The risk of endometrial cancer in women with BRCA1 and BRCA2 mutations. A prospective study.
OBJECTIVE
To evaluate the risk of endometrial cancer in women who carry a deleterious mutation in the BRCA1 or BRCA2 genes.


METHODS
Women known to carry a BRCA1 or BRCA2 mutation, aged 45 to 70, were identified from an international registry and were followed prospectively. A total of 857 women completed a baseline questionnaire and one or more follow-up questionnaires. Study subjects were followed until diagnosis of endometrial cancer, ovarian cancer, death or the date of completion of the last questionnaire. The expected number of endometrial cancers was calculated using age and country-specific incidence rates.


RESULTS
After an average follow-up period of 3.3 years, six women were diagnosed with endometrial cancer, compared to 1.13 cancers expected (SIR=5.3, p=0.0011). Four of these six patients used tamoxifen in the past. The risk among women who were never exposed to tamoxifen treatment was not significantly elevated (SIR=2.7, p=0.17), but among the 226 participants who had used tamoxifen (220 as treatment and six for the primary prevention of breast cancer) the relative risk for endometrial cancer was 11.6 (p=0.0004).


CONCLUSIONS
The main contributor to the increased risk of endometrial cancer among BRCA carriers is tamoxifen treatment for a previous breast cancer. The risk and benefits of prophylactic hysterectomy should be discussed with women with a BRCA mutation considering tamoxifen therapy.
Beiner
Mario E
ME
Centre for Research in Women's Health, 790 Bay Street, Toronto, ON, Canada M5G 1N8.
Finch
Amy
A
Rosen
Barry
B
Lubinski
Jan
J
Moller
Pal
P
Ghadirian
Parviz
P
Lynch
Henry T
HT
Friedman
Eitan
E
Sun
Ping
P
Narod
Steven A
SA
D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy; D016889:Endometrial Neoplasms / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D011446:Prospective Studies; D013629:Tamoxifen / Q000009:adverse effects
D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen