BRCA1 and BRCA2 Mutations: Surgery or Surveillance

By Emily Staub, PA-S

Background Information

• BRCA1 and BRCA2: – tumor-suppressor genes – autosomal dominant transmission – lifetime breast cancer risk is 60-80% – lifetime ovarian cancer risk is 40% – BRCA2 is associated with male breast cancer

Breast Cancer

• most common cancer diagnosed in women • the second leading cause of cancer death in women • 25% of familial breast cancers are attributed to the BRCA mutations

Who should get tested for the BRCA1 and BRCA2 mutation?

• “predictive” rather than “diagnostic” • multiple relatives with breast cancer or ovarian cancer diagnosis < 50 y/o • male relatives who have had breast cancer • relatives with bilateral breast cancer • need genetic counseling and risk assessment

Current Management

PICO Question

In women between the ages of 18-50 with BRCA1 or BRCA2 mutations, will a prophylactic bilateral mastectomy or surveillance with mammography and breast exams be more effective to prevent the development of breast cancer?

Studies

Rebbeck and colleagues of the PROSE study group

• PURPOSE: to show the effectiveness of bilateral prophylactic mastectomy for breast cancer risk reduction in women with BRCA1 and BRCA2 mutations • PATIENTS: (all had BRCA1 or 2 mutation and had no current or previous breast cancer diagnosis) – Group 1: – Group 2: 105 women underwent bilateral prophylactic mastectomy (control) 378 women did not undergo a bilateral prophylactic mastectomy

Studies

Rebbeck and colleagues of the PROSE study group

• METHODS: patients followed prospectively -Group 1: post surgery follow-up was 5.5 years -Group 2: (control) post surgery follow-up was 6.7 years • RESULTS: -Group 1: only 2 women were diagnosed with breast cancer -Group 2: 184 patients (about half) were diagnosed with breast cancer in the follow-up period • CONCLUSION: bilateral prophylactic mastectomy reduces the risk of breast cancer in women with BRCA1 and BRCA2 mutations by about 90%

Studies

Rebbeck and colleagues of the PROSE study group

Time to breast cancer diagnosis:

Studies

Fatouros and colleagues

• PURPOSE : this review compares the role of prophylactic surgery and nonsurgical preventative interventions for women with the BRCA1 and 2 mutations • METHODS : searched PubMed and Medline for articles about optimizing prevention and treating women with familial susceptibility to breast and ovarian cancer • RESULTS : -139 nonrandomized patients with mutations had no diagnosis of breast cancer at 3 years follow-up after a prophylactic bilateral mastectomy compared to a 13% breast cancer incidence among the women who did not have the procedure

Studies

Fatouros and colleagues

• RESULTS: - prophylactic bilateral mastectomy reduced the risk of breast cancer by roughly 95% in women with previous or concurrent prophylactic bilateral mastectomy and reduced the risk of about 90% in women with intact ovaries - PBSO reduced the risk of ovarian cancer by 90% and breast cancer by 50% • CONCLUSION : - prophylactic bilateral salpingo-oophorectomy is superior to prophylactic bilateral mastectomy after childbearing age or aged 35 40 years - it reduces the risks of both ovarian and breast cancer as well as mortality

Studies

Fatouros and colleagues

Studies

• • • •

Uyei and colleagues

Purpose: compared risk-reduction interventions high risk women chose after genetic testing when considering demographic and clinical characteristics (race, personal history of cancer, family history of cancer) Methods: retrospective review of records for 554 women who were tested for the BRCA1 and BRCA2 mutations Results: 78 had the BRCA1 mutation, 54 had the BRCA2 mutation, 85 underwent prophylactic mastectomy, 30 underwent prophylactic oophorectomy, 52 both surgeries, and 387 opted for surveillance Conclusion: - women who were BRCA carriers, women with a history of breast cancer, DCIS or breast biopsy, or women who had a family history of ovarian cancer were more likely to undergo prophylactic surgery for cancer risk reduction - women who were already diagnosed with ovarian cancer or advanced breast cancer were more likely to choose surveillance

Studies

Jatoi and colleagues

• Purpose: a review was conducted to determine which management options women with a genetic predisposition for breast cancer used as preventative strategies when they compared screening, prophylactic surgery, and chemoprevention • Results: - four randomized, prospective trials showed Tamoxifen reduced the risk of invasive breast cancer by 38% - in a retrospective analysis of women who had a family history of breast cancer, they found that the patient at high risk reduced their incidence of breast cancer by 90% when they opted for a bilateral prophylactic mastectomy

Studies

Jatoi and colleagues

• Results: - six prospective, nonrandomized studies found that screening MRI had a sensitivity of 77%-100% and the sensitivity of mammography or ultrasound was only 16% to 40%. Also, specificity of MRI was 88% compared with 95% for mammography • Conclusions: - tamoxifen is effective in preventing breast cancer in BRCA mutation carriers and also is associated with a lower risk of contralateral breast cancer in BRCA1 mutation carriers - prophylactic mastectomy significantly reduces breast cancer risk lower - MRI is more sensitive than mammography but its specificity is

Studies

Lostumbo and colleagues

• Purpose: performed a systemic review in order to determine whether prophylactic mastectomy reduces death from any cause in women who has had breast cancer in one breast and women who have never had breast cancer • Methods: - searched for randomized trials and cohort, case control studies - observed the effect of prophylactic mastectomy on other endpoints such as: breast cancer incidence, breast cancer mortality, disease-free survival, physical morbidity, and psychosocial outcomes • Conclusion: bilateral prophylactic mastectomy was effective in reducing both the incidence of and death from breast cancer

Conclusions

• bilateral prophylactic mastectomy is far more superior in reducing the risk of breast cancer in BRCA1 and BRCA2 mutation carriers • prophylactic bilateral salpingo-oophorectomy reduces the risks of both ovarian and breast cancer • it’s important to weigh the risks and benefits of each management option • it is ultimately up to the patient

Things to Consider

RISKS • tamoxifen increases your risk for endometrial cancer and thromboembolism • mastectomy may affect a woman’s perception of her body image but there are reconstructive options • oophorectomy prevents childbearing and makes the patient menopausal; however, patients may wait until after childbearing • invasive procedure and increases morbidity BENEFITS • surgery provides cancer risk reduction • gives the patient psychological peace of mind

Reconstructive Options

TRAM flap

Reconstructive Options

Latissimus Dorsi flap

Application

• assess a patient’s risk for the mutation and the possible need for genetic testing • after discovering a patient has a BRCA mutation, this knowledge will assist in managing the patient and starting screening exams as early as possible • discuss risk and benefits to help patient choose the appropriate management option • teach patient to do monthly self breast exams

Future

• randomized trials are needed

References

Fatouros, M. MD, Baltoyiannis, G. MD, & Roukos, D. MD (2008). The predominant role of surgery in the prevention and new trends in the surgical treatment of women with BRCA1/2 mutations.

Annals of Surgical Oncology

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15

, 21-33.

Jatoi, I. MD, PhD, & Anderson, W. F. MD, MPH (2008). Management of women who have a genetic predisposition for breast cancer.

Surgical Clinics of North America

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88

, 845-861. Lostumbo, L, Carbine, NE, Wallace, J, Ezzo, J, & Dickersin, K. Prophylactic mastectomy for the prevention of breast cancer.

Cochrane Database of Systematic Reviews 2004

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Issue 4

. Art. No.: CD002748. DOI: 10.1002/1451858.CD002748.pub2.

Rebbeck, T. R., Friebel, T., Lynch, H. T., Neuhausen, S. L., Veer, L., & Garber, J. E. (2004). Bilateral prophylactic mastectomy reduces breast cancer risk in BRCA1 and BRCA2 mutation carriers: The PROSE study group.

22

, 1055-1062. Uyei, A., MD, Peterson, S. K., MD, Erlichman, J., MS, Broglio, K., MS, Yekell, S., BS, & Schmeler, K., MD (2006). Association between clinical characteristics and risk reduction interventions in women who underwent BRCA1 and BRCA2 testing.

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