Kotsopoulos Joanne, Librach Clifford L, Lubinski Jan, Gronwald Jacek, Kim-Sing Charmaine, Ghadirian Parviz, Lynch Henry T, Moller Pal, Foulkes William D, Randall Susan, Manoukian Siranoush, Pasini Barbara, Tung Nadine, Ainsworth Peter J, Cummings Shelly, Sun Ping, Narod Steven A
Women's College Research Institute, Women's College Hospital, University of Toronto, Toronto, ON, Canada.
Cancer Causes Control. 2008 Dec;19(10):1111-9. doi: 10.1007/s10552-008-9175-0. Epub 2008 May 29.
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.
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.
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).
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.
携带乳腺癌易感基因1(BRCA1)或乳腺癌易感基因2(BRCA2)突变的女性患乳腺癌和卵巢癌的风险增加。各种生殖和激素因素已被证明会改变乳腺癌风险。这些研究表明,雌激素暴露和缺乏在遗传性癌症的病因中很重要。许多患者对生育治疗对乳腺癌风险的潜在不利影响感兴趣。评估不孕本身或接触生育药物是否会增加遗传易感性女性患乳腺癌的风险很重要。
我们对1380对携带BRCA1或BRCA2突变的女性进行了一项匹配病例对照研究,以确定不孕史、使用生育药物或接受体外受精(IVF)是否与乳腺癌风险增加相关。
16%的研究对象报告有生育问题,4%使用过生育药物。与未使用者相比,使用过生育药物的女性患乳腺癌的风险没有显著增加(优势比[OR]=1.21;95%置信区间[CI]=0.81-1.82)。此外,按产次分层时,使用生育药物的历史与风险无关:未生育女性的OR=1.29;95%CI=0.83-2.01,已生育女性的OR=0.81;95%CI=0.30-2.22。
本研究结果表明,使用生育药物不会对BRCA突变携带者患乳腺癌的风险产生不利影响。鉴于暴露亚组规模较小,这些发现应谨慎解释,需要进行验证性研究。