Basser Center for BRCA, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, New York.
JAMA Oncol. 2021 Jul 1;7(7):1045-1050. doi: 10.1001/jamaoncol.2021.1492.
The prevalence of germline pathogenic variants (PVs) in cancer susceptibility genes in US Black women compared with non-Hispanic White women with breast cancer is poorly described.
To determine whether US Black and non-Hispanic White women with breast cancer have a different prevalence of PVs in 12 cancer susceptibility genes.
DESIGN, SETTING, AND PARTICIPANTS: Multicenter, population-based studies in the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium. Participants were Black and non-Hispanic White women diagnosed with breast cancer, unselected for family history or age at diagnosis. Data were collected from June 1993 to June 2020; data analysis was performed between September 2020 and February 2021.
Prevalence of germline PVs in 12 established breast cancer susceptibility genes.
Among 3946 Black women (mean [SD] age at diagnosis, 56.5 [12.02] y) and 25 287 non-Hispanic White women (mean [SD] age at diagnosis, 62.7 [11.14] y) with breast cancer, there was no statistically significant difference by race in the combined prevalence of PVs in the 12 breast cancer susceptibility genes evaluated (5.65% in Black vs 5.06% in non-Hispanic White women; P = .12). The prevalence of PVs in CHEK2 was higher in non-Hispanic White than Black patients (1.29% vs 0.38%; P < .001), whereas Black patients had a higher prevalence of PVs in BRCA2 (1.80% vs 1.24%; P = .005) and PALB2 (1.01% vs 0.40%; P < .001). For estrogen receptor-negative breast cancer, the prevalence of PVs was not different except for PALB2, which was higher in Black women. In women diagnosed before age 50 years, there was no difference in overall prevalence of PVs in Black vs non-Hispanic White women (8.83% vs 10.04%; P = .25), and among individual genes, only CHEK2 PV prevalence differed by race. After adjustment for age at diagnosis, the standardized prevalence ratio of PVs in non-Hispanic White relative to Black women was 1.08 (95% CI, 1.02-1.14), and there was no longer a statistically significant difference in BRCA2 PV prevalence.
This large population-based case-control study revealed no clinically meaningful differences in the prevalence of PVs in 12 breast cancer susceptibility genes between Black and non-Hispanic White women with breast cancer. The findings suggest that there is not sufficient evidence to make policy changes related to genetic testing based on race alone. Instead, all efforts should be made to ensure equal access to and uptake of genetic testing to minimize disparities in care and outcomes.
与患有乳腺癌的非西班牙裔白种美国女性相比，美国黑种女性中种系致病性变异（PVs）在癌症易感性基因中的流行情况描述甚少。
确定患有乳腺癌的美国黑人和非西班牙裔白种女性是否在 12 种癌症易感性基因中具有不同的 PVs 患病率。
设计、环境和参与者：癌症风险相关易感性（CARRIERS）联盟中的多中心、基于人群的研究。参与者为被诊断患有乳腺癌的黑人和非西班牙裔白种女性，未按家族史或诊断时的年龄选择。数据于 1993 年 6 月至 2020 年 6 月收集；数据分析于 2020 年 9 月至 2021 年 2 月进行。
12 种已确立的乳腺癌易感性基因中种系 PVs 的流行率。
在 3946 名黑种女性（诊断时的平均[SD]年龄，56.5[12.02]岁）和 25287 名非西班牙裔白种女性（诊断时的平均[SD]年龄，62.7[11.14]岁）中，按种族评估的 12 种乳腺癌易感性基因中 PVs 的综合流行率无统计学显著差异（黑种女性为 5.65%，非西班牙裔白种女性为 5.06%；P = .12）。非西班牙裔白种女性 CHEK2 中的 PVs 患病率高于黑种女性（1.29%比 0.38%；P < .001），而黑种女性 BRCA2（1.80%比 1.24%；P = .005）和 PALB2（1.01%比 0.40%；P < .001）中的 PVs 患病率较高。对于雌激素受体阴性乳腺癌，除了 PALB2 之外，PVs 的患病率没有差异，而黑种女性的 PALB2 患病率较高。在诊断年龄小于 50 岁的女性中，黑种与非西班牙裔白种女性的总体 PVs 患病率无差异（8.83%比 10.04%；P = .25），且在个体基因中，只有 CHEK2 的 PV 患病率存在种族差异。调整诊断时的年龄后，非西班牙裔白种女性相对于黑种女性的 PVs 标准化患病率比为 1.08（95%CI，1.02-1.14），BRCA2 的 PV 患病率差异不再具有统计学意义。
这项大型基于人群的病例对照研究显示，黑种和非西班牙裔白种女性乳腺癌患者在 12 种乳腺癌易感性基因中的 PVs 患病率无临床意义差异。这些发现表明，没有足够的证据仅根据种族来制定与基因检测相关的政策变化。相反，应尽一切努力确保平等获得和接受基因检测，以最大限度地减少护理和结果方面的差异。
