Table 19Studies of Risk-Reducing Surgery

Author, year, quality ratingInclusion criteriaRisk factors Enrolled, nMean age at surgery, yBreast cancer incidence Risk estimate (95% CI)Ovarian cancer incidence Risk estimate (95% CI)Mortality Risk estimate (95% CI)Mean followup,* y
Mastectomy
 Surgery vs. no surgery
Domchek et al, 2010292
Fair
BRCA 1/2 carrier
No history of salpingo-oophorectomy
BRCA1 positive
n=415
370/43 vs. 19/372
HR NA
NRNR2.7
BRCA2 positive
n=245
390/32 vs. 15/213
HR NA
NRNR2.5
Skytte et al, 2011294
Good
BRCA1/2 carrier No history of mastectomy or salpingo-oophorectomyBRCA1 positive
n=201
BRCA2 positive
n=10
NR3/96 vs. 16/211
HR, 0.39 (0.12 to 1.36)
NRNRNR§
 Surgery group (observed vs. expected)
Evans et al, 2009293
NA
Lifetime risk of breast cancer >25%High-risk
BRCA1/2 positive**
n=202
NR0/307 vs. 21.3
HR NA
NRNR7.5
Salpingo-oophorectomy or oophorectomy
 Surgery vs. no surgery
Domchek et al, 2010292
Fair
BRCA1/2 carrier
No history of salpingo-oophorectomy
BRCA1 positive
n=1003
4214% (32/236) vs. 20% (129/633)
HR, 0.63 (0.41 to 0.96)
2% (6/342) vs. 7% (49/661)
HR, 0.31 (0.12 to 0.82)
All cause: 2% (8/327) vs. 7% (43/608)
HR, 0.52 (0.24 to 1.14)
5.6
BRCA2 positive
n=554
467% (7/100) vs. 23% (94/401)
HR, 0.36 (0.16 to 0.82)
0/123 vs. 14/431
HR NA
All cause: 0/120 vs. 17/403
HR NA
5.8
Kramer et al, 2005185††
Fair
BRCA1-positive family‡‡; no history of bilateral mastectomyBRCA1 positive
n=98
NR18% (6/33) vs. 42% (27/65)
HR, 0.38 (0.15 to 0.97)
NRNR16.5
BRCA1 negative
n=353
NR3% (1/34) vs. 1% (4/319)
HR NR
NRNR16.5
Undetermined mutation status
n=222
NR0% (0/18) vs. 2.5% (5/204)
HR NA
NRNR16.5
 Surgery group (observed vs. expected)§§
Olson et al, 2004296††
NA
Women with bilateral oophorectomyHigh-risk║║
Surgery <60 years
n=55
<603/55 vs. 5.4
RR, 0.56 (0.11 to 1.33)
NRNRNA
Surgery <50 years
n=41
<501/41 vs. 3.9
RR, 0.26 (0.001 to 0.99)
NRNRNA
Moderate risk¶¶
Surgery <60 years
n=193
<609/193 vs. 10.9
RR, 0.83 (0.38 to 1.44)
NRNRNA
Surgery <50 years
n=130
<505/130 vs. 7.7
RR, 0.65 (0.21 to 1.32)
NRNRNA
Prior report
 Mastectomy
Hartmann et al, 1999290
Hartmann et al, 2001291
NA
Family history of breast cancerHigh risk
n=214
423/214 vs. 37 expected***; risk reduction, 92% (77% to 98%)n=2Breast cancer: 2/214 vs.10 expected***; risk reduction, 81% (31% to 98%)14 (median)
Moderate risk
n=425
4/425 vs. 37 expected‡‡; risk reduction, 89.5% (p<0.001)n=0Breast cancer: 0/425 vs. 10 expected‡‡; risk reduction, 100% (70% to 100%)
BRCA1 or BRCA2 positive†††
n=18
410/18 vs. 6.1/18 expected‡‡‡; risk reduction, 100% (51% to 100%)
0/18 vs. 4.5/18 expected§§§; risk reduction, 100% (33% to 100%)
NRNR13.4 (median)
 Oophorectomy (surgery vs. no surgery)
Struewing et al,1995229
Poor
Families with ≥3 cases of ovarian cancer or ≥2 cases of ovarian cancer and ≥1 cases of breast cancer <age 50First-degree relatives of breast or ovarian cancer cases
n=390
N =12 families
NR3/44 vs. 14/346
Risk estimate: NR
2/44 vs. 8/346║║║
Risk estimate: NR
NRNR¶¶¶
*

Based on followup to censoring date.

BRCA1 carriers evaluated in group including those with and without surgery.

BRCA2 carriers evaluated in group including those with and without surgery.

§

Total at-risk time in surgery group was 378.7 years vs. 934.6 years in the no surgery group.

Expected incidence based on life tables.

Study included women with prior breast cancer; only data on women with no prior breast cancer included in evidence review.

**

Total number of women with BRCA1/2 mutation, regardless of breast cancer history; study did not provide the number of women with a mutation and no prior history of breast cancer.

††

Oophorectomy performed.

‡‡

Families testing positive for BRCA1 mutation; families had multiple breast and ovarian cancer cases prior to testing.

§§

Expected incidence based on Gail model.

║║

One first-degree relative with breast cancer before age 50 years or one first-degree relative with ovarian cancer at any age and at least one other first- or second-degree relative with either diagnosis at any age.

¶¶

One first-degree relative with breast cancer at any age.

***

Based on control group of sisters.

†††

Subgroup of high-risk group.

‡‡‡

Based on high-penetrance model.

§§§

Based on low-penetrance model.

║║║

Incidence includes postoophorectomy ovarian carcinomatosis.

¶¶¶

Followup for ovarian cancer incidence was 1665 person-years for no surgery group, 460 person-years for surgery group; followup for breast cancer incidence was 1587 person-years for no surgery group, 484 person-years for surgery group.

Abbreviations: CI = confidence interval; HR = hazard ratio; NA = not applicable; NR = not reported; RR = relative risk.

Based on followup to censoring date.

BRCA1 carriers evaluated in group including those with and without surgery.

BRCA2 carriers evaluated in group including those with and without surgery.

Total at-risk time in surgery group was 378.7 years vs. 934.6 years in the no surgery group.

Expected incidence based on life tables.

Study included women with prior breast cancer; only data on women with no prior breast cancer included in evidence review.

Total number of women with BRCA1/2 mutation, regardless of breast cancer history; study did not provide the number of women with a mutation and no prior history of breast cancer.

Oophorectomy performed.

Families testing positive for BRCA1 mutation; families had multiple breast and ovarian cancer cases prior to testing.

Expected incidence based on Gail model.

One first-degree relative with breast cancer before age 50 years or one first-degree relative with ovarian cancer at any age and at least one other first- or second-degree relative with either diagnosis at any age.

One first-degree relative with breast cancer at any age.

Based on control group of sisters.

Subgroup of high-risk group.

Based on high-penetrance model.

Based on low-penetrance model.

Incidence includes postoophorectomy ovarian carcinomatosis.

Followup for ovarian cancer incidence was 1665 person-years for no surgery group, 460 person-years for surgery group; followup for breast cancer incidence was 1587 person-years for no surgery group, 484 person-years for surgery group.

From: 3, RESULTS

Cover of Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer
Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer: Systematic Review to Update the U.S. Preventive Services Task Force Recommendation [Internet].
Evidence Syntheses, No. 101.
Nelson HD, Fu R, Goddard K, et al.

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