Department of Medical Oncology, Dr. B.R.A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India.
Department of Surgical Oncology, All India Institute of Medical Sciences, New Delhi, India.
Ann Surg Oncol. 2022 Feb;29(2):1423-1432. doi: 10.1245/s10434-021-10870-w. Epub 2021 Oct 2.
The burden of hereditary breast cancer in India is not well defined. Moreover, genetic testing criteria (National Comprehensive Cancer Network [NCCN] and Mainstreaming Cancer Genetics [MCG] Plus) have never been validated in the Indian population.
All new female breast cancer patients from 1st March 2019 to 28th February 2020 were screened. Those providing informed consent and without previous genetic testing were recruited. Multigene panel testing (107 genes) by next-generation sequencing was performed for all patients. The frequency of pathogenic/likely pathogenic (P/LP) mutations between patients qualifying and not qualifying the testing criteria was compared and their sensitivity was computed.
Overall, 275 breast cancer patients were screened and 236 patients were included (median age 45 years); 30 patients did not consent and 9 patients previously underwent genetic testing. Thirty-four (14%) women had a positive family history and 35% had triple-negative breast cancer. P/LP mutations were found in 44/236 (18.64%) women; mutations in BRCA1 (22/47, 46.8%) and BRCA2 (9/47, 19.1%) were the most common, with 34% of mutations present in non-BRCA genes. Patients qualifying the testing criteria had a higher risk of having a P/LP mutation (NCCN: 23.6% vs. 7.04%, p = 0.03; MCG plus: 24.8% vs. 7.2%, p = 0.01). The sensitivity of the NCCN criteria was 88.6% (75.4-96.2) and 86.36% (72.65-94.83) for MCG plus. More than 95% sensitivity was achieved if all women up to 60 years of age were tested. Cascade testing was performed in 31 previous (16/44 families), with 23 testing positive.
The frequency of P/LP mutations in India is high, with significant contribution of non-BRCA genes. Testing criteria need modification to expand access to testing.
印度遗传性乳腺癌的负担尚未明确。此外，国家综合癌症网络（NCCN）和主流癌症遗传学（MCG）标准从未在印度人群中得到验证。
筛选 2019 年 3 月 1 日至 2020 年 2 月 28 日期间的所有新诊断的女性乳腺癌患者。对提供知情同意且无既往基因检测的患者进行招募。对所有患者进行下一代测序的多基因 panel 检测（107 个基因）。比较符合和不符合检测标准的患者中致病性/可能致病性（P/LP）突变的频率，并计算其敏感性。
共筛选了 275 例乳腺癌患者，纳入了 236 例患者（中位年龄 45 岁）；30 例患者不同意，9 例患者之前进行过基因检测。34 例（14%）女性有阳性家族史，35%为三阴性乳腺癌。236 例患者中有 44 例（18.64%）发现 P/LP 突变；BRCA1（22/47，46.8%）和 BRCA2（9/47，19.1%）突变最常见，非 BRCA 基因中有 34%的突变。符合检测标准的患者发生 P/LP 突变的风险更高（NCCN：23.6% vs. 7.04%，p=0.03；MCG 加：24.8% vs. 7.2%，p=0.01）。NCCN 标准的敏感性为 88.6%（75.4-96.2），MCG 加的敏感性为 86.36%（72.65-94.83）。如果对所有 60 岁以下的女性进行检测，则可达到 95%以上的敏感性。对 31 个先前（16/44 个家族）进行了级联检测，其中 23 个检测呈阳性。
印度 P/LP 突变的频率较高，非 BRCA 基因的贡献显著。需要修改检测标准以扩大检测范围。
