

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

IS - 1

ER -

Bilateral Oophorectomy and Breast Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

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