The incidence of endometrial cancer in women with BRCA1 and BRCA2 mutations

An international prospective cohort study

Yakir Segev, Javaid Iqbal, Jan Lubinski, Jacek Gronwald, Henry T. Lynch, Pal Moller, Parviz Ghadirian, Barry Rosen, Nadine Tung, Charmaine Kim-Sing, William D. Foulkes, Susan L. Neuhausen, Leigha Senter, Christian F. Singer, Beth Karlan, Sun Ping, Steven A. Narod

Research output: Contribution to journalArticle

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Abstract

Objective To evaluate the risk of endometrial cancer in women who carry a mutation in the BRCA1 or the BRCA2 gene. Methods We followed 4456 women with a BRCA1 or a BRCA2 mutation for incident cases of endometrial cancer. The incidence of endometrial cancer was estimated per 100,000 women per year. The hazard ratios for endometrial cancer were estimated by calculating standardized incidence ratios (SIRs) according to age group and country of residence. We estimated the impact of tamoxifen and hormone replacement therapy on the incidence of endometrial cancer in BRCA1 and BRCA2 carriers. Results After a mean follow-up of 5.7 years, we identified 17 endometrial cancers (13 cases in BRCA1 and 4 cases in BRCA2). The SIR for BRCA1 carriers was 1.91 (95% CI: 1.06-3.19, p = 0.03) and for BRCA2 carriers was 1.75 (95% CI: 0.55-4.23, p = 0.2). The SIR was 4.14 (95% CI: 1.92 to 7.87) for women who received tamoxifen and was 1.67 (95% CI: 0.81 to 3.07) for women who did not receive tamoxifen. The ten-year cumulative risk of endometrial cancer in women who were treated with tamoxifen was 2.0%. Conclusions The risk of endometrial cancer is higher in BRCA1 mutation carriers than in the general population. The excessive risk is largely attributable to a history of tamoxifen use, but the actual risk of endometrial cancer associated with tamoxifen is small. It is important to discuss hysterectomy at the time of prophylactic bilateral salpingo-oophorectomy if tamoxifen is to be considered.

Original languageEnglish
Pages (from-to)127-131
Number of pages5
JournalGynecologic Oncology
Volume130
Issue number1
DOIs
StatePublished - Jul 2013

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Endometrial Neoplasms
Tamoxifen
Cohort Studies
Prospective Studies
Mutation
Incidence
BRCA2 Gene
Hormone Replacement Therapy
Ovariectomy
Hysterectomy
Age Groups

All Science Journal Classification (ASJC) codes

  • Obstetrics and Gynecology
  • Oncology

Cite this

The incidence of endometrial cancer in women with BRCA1 and BRCA2 mutations : An international prospective cohort study. / Segev, Yakir; Iqbal, Javaid; Lubinski, Jan; Gronwald, Jacek; Lynch, Henry T.; Moller, Pal; Ghadirian, Parviz; Rosen, Barry; Tung, Nadine; Kim-Sing, Charmaine; Foulkes, William D.; Neuhausen, Susan L.; Senter, Leigha; Singer, Christian F.; Karlan, Beth; Ping, Sun; Narod, Steven A.

In: Gynecologic Oncology, Vol. 130, No. 1, 07.2013, p. 127-131.

Research output: Contribution to journalArticle

Segev, Y, Iqbal, J, Lubinski, J, Gronwald, J, Lynch, HT, Moller, P, Ghadirian, P, Rosen, B, Tung, N, Kim-Sing, C, Foulkes, WD, Neuhausen, SL, Senter, L, Singer, CF, Karlan, B, Ping, S & Narod, SA 2013, 'The incidence of endometrial cancer in women with BRCA1 and BRCA2 mutations: An international prospective cohort study', Gynecologic Oncology, vol. 130, no. 1, pp. 127-131. https://doi.org/10.1016/j.ygyno.2013.03.027
Segev, Yakir ; Iqbal, Javaid ; Lubinski, Jan ; Gronwald, Jacek ; Lynch, Henry T. ; Moller, Pal ; Ghadirian, Parviz ; Rosen, Barry ; Tung, Nadine ; Kim-Sing, Charmaine ; Foulkes, William D. ; Neuhausen, Susan L. ; Senter, Leigha ; Singer, Christian F. ; Karlan, Beth ; Ping, Sun ; Narod, Steven A. / The incidence of endometrial cancer in women with BRCA1 and BRCA2 mutations : An international prospective cohort study. In: Gynecologic Oncology. 2013 ; Vol. 130, No. 1. pp. 127-131.
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title = "The incidence of endometrial cancer in women with BRCA1 and BRCA2 mutations: An international prospective cohort study",
abstract = "Objective To evaluate the risk of endometrial cancer in women who carry a mutation in the BRCA1 or the BRCA2 gene. Methods We followed 4456 women with a BRCA1 or a BRCA2 mutation for incident cases of endometrial cancer. The incidence of endometrial cancer was estimated per 100,000 women per year. The hazard ratios for endometrial cancer were estimated by calculating standardized incidence ratios (SIRs) according to age group and country of residence. We estimated the impact of tamoxifen and hormone replacement therapy on the incidence of endometrial cancer in BRCA1 and BRCA2 carriers. Results After a mean follow-up of 5.7 years, we identified 17 endometrial cancers (13 cases in BRCA1 and 4 cases in BRCA2). The SIR for BRCA1 carriers was 1.91 (95{\%} CI: 1.06-3.19, p = 0.03) and for BRCA2 carriers was 1.75 (95{\%} CI: 0.55-4.23, p = 0.2). The SIR was 4.14 (95{\%} CI: 1.92 to 7.87) for women who received tamoxifen and was 1.67 (95{\%} CI: 0.81 to 3.07) for women who did not receive tamoxifen. The ten-year cumulative risk of endometrial cancer in women who were treated with tamoxifen was 2.0{\%}. Conclusions The risk of endometrial cancer is higher in BRCA1 mutation carriers than in the general population. The excessive risk is largely attributable to a history of tamoxifen use, but the actual risk of endometrial cancer associated with tamoxifen is small. It is important to discuss hysterectomy at the time of prophylactic bilateral salpingo-oophorectomy if tamoxifen is to be considered.",
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T1 - The incidence of endometrial cancer in women with BRCA1 and BRCA2 mutations

T2 - An international prospective cohort study

AU - Segev, Yakir

AU - Iqbal, Javaid

AU - Lubinski, Jan

AU - Gronwald, Jacek

AU - Lynch, Henry T.

AU - Moller, Pal

AU - Ghadirian, Parviz

AU - Rosen, Barry

AU - Tung, Nadine

AU - Kim-Sing, Charmaine

AU - Foulkes, William D.

AU - Neuhausen, Susan L.

AU - Senter, Leigha

AU - Singer, Christian F.

AU - Karlan, Beth

AU - Ping, Sun

AU - Narod, Steven A.

PY - 2013/7

Y1 - 2013/7

N2 - Objective To evaluate the risk of endometrial cancer in women who carry a mutation in the BRCA1 or the BRCA2 gene. Methods We followed 4456 women with a BRCA1 or a BRCA2 mutation for incident cases of endometrial cancer. The incidence of endometrial cancer was estimated per 100,000 women per year. The hazard ratios for endometrial cancer were estimated by calculating standardized incidence ratios (SIRs) according to age group and country of residence. We estimated the impact of tamoxifen and hormone replacement therapy on the incidence of endometrial cancer in BRCA1 and BRCA2 carriers. Results After a mean follow-up of 5.7 years, we identified 17 endometrial cancers (13 cases in BRCA1 and 4 cases in BRCA2). The SIR for BRCA1 carriers was 1.91 (95% CI: 1.06-3.19, p = 0.03) and for BRCA2 carriers was 1.75 (95% CI: 0.55-4.23, p = 0.2). The SIR was 4.14 (95% CI: 1.92 to 7.87) for women who received tamoxifen and was 1.67 (95% CI: 0.81 to 3.07) for women who did not receive tamoxifen. The ten-year cumulative risk of endometrial cancer in women who were treated with tamoxifen was 2.0%. Conclusions The risk of endometrial cancer is higher in BRCA1 mutation carriers than in the general population. The excessive risk is largely attributable to a history of tamoxifen use, but the actual risk of endometrial cancer associated with tamoxifen is small. It is important to discuss hysterectomy at the time of prophylactic bilateral salpingo-oophorectomy if tamoxifen is to be considered.

AB - Objective To evaluate the risk of endometrial cancer in women who carry a mutation in the BRCA1 or the BRCA2 gene. Methods We followed 4456 women with a BRCA1 or a BRCA2 mutation for incident cases of endometrial cancer. The incidence of endometrial cancer was estimated per 100,000 women per year. The hazard ratios for endometrial cancer were estimated by calculating standardized incidence ratios (SIRs) according to age group and country of residence. We estimated the impact of tamoxifen and hormone replacement therapy on the incidence of endometrial cancer in BRCA1 and BRCA2 carriers. Results After a mean follow-up of 5.7 years, we identified 17 endometrial cancers (13 cases in BRCA1 and 4 cases in BRCA2). The SIR for BRCA1 carriers was 1.91 (95% CI: 1.06-3.19, p = 0.03) and for BRCA2 carriers was 1.75 (95% CI: 0.55-4.23, p = 0.2). The SIR was 4.14 (95% CI: 1.92 to 7.87) for women who received tamoxifen and was 1.67 (95% CI: 0.81 to 3.07) for women who did not receive tamoxifen. The ten-year cumulative risk of endometrial cancer in women who were treated with tamoxifen was 2.0%. Conclusions The risk of endometrial cancer is higher in BRCA1 mutation carriers than in the general population. The excessive risk is largely attributable to a history of tamoxifen use, but the actual risk of endometrial cancer associated with tamoxifen is small. It is important to discuss hysterectomy at the time of prophylactic bilateral salpingo-oophorectomy if tamoxifen is to be considered.

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