Yao K Katharine A, Clifford Jacob, Li Shuwei, LaDuca Holly, Hulick Peter, Gutierrez Stephanie, Black Mary Helen
Department of Surgery, NorthShore University HealthSystem, Evanston, IL, USA.
Ambry Genetics, Aliso Viejo, CA, USA.
JNCI Cancer Spectr. 2020 Oct 26;4(6):pkaa094. doi: 10.1093/jncics/pkaa094. eCollection 2020 Dec.
Few studies have examined gene-specific associations with contralateral and/or second breast cancer (SBC).
The frequency of pathogenic and likely pathogenic (P/LP) variants in clinically actionable genes (, , , , , , , , , and ) was compared between women with a primary breast cancer (PBC) and SBC who underwent multigene panel testing at a single diagnostic testing laboratory. Race- and ethnicity-specific logistic regression burden tests adjusted for age at diagnosis of first breast cancer, histology, presence of first- or second-degree relatives with breast cancer, and prior testing for genes were used to test for associations with SBC. All statistical tests were 2-sided.
The study was comprised of 75 550 women with PBC and 7728 with SBC. Median time between breast cancers for SBC was 11 (interquartile range = 6-17) years. Restricting to women tested for all actionable genes (n = 60 310), there were 4231 (7.8%) carriers of P/LP variants in actionable genes among the controls (PBC) compared with 652 (11.1%) women with SBC (< .001). Among Caucasians, exclusive of Ashkenazi Jewish women, those carrying a P/LP variant in a clinically actionable gene were 1.44 (95% confidence interval [CI] = 1.30 to 1.60) times as likely to have SBC than noncarriers, after accounting for potential confounders. Among African American and Hispanic women, a P/LP variant in a clinically actionable gene was 1.88 (95% CI = 1.36 to 2.56) and 1.66 (9% CI = 1.02 to 2.58) times as likely to be associated with SBC, respectively ( < .001 and = .03).
Women with P/LP variants in breast cancer predisposition genes are more likely to have SBC than noncarriers. Prospective studies are needed confirm these findings.
很少有研究探讨基因特异性与对侧和/或第二原发性乳腺癌（SBC）之间的关联。
在一家诊断检测实验室接受多基因检测的原发性乳腺癌（PBC）和SBC女性中，比较临床可操作基因（、、、、、、、、和）中致病和可能致病（P/LP）变异的频率。采用种族和族裔特异性逻辑回归负担检验，对首次乳腺癌诊断时的年龄、组织学类型、是否有一级或二级亲属患乳腺癌以及先前对基因的检测进行调整，以检验与SBC的关联。所有统计检验均为双侧检验。
该研究包括75550名PBC女性和7728名SBC女性。SBC患者两次乳腺癌之间的中位时间为11年（四分位间距=6-17年）。将范围限制在对所有可操作基因进行检测的女性（n=60310）中，对照组（PBC）中有4231名（7.8%）可操作基因的P/LP变异携带者，而SBC女性中有652名（11.1%）（<.001）。在不包括阿什肯纳兹犹太女性的白种人中，在考虑潜在混杂因素后，携带临床可操作基因P/LP变异的人患SBC的可能性是非携带者的1.44倍（95%置信区间[CI]=1.30至1.60）。在非裔美国人和西班牙裔女性中，临床可操作基因中的P/LP变异与SBC相关的可能性分别为1.88倍（95%CI=1.36至2.56）和1.66倍（9%CI=1.02至2.58）（<.001和=.03）。
乳腺癌易感基因中有P/LP变异的女性比非携带者更易患SBC。需要进行前瞻性研究来证实这些发现。
