What Are The Considerations in Patient Selection and Timing of Risk-Reducing Mastectomy
What Are The Considerations in Patient Selection and Timing of Risk-Reducing Mastectomy
What Are The Considerations in Patient Selection and Timing of Risk-Reducing Mastectomy
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PEDERSON AND COLLEAGUES
approach currently is risk-reducing medication given ■ BRCA, OVARIAN CANCER, AND BREAST CANCER
its effectiveness.5
Women with BRCA mutations who have devel-
Gene carriers and risk oped ovarian cancer, the most lethal gynecologic
There are 6 gene carriers for which a discussion malignancy,18 have an overall 5-year survival rate
about risk-reducing mastectomy is indicated due to of 45.6%.19 Experts suggest that women with stage I
their absolute estimated risk of developing breast ovarian cancer who are disease-free for at least one
cancer: BRCA1 (72%),1 BRCA2 (69%),1 PALB2 year, are most likely to benefit from risk-reducing
(up to 53%),7 PTEN (up to 85%),8 CDH1 (43%),9 mastectomy.7,18,20 In patients with stage II/III disease,
and TP53 (85%).8,10 Some patients have clinical BRCA mutation carriers have a relatively low risk of
features of Cowden syndrome but test negative for a breast cancer and their prognosis is largely determined
PTEN mutation (clinical Cowden syndrome). These by their ovarian cancer diagnosis. Studies show a 2%
patients are felt to be at lower risk for breast cancer,11 to 6% incidence of breast cancer in the first 5 years
and consideration of risk-reducing mastectomy should and an approximate 10% risk in the first 10 years fol-
be based on family history.6 Excellent long-term lowing epithelial ovarian cancer diagnosis.7,18,20,21 The
results have been reported for bilateral nipple-sparing risk of breast cancer is lower in ovarian cancer survi-
mastectomy for breast cancer risk-reduction in appro- vors who carry BRCA mutations than that reported
priate patients.12 for BRCA carriers who have not developed ovarian
Genes for which evidence is insufficient for risk-re- cancer (possibly due to oophorectomy or use of che-
ducing mastectomy and those to be managed based on motherapy that could eliminate microscopic breast
family history include CHEK2, NF1, STK11, ATM, cancer at the cellular level).
and BARD1. Genes for which there is insufficient
data, where management (including magnetic reso- Consideration of risk-reducing mastectomy after
nance imaging screening) is based on family history ovarian cancer diagnosis
include BRIP1, RAD51C, and RAD51D.6,13 In a modelling study by Gamble et al,20 the added gain
in survival benefit in months following risk-reducing
Treatment determination mastectomy, if performed in the first several years after
The risk associated with many genetic variants an ovarian cancer diagnosis, was small and greatest in
decreases with age,1 and patient selection is criti- women under 50.20 The study also noted that risk-re-
cal. Regarding timing, the risk of breast cancer is ducing mastectomy is not indicated within 5 years
quite low under the age of 30, and the residual risk of an ovarian cancer diagnosis due to a high rate of
decreases after the age of 50.1 Older women should ovarian cancer relapse.20 It has been suggested that
be advised that their residual risk declines with age, consideration of risk-reducing mastectomy for BRCA
informing decision-making. The benefit of risk-re- carriers be reserved for those who remain in remission
ducing mastectomy may be offset by operative risks for 5 years,7 and possibly for women age 50 or younger
and other causes for mortality.1,14 There is no absolute at ovarian cancer diagnosis.18,22 Furthermore, a study of
age at which risk-reducing mastectomy is no longer 1,455 women who developed primary breast cancer after
recommended. However, it is important to provide ovarian cancer showed mean time from ovarian cancer
age-specific cancer risk estimates to determine appro- diagnosis to breast cancer diagnosis of 7.3 years.23
priate interventions.1,14 In a recent study, the cumula-
tive risk of invasive breast cancer in women ages 60 ■ TAKE-HOME POINTS
to 80 was 20.1% for BRCA1 carriers and 17.3% for
BRCA2 carriers.1,14 • Discuss the option of risk-reducing mastectomy in
Chemoprevention is a risk management alterna- patients with pathogenic or likely pathogenic vari-
tive, although BRCA1 carriers under age 50 are predis- ants in BRCA1, BRCA2, PALB2, PTEN, TP53
posed to triple-negative breast cancer, and preventive and CDH1.
medication is likely to offer little benefit.1,5,13,15 Older • Consider risk-reducing mastectomy in patients
women with BRCA1 are more commonly diagnosed with compelling family history or with a past his-
with estrogen-receptor−positive disease,16 and it is tory of thoracic radiation therapy under the age of
reasonable to offer preventive medication to BRCA1 30.
carriers over age 50.2 RAD51C and RAD51D carriers • Discuss the option of risk-reducing mastectomy in
are predisposed to estrogen-receptor−negative disease BRCA carriers following an ovarian cancer diag-
and may not benefit from preventive therapy.17 nosis only after 5 years of remission.
CLEVELAND CLINIC JOURNAL OF MEDICINE VOLUME 89 • NUMBER 8 AUGUST 2022 443
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RISK-REDUCING MASTECTOMY
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