Golan Talia, Casolino Raffaella, Biankin Andrew V, Hammel Pascal, Whitaker Kristen D, Hall Michael J, Riegert-Johnson Douglas L
Institute of Oncology, Sheba Medical Center, Tel Hashomer 52621, Israel.
Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
Ther Adv Med Oncol. 2023 Sep 15;15:17588359231189127. doi: 10.1177/17588359231189127. eCollection 2023.
Prognosis is generally poor for patients with pancreatic ductal adenocarcinoma. However, patients with germline or mutations (gBRCAm) may benefit from first-line platinum-based chemotherapy and maintenance therapy with the poly(adenosine diphosphate-ribose) polymerase inhibitor olaparib following at least 16 weeks of first-line platinum-based chemotherapy without disease progression. Germline breast cancer gene (BRCA) testing is therefore important to ensure that patients receive the most effective treatment. In addition, testing for other DNA damage response gene mutations beyond gBRCAm may also guide treatment decisions. However, clinical pathways for genetic testing are often suboptimal, leading to delays in treatment initiation or missed opportunities for personalized therapy. Barriers to testing include low rates of referral and uptake, delays to referral and slow result turnaround times, cost, and biopsy and assay limitations if somatic testing is performed, leading to the requirement for subsequent dedicated germline testing. Low rates of referral may result from lack of awareness among physicians of the clinical value of testing, coupled with low confidence in interpreting test results and poor availability of genetic counseling services. Among patients, barriers to uptake may include similar lack of awareness of the clinical value of testing, anxiety regarding the implications of test results, lack of insurance coverage, fear of negative insurance implications, and socioeconomic factors. Potential solutions include innovative approaches to testing pathways, including 'mainstreaming' of testing in which BRCA tests are routinely arranged by the treating oncologist, with the involvement of genetic counselors if a patient is found to have a gBRCAm. More recently, the utility of multigene panel analyses has also been explored. Access to genetic counseling may also be improved through initiatives such as having a genetic counseling appointment for all new patient visits and telemedicine approaches, including the use of telephone consultations or DVD-assisted counseling. Educational programs will also be beneficial, and cost effectiveness is likely to improve as the number of targeted treatments increases and when the earlier detection of tumors in family members following cascade testing is considered.
胰腺导管腺癌患者的预后通常较差。然而，携带种系或体细胞突变（gBRCAm）的患者可能从一线铂类化疗以及在至少16周一线铂类化疗无疾病进展后使用聚（二磷酸腺苷 - 核糖）聚合酶抑制剂奥拉帕利进行维持治疗中获益。因此，种系乳腺癌基因（BRCA）检测对于确保患者接受最有效的治疗很重要。此外，检测gBRCAm以外的其他DNA损伤反应基因突变也可能指导治疗决策。然而，基因检测的临床路径往往不尽人意，导致治疗开始延迟或错失个性化治疗的机会。检测的障碍包括转诊和接受检测的比例低、转诊延迟和结果周转时间长、成本，以及如果进行体细胞检测时活检和检测的局限性，这导致需要后续专门的种系检测。转诊率低可能是由于医生对检测的临床价值缺乏认识，加上对解读检测结果缺乏信心以及遗传咨询服务的可及性差。在患者中，接受检测的障碍可能包括类似的对检测临床价值缺乏认识、对检测结果影响的焦虑、缺乏保险覆盖、担心对保险有负面影响以及社会经济因素。潜在的解决方案包括创新的检测途径方法，包括检测的“主流化”，即由主治肿瘤学家常规安排BRCA检测，如果发现患者有gBRCAm则有遗传咨询师参与。最近，也探索了多基因检测板分析的效用。通过诸如为所有新患者就诊安排遗传咨询预约以及远程医疗方法（包括使用电话咨询或DVD辅助咨询）等举措，也可以改善获得遗传咨询的机会。教育项目也将有益，并且随着靶向治疗数量的增加以及考虑到级联检测后家庭成员中肿瘤的早期发现，成本效益可能会提高。
