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Case 14
Published in Andrew Solomon, Julia Anstey, Liora Wittner, Priti Dutta, Clinical Cases, 2021
Andrew Solomon, Julia Anstey, Liora Wittner, Priti Dutta
In this situation, if evidence of a possible family history were uncovered, it might be appropriate to discuss testing for BRCA1, BRCA2, PRSS1 and PALB2 with a geneticist as all of these are associated with an increased risk of pancreatic cancer.
BRCA Mutation and PARP Inhibitors
Published in Sherry X. Yang, Janet E. Dancey, Handbook of Therapeutic Biomarkers in Cancer, 2021
Arjun Mittra, James H. Doroshow, Alice P. Chen
The PALB2 (partner and localizer of BRCA2) was initially identified as an important protein interaction partner responsible for BRCA2 nuclear localization and DNA damage response functions. It has more recently been shown to interact with BRCA1, and is now known to also be a linker protein for BRCA2. Germline loss of function of both alleles of PALB2 causes Fanconi’s anemia, whereas monoallelic loss of function mutations is associated with an increased risk of developing breast and pancreatic cancer [12, 92].
Breast Surgery
Published in Tjun Tang, Elizabeth O'Riordan, Stewart Walsh, Cracking the Intercollegiate General Surgery FRCS Viva, 2020
Gaural Patel, Lucy Kate Satherley, Animesh JK Patel, Georgina SA Phillips
PALB2 mutation PALB2 is the partner and localiser of BRCA2. It works with BRCA2 to repair damaged DNA and stop tumour growthPALB2 mutation increases breast cancer risk by 5–9 times compared to normal
Impact of genetic counseling on the uptake of contralateral prophylactic mastectomy among younger women with breast cancer
Published in Acta Oncologica, 2020
Thorkild Terkelsen, Hanne Rønning, Anne-Bine Skytte
Due to the moderate size of the study population, we had to combine the two lowest genetic risk categories in the Cox proportional hazards regression model. This was reasonable, given that CPM was considered an option for high-risk patients, not population risk or moderate risk individuals. Yet it would have been interesting to compare the uptake between these two genetic risk categories as well. As the genetic counseling program was aimed at identifying women at high risk of breast cancer, it was offered exclusively to those patients more likely to harbor pathogenic variants in BRCA1 or BRCA2, such as younger women or those with triple negative breast cancer or a positive family history. The absence of a control group, that did not undergo genetic counseling, limited us from assessing the overall impact of the program. As the patients were not asked to answer decision-making questionnaires, we were restricted to observe the long-term differences in CPM uptake between groups defined by genetic risk category, age of onset, and family history, whereas the impact of additional motivation factors did not come to light. As the genetic testing was restricted to BRCA1 and BRCA2, other studies will be needed to assess the impact of positive test results for moderate risk genes, such as PALB2, CHEK2, and ATM. Interestingly, a CPM uptake comparable to BRCA carriers was recently reported for non-BRCA carriers with positive multigene panel testing results [24].
Chromosomal radiosensitivity of triple negative breast cancer patients
Published in International Journal of Radiation Biology, 2019
Flavia Zita Francies, Olivia Herd, Alan Cairns, Sarah Nietz, Marshall Murdoch, Jacobus Slabbert, Kathleen B. M. Claes, Anne Vral, Ans Baeyens
In agreement with literature, 18% (3/17) of all our TN patients were positive for germline BRCA1/2 or CHEK2 c.1100delC mutations (Peshkin et al. 2010; Gonzalez-Angulo et al. 2011) and a slightly higher proportion (2/9; 22%) of young patients that have TNBC (Young et al. 2009). This could be due to the difference in age; Young et al. categorized patients less than 40 years as ‘young’ whereas patients in our study under 50 years were classified as ‘young’ (Young et al. 2009). In our luminal cohort, 11% (3/28) of young patients were positive for a BRCA2 or CHEK2 c.1100delC mutation and 5% (2/38) older patients had mutations in BRCA1/2. These results indicate the importance of screening young breast cancer patients, particularly those with TN status, for mutations in breast cancer susceptibility genes. Germline mutations in PALB2 were not identified in our population.
The evolution into personalized therapies in pancreatic ductal adenocarcinoma: challenges and opportunities
Published in Expert Review of Anticancer Therapy, 2018
Anteneh A. Tesfaye, Mandana Kamgar, Asfar Azmi, Philip A. Philip
PDAC is a drug-resistant disease. Only few conventional cytotoxic agents have shown activity in this cancer. There is a continued work being done to optimize the delivery of these drugs, especially how they should be sequenced to improve the outcome of patients. The cytotoxic chemotherapy platforms of either gemcitabine/nab-paclitaxel or FOLFIRINOX will continue to be used especially in frontline setting to which will be added any newly developed agent. A number of targeted and novel agents are currently in phase I–III clinical trials. Within the next 2–3 years, we may be able to see the clinical activities of these agents. High interest agents include PEGPH20 targeting hyaluronan, and platinum compounds with or without PARP inhibitors in patients with defective DNA repair pathways. PARP inhibitors may be used as maintenance therapy following the use of combination cytotoxic therapy in select patients with BRCA mutations. Biomarkers that may be of high interest in the next few years and be part of the everyday clinical practice include BRCA and other DNA repair gene mutations, hyaluronan expression, and mesothelin expression. Innovative immunotherapy approaches are currently being actively pursued. No major immunotherapeutic breakthrough is anticipated in the near future for this disease. Molecular profiling of pancreatic cancers will expand in clinical practice and to guide clinical trial eligibility. Microsatellite testing, BRCA and related gene testing (e.g. PALB2, ATM) are examples of tests that are increasingly adopted by oncologists. Improvements in tissue collection and capture of CTCs and cfDNA are to be expected.