Prophylactic Oophorectomy to Reduce the Risk of Ovarian and Breast Cancer in Carriers ofBRCAMutations

PURPOSE: BRCA1 mutation carriers have a high risk of developing breast and ovarian cancer. Carriers may opt for prophylactic surgery and screening. Recent data suggesting that prophylactic oophorectomy reduces breast cancer risk have been incorporated in a decision analysis. METHODS: A Markov model was developed to compare LE and QALE following four strategies: (1) prophylactic mastectomy and prophylactic oophorectomy (PMPO), (2) screening for breast cancer and prophylactic oophorectomy (BSPO), (3) prophylactic mastectomy and screening for ovarian cancer (PMOS), and (4) screening for breast and ovarian cancer (BSOS). The analysis was performed for a high (85% breast cancer, 63% ovarian cancer) and medium (56% breast cancer, 16% ovarian cancer) risk level. Utilities for the health states after prophylactic surgery were obtained from mutation carriers. Other model parameter values were obtained from the literature. Sensitivity analyses were performed. RESULTS: When compared with BSOS, the average gain in LE for 30-year-old carriers in the high (medium) risk group was 11.7 (6.6) years for PMPO, 9.5 (5.3) years for BSPO, and 4.9 (4.4) years for PMOS. For 30-year-old carriers, BSPO had a QALE advantage when PO was performed before age 40. In the medium-risk group, there was a stronger advantage for BSPO when QALE was considered. CONCLUSION: PMPO is the most effective strategy to prolong life. However, if patient preferences were taken into account, BSPO tends to be a better strategy in most women at medium risk or in young women at high risk when PO was performed before age 40.

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Prophylactic Oophorectomy Reduces Breast Cancer Penetrance During Prospective, Long-Term Follow-Up ofBRCA1Mutation Carriers

Journal of Clinical Oncology ◽

10.1200/jco.2005.02.9199 ◽

2005 ◽

Vol 23 (34) ◽

pp. 8629-8635 ◽

Cited By ~ 103

Author(s):

Joan L. Kramer ◽

Isela A. Velazquez ◽

Bingshu E. Chen ◽

Philip S. Rosenberg ◽

Jeffery P. Struewing ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Protective Effect ◽

Brca1 Mutation ◽

Prophylactic Oophorectomy ◽

Brca1 Mutations ◽

Mutation Carriers ◽

Multiple Case

PurposeBreast cancer penetrance estimates in BRCA1 mutation carriers have varied from 40% to 85%; this heterogeneity has been attributed to variations in risk among different study populations. No study has taken oophorectomy status into account in estimating penetrance. Because prophylactic oophorectomy reduces breast cancer risk by approximately 50%, we hypothesized that population differences in oophorectomy prevalence might significantly influence breast cancer penetrance estimates.MethodsFemales from multiple-case breast/ovarian cancer families that segregate deleterious BRCA1 mutations were observed prospectively for breast cancer incidence and oophorectomy.ResultsWithin this cohort, 33 cases of breast cancer developed in 98 women with deleterious BRCA1 mutations during follow-up, yielding an estimated cumulative lifetime breast cancer risk of 80%. This estimate increased to 94% when the study participants were censored at the time of oophorectomy. Six of the 33 mutation-positive women who underwent oophorectomy during follow-up developed breast cancer, compared with 27 of 65 mutation carriers with intact ovaries (hazard ratio = 0.38; 95% CI, 0.15 to 0.97). Estimates of absolute breast cancer risk demonstrated that the protective effect of oophorectomy was strongest among women who were premenopausal at the time of surgery. When surgical status was ignored, the strong protective effect of oophorectomy, coupled with the high prevalence of the procedure in these families, led to a significantly lower estimate of the breast cancer penetrance in BRCA1 mutation carriers.ConclusionDiffering rates of oophorectomy likely represent an underappreciated basis for a portion of the heterogeneity in estimated breast cancer penetrance described in BRCA mutation carriers, particularly mutation carriers from extensively affected, multiple-case families.

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Clinical factors that affect breast cancer risk reduction decisions in high risk women tested for the BRCA1/2 genetic mutation

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.1013 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 1013-1013

Author(s):

A. R. Uyei ◽

K. R. Broglio ◽

T. L. Solomon ◽

K. J. Vogel ◽

C. I. Amos ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Family History ◽

Risk Reduction ◽

Breast Biopsy ◽

Prophylactic Mastectomy ◽

Prophylactic Surgery ◽

Clinical Factors ◽

Prophylactic Oophorectomy ◽

History Of

1013 Background: Women with an increased risk for breast cancer have many risk reduction options including: prophylactic mastectomy, prophylactic oophorectomy, chemoprevention, and screening. Women without breast cancer make such decisions in a purely preventive setting and factors that affect their decisions are unclear. Method: We performed an IRB approved retrospective review of the medical records on women who underwent BRCA testing. We evaluated the women without a history of breast cancer to assess clinical characteristics and their relation to decision making. The risk reduction categories analyzed were: prophylactic mastectomy, prophylactic oophorectomy, tamoxifen, increased surveillance with MRI, and standard screening (clinical breast exam and mammography). Patient characteristics were tabulated by clinical decision group and the chi-square test or Fisher’s exact test was used. Results: From 2001, 627 patients have undergone genetic testing. 202 of these women did not have a history of breast cancer among whom 58 were mutation carriers. Most patients chose standard screening (47%) or increased surveillance (38%). 4% chose tamoxifen, 7% chose prophylactic mastectomy, 3% chose both prophylactic mastectomy and oophorectomy, and 5% chose oophorectomy. The tamoxifen group was too small to do further analysis. Increased surveillance did not show any significant association with any of the clinical factors that we evaluated. The majority of women who chose standard screening had a personal history of ovarian cancer (p<0.0001) and had no family history of ovarian cancer (p=0.02). Prophylactic surgeries were significantly associated with positive BRCA status (p=0.01). Women with a family history of ovarian cancer tended to have prophylactic surgery (p=0.02). Women who had DCIS or a breast biopsy tended to have prophylactic mastectomies (p=0.0001 and p<0.001 respectively). Conclusion: In breast cancer free women, BRCA status, family history of ovarian cancer, DCIS, and breast biopsy were associated with prophylactic surgeries. Having ovarian cancer or no family history of ovarian cancer were associated with standard screening. We are performing a questionnaire study to determine the reasons behind these women’s choices. No significant financial relationships to disclose.

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Value of prophylactic oophorectomy in advanced breast cancer with parasternal lymph nodes metastasis

The Japanese Journal of Surgery ◽

10.1007/bf02469386 ◽

1977 ◽

Vol 7 (2) ◽

pp. 49-53

Author(s):

Masafumi Jimi ◽

Mitsuo Katano ◽

Hideki Kishikawa

Keyword(s):

Breast Cancer ◽

Lymph Nodes ◽

Advanced Breast Cancer ◽

Advanced Breast ◽

Prophylactic Oophorectomy ◽

Lymph Nodes Metastasis

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Update on chemoprevention in BRCA1 and BRCA2 mutation carriers

Breast Cancer Online ◽

10.1017/s1470903105002890 ◽

2005 ◽

Vol 8 (9) ◽

Author(s):

M. Stumacher ◽

S. M. Domchek

Keyword(s):

Breast Cancer ◽

Prophylactic Mastectomy ◽

Brca Mutation ◽

Brca2 Mutation ◽

Breast Cancers ◽

Brca1 And Brca2 ◽

Prophylactic Oophorectomy ◽

Estrogen Exposure ◽

Mutation Carriers ◽

Increased Risk

Chemoprevention with tamoxifen and oophorectomy are thought to be effective in decreasing the incidence of breast cancer in women at increased risk for the disease. There is mounting data supporting the idea that hormonal interventions that reduce estrogen exposure to breast epithelium, such as prophylactic oophorectomy and tamoxifen, are effective in breast cancer prevention in both BRCA1 and BRCA2 mutations carriers. Several recent studies directly address the protective effect of tamoxifen and oophorectomy in BRCA mutation carriers and suggest that these endocrine manipulations decrease the risk of primary and secondary breast cancers. Ongoing studies aim to better define the effect of tamoxifen in these very high-risk women and determining whether factors, such as earlier age of use or prior prophylactic oophorectomy, impact tamoxifen's effect. Based on existing data, we recommend that women with deleterious mutations in BRCA1 or BRCA2 be informed of the beneficial effect of oophorectomy on breast cancer risk and that women who choose breast cancer screening instead of prophylactic mastectomy be offered tamoxifen as a prevention option.

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Breast Cancer Risk After Bilateral Prophylactic Oophorectomy in BRCA1 Mutation Carriers

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/91.17.1475 ◽

1999 ◽

Vol 91 (17) ◽

pp. 1475-1479 ◽

Cited By ~ 467

Author(s):

T. R. Rebbeck ◽

A. M. Levin ◽

A. Eisen ◽

C. Snyder ◽

P. Watson ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Brca1 Mutation ◽

Prophylactic Oophorectomy ◽

Mutation Carriers

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Effect of Short-Term Hormone Replacement Therapy on Breast Cancer Risk Reduction After Bilateral Prophylactic Oophorectomy in BRCA1 and BRCA2 Mutation Carriers: The PROSE Study Group

Journal of Clinical Oncology ◽

10.1200/jco.2004.00.8151 ◽

2005 ◽

Vol 23 (31) ◽

pp. 7804-7810 ◽

Cited By ~ 276

Author(s):

Timothy R. Rebbeck ◽

Tara Friebel ◽

Theresa Wagner ◽

Henry T. Lynch ◽

Judy E. Garber ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Risk Reduction ◽

Hormone Replacement ◽

Short Term ◽

Prophylactic Oophorectomy ◽

Mutation Carriers ◽

Breast Cancer Risk Reduction ◽

Cancer Risk Reduction

Purpose Bilateral prophylactic oophorectomy (BPO) is widely used for cancer risk reduction in women with BRCA1/2 mutations. Many premenopausal women choose to take hormone replacement therapy (HRT) after undergoing BPO to abrogate immediate symptoms of surgically-induced menopause. Thus, we evaluated whether the breast cancer risk reduction conferred by BPO in BRCA1/2 mutation carriers is altered by use of post-BPO HRT. Methods We identified a prospective cohort of 462 women with disease-associated germline BRCA1/2 mutations at 13 medical centers to evaluate breast cancer risk after BPO with and without HRT. We determined the incidence of breast cancer in 155 women who had undergone BPO and in 307 women who had not undergone BPO on whom we had complete information on HRT use. Postoperative follow-up was 3.6 years. Results Consistent with previous reports, BPO was significantly associated with breast cancer risk reduction overall (hazard ratio [HR] = 0.40; 95%CI, 0.18 to 0.92). Using mutation carriers without BPO or HRT as the referent group, HRT of any type after BPO did not significantly alter the reduction in breast cancer risk associated with BPO (HR = 0.37; 95% CI, 0.14 to 0.96). Conclusion Short-term HRT use does not negate the protective effect of BPO on subsequent breast cancer risk in BRCA1/2 mutation carriers.

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