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Oophorectomy improves survival after breast cancer in BRCA1 carriers

Women with breast cancer and BRCA1 mutations had a lower risk of mortality if they underwent oophorectomy, and the benefit was apparent beyond age 50, investigators reported online April 23 in JAMA Oncology.

In the entire cohort that included women with BRCA1 and BRCA2 mutations, breast cancer–related mortality was reduced 56%, and all-cause mortality (including 9 deaths due to ovarian cancer) was reduced 65% with oophorectomy (adjusted HR, 0.35; 95% CI, 0.22-0.56; P < .001).

Dr. Kelly Metcalfe of the Women’s College Research Institute, Toronto, and her colleagues provided evidence in support of BRCA1 testing in women with early-stage breast cancer at the time of diagnosis.

“The data presented here suggest that oophorectomy should be discussed with the patient [with a BRCA1 mutation] shortly after diagnosis. We recommend that the operation be performed in the first year of treatment to maximize the benefit,” the investigators wrote (JAMA Oncol. 2015 Apr. 23 [doi:10.1001/jamaoncol.2015.0658]).

The historical cohort study evaluated 676 women with BRCA1 or BRCA2 mutations and early-stage breast cancer diagnosed between 1975 and 2008. In order to examine the impact of subsequent oophorectomy on mortality risk due to breast cancer, a requirement for inclusion was that both ovaries be intact at the time of diagnosis. The subsequent oophorectomy group included 345 women.

Among the women who underwent oophorectomy, women with a BRCA1 mutation had a significantly reduced risk of breast cancer–related death, but the association was not significant for those with BRCA2 mutations. However, the number of BRCA2 carriers was much smaller than the number of BRCA1 carriers, and the 95% CI range was wide (0.23-1.43). A larger sample is required to determine the strength of an association.

Regardless of BRCA1/2 mutation status, in patients with estrogen receptor–negative breast cancer, oophorectomy had a protective effect (HR, 0.07; 95% CI, 0.01-0.51; P = .009).

Among 14 women over age 50 with estrogen receptor–negative cancer who did not undergo oophorectomy, 3 (21%) died; of the 15 who underwent the surgery, none died. Based on this finding, and a previous study indicating a protective effect of oophorectomy on the risk of primary breast cancer in women over 50, the researchers concluded that “the postmenopausal ovary remains active in terms of androgen production and that this affects cancer risk and progression, either directly or through aromatization to estrogen.”

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Women with breast cancer and BRCA1 mutations had a lower risk of mortality if they underwent oophorectomy, and the benefit was apparent beyond age 50, investigators reported online April 23 in JAMA Oncology.

In the entire cohort that included women with BRCA1 and BRCA2 mutations, breast cancer–related mortality was reduced 56%, and all-cause mortality (including 9 deaths due to ovarian cancer) was reduced 65% with oophorectomy (adjusted HR, 0.35; 95% CI, 0.22-0.56; P < .001).

Dr. Kelly Metcalfe of the Women’s College Research Institute, Toronto, and her colleagues provided evidence in support of BRCA1 testing in women with early-stage breast cancer at the time of diagnosis.

“The data presented here suggest that oophorectomy should be discussed with the patient [with a BRCA1 mutation] shortly after diagnosis. We recommend that the operation be performed in the first year of treatment to maximize the benefit,” the investigators wrote (JAMA Oncol. 2015 Apr. 23 [doi:10.1001/jamaoncol.2015.0658]).

The historical cohort study evaluated 676 women with BRCA1 or BRCA2 mutations and early-stage breast cancer diagnosed between 1975 and 2008. In order to examine the impact of subsequent oophorectomy on mortality risk due to breast cancer, a requirement for inclusion was that both ovaries be intact at the time of diagnosis. The subsequent oophorectomy group included 345 women.

Among the women who underwent oophorectomy, women with a BRCA1 mutation had a significantly reduced risk of breast cancer–related death, but the association was not significant for those with BRCA2 mutations. However, the number of BRCA2 carriers was much smaller than the number of BRCA1 carriers, and the 95% CI range was wide (0.23-1.43). A larger sample is required to determine the strength of an association.

Regardless of BRCA1/2 mutation status, in patients with estrogen receptor–negative breast cancer, oophorectomy had a protective effect (HR, 0.07; 95% CI, 0.01-0.51; P = .009).

Among 14 women over age 50 with estrogen receptor–negative cancer who did not undergo oophorectomy, 3 (21%) died; of the 15 who underwent the surgery, none died. Based on this finding, and a previous study indicating a protective effect of oophorectomy on the risk of primary breast cancer in women over 50, the researchers concluded that “the postmenopausal ovary remains active in terms of androgen production and that this affects cancer risk and progression, either directly or through aromatization to estrogen.”

Women with breast cancer and BRCA1 mutations had a lower risk of mortality if they underwent oophorectomy, and the benefit was apparent beyond age 50, investigators reported online April 23 in JAMA Oncology.

In the entire cohort that included women with BRCA1 and BRCA2 mutations, breast cancer–related mortality was reduced 56%, and all-cause mortality (including 9 deaths due to ovarian cancer) was reduced 65% with oophorectomy (adjusted HR, 0.35; 95% CI, 0.22-0.56; P < .001).

Dr. Kelly Metcalfe of the Women’s College Research Institute, Toronto, and her colleagues provided evidence in support of BRCA1 testing in women with early-stage breast cancer at the time of diagnosis.

“The data presented here suggest that oophorectomy should be discussed with the patient [with a BRCA1 mutation] shortly after diagnosis. We recommend that the operation be performed in the first year of treatment to maximize the benefit,” the investigators wrote (JAMA Oncol. 2015 Apr. 23 [doi:10.1001/jamaoncol.2015.0658]).

The historical cohort study evaluated 676 women with BRCA1 or BRCA2 mutations and early-stage breast cancer diagnosed between 1975 and 2008. In order to examine the impact of subsequent oophorectomy on mortality risk due to breast cancer, a requirement for inclusion was that both ovaries be intact at the time of diagnosis. The subsequent oophorectomy group included 345 women.

Among the women who underwent oophorectomy, women with a BRCA1 mutation had a significantly reduced risk of breast cancer–related death, but the association was not significant for those with BRCA2 mutations. However, the number of BRCA2 carriers was much smaller than the number of BRCA1 carriers, and the 95% CI range was wide (0.23-1.43). A larger sample is required to determine the strength of an association.

Regardless of BRCA1/2 mutation status, in patients with estrogen receptor–negative breast cancer, oophorectomy had a protective effect (HR, 0.07; 95% CI, 0.01-0.51; P = .009).

Among 14 women over age 50 with estrogen receptor–negative cancer who did not undergo oophorectomy, 3 (21%) died; of the 15 who underwent the surgery, none died. Based on this finding, and a previous study indicating a protective effect of oophorectomy on the risk of primary breast cancer in women over 50, the researchers concluded that “the postmenopausal ovary remains active in terms of androgen production and that this affects cancer risk and progression, either directly or through aromatization to estrogen.”

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Oophorectomy improves survival after breast cancer in BRCA1 carriers
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Oophorectomy improves survival after breast cancer in BRCA1 carriers
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FROM JAMA ONCOLOGY

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Key clinical point: Oophorectomy significantly improved the prognosis of women with breast cancer and a BRCA1 mutation.

Major finding: The adjusted hazard ratio for breast cancer mortality in women with a BRCA1 mutation who had breast cancer and a subsequent oophorectomy was 0.38 (95% CI, 0.19-0.077; P = .007).

Data source: The retrospective cohort study evaluated 676 women with BRCA1 or BRCA2 mutations and breast cancer diagnosed from 1975 to 2008.

Disclosures: Dr. Kelly Metcalfe reported having no disclosures. The research was funded by the Canadian Breast Cancer Foundation.