Infertility, treatment of infertility, and the risk of breast cancer among women with BRCA1 and BRCA2 mutations: a case-control study.
BACKGROUND
Women with a breast cancer susceptibility gene 1 (BRCA1) or breast cancer susceptibility gene 2 (BRCA2) mutation are at increased risk for developing breast and ovarian cancer. Various reproductive and hormonal factors have been shown to modify the risk of breast cancer. These studies suggest that estrogen exposure and deprivation are important in the etiology of hereditary cancer. Many patients are interested in the possibility of an adverse effect of fertility treatment on breast cancer risk. It is important to evaluate whether or not infertility per se or exposure to fertility medications increase the risk of breast cancer in genetically predisposed women.


METHODS
We conducted a matched case-control study of 1,380 pairs of women with a BRCA1 or BRCA2 mutation to determine if a history of infertility, the use of fertility medications, or undergoing in vitro fertilization (IVF) were associated with and increased the risk of breast cancer.


RESULTS
Sixteen percent of the study subjects reported having experienced a fertility problem and 4% had used a fertility medication. Women who had used a fertility medication were not at significantly increased risk of breast cancer (odds ratio [OR] = 1.21; 95% confidence interval [CI] = 0.81-1.82) compared to non-users. Furthermore, there was no risk associated with a history of use of a fertility medication when the subjects were stratified by parity: (OR = 1.29; 95% CI = 0.83-2.01 for nulliparous women and OR = 0.81; 95% CI = 0.30-2.22 for parous women).


CONCLUSIONS
The results of this study suggest that the use of fertility medications does not adversely affect the risk of breast cancer among BRCA mutation carriers. Given the small sizes of the exposed subgroups, these findings should be interpreted with caution and confirmatory studies are required.
Women's College Research Institute, Women's College Hospital, University of Toronto, Toronto, ON, Canada.
Joanne
J
Kotsopoulos
Clifford L
CL
Librach
Jan
J
Lubinski
Jacek
J
Gronwald
Charmaine
C
Kim-Sing
Parviz
P
Ghadirian
Henry T
HT
Lynch
Pal
P
Moller
William D
WD
Foulkes
Susan
S
Randall
Siranoush
S
Manoukian
Barbara
B
Pasini
Nadine
N
Tung
Peter J
PJ
Ainsworth
Shelly
S
Cummings
Ping
P
Sun
Steven A
SA
Narod
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics*; D001971:Bromocriptine / Q000627:therapeutic use; D016022:Case-Control Studies; D002996:Clomiphene / Q000627:therapeutic use; D004967:Estrogens / Q000627:therapeutic use; D005260:Female; D005300:Fertility Agents, Female / Q000627:therapeutic use; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D007246:Infertility / Q000188:drug therapy / Q000235:genetics*; D008596:Menotropins / Q000627:therapeutic use; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D012307:Risk Factors; D055815:Young Adult
D004967:Estrogens; D005300:Fertility Agents, Female; D002996:Clomiphene; D001971:Bromocriptine; D008596:Menotropins