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Familial Pancreatic Cancer
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Among inherited cancer syndromes that include pancreatic cancer as part of clinical features, hereditary pancreatitis (PRSS1), Peutz−Jeghers syndrome (STK11), familial atypical multiple mole melanoma (CDKN2A), hereditary breast-ovarian cancer syndrome (BRCA1, BRCA2), Lynch syndrome (MLH1, MSH2, MLH6, PMS2), and familial adenomatous polyposis (APC) are most notable, with lifetime risk of pancreatic cancer as high as 40% (Table 56.1) [4,7].
Epidemiologic Linkage: Diet, Genetics, and Cancer
Published in Maryce M. Jacobs, Vitamins and Minerals in the Prevention and Treatment of Cancer, 2018
Certain facets of hereditary cancer’s natural history appear with sufficient frequency among putative carriers of the deleterious cancer-prone gene(s) as to lead to their characterization as “cardinal principles of cancer genetics.” These features include the following: a) early age of cancer onset, often 15–20 years earlier than its sporadic counterpart.2,3,6,15 However, early onset is not an invariable finding in that we are now learning that an unknown fraction of hereditary cancer patients may show a later age of cancer onset; b) an excess of bilaterality when paired organs are of concern,2 such as the breast and ovary in hereditary breast/ovarian cancer syndrome;3,16 c) integral patterns of multiple primary cancer in specific hereditary cancer syndromes,17 such as in Lynch syndrome II; d) the occurrence of premonitory physical signs, as in the cancer-associated genodermatoses,4 and/or biomarkers which associate with the respective cancer-prone genotypes;18 e) Mendelian inherited patterns of cancer transmission within kindreds wherein the majority of such disorders appear to be consonant with an autosomal dominant mode of genetic transmission;2–6 and finally, f) in certain hereditary cancers, such as carcinoma of the breast and in colon cancer in Lynch syndromes I and II, there appears to be improved survival when these lesions are compared by appropriate staging with historical controls.19
Li-Fraumeni Syndrome
Published in Dongyou Liu, Tumors and Cancers, 2017
Differential diagnoses for LFS include hereditary breast–ovarian cancer syndrome (which tends to harbor a pathogenic variant in BRCA1 or BRCA2 instead of TP53 as germline TP53 pathogenic variants account for <1% of total breast cancer cases) and constitutional mismatch repair deficiency syndrome (CMMR-D syndrome, which is associated with childhood leukemia, brain tumors, or early-onset gastrointestinal cancer, but is caused by the inheritance of two mutated alleles of a mismatch repair gene, including MLH1, MSH2, MSH6, PMS1, and PMS2) [1].
A case of gastric cancer metastasis to the breast in a female with BRCA2 germline mutation and literature review
Published in Acta Chirurgica Belgica, 2019
Audrius Dulskas, Mahdi Al Bandar, Yoon Young Choi, Su-Jin Shin, Seung-Hoon Beom, Taeil Son, Hyung-Il Kim, Jae-Ho Cheong, Woo Jin Hyung, Sung Hoon Noh
The breast cancer 2 (BRCA2) gene is a tumor suppressor gene and its mutation is known to be related to hereditary breast-ovarian cancer syndrome. Individuals with BRCA2 alterations have a high risk of breast and ovarian cancer [6]. Thus, prophylactic surgery is recommended to reduce the risk of cancer for a patient with this mutation and a strong family history of breast and/or ovarian cancer [7]. Breast metastasis from extramammary tumor is rare [8] and breast metastasis from gastric cancer in a patient with the BRCA2 mutation has never been reported. Herein, we report a case of metastatic gastric cancer in the breast with the BRCA2 germline mutation.
Evaluating the role of FAMIly history of cancer and diagnosis of multiple neoplasms in cancer patients receiving PD-1/PD-L1 checkpoint inhibitors: the multicenter FAMI-L1 study
Published in OncoImmunology, 2020
Alessio Cortellini, Sebastiano Buti, Melissa Bersanelli, Raffaele Giusti, Fabiana Perrone, Pietro Di Marino, Nicola Tinari, Michele De Tursi, Antonino Grassadonia, Katia Cannita, Alessandra Tessitore, Federica Zoratto, Enzo Veltri, Francesco Malorgio, Marco Russano, Cecilia Anesi, Tea Zeppola, Marco Filetti, Paolo Marchetti, Andrea Botticelli, Gian Carlo Antonini Cappellini, Federica De Galitiis, Maria Giuseppa Vitale, Francesca Rastelli, Federica Pergolesi, Rossana Berardi, Silvia Rinaldi, Marianna Tudini, Rosa Rita Silva, Annagrazia Pireddu, Francesco Atzori, Daniela Iacono, Maria Rita Migliorino, Alain Gelibter, Mario Alberto Occhipinti, Francesco Martella, Alessandro Inno, Stefania Gori, Sergio Bracarda, Cristina Zannori, Claudia Mosillo, Alessandro Parisi, Giampiero Porzio, Domenico Mallardo, Maria Concetta Fargnoli, Marcello Tiseo, Daniele Santini, Paolo A Ascierto, Corrado Ficorella
Mismatch repair (MMR) deficiency, which leads to the condition of genetic hypermutability known as microsatellite instability (MSI), is related to the number of somatic mutations (especially in MSI-high cases); many studies have already confirmed its positive predictive role (MSI-high) for ICI treatment, particularly with anti-PD-1 (programmed death-1) antibodies.6,7 MSI is known to be the hallmark of Lynch syndrome (LS), a familial clustering of colorectal and endometrial cancers. LS is caused by several germline mutations, which result in a defective MMR and is inherited as dominant autosomal character. Similarly, BRCA 1 and 2 (Breast Cancer 1/2) mutations, which are associated with hereditary breast-ovarian cancer syndrome (HBOC), may correlate with the mutational landscape of the tumors, because of the homologous recombination repair deficiency.8 Moreover, patients with inherited cancer susceptibility syndromes are more likely to develop multiple primary tumors during their life.9 “BRCA-like” phenotype may be more sensitive to anti-PD-1/PD-L1 agents10; thus prospective clinical trials with anti-PD-1 for patients with germline BRCA 1/2 mutations are currently ongoing.11 LS and HBOC syndrome are just two of the forms of inherited cancer susceptibility. Even though notoriously only about 5% to 10% of all cancers result directly from germline mutations,12 we can hypothesize that much about family cancer syndromes and cancer predisposition is still unknown. Starting from this hypothesis and from the suggestion that tumors related to inherited cancer susceptibility syndromes seem to have an “immune sensitive phenotype,” we investigated if positive family history of cancer (FHC) and diagnosis of metachronous and/or synchronous multiple neoplasms (MN) could be somehow related to clinical outcomes with anti-PD-1/PD-L1 treatment.