Transcript Slide 1

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: 105 women underwent bilateral prophylactic
mastectomy
– Group 2: (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 3540 years
- it reduces the risks of both ovarian and breast cancer as well
as mortality
Studies
Fatouros and colleagues
Studies
Uyei and colleagues
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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
- MRI is more sensitive than mammography but its specificity is
lower
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
BENEFITS
• 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
• 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. 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. 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.
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 riskreduction interventions in women who underwent BRCA1 and BRCA2 testing. 107,
2745-2751.