bims-lifras Biomed News
on Li-Fraumeni syndrome
Issue of 2020–03–08
seventeen papers selected by
Joanna Zawacka-Pankau
  1. Genetic predisposition in acute leukaemia.
  2. Splicing profile by capture RNA-seq identifies pathogenic germline variants in tumor suppressor genes.
  3. A comprehensive analysis of candidate genes in familial pancreatic cancer families reveals a high frequency of potentially pathogenic germline variants.
  4. Genetic testing for epithelial ovarian cancer.
  5. Landscape of germline mutations in hereditary breast and ovarian cancer (HBOC) patients in Russia revealed by target panel sequencing.
  6. Gene Panel Testing in Hereditary Breast Cancer.
  7. Exceptional Response to Olaparib in a Patient With Recurrent Ovarian Cancer and an Entire BRCA1 Germline Gene Deletion.
  8. Variants of uncertain significance in the era of high-throughput genome sequencing: a lesson from breast and ovary cancers.
  9. Evaluation of Germline Genetic Testing Criteria in a Hospital-Based Series of Women With Breast Cancer.
  10. Prevalence of clinically actionable germline pathogenic variants (PVs) in advanced prostate cancer (aPC).
  11. Germline BRCA, chemotherapy response scores, and survival in the neoadjuvant treatment of ovarian cancer.
  12. Next-Generation Sequencing of Retinoblastoma Identifies Pathogenic Alterations beyond RB1 Inactivation That Correlate with Aggressive Histopathologic Features.
  13. BRCA1/BRCA2 germline mutations and chemotherapy-related hematological toxicity in breast cancer patients.
  14. Lynch syndrome-associated hereditary mutations cause breast and ovarian cancer: Results from Russian Heredetary Oncogenomics project.
  15. Breast Conserving Surgery for BRCA Mutation Carriers-A Systematic Review.
  16. Somatic and germline mutations of Chinese gastric cancer patients.
  17. Germline mutations in Chinese colorectal cancer patients with mismatch repair deficiency.
  1. Int J Lab Hematol. 2020 Mar 02.
    Genetic predisposition in acute leukaemia.
    Meredith Wiggins, William Stevenson.
      A small but important proportion of patients with myelodysplasia (MDS) and acute leukaemia (AL) have underlying germline mutations in leukaemia susceptibility genes. The majority of these variants predispose to myeloid neoplasms with a smaller number associated with acute lymphoblastic leukaemia (ALL). The 2016 revision of the WHO classification of tumours of haematopoietic and lymphoid tissues has defined a number of myeloid neoplasms with germline predisposition (Blood, 127, 2016, 2391) alerting clinicians to the importance of this underlying diagnosis. Advances in genetic technology and access to testing will undoubtably result in increased numbers of patients and families with leukaemia predisposition syndromes being identified. Here we summarize the salient biology and genetic and clinical features of a number of these conditions including some more recently described genetic variants.
    Keywords:  acute leukaemias; genetics
    DOI:  https://doi.org/10.1111/ijlh.13173
  2. NPJ Precis Oncol. 2020 ;4 4
    Splicing profile by capture RNA-seq identifies pathogenic germline variants in tumor suppressor genes.
    Tyler Landrith, Bing Li, Ashley A Cass, Blair R Conner, Holly LaDuca, Danielle B McKenna, Kara N Maxwell, Susan Domchek, Nichole A Morman, Christopher Heinlen, Deborah Wham, Cathryn Koptiuch, Jennie Vagher, Ragene Rivera, Ann Bunnell, Gayle Patel, Jennifer L Geurts, Morgan M Depas, Shraddha Gaonkar, Sara Pirzadeh-Miller, Rebekah Krukenberg, Meredith Seidel, Robert Pilarski, Meagan Farmer, Khateriaa Pyrtel, Kara Milliron, John Lee, Elizabeth Hoodfar, Deepika Nathan, Amanda C Ganzak, Sitao Wu, Huy Vuong, Dong Xu, Aarani Arulmoli, Melissa Parra, Lily Hoang, Bhuvan Molparia, Michele Fennessy, Susanne Fox, Sinead Charpentier, Julia Burdette, Tina Pesaran, Jessica Profato, Brandon Smith, Ginger Haynes, Emily Dalton, Joy Rae-Radecki Crandall, Ruth Baxter, Hsiao-Mei Lu, Brigette Tippin-Davis, Aaron Elliott, Elizabeth Chao, Rachid Karam.
      Germline variants in tumor suppressor genes (TSGs) can result in RNA mis-splicing and predisposition to cancer. However, identification of variants that impact splicing remains a challenge, contributing to a substantial proportion of patients with suspected hereditary cancer syndromes remaining without a molecular diagnosis. To address this, we used capture RNA-sequencing (RNA-seq) to generate a splicing profile of 18 TSGs (APC, ATM, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, MLH1, MSH2, MSH6, MUTYH, NF1, PALB2, PMS2, PTEN, RAD51C, RAD51D, and TP53) in 345 whole-blood samples from healthy donors. We subsequently demonstrated that this approach can detect mis-splicing by comparing splicing profiles from the control dataset to profiles generated from whole blood of individuals previously identified with pathogenic germline splicing variants in these genes. To assess the utility of our TSG splicing profile to prospectively identify pathogenic splicing variants, we performed concurrent capture DNA and RNA-seq in a cohort of 1000 patients with suspected hereditary cancer syndromes. This approach improved the diagnostic yield in this cohort, resulting in a 9.1% relative increase in the detection of pathogenic variants, demonstrating the utility of performing simultaneous DNA and RNA genetic testing in a clinical context.
    Keywords:  Cancer genetics; Genetic testing; Next-generation sequencing
    DOI:  https://doi.org/10.1038/s41698-020-0109-y
  3. EBioMedicine. 2020 Feb 26. pii: S2352-3964(20)30050-5. [Epub ahead of print]53 102675
    A comprehensive analysis of candidate genes in familial pancreatic cancer families reveals a high frequency of potentially pathogenic germline variants.
    Julie Earl, Cristina Galindo-Pumariño, Jessica Encinas, Emma Barreto, Maria E Castillo, Vanessa Pachón, Reyes Ferreiro, Mercedes Rodríguez-Garrote, Silvia González-Martínez, Teresa Ramon Y Cajal, Luis Robles Diaz, Isabel Chirivella-Gonzalez, Montse Rodriguez, Eva Martínez de Castro, David García-Seisdedos, Gloria Muñoz, Juan Manuel Rosa Rosa, Mirari Marquez, Nuría Malats, Alfredo Carrato.
       BACKGROUND: The 5-year survival rate of patients with pancreatic ductal adenocarcinoma (PDAC) is around 5% due to the fact that the majority of patients present with advanced disease that is treatment resistant. Familial pancreatic cancer (FPC) is a rare disorder that is defined as a family with at least two affected first degree relatives, with an estimated incidence of 4%-10%. The genetic basis is unknown in the majority of families although around 10%-13% of families carry germline mutations in known genes associated with hereditary cancer and pancreatitis syndromes.
    METHODS: Panel sequencing was performed of 35 genes associated with hereditary cancer in 43 PDAC cases from families with an apparent hereditary pancreatic cancer syndrome.
    FINDINGS: Pathogenic variants were identified in 19% (5/26) of PDAC cases from pure FPC families in the genes MLH1, CDKN2A, POLQ and FANCM. Low frequency potentially pathogenic VUS were also identified in 35% (9/26) of PDAC cases from FPC families in the genes FANCC, MLH1, PMS2, CFTR, APC and MUTYH. Furthermore, an important proportion of PDAC cases harboured more than one pathogenic, likely pathogenic or potentially pathogenic VUS, highlighting the multigene phenotype of FPC.
    INTERPRETATION: The genetic basis of familial or hereditary pancreatic cancer can be explained in 21% of families by previously described hereditary cancer genes. Low frequency variants in other DNA repair genes are also present in 35% of families which may contribute to the risk of pancreatic cancer development.
    FUNDING: This study was funded by the Instituto de Salud Carlos III (Plan Estatal de I + D + i 2013-2016): ISCIII (PI09/02221, PI12/01635, PI15/02101 and PI18/1034) and co-financed by the European Development Regional Fund ''A way to achieve Europe'' (ERDF), the Biomedical Research Network in Cancer: CIBERONC (CB16/12/00446), Red Temática de investigación cooperativa en cáncer: RTICC (RD12/0036/0073) and La Asociación Española contra el Cáncer: AECC (Grupos Coordinados Estables 2016).
    Keywords:  DNA repair and hereditary cancer genes; Familial pancreatic cancer; Panel sequencing; Pathogenic variants
    DOI:  https://doi.org/10.1016/j.ebiom.2020.102675
  4. Best Pract Res Clin Obstet Gynaecol. 2020 Jan 16. pii: S1521-6934(20)30017-1. [Epub ahead of print]
    Genetic testing for epithelial ovarian cancer.
    Noa Amin, Narda Chaabouni, Angela George.
      As the treatment of epithelial ovarian cancer (OC) moves further into personalised medicine, the importance of determining the presence or absence of inherited mutations in cancer susceptibility genes has grown. It is now becoming routine to test for germline mutations in the BRCA1 and BRCA2 genes, which are responsible for a significant proportion of hereditary epithelial OC and are established predictive biomarkers of potential benefit from poly ADP ribose polymerase (PARP) inhibitors. The identification of patients with hereditary OC allows the patient to benefit from personalised treatment, while allowing family members to undergo cascade testing, where identification of unaffected carriers can allow early detection, risk-reduction or prevention for both breast and OC, and ultimately improve long-term outcomes. Other susceptibility genes, include the Lynch Syndrome (mismatch repair) genes and several other genes involved in the homologous recombination pathway (HRD genes), are implicated in OC genesis, and are also becoming of increasing interest as therapeutic options grow for these patients. This review will highlight the importance of the early detection of a germline gene pathogenic variant, which informs on the clinical course of disease in a particular patient, and therefore, guides therapeutic management including risk reducing and personalised treatment.
    Keywords:  BRCA; Genetic; HRD (homologous recombination deficiency); Lynch; MMR (mismatch repair); PARP inhibitor
    DOI:  https://doi.org/10.1016/j.bpobgyn.2020.01.005
  5. Ann Oncol. 2018 Oct;pii: S0923-7534(19)48663-8. [Epub ahead of print]29 Suppl 8 viii76
    Landscape of germline mutations in hereditary breast and ovarian cancer (HBOC) patients in Russia revealed by target panel sequencing.
    E Shagimardanova, L H Shigapova, R F Enikeev, M Druzhkov, A Nikitin, O Gusev, M Gordiev.
      
    DOI:  https://doi.org/10.1093/annonc/mdy270.235
  6. Arch Iran Med. 2020 Mar 01. 23(3): 155-162
    Gene Panel Testing in Hereditary Breast Cancer.
    Parvin Rostami, Kazem Zendehdel, Reza Shirkoohi, Elmira Ebrahimi, Mitra Ataei, Hashem Imanian, Hossein Najmabadi, Mohammad Reza Akbari, Mohammad Hossein Sanati.
       BACKGROUND: Breast cancer (BC) is a highly complex, heterogeneous and multifactorial disease and is the most commonly diagnosed cancer and the leading cause of cancer-related mortality in women worldwide. Family history and genetic mutations are important risk factors for BC. While studies in twins have estimated that about 10%-30% of BC are due to hereditary factors, only 4%-5% of them are due to mutations in BRCA1 or BRCA2 genes. Our aim was to investigate the role of other BC genes in familial BC among the Iranian population.
    METHODS: We selected 61 BC patients who were wild-type for BRCA1 and BRCA2 mutations but who met the criteria for hereditary BC based on the American College of Medical Genetics and Genomics (ACMG) and the National Comprehensive Cancer Network (NCCN) guidelines. We performed targeted sequencing covering the exons of 130 known cancer susceptibility genes based on the Cancer Gene Census list.
    RESULTS: We found seven mutations in seven known BC susceptibility genes (RAD50, PTEN, TP53, POLH, DKC1, WRN and CHEK2) in seven patients including two pathogenic frameshift variants in RAD50 and WRN genes, four pathogenic missense variants in TP53, PTEN, POLH, and DKC1 genes and a pathogenic splice donor variant in the CHEK2 gene. The presence of all these variants was confirmed by Sanger sequencing and Gap reverse transcription-polymerase chain reaction (RT-PCR) for the splice variant. In silico analysis of all of these variants predicted them to be pathogenic.
    CONCLUSION: Panel testing of BC patients who met the established criteria for hereditary BC but who were negative for BRCA1/2 mutations provided additional relevant clinical information for approximately 11.5% of the families. Our findings indicate that next generation sequencing (NGS) is a powerful tool to investigative putative mutagenic variants among patients who meet the criteria for hereditary BC, but with negative results on BRCA1/2 testing.
    Keywords:  Breast neoplasms; Iran; Mutation; Next generation sequencing
  7. J Natl Compr Canc Netw. 2020 03;pii: jnccn19161. [Epub ahead of print]18(3): 223-228
    Exceptional Response to Olaparib in a Patient With Recurrent Ovarian Cancer and an Entire BRCA1 Germline Gene Deletion.
    Megan Randall, Kelly Burgess, Lela Buckingham, Lydia Usha.
      PARP inhibitors are known to be effective in patients with ovarian cancer (OC) and germline mutations in BRCA1 and BRCA2 genes (BRCA mutations). Little is known, however, about any correlation between the deletion size and location of the BRCA mutation and the response to PARP inhibitors. Women with OC commonly undergo genetic testing because the presence of a germline BRCA mutation impacts therapeutic decisions and is important for cancer surveillance in patients and their family members. This report presents a case of a rare entire germline BRCA1 gene deletion and an exceptional response to a PARP inhibitor, olaparib, in a heavily pretreated patient with OC. Her disease course was also remarkable for complete responses to platinum-based chemotherapy and long chemotherapy-free intervals. Interestingly, the deletion of the entire BRCA1 gene was found after previously negative BRCA test results and is associated with a deletion of 6 adjacent genes without known clinical significance. She has remained progression-free and asymptomatic for >3 years on olaparib, with an overall survival of >12 years. We postulate that this unusually favorable response and prolonged overall survival is related to the cancer cells' inability to reverse the entire gene deletion to wild-type (a common mechanism of resistance to PARP inhibition). This case shows the value of genetic testing for patients with OC and highlights the utility of additional testing with previously negative results and limited genetic testing. It also provides insight into a potential mechanism of an exceptional response to PARP inhibition.
    DOI:  https://doi.org/10.6004/jnccn.2019.7378
  8. J Exp Clin Cancer Res. 2020 Mar 04. 39(1): 46
    Variants of uncertain significance in the era of high-throughput genome sequencing: a lesson from breast and ovary cancers.
    Giulia Federici, Silvia Soddu.
      The promising expectations about personalized medicine have opened the path to routine large-scale sequencing and increased the importance of genetic counseling for hereditary cancers, among which hereditary breast and ovary cancers (HBOC) have a major impact. High-throughput sequencing, or Next-Generation Sequencing (NGS), has improved cancer patient management, ameliorating diagnosis and treatment decisions. In addition to its undeniable clinical utility, NGS is also unveiling a large number of variants that we are still not able to clearly define and classify, the variants of uncertain significance (VUS), which account for about 40% of total variants. At present, VUS use in the clinical context is challenging. Medical reports may omit this kind of data and, even when included, they limit the clinical utility of genetic information. This has prompted the scientific community to seek easily applicable tests to accurately classify VUS and increase the amount of usable information from NGS data. In this review, we will focus on NGS and classification systems for VUS investigation, with particular attention on HBOC-related genes and in vitro functional tests developed for ameliorating and accelerating variant classification in cancer.
    Keywords:  ATM gene; Functional tests; Germline and somatic mutations; Next-generation sequencing; Variant classification; Variants of uncertain significance
    DOI:  https://doi.org/10.1186/s13046-020-01554-6
  9. J Clin Oncol. 2020 Mar 03. JCO1902190
    Evaluation of Germline Genetic Testing Criteria in a Hospital-Based Series of Women With Breast Cancer.
    Siddhartha Yadav, Chunling Hu, Steven N Hart, Nicholas Boddicker, Eric C Polley, Jie Na, Rohan Gnanaolivu, Kun Y Lee, Tricia Lindstrom, Sebastian Armasu, Patrick Fitz-Gibbon, Karthik Ghosh, Daniela L Stan, Sandhya Pruthi, Lonzetta Neal, Nicole Sandhu, Deborah J Rhodes, Christine Klassen, Prema P Peethambaram, Tufia C Haddad, Janet E Olson, Tanya L Hoskin, Matthew P Goetz, Susan M Domchek, Judy C Boughey, Kathryn J Ruddy, Fergus J Couch.
       PURPOSE: To determine the sensitivity and specificity of genetic testing criteria for the detection of germline pathogenic variants in women with breast cancer.
    MATERIALS AND METHODS: Women with breast cancer enrolled in a breast cancer registry at a tertiary cancer center between 2000 and 2016 were evaluated for germline pathogenic variants in 9 breast cancer predisposition genes (ATM, BRCA1, BRCA2, CDH1, CHEK2, NF1, PALB2, PTEN, and TP53). The performance of the National Comprehensive Cancer Network (NCCN) hereditary cancer testing criteria was evaluated relative to testing of all women as recommended by the American Society of Breast Surgeons.
    RESULTS: Of 3,907 women, 1,872 (47.9%) meeting NCCN criteria were more likely to carry a pathogenic variant in 9 predisposition genes compared with women not meeting criteria (9.0% v 3.5%; P < .001). Of those not meeting criteria (n = 2,035), 14 (0.7%) had pathogenic variants in BRCA1 or BRCA2. The sensitivity of NCCN criteria was 70% for 9 predisposition genes and 87% for BRCA1 and BRCA2, with a specificity of 53%. Expansion of the NCCN criteria to include all women diagnosed with breast cancer at ≤ 65 years of age achieved > 90% sensitivity for the 9 predisposition genes and > 98% sensitivity for BRCA1 and BRCA2.
    CONCLUSION: A substantial proportion of women with breast cancer carrying germline pathogenic variants in predisposition genes do not qualify for testing by NCCN criteria. Expansion of NCCN criteria to include all women diagnosed at ≤ 65 years of age improves the sensitivity of the selection criteria without requiring testing of all women with breast cancer.
    DOI:  https://doi.org/10.1200/JCO.19.02190
  10. Ann Oncol. 2018 Oct;pii: S0923-7534(19)49371-X. [Epub ahead of print]29 Suppl 8 viii294
    Prevalence of clinically actionable germline pathogenic variants (PVs) in advanced prostate cancer (aPC).
    A W Hahn, A L Kapron, J Boyle, W Kohlmann, A Poole, D M Gill, S Greenberg, P Hale, C Teerlink, B L Maughan, L Cannon-Albright, N Agarwal, K A Cooney.
      
    DOI:  https://doi.org/10.1093/annonc/mdy284.050
  11. BMC Cancer. 2020 Mar 04. 20(1): 185
    Germline BRCA, chemotherapy response scores, and survival in the neoadjuvant treatment of ovarian cancer.
    Yong Jae Lee, Hyun-Soo Kim, John Hoon Rim, Jung-Yun Lee, Eun Ji Nam, Sang Wun Kim, Sunghoon Kim, Young Tae Kim.
       BACKGROUND: To analyze the effects of BRCA1/2 mutations on chemotherapy response scores (CRS) and survival in a cohort of patients with advanced-stage ovarian cancer who were treated with neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS).
    METHODS: We retrospectively reviewed the medical records of 169 high-grade serous ovarian cancer patients who underwent a germline BRCA1/2 test and received three cycles of NAC at the Yonsei Cancer Center from 2006 to 2018. Chemotherapy response scores were compared in patients with and without BRCA1/2 mutations. The effects of BRCA1/2 mutations and CRS on survival were evaluated.
    RESULTS: BRCA1/2 mutations were detected in 47 (28.1%) of the 169 patients. Overall, 16 (34.0%) patients with BRCA1/2 mutations had a CRS 3 to chemotherapy compared to scores of 43 in patients (35.2%) without a mutation. Response scores of 3 in patients with BRCA1/2 mutations were not significantly associated with either improved progression-free survival (PFS) (P = 0.949) or overall survival (OS) (P = 0.168). However, CRS 3 in patients without BRCA mutations was significantly associated with both improved PFS (P = 0.030) and OS (P = 0.039). In patients with CRS1/2, carriers of BRCA1/2 mutations had better PFS (P = 0.0344) and OS (P = 0.043) than wild-type BRCA genotype patients.
    CONCLUSION: In ovarian cancer patients treated with NAC, CRS did not predict survival for BRCA 1/2 mutation carriers but did for BRCA wild-type patients.
    Keywords:  Chemotherapy response scores; Germline BRCA; Neoadjuvant chemotherapy; Ovarian cancer
    DOI:  https://doi.org/10.1186/s12885-020-6688-8
  12. Ophthalmology. 2019 Dec 12. pii: S0161-6420(19)32330-9. [Epub ahead of print]
    Next-Generation Sequencing of Retinoblastoma Identifies Pathogenic Alterations beyond RB1 Inactivation That Correlate with Aggressive Histopathologic Features.
    Armin R Afshar, Melike Pekmezci, Michele M Bloomer, Nicola J Cadenas, Meredith Stevers, Anuradha Banerjee, Ritu Roy, Adam B Olshen, Jessica Van Ziffle, Courtney Onodera, W Patrick Devine, James P Grenert, Boris C Bastian, David A Solomon, Bertil E Damato.
       PURPOSE: To determine the usefulness of a comprehensive, targeted-capture next-generation sequencing (NGS) assay for the clinical management of children undergoing enucleation for retinoblastoma.
    DESIGN: Cohort study.
    PARTICIPANTS: Thirty-two children with retinoblastoma.
    METHODS: We performed targeted NGS using the UCSF500 Cancer Panel (University of California, San Francisco, San Francisco, CA) on formalin-fixed, paraffin-embedded tumor tissue along with constitutional DNA isolated from peripheral blood, buccal swab, or uninvolved optic nerve. Peripheral blood samples were also sent to a commercial laboratory for germline RB1 mutation testing.
    MAIN OUTCOME MEASURES: Presence or absence of germline RB1 mutation or deletion, tumor genetic profile, and association of genetic alterations with clinicopathologic features.
    RESULTS: Germline mutation or deletion of the RB1 gene was identified in all children with bilateral retinoblastoma (n = 12), and these NGS results were 100% concordant with commercial germline RB1 mutation analysis. In tumor tissue tested with NGS, biallelic inactivation of RB1 was identified in 28 tumors and focal MYCN amplification was identified in 4 tumors (2 with wild-type RB1 and 2 with biallelic RB1 inactivation). Additional likely pathogenic alterations beyond RB1 were identified in 13 tumors (41%), several of which have not been reported previously in retinoblastoma. These included focal amplifications of MDM4 and RAF1, as well as damaging mutations involving BCOR, ARID1A, MGA, FAT1, and ATRX. The presence of additional likely pathogenetic mutations beyond RB1 inactivation was associated with aggressive histopathologic features, including higher histologic grade and anaplasia, and also with both unilateral and sporadic disease.
    CONCLUSIONS: Comprehensive NGS analysis reliably detects relevant mutations, amplifications, and chromosomal copy number changes in retinoblastoma. The presence of genetic alterations beyond RB1 inactivation correlates with aggressive histopathologic features.
    DOI:  https://doi.org/10.1016/j.ophtha.2019.12.005
  13. Ann Oncol. 2018 Oct;pii: S0923-7534(19)48661-4. [Epub ahead of print]29 Suppl 8 viii76
    BRCA1/BRCA2 germline mutations and chemotherapy-related hematological toxicity in breast cancer patients.
    A Friedlaender, A Vuillemier, V Viassolo, A Ayme, S De Talhouet, J-D Combes, J Peron, A Bodmer, S Giraud, A Buisson, V Bonadona, I Gauchat-Bouchardy, O Tredan, P Chappuis, S I Labidi-Galy.
      
    DOI:  https://doi.org/10.1093/annonc/mdy270.233
  14. Ann Oncol. 2018 Oct;pii: S0923-7534(19)48664-X. [Epub ahead of print]29 Suppl 8 viii77
    Lynch syndrome-associated hereditary mutations cause breast and ovarian cancer: Results from Russian Heredetary Oncogenomics project.
    M Gordiev, L H Shigapova, O Brovkina, R F Enikeev, M Druzhkov, A Nikitin, E Shagimardanova, O Gusev.
      
    DOI:  https://doi.org/10.1093/annonc/mdy270.236
  15. Clin Breast Cancer. 2019 Aug 22. pii: S1526-8209(19)30661-5. [Epub ahead of print]
    Breast Conserving Surgery for BRCA Mutation Carriers-A Systematic Review.
    Michael Co, Thomas Liu, Jason Leung, Chung Hin Li, Theo Tse, Michael Wong, Ava Kwong.
      Similar to mastectomy, breast conserving surgery (BCS) is currently the reference standard of surgical treatment of sporadic breast cancer in patients. However, its oncologic safety for BRCA mutation carriers has remained controversial. Thus, we conducted a systematic review to critically evaluate the best evidence from reported studies. A comprehensive search was performed of the Medline, EMBASE, CINAHL, and Cochrane databases using a predefined strategy. The retrieved studies were independently screened and rated for relevance. Data were extracted for qualitative synthesis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol for systematic reviews. No randomized controlled trial has directly compared BCS and mastectomy for BRCA mutation carriers. Of the 18 studies included in our review, the pooled analysis of overall survival at 5, 10, and 15 years were comparable between BCS and mastectomy (88.7%, 89.0% and 83.6% with BCS and 83%, 86.0%, and 83.2% with mastectomy, respectively). However, the pooled ipsilateral breast cancer recurrence rates at 5, 10, and 15 years were higher in the BCS group (8.2%, 15.5%, and 23%, respectively) than in the mastectomy group (3.4%, 4.9%, and 6.4%, respectively). BCS was associated with a greater rate of ipsilateral breast cancer recurrence in BRCA mutation carriers. However, it was not associated with adverse short- and long-term survival outcomes. BCS should be offered as an option to BRCA mutation carriers with proper preoperative counseling.
    Keywords:  Breast neoplasms; Hereditary breast and ovarian cancer syndrome; Mastectomy; Segmental mastectomy; Survival
    DOI:  https://doi.org/10.1016/j.clbc.2019.07.014
  16. Ann Oncol. 2018 Oct;pii: S0923-7534(19)48593-1. [Epub ahead of print]29 Suppl 8 viii52-viii53
    Somatic and germline mutations of Chinese gastric cancer patients.
    Y Wang, W Gu, Y Zhang, K Li, Z Niu, Y Zheng, Q Cui, A Wang, H Chen, W Shi, K Wang, M Yao.
      
    DOI:  https://doi.org/10.1093/annonc/mdy269.165
  17. Ann Oncol. 2018 Oct;pii: S0923-7534(19)49064-9. [Epub ahead of print]29 Suppl 8 viii199-viii200
    Germline mutations in Chinese colorectal cancer patients with mismatch repair deficiency.
    Y Yuan, L Zhu, D Xu, C Liu, X Mao.
      
    DOI:  https://doi.org/10.1093/annonc/mdy281.146
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