Turza Lauren, Lovejoy Leann A, Turner Clesson E, Shriver Craig D, Ellsworth Rachel E
Department of Surgery, Rebecca Fortney Breast Center, Anne Arundel Medical Center, Annapolis, MD, United States.
Clinical Breast Care Project, Chan Soon-Shiong Institute of Molecular Medicine at Windber, Windber, PA, United States.
Front Oncol. 2022 Aug 26;12:918757. doi: 10.3389/fonc.2022.918757. eCollection 2022.
Ductal carcinoma (DCIS) is a malignant, yet pre-invasive disease of the breast. While the majority of DCIS have low risk of recurrence, a subset of women with germline pathogenic variants (PV) in cancer predisposition genes are at increased risk for recurrence. Uptake of genetic testing and subsequent surgical intervention in women with DCIS has not been well-studied. The aim of this study was to evaluate test eligibility parameters, uptake of clinical testing, impact on surgical decision making and second cancer events (SCE) in women with DCIS.
Four-hundred eighty-four women diagnosed with unilateral DCIS 2001-2020 were eligible for this study. Demographic, commercial genetic test results and surgical procedures were extracted from the database. Test-eligibility was assigned using National Comprehensive Cancer Network (NCCN) criteria. Panel genetic testing was performed in the research laboratory across 94 cancer predisposition genes. Statistical analyses were performed using Fisher's exact tests and Chi-square analyses with < 0.05 defining significance.
Forty-four percent of women were test-eligible at diagnosis of which 63.4% pursued genetic testing before definitive surgery; 9.9% pursued testing only after a second cancer event. Bilateral mastectomy (BM) was significantly higher (p<0.001) in women who had testing before definitive surgery (46.9%) compared to those who had testing afterword (10.8%) and in women who underwent testing before definitive surgery with PV (75%) compared to those without PV (37.5%. p=0.045). Of the 39 women with PV, 20 (51.3%) were detected only in the research setting, with 7 (17.9%) of these women not eligible for genetic testing based on NCCN criteria. In women who did not undergo BM at diagnosis, SCE were significantly higher (p=0.001) in women with PV (33.3%) compared to those without PV (11.9%).
Pursuit of genetic testing and subsequent use of risk-reducing surgeries in women with PV was suboptimal in women with a primary diagnosis of DCIS. In conjunction, >50% of PV were detected only in the research setting. Because omission of genetic testing in women with DCIS may represent a lost opportunity for prevention, genetic testing at the time of diagnosis should be standard for all women with DCIS.
导管原位癌（DCIS）是一种乳腺恶性但仍处于侵袭前阶段的疾病。虽然大多数DCIS复发风险较低，但一部分携带癌症易感基因种系致病变异（PV）的女性复发风险增加。对于DCIS女性进行基因检测及后续手术干预的情况尚未得到充分研究。本研究的目的是评估DCIS女性的检测资格参数、临床检测的接受情况、对手术决策的影响以及第二原发癌事件（SCE）。
2001年至2020年期间诊断为单侧DCIS的484名女性符合本研究条件。从数据库中提取人口统计学信息、商业基因检测结果和手术程序。使用美国国立综合癌症网络（NCCN）标准确定检测资格。在研究实验室对94个癌症易感基因进行基因panel检测。采用Fisher精确检验和卡方分析进行统计分析，P<0.05为有统计学意义。
44%的女性在诊断时符合检测条件，其中63.4%在确定性手术前进行了基因检测；9.9%仅在发生第二原发癌事件后进行检测。在确定性手术前进行检测的女性中，双侧乳房切除术（BM）的比例（46.9%）显著高于术后进行检测的女性（10.8%），在确定性手术前检测出PV的女性中，双侧乳房切除术的比例（75%）显著高于未检测出PV的女性（37.5%，P=0.045）。在39名携带PV的女性中，20名（51.3%）仅在研究环境中被检测出，其中7名（17.9%）女性根据NCCN标准不符合基因检测资格。在诊断时未进行BM的女性中，携带PV的女性发生SCE的比例（33.3%）显著高于未携带PV的女性（11.9%，P=0.001）。
对于初诊为DCIS的女性，携带PV的女性进行基因检测及后续使用降低风险手术的情况并不理想。此外，超过50%的PV仅在研究环境中被检测出。由于DCIS女性遗漏基因检测可能意味着失去预防机会，因此对所有DCIS女性在诊断时进行基因检测应成为标准做法。
