Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality.
BACKGROUND
Mastectomy and salpingo-oophorectomy are widely used by carriers of BRCA1 or BRCA2 mutations to reduce their risks of breast and ovarian cancer.


OBJECTIVE
To estimate risk and mortality reduction stratified by mutation and prior cancer status.


METHODS
Prospective, multicenter cohort study of 2482 women with BRCA1 or BRCA2 mutations ascertained between 1974 and 2008. The study was conducted at 22 clinical and research genetics centers in Europe and North America to assess the relationship of risk-reducing mastectomy or salpingo-oophorectomy with cancer outcomes. The women were followed up until the end of 2009.


METHODS
Breast and ovarian cancer risk, cancer-specific mortality, and overall mortality.


RESULTS
No breast cancers were diagnosed in the 247 women with risk-reducing mastectomy compared with 98 women of 1372 diagnosed with breast cancer who did not have risk-reducing mastectomy. Compared with women who did not undergo risk-reducing salpingo-oophorectomy, women who underwent salpingo-oophorectomy had a lower risk of ovarian cancer, including those with prior breast cancer (6% vs 1%, respectively; hazard ratio [HR], 0.14; 95% confidence interval [CI], 0.04-0.59) and those without prior breast cancer (6% vs 2%; HR, 0.28 [95% CI, 0.12-0.69]), and a lower risk of first diagnosis of breast cancer in BRCA1 mutation carriers (20% vs 14%; HR, 0.63 [95% CI, 0.41-0.96]) and BRCA2 mutation carriers (23% vs 7%; HR, 0.36 [95% CI, 0.16-0.82]). Compared with women who did not undergo risk-reducing salpingo-oophorectomy, undergoing salpingo-oophorectomy was associated with lower all-cause mortality (10% vs 3%; HR, 0.40 [95% CI, 0.26-0.61]), breast cancer-specific mortality (6% vs 2%; HR, 0.44 [95% CI, 0.26-0.76]), and ovarian cancer-specific mortality (3% vs 0.4%; HR, 0.21 [95% CI, 0.06-0.80]).


CONCLUSIONS
Among a cohort of women with BRCA1 and BRCA2 mutations, the use of risk-reducing mastectomy was associated with a lower risk of breast cancer; risk-reducing salpingo-oophorectomy was associated with a lower risk of ovarian cancer, first diagnosis of breast cancer, all-cause mortality, breast cancer-specific mortality, and ovarian cancer-specific mortality.
Domchek
Susan M
SM
Abramson Cancer Center and Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, USA.
Friebel
Tara M
TM
Singer
Christian F
CF
Evans
D Gareth
DG
Lynch
Henry T
HT
Isaacs
Claudine
C
Garber
Judy E
JE
Neuhausen
Susan L
SL
Matloff
Ellen
E
Eeles
Rosalind
R
Pichert
Gabriella
G
Van t'veer
Laura
L
Tung
Nadine
N
Weitzel
Jeffrey N
JN
Couch
Fergus J
FJ
Rubinstein
Wendy S
WS
Ganz
Patricia A
PA
Daly
Mary B
MB
Olopade
Olufunmilayo I
OI
Tomlinson
Gail
G
Schildkraut
Joellen
J
Blum
Joanne L
JL
Rebbeck
Timothy R
TR
D000293:Adolescent; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics / Q000401:mortality* / Q000517:prevention & control; D002423:Cause of Death; D005187:Fallopian Tubes / Q000601:surgery; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D008408:Mastectomy; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics / Q000401:mortality* / Q000517:prevention & control; D010052:Ovariectomy; D011446:Prospective Studies; D012306:Risk
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