Journal articles on the topic 'Hereditary breast cancer patient'
To see the other types of publications on this topic, follow the link: Hereditary breast cancer patient.
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Hereditary breast cancer patient.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Chauhan, Preeti, Arockia M. Babu, Palki sahib kaur, and vikas Menon. "Hereditary Breast Cancer: A Systematic Review." CGC International Journal of Contemporary Technology and Research 2, no. 1 (December 30, 2019): 48–52. http://dx.doi.org/10.46860/cgcijctr/2019.12.30.48.
Full textAbstract:
Breast cancer is a heterogeneous group of tumours with variable prognosis. It is the second leading cause of cancer related death among women.Hereditary breast cancers (HBC) showed around ten percent of the total burden of breast cancer. Most of the breast cancer cases found due to a BRCA germ line mutation. According to estimation, 15–20% breast cancer patients to have one or more 1st or 2nd degree relatives affected with breast cancer. The factors included the genotypic and phenotypic heterogeneity. Many studies found association of HBC with different carcinoma syndromes. The most common association is with ovarian carcinoma so known as hereditary breast ovarian (BO) carcinoma syndrome involving BRCA1 and 2 mutations. Some other factors like reproductive risk factors including age at diagnosis of breast cancer, pregnancy history, and twin history were also studied and were found associated with breast cancer risk. In this review it is reported that knowledge of genetics of hereditary breast cancers may contribute to identification of patient’s increased risk of disease. These patients could be subjected to genetic counseling that can be definitely benefited from early diagnosis.
2
Zarubina, N. A., V. D. Petrova, T. V. Sinkina, S. A. Terekhova, A. F. Lazarev, U. A. Boyarskikh, E. V. Pechkovsky, O. V. Mishukova, and M. L. Filipenko. "Expression of steroids and HER2-neu receptors in breast tumors associated with BRCA1 gene mutations." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): e22223-e22223. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.e22223.
Full textAbstract:
e22223 Background: Hereditary breast carcinomas that are attributable to BRCA1 mutations have their own morphological and immunohistochemical characteristics. This study was aimed to analyze the level of expression of steroids (estrogen and progesterone) and HER2-neu receptors in BRCA1 associated breast cancer. Methods: DNA patterns from 264 patients with hereditary breast cancers (breast cancer diagnosed at the age under 40; bilateral breast cancer; combination of breast and ovarian cancers; 2 and more breast cancers in blood relatives). All the patients were residents of the Altai Territory. BRCA1 gene mutations were registered in 34 patients (12.9%): 5382insC gene mutation - in 28 patients; 300A/C - in 2 patients; 4153del - in 3 patients; 185del - in 1 patient. The frequency of the BRCA1 5382insC allele mutation was 7.3; 300A/C - 0.52; 4153del - 0.26; 185del - 0.83. Immunohistochemical characteristics of BRCA1-associated breast tumors tissue from these patients were investigated. Results: 32 BRCA1-associated breast carcinomas were estrogen receptor- negative; 1 - week positive (H-score 50–100); 1 - moderate positive (H- score 100–200). 33 BRCA1-associated breast carcinomas were progesterone receptor- negative; 1 - positive (H-score 200 and more). HER2-negative were 31 BRCA1-associated breast carcinomas; 2 were week positive (HER2-neu +); 1 - was moderate positive (HER2-neu ++). Conclusion: BRCA1-associated beast carcinomas have been found to be more frequently estrogen receptor-, progesterone receptor-, and HER2- negative. These data show that hereditary breast cancer associated with BRCA1 gene mutations poses poor prognosis. No significant financial relationships to disclose.
3
Ebrahimi, E., E. Sellars, R. Shirkoohi, I. Harirchi, R. Ghiasvand, E. Mohebbi, K. Zendehdel, and M. R. Akbari. "NGS-Based BRCA1, BRCA2, and PALB2 Mutation Testing in Iranian Population With Breast Cancer." Journal of Global Oncology 4, Supplement 2 (October 1, 2018): 208s. http://dx.doi.org/10.1200/jgo.18.84100.
Full textAbstract:
Background: Identification of individuals who have a pathogenic mutation in breast cancer susceptibility genes is an important step to take advantage of genetic counseling, screening, and potentially life-saving prevention strategies. Based on the National Comprehensive Cancer Network (NCCN) guideline, genetic testing is deemed suitable for breast cancer patients with young age at onset, positive family history of cancers, male breast cancer, or diagnosis with a multifocal or triple negative breast cancer. Aim: Since, it is not known what proportion of breast cancers in Iran is hereditary and related to mutations in BRCA1/2 and PALB2 genes, therefore, we screened these 3 genes in multiethnic Iranian population to determine the spectrum of the breast cancer susceptibility gene mutations and to further assess the predictive value of the hereditary breast cancer risk criteria for genetic testing. Methods: Next generation sequencing (NGS) was conducted on a population consisted of 299 and 125 breast cancer patients, with and without hereditary cancer risk criteria for genetic testing, respectively. Results: Pathogenic mutation rate was 10.36% in patients with hereditary criteria for breast cancer vs 1.6% in no criteria group ( P = 0.002). All the patients who only met the young age at onset (<40) criterion tested negative for a gene mutation. This is while patients who had only 1 hereditary criterion (OR: 5.48, 95% CI: 1.09, 52.90, P = 0.017) and patients with multiple hereditary criteria (OR: 22.5, 95% CI: 5.19, 201.31, P < 0.0001) had a significantly higher probability of finding a mutation compared with no risk-criteria group. Conclusion: The first application of NGS on Iranian breast cancer population added to the cumulative evidence that BRCA1/2 mutations are seen commonly among Iranian breast cancer patients especially those with hereditary breast cancer criteria and indicated that PALB2 should be concerned in hereditary breast cancer screening alongside BRCA1/2. Investigating the predictive potential of hereditary breast cancer risk criteria our results suggest that offering genetic testing to women with early age at onset of <40 with no other hereditary criteria, may not be cost effective and should be considered for optimization of genetic counseling and genetic testing of the Iranian population.
4
Tan, D. S. P., C. Marchiò, and J. S. Reis-Filho. "Hereditary breast cancer: from molecular pathology to tailored therapies." Journal of Clinical Pathology 61, no. 10 (August 4, 2008): 1073–82. http://dx.doi.org/10.1136/jcp.2008.057950.
Full textAbstract:
Hereditary breast cancer accounts for up to 5–10% of all breast carcinomas. Recent studies have demonstrated that mutations in two high-penetrance genes, namely BRCA1 and BRCA2, are responsible for about 16% of the familial risk of breast cancer. Even though subsequent studies have failed to find another high-penetrance breast cancer susceptibility gene, several genes that confer a moderate to low risk of breast cancer development have been identified; moreover, hereditary breast cancer can be part of multiple cancer syndromes. In this review we will focus on the hereditary breast carcinomas caused by mutations in BRCA1, BRCA2, Fanconi anaemia (FANC) genes, CHK2 and ATM tumour suppressor genes. We describe the hallmark histological features of these carcinomas compared with non-hereditary breast cancers and show how an accurate histopathological diagnosis may help improve the identification of patients to be screened for mutations. Finally, novel therapeutic approaches to treat patients with BRCA1 and BRCA2 germ line mutations, including cross-linking agents and PARP inhibitors, are discussed.
5
Heidari, Alireza, Katrina Schmitt, Maria Henderson, and Elizabeth Besana. "Hereditary immunity in cancer." International Journal of Advanced Chemistry 8, no. 1 (April 28, 2020): 94. http://dx.doi.org/10.14419/ijac.v8i1.30607.
Full textAbstract:
Cancer is one of the malignant diseases and millions of people worldwide die from cancer annually. Breast cancer diagnosis requires the analysis of images and attributes as well as collecting many clinical and mammography variables. In diagnosis of breast cancer, it is im-portant to determine whether a tumor is benign or malignant. The information about breast cancer risk prediction along with the type of tu-mor are crucial for patients and effective medical decision making. An ideal diagnostic system could effectively distinguish between benign and malignant cells; however, such a system has not been created yet. In this study, a model is developed to improve the prediction probabil-ity of breast cancer. It is necessary to have such a prediction model as the survival probability of breast cancer is high when patients are diagnosed at early stages.
6
Ryu, Jai Min, Seok Jin Nam, Seok Won Kim, Jeong Eon Lee, Byung Joo Chae, Se Kyung Lee, and Jonghan Yu. "Prognosis of BRCA1/2-negative breast cancer patients with HBOC risk factors compared with sporadic breast cancer patients without HBOC risk factors." Japanese Journal of Clinical Oncology 50, no. 2 (January 11, 2020): 104–13. http://dx.doi.org/10.1093/jjco/hyz147.
Full textAbstract:
Abstract Objective Demands for genetic counseling with BRCA1/2 examination have markedly increased. Accordingly, the incidence of uninformative results on BRCA1/2 mutation status has also increased. Because most patients examined for BRCA1/2 mutation have a high risk of hereditary breast and/or ovarian cancer, many patients suffer psychological distress even when the BRCA1/2 result is negative. We compared oncological outcomes between BRCA1/2-negative breast cancer with high risk of hereditary breast and/or ovarian cancer and sporadic breast cancer without risk of hereditary breast and/or ovarian cancer. Methods The criteria for high risk for hereditary breast and/or ovarian cancer were defined as family history of breast and/or ovarian cancer in first- or second-degree relative, early onset breast cancer at <35 years old and bilateral breast cancer. Patients were matched maximally 1:3 into those who identified as negative for BRCA1/2 mutation with risk of hereditary breast and/or ovarian cancer (study group) and those who were not examined for BRCA1/2 mutation without risk for hereditary breast and/or ovarian cancer (control group). Matched variables were pathologic stage, estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 status. Results All matching variables were successfully matched. Median follow-up duration was 57.8 months. There was no significant difference between the groups in disease-free survival (log-rank P = 0.197); however, the study group showed significantly better overall survival and breast cancer-specific survival (both P < 0.0001). We conducted subgroup analysis in the middle-aged group (36–54) and showed no significant difference for disease-free survival (P = 0.072) but significantly better overall survival and breast cancer-specific survival in the study group (P = 0.002 and P < 0.0001). Conclusions BRCA1/2-negative breast cancer patients who had hereditary breast and/or ovarian cancer risk factors showed similar disease-free survival and better overall survival and breast cancer-specific survival compared with those with sporadic breast cancer without hereditary breast and/or ovarian cancer risk factors.
7
Byakhova, M. M., A. B. Semenova, V. N. Galkin, C. V. Homushku, A. E. Zod»binova, M. V. Makarova, E. E. Baranova, et al. "Breast cancer as part of Cowden syndrome." Malignant tumours 12, no. 2 (April 18, 2022): 36–44. http://dx.doi.org/10.18027/2224-5057-2022-12-2.
Full textAbstract:
Cowden syndrome is a rare disease characterized by multiple hamartomas and increased breast, thyroid, kidney and uterine neoplasm risk. The lifetime breast cancer risk for patients with Cowden syndrome is 85 %, with an average age of diagnosis between 38 and 46 years. The diagnostic criteria for Cowden syndrome have been established by the International Cowden Consortium (ICC) and the National Comprehensive Cancer Network (NCCN), and are regularly revised, but the diagnosis of Cowden syndrome remains difficult due to the variety of phenotypic and clinical features of the disease. At the same time, the genetic variants associated with Cowden syndrome analysis is not a standard for patients with breast cancer.Objective: To demonstrate the non‑BRCA hereditary breast cancer detection using whole genome sequencing on the Cowden syndrome clinical case example.Materials and methods: The article describes a clinical case of a 37‑year‑old female patient with breast cancer, normal intelligence and phenotype, structural abnormalities of the thyroid gland (multinodular goiter). Whole genome sequencing was used to identify clinically significant genetic variants associated with hereditary tumor syndromes.Clinical case: The article presents a brief literature review on the clinical presentation of Cowden syndrome and indications for its molecular diagnosis. Also, the presented clinical case describes patient R., 37 years old female with breast cancer, who underwent treatment in the City Clinical Oncological Hospital № 1 of the Moscow City Health Department in 2021. The patient was fully examined and enrolled in the whole genome sequencing project under the Order № 69 of Moscow Healthcare Department dated February 1, 2021 «Oncogenetic research organization in Moscow». The results revealed a pathogenic variant in the PTEN gene, previously associated with Cowden syndrome.Conclusion: The use of whole genome sequencing allows to identify hereditary tumor syndromes, the clinical manifestation of which may be breast cancer.
8
Byakhova, M. M., A. B. Semenova, V. N. Galkin, C. V. Homushku, A. E. Zod»binova, M. V. Makarova, E. E. Baranova, et al. "Breast cancer as part of Cowden syndrome." Malignant tumours 12, no. 2 (April 18, 2022): 36–44. http://dx.doi.org/10.18027/2224-5057-2022-12-2-36-44.
Full textAbstract:
Cowden syndrome is a rare disease characterized by multiple hamartomas and increased breast, thyroid, kidney and uterine neoplasm risk. The lifetime breast cancer risk for patients with Cowden syndrome is 85 %, with an average age of diagnosis between 38 and 46 years. The diagnostic criteria for Cowden syndrome have been established by the International Cowden Consortium (ICC) and the National Comprehensive Cancer Network (NCCN), and are regularly revised, but the diagnosis of Cowden syndrome remains difficult due to the variety of phenotypic and clinical features of the disease. At the same time, the genetic variants associated with Cowden syndrome analysis is not a standard for patients with breast cancer.Objective: To demonstrate the non‑BRCA hereditary breast cancer detection using whole genome sequencing on the Cowden syndrome clinical case example.Materials and methods: The article describes a clinical case of a 37‑year‑old female patient with breast cancer, normal intelligence and phenotype, structural abnormalities of the thyroid gland (multinodular goiter). Whole genome sequencing was used to identify clinically significant genetic variants associated with hereditary tumor syndromes.Clinical case: The article presents a brief literature review on the clinical presentation of Cowden syndrome and indications for its molecular diagnosis. Also, the presented clinical case describes patient R., 37 years old female with breast cancer, who underwent treatment in the City Clinical Oncological Hospital № 1 of the Moscow City Health Department in 2021. The patient was fully examined and enrolled in the whole genome sequencing project under the Order № 69 of Moscow Healthcare Department dated February 1, 2021 «Oncogenetic research organization in Moscow». The results revealed a pathogenic variant in the PTEN gene, previously associated with Cowden syndrome.Conclusion: The use of whole genome sequencing allows to identify hereditary tumor syndromes, the clinical manifestation of which may be breast cancer.
9
Nguyen, Jonathan V., and Martha H. Thomas. "Beyond BRCA: Review of Hereditary Syndromes Predisposing to Breast Cancer." Journal of Breast Imaging 1, no. 2 (June 2019): 84–91. http://dx.doi.org/10.1093/jbi/wbz014.
Full textAbstract:
Abstract The majority of our hereditary breast cancer genes incur not only an increased risk for breast cancer but for other malignancies as well. Knowing whether an individual carries a pathogenic variant in a hereditary breast cancer gene can affect not only screening for the patient but for his or her family members as well. Identifying and appropriately testing individuals via multigene panels allows for risk reduction and early surveillance in at-risk individuals. Radiologists can serve as first-line identifiers of women who are at risk of having an inherited predisposition to breast cancer because they are interacting with all women receiving routine screening mammograms, and collecting family history suggestive of the presence of a mutation. We outline here the 11 genes associated with high breast cancer risk discussed in the National Comprehensive Cancer Network Genetic/Familial High-Risk: Breast and Ovarian (version 3.2019) as having additional breast cancer screening recommendations outside of annual mammography to serve as a guide for breast cancer screening and risk reduction, as well as recommendations for surveillance of nonbreast cancers.
10
Ueda, Mako, Hiroshi Tsubamoto, Mina Kashima-Morii, Yoshitaka Torii, Mariko Kamihigashi, Yu Wakimoto, Nami Nakagomi, Tomoko Hashimoto-Tamaoki, Hideaki Sawai, and Hiroaki Shibahara. "Challenges in Managing Patients with Hereditary Cancer at Gynecological Services." Obstetrics and Gynecology International 2019 (May 27, 2019): 1–9. http://dx.doi.org/10.1155/2019/4365754.
Full textAbstract:
Aim. To reveal current problems and challenges faced by our gynecologic services department in managing patients with hereditary cancers. Methods. We collected clinical data of patients with hereditary cancers, identified via genetic testing (or clinically diagnosed in cases of Cowden syndrome or Peutz–Jeghers syndrome), and treated in our gynecological department from 2012 to 2018. Results. Fifteen patients had hereditary breast and ovarian cancer (HBOC), 6 had Lynch syndrome, 2 had Cowden syndrome, and 2 had Peutz–Jeghers syndrome. Five patients diagnosed with HBOC were younger than 40 years at diagnosis. Risk-reducing salpingo-oophorectomy (RRSO) was performed on 1 patient with a BRCA1 mutation at age 38 years. Seven patients overall underwent RRSO, and none had malignancies on pathological examinations. Peritoneal washing cytology (PWC) was suspicious for malignancy in one patient; however, subsequent PWC at 6 months after RRSO was negative. A patient with endometrial cancer and Lynch syndrome and a patient with atypical endometrial hyperplasia (AEH) and Cowden syndrome strongly desired fertility preservation. They achieved remission after medroxyprogesterone acetate treatment and multiple dilations and curettages, respectively. One patient with Lynch syndrome developed AEH after 11 years of surveillance. Laparotomy revealed adjacent low-grade and high-grade serous ovarian cancer with positive ascites cytology. She had no recurrence during 7-year follow-up after laparotomy. Conclusion. Managing patients with hereditary cancer, positive or false-positive ascites cytology discovered during RRSO, and desired preservation of fertility is highly challenging.
11
Shin, Hee-Chul, Wonshik Han, Han-Byoel Lee, Hyeong-Gon Moon, Eunshin Lee, and Dong Young Noh. "Frequency of germline patghogenic mutation in breast cancer patients at high risk hereditary cancer." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): e13110-e13110. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e13110.
Full textAbstract:
e13110 Background: Next-generation sequencing technology allows the simultaneous sequencing of multiple target genes. We developed a gene panel containing 64 genes which were associated with various hereditary cancers. This study was performed to evaluate the frequency of pathogenic mutations associated with hereditary cancer among Korean patients at high risk hereditary breast cancer using multi-gene sequencing panel. Methods: A total of 252 breast cancer patients with high-risk hereditary cancer were included. Among them, 179 patients (71.0%) had multiple primary cancers including breast cancer, 27 patients (10.7%) were diagnosed with bilateral breast cancer at age 40 or younger. Thirty-five patients (13.9%) had breast cancer family history of more than 2 relatives. With the 64 gene panel, sequence variants were detected by next-generation sequencing technology. Results: Sixty seven patients (26.8%) were found to have 77 germline pathogenic mutations, 12 in BRCA1, 13 in BRCA2, 9 in CDH1, 3 in FH, 5 in MSH2, 2 in MSH6, 4 in NAT1, 6 in PTCH1, 3 in RAD51, 7 in RET, 4 in SPINK1, 3 in TP53 and one each in ALK, BRIP1, CHEK2, MLH2, MUTYH, and PTEN. In 20 patients (4.0%), 2 (n = 9) or 3 (n = 1) pathogenic mutations were detected. In 227 patients with BRCA1/2 negative, CDH1 (n = 7), RET (n = 7), PTCH1 (n = 5), and MSH2 (n = 5) were the most prevalent pathogenic mutations. Conclusions: The 64 gene panel detected germline pathogenic mutations in 26.8% of Korean breast cancer patients with feature of hereditary cancer. Mutations of BRCA1, BRCA2, CDH1, RET, and PTCH1 were the most prevalent variants.Mutation carriers were considered as high risk to develop malignancy and recommended to receive genetic counseling and intensive cancer screening.
12
Litton, Jennifer K., Harold J. Burstein, and Nicholas C. Turner. "Molecular Testing in Breast Cancer." American Society of Clinical Oncology Educational Book, no. 39 (May 2019): e1-e7. http://dx.doi.org/10.1200/edbk_237715.
Full textAbstract:
Molecular testing for genetic and genomic variation has become an integral part of breast cancer management. Patients with a family history of breast cancer or other tumors, bilateral breast cancers, or early-onset breast cancers warrant genetic testing to determine whether a hereditary cancer syndrome is present. The availability of PARP inhibitors—drugs that are selectively active in BRCA1/2-associated breast cancers—has created the need for hereditary cancer testing for all patients diagnosed with advanced breast cancer. Tumor genomic profiling is the standard of care for many types of malignancies and is becoming increasingly important in the management of advanced breast cancer. Targetable mutations in advanced breast cancer include PIK3CA, HER2, and rare instances of mismatch deficiency or other targets for tyrosine kinase inhibitors. The development of methods for sequencing cell-free DNA should allow for broader and easier implementation of tumor genomic testing. Transcriptome-based expression signatures have become the standard of care in the management of early-stage estrogen receptor–positive breast cancers. These assays provide prognostic significance in the setting of adjuvant endocrine therapy and are predictive for benefit from adjuvant chemotherapy. Collectively, these developments underscore the contemporary reality that molecular testing is now part of the clinical management for the majority of patients with breast cancer.
13
Casey, Murray Joseph, Chhanda Bewtra, Henry T. Lynch, Carrie L. Snyder, and Mark Stacey. "Endometrial Cancers in Mutation Carriers From Hereditary Breast Ovarian Cancer Syndrome Kindreds: Report From the Creighton University Hereditary Cancer Registry With Review of the Implications." International Journal of Gynecologic Cancer 25, no. 4 (May 2015): 650–56. http://dx.doi.org/10.1097/igc.0000000000000402.
Full textAbstract:
ObjectiveThe aim of this study was to categorize and report endometrial cancers in mutation carriers from hereditary breast ovarian cancer families.MethodsOur Hereditary Cancer Registry was searched for gynecologic and peritoneal cancers linked to mutations in BRCA1 or BRCA2. Invasive cancers were registered in 101 mutation carriers with complete pathology reports. Efforts were made to secure diagnostic surgical pathology tissues for review. All records and available diagnostic slides were meticulously studied, and primary cancers were classified.FindingsEight malignancies were classified as primary endometrial cancers. Five of these were low- or intermediate-grade endometrioid carcinomas, and 3 were pure serous carcinomas or contained serous carcinoma elements mixed with high-grade endometrioid carcinoma. Breast cancers were diagnosed in 5 patients before and in 1 patient after endometrial carcinoma. Three endometrioid carcinomas were preceded by estrogen treatment, 2 for many years and the other for only 2 months, and 2 of the patients with serous carcinoma had been treated with tamoxifen.ConclusionsThe finding that 8 of gynecologic and peritoneal cancers in 101 mutation carriers were endometrial cancers with a smaller proportion of endometrioid carcinomas than reported in general populations is added to the current controversial literature on endometrial cancer, particularly regarding serous carcinomas, in hereditary breast ovarian cancer syndrome. Well-designed prospective programs for standardized surgical and pathologic handling, processing, and reporting are essential for working out the pathogenesis, true risks, and best management of this disease in carriers of deleterious BRCA1 and BRCA2 germline mutations.
14
Hu, Chunling, Holly LaDuca, Hermela Shimelis, Eric C. Polley, Jenna Lilyquist, Steven N. Hart, Jie Na, et al. "Multigene Hereditary Cancer Panels Reveal High-Risk Pancreatic Cancer Susceptibility Genes." JCO Precision Oncology, no. 2 (November 2018): 1–28. http://dx.doi.org/10.1200/po.17.00291.
Full textAbstract:
Purpose The relevance of inherited pathogenic mutations in cancer predisposition genes in pancreatic cancer is not well understood. We aimed to assess the characteristics of patients with pancreatic cancer referred for hereditary cancer genetic testing and to estimate the risk of pancreatic cancer associated with mutations in panel-based cancer predisposition genes in this high-risk population. Methods Patients with pancreatic cancer (N = 1,652) were identified from a 140,000-patient cohort undergoing multigene panel testing of predisposition genes between March 2012 and June 2016. Gene-level mutation frequencies relative to Exome Aggregation Consortium and Genome Aggregation Database reference controls were assessed. Results The frequency of germline cancer predisposition gene mutations among patients with pancreatic cancer was 20.73%. Mutations in ATM, BRCA2, CDKN2A, MSH2, MSH6, PALB2, and TP53 were associated with high pancreatic cancer risk (odds ratio, > 5), and mutations in BRCA1 were associated with moderate risk (odds ratio, > 2). In a logistic regression model adjusted for age at diagnosis and family history of cancer, ATM and BRCA2 mutations were associated with personal history of breast or pancreatic cancer, whereas PALB2 mutations were associated with family history of breast or pancreatic cancer. Conclusion These findings provide insight into the spectrum of mutations expected in patients with pancreatic cancer referred for cancer predisposition testing. Mutations in eight genes confer high or moderate risk of pancreatic cancer and may prove useful for risk assessment for pancreatic and other cancers. Family and personal histories of breast cancer are strong predictors of germline mutations.
15
Motuziuk, I., O. Sydorchuk, Y. Kostiuchenko, N. Kovtun, P. Poniatovskyi, and A. Holubovska. "HEREDITARY BREAST CANCER SURGICAL TREATMENT." Український радіологічний та онкологічний журнал 28, no. 1 (March 25, 2020): 25–28. http://dx.doi.org/10.46879/ukroj.1.2020.25-28.
Full textAbstract:
Abstract. In this article we present analysis results of the surgical treatment of 56 breast cancer patients who have a high risk of heredity of the disease and meet one or more criteria of genetic testing according to the NCCN vers. 2.2019 guidelines. According to the results of genetic testing by DNA sequencing, 33 mutations were found in 12 genes in 52.7 % of patients. It has been shown that the type of surgery differs depending on the result of genetic testing.
16
Ferreira, Thamara, Thais Ferreira Bomfim-Palma, Isabelle Joyce de Lima Silva-Fernandes, Gabriela Espirito Santo Felix, Inacelli Queiroz De Souza Caires, Leandro Apolinário Silva, Luciana Garcia Landeiro, et al. "PALB2 mutations in Brazilian patients from North-Northeast regions." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): e13670-e13670. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e13670.
Full textAbstract:
e13670 Background: Loss-of-function mutations in PALB2 gene are associated with increased risk for breast cancer and possibly pancreatic, ovarian, male breast, prostate, colorectal as others cancers. In Brazil it has been estimated that up to 1,516 new cases of hereditary breast cancer for 2020 in the North and Northeast regions. Analysis of susceptibility gene mutations helps identify precisely the high-risk patient and their families, whom need specific and personalized clinical management as high-risk individuals. Methods: Twenty-six patients with pathogenic mutations in PALB2 gene identify by next-generation sequencing from states of Bahia (11), Ceará (9), Pernambuco (5) and Rondônia (1) in the North and Northeast regions were analyzed. Results: Most of the patients analyzed had only breast cancer (80%), including two cases of male breast cancer (9,5%); the others were isolated cases of endometrial cancer (4%), breast and pancreas cancers (4%), breast and lung cancers (4%), only ovarian cancer (4%) and ovarian and breast cancers (4%). Most cancers were stage II or III (65%). Family history of cancer was observed in 22/26 (84%); the most common tumors were breast, prostate, pancreas and thyroid. The founder mutations were more frequent in exons: 4 (58%) and 12 (15%). Eleven variants were found as follow: c.1240C > T (19%); c.3256delC (15%); c.1671_1674delTATT (11.5%); c.355delC (11.5%); NC_000016.9:g.(?_23632673)_(23652488_?)del (11,5%). The greatest variety of mutations was found in the state of Bahia, probably due to the greater number of patients included (42%). Conclusions: These data suggest that changes in clinical management of PALB2 patients are needed since the phenotype observed exhibited pattern of hereditary tumors, including male breast cancer. Besides that, PALB2 gene should be included in painel gene analysis in patients from the North and Northeast of Brazil because its high frequency of pathogenic variants.
17
Levonian, Peter J., Jeffrey Landercasper, Choua Vang, Kristen Marcou, Rima Al Hajj, and Mohammed Al-Hamadani. "Resource and quality information provided by compliance with NCCN hereditary breast cancer guidelines." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): e17583-e17583. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.e17583.
Full textAbstract:
e17583 Background: NCCN provides guidelines for breast cancer genetic risk assessment and testing. Measuring compliance with NCCN Guidelines (NG) can identify quality gaps. Methods: After IRB approval, a retrospective review of a prospective database of breast cancer patients was conducted to measure compliance with NG for genetic counseling and BRCA testing. Entry criteria were breast cancer patients with diagnosis and treatment at our center, during the 3 year period ending 12/31/11. Genetic counselors (GC) used NG and BRCAPRO modeling in all patients. Surgeon and GC pedigree analyses were compared. A change to the history was significant if the GC identified information that led to increased or decreased cases of breast or ovarian ca. Results: Surgeons constructed pedigrees in 675 breast cancer patients and referred 42% (286/675) to the GC. The decision to refer was NCCN compliant in 671/675 (99%). The GC corrected the pedigree in 14% (39/286); nearly all due to the GC identifying extra breast or ovarian cancers. The mean BRCAPRO probability in referred patients was 7.2%. Fifty-nine percent (170/286) of patients seen by the GC received a recommendation for BRCA testing. The NG compliance rate for testing was 98% (170/174). Of 174 BRCA tests offered to patients, 74% (128/174) underwent testing. In tested patients, there were 4% BRCA1+, 5% BRCA 2+, and 1% uncertain variants. Total patient charges for 128 tests were $696,000 ($4000/test). If the threshold for testing was BRCAPRO > 5% or >10%, then 69 ($276,000) and 45($180,000) (p<0.001) patient charges would have occurred, and no patient with BRCA + status would have been missed. Conclusions: High rates of NCCN guideline compliance for genetic counseling and testing are achievable. Our GC's improve accuracy of pedigree assessment and demonstrate adherence to NCCN guidelines, resulting in more testing compared to BRCAPRO modeling. The balance between different methods to trigger testing, their sensitivity, and cost deserves more study, but the observational data contained herein provides information for provider and payer stakeholders regarding estimated GC resources and cost of care.
18
Krivokuca, Ana M., Milena R. Cavic, Emina J. Malisic, Jelena D. Rakobradovic, Daniela Kolarevic-Ivankovic, Zorica I. Tomasevic, and Mirjana V. Brankovic-Magic. "Polymorphisms in Cancer Susceptibility Genes XRCC1, RAD51 and TP53 and the Risk of Breast Cancer in Serbian Women." International Journal of Biological Markers 31, no. 3 (July 2016): 258–63. http://dx.doi.org/10.5301/jbm.5000201.
Full textAbstract:
Background Thanks to immense improvements in technology over the past few decades, we have witnessed a major shift towards the idea that breast cancer results from a combined effect of multiple common alleles conferring low risk. This study investigates the role of 3 nonsynonymous SNPs in the DNA repair genes XRCC1 (R399Q), RAD51 (G135C) and TP53 (Arg72Pro) in breast cancer in Serbian women. Patients and Methods Cases of BRCA1/2-negative hereditary breast cancer (n = 52), sporadic breast cancer (n = 106) and age-matched cancer-free female controls (n = 104) were obtained from the Institute for Oncology and Radiology of Serbia's blood bank. Restriction fragment length polymorphism analysis was used for genotyping. Descriptive analyses included genotype and allelic frequencies; the odds ratio and 95% confidence interval were calculated as an estimate of the relative risk. Results A significant difference in QQ+RQ versus RR genotype distribution of XRCC1 was observed between hereditary breast cancer patients and cancer-free controls. The association was confirmed among young breast cancer patients from these high-risk families. The existence of 3 recessive alleles in the RAD51 and XRCC1 genotype combination showed an association with hereditary breast cancer. Odds ratio analysis indicated a strong protective role of the RAD51 GG + TP53 ArgArg + XRCC1 RR combined genotype against hereditary breast cancer negative for BRCA1/2 mutations. Conclusions The XRCC1 R399Q polymorphism showed an association with increased breast cancer risk in Serbia, especially in the hereditary form of the disease and in young breast cancer patients. Dominant alleles of RAD51, TP53 and XRCC1 combined genotypes indicated a strong protective role against hereditary breast cancer.
19
Giorgetti, G., E. Galizia, F. Bianchi, C. Ferretti, F. Corradini, L. Belvederesi, G. Piccinini, C. Loretelli, A. Santinelli, and R. Cellerino. "Genotype and phenotype in hereditary and sporadic breast cancers." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 10538. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.10538.
Full textAbstract:
10538 Background: BRCA1 protein is involved in distinct DNA-repair processes. Germline mutations in BRCA1 gene confer cancer susceptibility. A frequent mechanism for epigenetic inactivation is hypermethylation of the CpG island in promoters of tumours suppressor genes. BRCA1 promoter hypermethylation has been found in a variable percentage of breast cancers (15–30%). BRCA1-associated breast cancers are usually high-grade, poorly differentiated and stain negative for HER2/neu, oestrogen and progesterone receptors (ER, PgR). Many studies have shown that hereditary BRCA1 and basal-like sporadic breast tumours have a similar phenotype and gene expression signature. Methods: By clinical criteria, 223 patients were selected and, for each patient, the probability to carry a BRCA1 mutation was calculated using the software BRCAPRO and Manchester Score System. All patients were studied by direct sequencing and MLPA of BRCA1 Open Reading Frames (ORFs). Thirty sporadic breast carcinomas, from women undergone surgery for primary invasive breast carcinoma between 1995 and 2001, were selected on the basis of negative staining for ER, PgR and HER2/neu (“BRCA-like”). In these patients, Methylation Specific-PCR and Bisulfite Sequencing on genomic DNA (obtained from sections of paraffin-embedded tissues and modified with sodium bisulfite) were used to assess the methylation pattern of BRCA1 promoter. BRCA1 immunohystochemical analysis (IHC) was performed in all patients. Results: We identified 17 patients with deleterious germline mutations in BRCA1. In “BRCA-like” patients, 13 methylated and 17 unmethylated cases were found by methylation analysis of BRCA1 promoter. The BRCA1 IHC was performed in all available samples ( table 1 ). Conclusions: Hypermethylation of BRCA1 promoter was found in 43% of “BRCA- like” patients. Expression of BRCA1 seems to correlate with hypermethylation of its promoter. Further studies are in progress to better understand the possible role of BRCA1 promoter hypermethylation in sporadic breast cancers. [Table: see text] No significant financial relationships to disclose.
20
Walcott, Farzana L., Rebecca Davidson Kaltman, Elizabeth Hatcher, Cam Ha, Tara Biagi, Elizabeth Stark, Allison McHenry, and April Barbour. "Adult cancer survivorship referrals for hereditary cancer genetic testing." Journal of Clinical Oncology 36, no. 7_suppl (March 1, 2018): 183. http://dx.doi.org/10.1200/jco.2018.36.7_suppl.183.
Full textAbstract:
183 Background: Genetic testing for hereditary cancer syndromes is underutilized among cancer patients. Cancer survivorship clinics may identify individuals at risk for hereditary cancer. We present the number of referrals from George Washington (GW) Adult Cancer Survivorship Clinic (ACS) to the GW Ruth Paul Hereditary Cancer Program (RPHCP) to demonstrate the feasibility of identifying high risk individuals in cancer survivorship. Methods: We reviewed the number of patients seen at the GW ACS and subsequent referrals to the GW RPHCP for genetic counseling/testing. An IRB approved research registry was used for retrieval of the data. The ACS clinic is staffed by a physician internist trained in clinical cancer genetics and a nurse practitioner trained in cancer survivorship. Results: 261 patients were seen in ACS from January 1, 2016, to September 30, 2017. Twenty patients (7.6%) were referred to RPHCP based on personal/family cancer history. Three patients were not consented for the research registry, leaving a total of 17 patients for this analysis. Fifteen (88.2%) patients were referred by the physician and 2/17 (11.7%) were referred by the nurse practitioner. Sixteen patients had genetic testing (94.1%) and results were: 5/16 (31.2%) positive, 6/16 (37.5%) negative, and 3/16 (18.7%) had a variant of unknown significance (VUS). Results on 2 patients are pending. One patient deferred testing. Of the 17 patients referred, 14/17 (82.3%) had personal/family history of cancer and had seen an oncologist. Cancer sites and germline mutations identified were: bilateral breast cancer and bladder cancer (BRCA2), prostate cancer (MUTYH), breast and ovarian cancer (BRCA1), endometrial cancer (APC). One patient without cancer was referred by an oncologist for a previously identified familial MLH1 mutation, and was positive. Conclusions: Cancer survivorship clinics may identify individuals appropriate for genetic testing for hereditary cancer syndromes. This is likely an underestimate as not all cancer patients are seen in survivorship clinic. Systematic capture of personal and family history of cancer in cancer survivors may enhance utilization of genetic testing services among cancer survivors and identification of high risk individuals.
21
Levonian, Peter J., Jeffrey Landercasper, Choua Vang, Kristen Marcou, Rima Al Hajj, and Mohammed Al-Hamadani. "Resource and quality information provided by compliance with NCCN hereditary breast cancer guidelines." Journal of Clinical Oncology 31, no. 26_suppl (September 10, 2013): 5. http://dx.doi.org/10.1200/jco.2013.31.26_suppl.5.
Full textAbstract:
5 Background: NCCN provides guidelines for breast cancer genetic risk assessment and testing. Measuring compliance with NCCN Guidelines (NG) can identify quality gaps. Methods: After IRB approval, a retrospective review of a prospective database of breast cancer patients was conducted to measure compliance with NG for genetic counseling and BRCA testing. Entry criteria were breast cancer patients with diagnosis and treatment at our center, during the 3 year period ending 12/31/11. Genetic counselors (GC) used NG and BRCAPRO modeling in all patients. Surgeon and GC pedigree analyses were compared. Results: Surgeons constructed pedigrees in 675 breast cancer patients and referred 42% (286/675) to the GC. The decision to refer was NCCN compliant in 671/675 (99%). The GC corrected the pedigree in 14% (39/286); nearly all due to the GC identifying extra breast or ovarian cancers. The mean BRCAPRO probability in referred patients was 7.2%. Fifty-nine percent (170/286) of patients seen by the GC received a recommendation for BRCA testing. The NG compliance rate for testing was 98% (170/174). Of 174 BRCA tests offered to patients, 74% (128/174) underwent testing. In tested patients, there were 4% BRCA1+, 5% BRCA 2+, and 1% uncertain variants. Total patient charges for 128 tests were $696,000 ($4,000/test). If the threshold for testing was BRCAPRO > 5% or >10%, then 69 ($276,000) and 45 ($180,000) (p<0.001) patient charges would have occurred, and no patient with BRCA + status would have been missed. Conclusions: High rates of NCCN guideline compliance for genetic counseling and testing are achievable. Our GC's improve accuracy of pedigree assessment and demonstrate adherence to NCCN guidelines, resulting in more testing compared to BRCAPRO modeling. The balance between different methods to trigger testing, their sensitivity, and cost deserves more study, but the observational data contained herein provides information for provider and payer stakeholders regarding estimated GC resources and cost of care.
22
Shatova, Yu S., E. A. Chebotareva, E. Yu Zlatnik, I. A. Novikova, D. I. Vodolazhskiy, and E. A. Dzhenkova. "Some clinical morphological and molecular genetic aspects in patients with clinical signs of hereditary breast cancer." Kazan medical journal 99, no. 2 (April 15, 2018): 224–29. http://dx.doi.org/10.17816/kmj2018-224.
Full textAbstract:
Aim. To study the clinical morphological and molecular genetic characteristics of clinically hereditary breast cancer with and without verified mutation of BRCA1, BRCA2 compared to sporadic breast cancer.
Methods. The study included 191 female patients with verified breast cancer stage I-IIA and clinical signs of hereditary breast cancer. In order to identify mutations in genes ВRCA1/2 molecular genetic analysis of deoxyribonucleic acid from peripheral blood leukocytes was performed.
Results. The total frequency of mutations in the genes BRCA1 and ВRCA2 amounted 14.1% of the total number of examined patients. The most common mutation in clinically hereditary breast cancer among residents of the Rostov Region was 5382insC in BRCA1 gene, which corresponds to the nationwide data. Also common features of hereditary breast cancer compared to sporadic breast cancer were identified: young age at the time of disease manifestation, high prevalence of triple-negative cancer, history of infertility, increased level of p53 and androgen receptor expression, decreased level of aneuploid cell and proliferation index in the tumor.
Conclusion. In a number of clinical morphological and molecular genetic parameters, clinically hereditary breast cancer differs from sporadic breast cancer. These indicators in the future can be used as criteria for selection of patients with clinically hereditary breast cancer without confirmed BRCA1/2 mutation by standard panels for in-depth genetic testing.
23
Wittersheim, Maike, Reinhard Büttner, and Birgid Markiefka. "Genotype/Phenotype Correlations in Patients with Hereditary Breast Cancer." Breast Care 10, no. 1 (2015): 22–26. http://dx.doi.org/10.1159/000380900.
Full textAbstract:
Of all breast cancer cases, 5-10% can be attributed to germline mutations, and the high-susceptibility genes BRCA1 and BRCA2 account for about 25-28% of these cases. For the remainder, several genes of moderate and low penetrance have been discovered. Histopathologic characteristics have been studied in small cohorts, but for most of the known non-BRCA1/2-associated hereditary breast cancers, the histologic and immunohistochemical phenotypes are not yet identified. Particularly BRCA1 tumors are associated with a distinct morphology and immunohistochemical characteristics that differ from sporadic breast cancer of age-matched controls. The recognition of features characteristic of these mutations can be helpful to identify patients likely to carry a germline mutation and to assess which gene should be screened for first, in families with a high occurrence of breast and ovarian cancer.
24
Gómez García, E. B., M. B. I. Lobbes, K. van de Vijver, K. Keymeulen, F. van der Ent, H. G. Yntema, V. C. Tjan-Heijnen, and C. Boetes. "Occult Breast Cancer due to Multiple Calcified Hamartomas in a Patient with Cowden Syndrome." Case Reports in Radiology 2012 (2012): 1–4. http://dx.doi.org/10.1155/2012/638725.
Full textAbstract:
Cowden syndrome (CS) is an autosomal dominant disorder characterized by presence of multiple hamartomas, and other benign and malignant abnormalities of the breasts, skin, thyroid, endometrium, gastrointestinal tract, and central nervous system. Hamartomas are benign, developmentally disorganized tumors that can develop in any of the above mentioned organs. The presence of massive calcifications in the breasts in very young women is an indication to perform a breast MRI to exclude a neoplasm since, like in the current case report, presence of breast calcifications may obscure a neoplasm. Although fibrocystic disease and cooccurrence of fibrocystic disease and breast cancer are much more common than CS, the presence of massive calcifications in the breasts of very young women should elicit the possibility of an underlying genetic disease. Furthermore, breast cancer and macrocephaly are considered major criteria for the diagnosis of CS and the combination of both is enough to establish the clinical diagnosis of this entity. Fibrocystic disease of the breasts and multinodular goiter are minor criteria. Family history is also important for the diagnosis of (any) hereditary disease.
25
Prolla, Carmen Maria Dornelles, Patrícia Santos da Silva, Cristina Brinckmann Oliveira Netto, José Roberto Goldim, and Patricia Ashton-Prolla. "Knowledge about breast cancer and hereditary breast cancer among nurses in a public hospital." Revista Latino-Americana de Enfermagem 23, no. 1 (February 2015): 90–97. http://dx.doi.org/10.1590/0104-1169.0185.2529.
Full textAbstract:
OBJECTIVE: To assess the knowledge of nurses involved in the care of oncology patients in a public university hospital, regarding breast cancer and hereditary breast cancer, and to verify the use of such knowledge in their daily practice.METHODS: This is a descriptive cross-sectional study. Data were obtained through a structured, self-administered questionnaire. Out of 154 nurses, 137 (88.9%) agreed to participate in the study. Two questionnaires were excluded such that 135 questionnaires were analyzed.RESULTS: The global percentage of correct answers was not associated with age (p=0.173) or degree/specialization (p=0.815). Questions were classified into categories. In categories involving knowledge of established breast cancer risk factors and indicators of hereditary breast cancer, the rate of correct answers was 65.8% and 66.4%, respectively. On the practice of genetic counseling, 40.7% of those interviewed were not sure about the definition of genetic counseling and 78.5% reported never having identified or referred a patient at genetic risk for specialized risk assessment. Practice of educational actions regarding this subject was reported by 48.5% of those interviewed.CONCLUSION: This study reinforces the need to develop qualifying actions for nurses, so that strategies to control breast cancer become effective in their health care practice.
26
Piombino, Claudia, Laura Cortesi, Matteo Lambertini, Kevin Punie, Giovanni Grandi, and Angela Toss. "Secondary Prevention in Hereditary Breast and/or Ovarian Cancer Syndromes Other Than BRCA." Journal of Oncology 2020 (July 14, 2020): 1–10. http://dx.doi.org/10.1155/2020/6384190.
Full textAbstract:
BRCA1- and BRCA2-associated hereditary breast and ovarian cancer syndromes are among the best-known and most extensively studied hereditary cancer syndromes. Nevertheless, many patients who proved negative at BRCA genetic testing bring pathogenic mutations in other suppressor genes and oncogenes associated with hereditary breast and/or ovarian cancers. These genes include TP53 in Li–Fraumeni syndrome, PTEN in Cowden syndrome, mismatch repair (MMR) genes in Lynch syndrome, CDH1 in diffuse gastric cancer syndrome, STK11 in Peutz–Jeghers syndrome, and NF1 in neurofibromatosis type 1 syndrome. To these, several other genes can be added that act jointly with BRCA1 and BRCA2 in the double-strand break repair system, such as PALB2, ATM, CHEK2, NBN, BRIP1, RAD51C, and RAD51D. Management of primary and secondary cancer prevention in these hereditary cancer syndromes is crucial. In particular, secondary prevention by screening aims to discover precancerous lesions or cancers at their initial stages because early detection could allow for effective treatment and a full recovery. The present review aims to summarize the available literature and suggest proper screening strategies for hereditary breast and/or ovarian cancer syndromes other than BRCA.
27
Frank, Tom S. "Laboratory Determination of Hereditary Susceptibility to Breast and Ovarian Cancer." Archives of Pathology & Laboratory Medicine 123, no. 11 (November 1, 1999): 1023–26. http://dx.doi.org/10.5858/1999-123-1023-ldohst.
Full textAbstract:
Abstract Inherited mutations in the genes BRCA1 and BRCA2 are associated with a significantly increased risk of breast cancer, particularly before the age of 50 years, as well as an increased risk of ovarian cancer. Patients with early-onset breast cancer or ovarian cancer at any age with a family history of either disease are at higher risk of carrying a mutation in BRCA1 or BRCA2. Laboratory analysis of these genes can determine whether a patient has inherited an increased risk of breast and ovarian cancer. In the absence of a mutation that has been previously identified in a family member, most tests for hereditary breast-ovarian cancer risk analyze the entire coding sequences of BRCA1 and BRCA2. The gene sequencing process itself can be automated, but the data must be interpreted by an individual with training in molecular diagnostics. Management options generally available to individuals with hereditary susceptibility to breast and ovarian cancer include heightened surveillance, prophylactic surgery, and chemoprevention. The use of genetic techniques to identify women with increased risk of cancer demonstrates the application of recent advances in the understanding of the genetic basis of malignancy to laboratory medicine and clinical care.
28
Yararbas, K., and PB Atalay. "Association of E-selectin S128R polymorphism with hereditary breast carcinoma susceptibility in Turkish patients without BRCA1/2 germline mutations." Balkan Journal of Medical Genetics 21, no. 1 (October 29, 2018): 27–31. http://dx.doi.org/10.2478/bjmg-2018-0004.
Full textAbstract:
Abstract Inherited genetic factors play an important role in breast cancer susceptibility. The BRCA1 and BRCA2 mutations are the most well-known genetic factors associated with increased risk of breast cancer. E-selectin is a cell surface glycoprotein and its serum levels are known to increase in various cancers. The present retrospective study aimed to evaluate whether E-selectin S128R polymorphism (NG_012124.1: g.7161A>C, NM_000450.2: c.445A>C, NP_000441.2: p.Ser149Arg), which is known to have a role in cancer risk, is associated with breast cancer susceptibility in BRCA 1/2 mutation non carriers with breast cancer. The study included 90 patients with breast cancer and 270 healthy controls. All breast cancer patients were screened for BRCA 1/2 mutations and confirmed to be BRCA 1/2 mutation non carriers before inclusion in the study. Genotyping for the E-selectin S128R polymorphism was performed using real-time polymerase chain reaction (PCR) analysis. The frequencies of the AA, AC and CC genotypes were 70.0, 25.5 and 4.5%, respectively, in the patient group and 79.25, 19.25 and 1.5%, respectively, in the controls. The frequencies of A and C alleles were 84.8 and 15.2% in the patient group, respectively, and 88.9 and 11.1%, respectively, in the controls. No significant differences were determined in the genotype and allele frequencies of the E-selectin S128R polymorphism between the patient and control groups (p = 0.095). The S128R (A/C) polymorphism was not found to be associated with an increased risk of breast cancer [odds ratio (OR) = 0.69; 95% confidence interval (95% CI): 0.43-1.10; p = 0.1248). There was no association between the S128R polymorphism and breast cancer susceptibility in BRCA 1/2 mutation non carriers with breast cancer in the studied Turkish population. Further studies with larger sample sizes are needed to validate our findings.
29
Rofes, Paula, Jesús Del Valle, Sara Torres-Esquius, Lídia Feliubadaló, Agostina Stradella, José Marcos Moreno-Cabrera, Adriana López-Doriga, et al. "BARD1 Pathogenic Variants Are Associated with Triple-Negative Breast Cancer in a Spanish Hereditary Breast and Ovarian Cancer Cohort." Genes 12, no. 2 (January 23, 2021): 150. http://dx.doi.org/10.3390/genes12020150.
Full textAbstract:
Only a small fraction of hereditary breast and/or ovarian cancer (HBOC) cases are caused by germline variants in the high-penetrance breast cancer 1 and 2 genes (BRCA1 and BRCA2). BRCA1-associated ring domain 1 (BARD1), nuclear partner of BRCA1, has been suggested as a potential HBOC risk gene, although its prevalence and penetrance are variable according to populations and type of tumor. We aimed to investigate the prevalence of BARD1 truncating variants in a cohort of patients with clinical suspicion of HBOC. A comprehensive BARD1 screening by multigene panel analysis was performed in 4015 unrelated patients according to our regional guidelines for genetic testing in hereditary cancer. In addition, 51,202 Genome Aggregation Database (gnomAD) non-Finnish, non-cancer European individuals were used as a control population. In our patient cohort, we identified 19 patients with heterozygous BARD1 truncating variants (0.47%), whereas the frequency observed in the gnomAD controls was 0.12%. We found a statistically significant association of truncating BARD1 variants with overall risk (odds ratio (OR) = 3.78; CI = 2.10–6.48; p = 1.16 × 10−5). This association remained significant in the hereditary breast cancer (HBC) group (OR = 4.18; CI = 2.10–7.70; p = 5.45 × 10−5). Furthermore, deleterious BARD1 variants were enriched among triple-negative BC patients (OR = 5.40; CI = 1.77–18.15; p = 0.001) compared to other BC subtypes. Our results support the role of BARD1 as a moderate penetrance BC predisposing gene and highlight a stronger association with triple-negative tumors.
30
Benusiglio, Patrick R., Vincent Fallet, Mateo Sanchis-Borja, Florence Coulet, and Jacques Cadranel. "Lung cancer is also a hereditary disease." European Respiratory Review 30, no. 162 (October 20, 2021): 210045. http://dx.doi.org/10.1183/16000617.0045-2021.
Full textAbstract:
Pathogenic genetic variants (formerly called mutations) present in the germline of some individuals are associated with a clinically relevant increased risk of developing lung cancer. These germline pathogenic variants are hereditary and are transmitted in an autosomal dominant fashion. There are two major lung cancer susceptibility syndromes, and both seem to be specifically associated with the adenocarcinoma subtype. Li-Fraumeni syndrome is caused by variants in the TP53 tumour-suppressor gene. Carriers are mainly at risk of early-onset breast cancer, sarcoma, glioma, leukaemia, adrenal cortical carcinoma and lung cancer. EGFR variants, T790M in particular, cause the EGFR susceptibility syndrome. Risk seems limited to lung cancer. Emerging data suggest that variants in ATM, the breast and pancreatic cancer susceptibility gene, also increase lung adenocarcinoma risk. As for inherited lung disease, cancer risk is increased in SFTPA1 and SFTPA2 variant carriers independently of the underlying fibrosis. In this review, we provide criteria warranting the referral of a lung cancer patient to the cancer genetics clinic. Pathogenic variants are first identified in patients with cancer, and then in a subset of their relatives. Lung cancer screening should be offered to asymptomatic carriers, with thoracic magnetic resonance imaging at its core.
31
Gardovskis, Jānis, Ilze Štrumfa, Edvīns Miklaševičs, Arvīds Irmejs, Genādijs Trofimovičs, Egils Vjaters, Viktors Borošenko, et al. "Epidemiological, Clinical, Molecular Features and Early Detection Strategy of Most Frequent Hereditary Cancers in Latvia." Proceedings of the Latvian Academy of Sciences. Section B. Natural, Exact, and Applied Sciences. 63, no. 4-5 (January 1, 2009): 131–40. http://dx.doi.org/10.2478/v10046-009-0042-5.
Full textAbstract:
Epidemiological, Clinical, Molecular Features and Early Detection Strategy of Most Frequent Hereditary Cancers in Latvia The aim of the study was to determine epidemiological, clinical and molecular features of hereditary breast-ovarian, colorectal, endometrial, prostate and pancreatic cancer in Latvia. The study was performed from 2006 to 2009. Family cancer histories and DNA samples from 5,040 cancer cases were collected, and more than 6,000 molecular tests were performed including multiplex PCR, direct sequencing, denaturing high performance liquid chromatography and others. For the first time, a BRCA2 gene mutation positive hereditary breast cancer family was identified. The necessity of 2 BRCA1 gene founder mutations testing, irrespective of family cancer history for breast and ovarian cancer patients, was confirmed on a large number of positive cases. Regarding hereditary ovarian cancer, every ninth case affected with this malignancy was associated with the BRCA1 gene mutation. For the first time, positive familial adenomatous polyposis cases positive for APC gene mutation were reported and data on the clinical frequency of hereditary endometrial and prostate cancer were provided. In pancreatic cancer patients there was a 3.5% frequency of BRCA1 gene founder mutations.
32
Austin, Sarah, Erika Hanson, Jennifer J. Griggs, Ken Resnicow, and Elena Martinez Stoffel. "Family history assessment to identify patients at risk for hereditary cancer syndromes in community oncology practices." Journal of Clinical Oncology 40, no. 16_suppl (June 1, 2022): e18735-e18735. http://dx.doi.org/10.1200/jco.2022.40.16_suppl.e18735.
Full textAbstract:
e18735 Background: Identification of hereditary cancer syndromes can have implications for cancer treatment and prevention. However, only a fraction of cancer patients undergo germline genetic testing (GT). We employed a family health history tool (FHHT) to assist in identifying cancer patients eligible for GT in the outpatient oncology setting. Methods: Patients with cancer with a visit scheduled at one of two community-based oncology practices received email invitations to complete a web-based FHHT that elicits cancer type and age at diagnosis for 1st and 2nd degree relatives. NCCN guidelines were applied to identify individuals meeting clinical criteria for GT. We compared proportions of individuals eligible for GT by sex and cancer type using Fisher’s exact tests. Results: Of the 1292 cancer patients seen over a 4-month period, 276 (21.4%) completed the FHHT. Of those, 58% were female (N = 160) and breast cancer was the most common cancer diagnosis (N = 73, 26.4%), followed by prostate (N = 25, 9.1%) and colorectal cancer (CRC) (N = 15, 5.4%). 59 (21.3%) patients met criteria for GT, including 49.3% of those with breast cancer (N = 36), 66.7% of those with CRC (N = 10), 28% of those with prostate (N = 7), and 100% of those with pancreatic and ovarian cancers (N = 3 each). Breast cancer accounted for 61% of those meeting GT criteria, including personal history of breast cancer age < 50 (N = 17), and personal history of breast cancer with family history of ovarian cancer (N = 7). The proportion of CRC patients meeting GT criteria was higher than for breast cancer (66.7% vs 49.3%). Seven of 10 (70%) CRC patients meeting GT criteria would not have been identified without their accompanying family history. Overall, women were more likely than men to meet GT criteria (OR 1.8, 95% CI: 1.01 to 3.47, p = 0.045). Conclusions: Approximately 1 in 5 cancer patients who were invited to complete the FHHT met NCCN guidelines for GT. While a personal history of young breast cancer was the most common GT eligibility criterion, the proportion of patients eligible for GT was highest among CRC. Across all cancer types, family history increased the number of patient meeting GT criteria by 42.4%. Implementing a patient-facing family history tool can assist community oncologists in clinically appropriate identification of cancer patients who are eligible for GT. While 48% of patients who completed the FHHT met GT criteria, generalizability is limited due to small sample size.[Table: see text]
33
Beitsch, Peter D., Pat W. Whitworth, Kevin Hughes, Rakesh Patel, Barry Rosen, Gia Compagnoni, Paul Baron, et al. "Underdiagnosis of Hereditary Breast Cancer: Are Genetic Testing Guidelines a Tool or an Obstacle?" Journal of Clinical Oncology 37, no. 6 (February 20, 2019): 453–60. http://dx.doi.org/10.1200/jco.18.01631.
Full textAbstract:
Purpose An estimated 10% of breast and ovarian cancers result from hereditary causes. Current testing guidelines for germ line susceptibility genes in patients with breast carcinoma were developed to identify carriers of BRCA1/ 2 variants and have evolved in the panel-testing era. We evaluated the capability of the National Comprehensive Cancer Network (NCCN) guidelines to identify patients with breast cancer with pathogenic variants in expanded panel testing. Methods An institutional review board–approved multicenter prospective registry was initiated with 20 community and academic sites experienced in cancer genetic testing and counseling. Eligibility criteria included patients with a previously or newly diagnosed breast cancer who had not undergone either single- or multigene testing. Consecutive patients 18 to 90 years of age were consented and underwent an 80-gene panel test. Health Insurance Portability and Accountability Act–compliant electronic case report forms collected information on patient demographics, diagnoses, phenotypes, and test results. Results More than 1,000 patients were enrolled, and data records for 959 patients were analyzed; 49.95% met NCCN criteria, and 50.05% did not. Overall, 8.65% of patients had a pathogenic/likely pathogenic (P/LP) variant. Of patients who met NCCN guidelines with test results, 9.39% had a P/LP variant. Of patients who did not meet guidelines, 7.9% had a P/LP variant. The difference in positive results between these groups was not statistically significant (Fisher’s exact test P = .4241). Conclusion Our results indicate that nearly half of patients with breast cancer with a P/LP variant with clinically actionable and/or management guidelines in development are missed by current testing guidelines. We recommend that all patients with a diagnosis of breast cancer undergo expanded panel testing.
34
Kamihara, Junne, Holly LaDuca, Emily Dalton, Virginia Speare, Judy Ellen Garber, and Mary Helen Black. "Germline mutations in cancer predisposition genes among patients with thyroid cancer." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 1581. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.1581.
Full textAbstract:
1581 Background: Thyroid cancers are known component tumors of both well-described and emerging hereditary cancer syndromes. To assess the contribution of germline variants in thyroid cancer predisposition, we examined the prevalence of germline mutations among individuals with a history of thyroid cancer, compared to those with thyroid and breast cancer or breast cancer alone. Methods: Clinical histories and molecular results were reviewed for individuals with a history of thyroid and/or breast cancer, ascertained from a cohort of > 140,000 patients who underwent hereditary cancer multigene panel testing at a single commercial laboratory. Clinical history information was obtained from test requisition forms completed by ordering clinicians and from pedigrees/clinic notes, if provided. Results: Among 2,678 thyroid cancer patients, the majority were Caucasian (66.9%), female (92.3%), and/or had an additional cancer primary (71.9%), with nearly half reporting an additional breast cancer primary (49.1%). Among those with available pathology information, 4.1% had medullary thyroid cancer. The median (IQR) age at diagnosis was 38 (26,48) years, and while 94.1% had a family history of cancer, 78.8% had at least one affected 1st degree relative. Overall, 11.1% were identified as mutation carriers, defined as ≥1 pathogenic or likely pathogenic variant. Among those with thyroid cancer alone, 9.7% had a mutation, similar to those with breast cancer alone (9.7%) and those with breast and thyroid cancer only (10.5%). Genes most frequently mutated in the thyroid only group included CHEK2 (3.1%), MUTYH (monoallelic) (2.4%), APC (2.0%), ATM (1.6%), and PALB2 (1.2%). CHEK2 was the most frequently mutated gene observed in all groups, with a higher frequency seen among those with thyroid and breast cancer (5.5%) compared to breast cancer (2.5%) or thyroid cancer (3.1%) alone (p < 0.001). Conclusions: A high rate of germline mutations is observed among individuals with thyroid cancer presenting for clinical genetic testing, even in the absence of other primary cancer diagnoses. Thyroid cancer may be an under-recognized component tumor of hereditary cancer predisposition syndromes suggesting the need for further investigation.
35
Takahashi, Eriko, Kaori Terata, Hiroshi Nanjo, Koichi Ishiyama, Yuko Hiroshima, Ayuko Yamaguchi, Misako Yatsuyanagi, et al. "A male with primary accessory breast carcinoma in an axilla is strongly suspected of having hereditary breast cancer." International Cancer Conference Journal 10, no. 2 (January 10, 2021): 107–11. http://dx.doi.org/10.1007/s13691-020-00466-8.
Full textAbstract:
AbstractWe herein report on a male with primary accessory breast cancer in an axilla. A 75-year-old man first noticed a subcutaneous nodule about 2 cm in diameter in the area of his right axilla. The patient underwent extirpation of the mass in a public hospital. Histological examination revealed invasive breast carcinoma of no special type associated with mucinous carcinoma, invasive micropapillary carcinoma and intraductal components. Immunohistochemical analysis showed that the tumor cells were positive for Gross cystic disease fluid protein (GCDFP)-15, mammaglobin and GATA3. Staining for estrogen receptor (ER) and progesterone receptor (PR) was positive, and human epidermal growth factor receptor 2 (HER2) was negative. The Ki67 labeling index (LI) was 33.6%. Imaging revealed no evidence of a primary tumor in any other organ or in the bilateral mammary gland. We performed radical resection of the right axilla, including the scar, and axillary lymph node dissection. The final pathological examination of the surgical specimen showed normal mammary gland tissue that was not connected to the proper mammary gland, and no residual cancer or metastatic lymph nodes. Based on our clinical and pathological findings, this tumor was diagnosed as breast cancer originating from the accessory mammary gland in the right axilla. After surgery, tamoxifen was administered as adjuvant therapy. Since the surgery, 2 years ago, there has been no evidence of recurrence. Hereditary Breast and Ovarian Cancer syndrome was suspected in this case because the patient was a male with breast cancer, and he had two first-degree relatives with breast cancer. This patient had no BRCA mutations on genetic testing. Nonetheless, in cases of male breast cancer, it is necessary to obtain genetic information due to the possibility of hereditary breast cancer, including cancers associated with BRCA gene mutation.
36
Zagorodnev, Kirill, Alexandr Romanko, Anna P. Sokolenko, Ilya Bizin, and Ekaterina S. Kuligina. "New Candidate Predisposition Genes for Hereditary Breast Cancer: SLIT3, CREB3, USP39." Medical Laboratory Technology Journal 7, no. 1 (October 26, 2021): 92. http://dx.doi.org/10.31964/mltj.v7i1.401.
Full textAbstract:
Breast cancer is the most common type of malignant neoplasm in women. <em>BRCA1</em><em> </em>and<em> <em>BRCA2</em></em> are the most commonly mutated genes, but only up to 30% of hereditary breast cancer cases are attributed to alterations in these genes. A large proportion of genetic causes of hereditary breast cancer remains unknown. Thus, the search for new hereditary mutations and establishing a genetic alteration in each case of hereditary breast cancer is a clinically significant task; be the goal of our research. Next-generation sequencing (NGS) allows for simultaneous analysis of hundreds to thousands of genes at one time. We analyzed the genetic material of 49 patients of the northwest Russian population with clinical signs of hereditary breast cancer and identified new mutations associated with hereditary breast cancer. Research results show two missense mutations - SLIT3 p.Arg154Cys, CREB3 p.Lys157Glu, and truncating mutation - USP39 c.*208G>C. Research conclusion; The identified mutations can explain only a tiny fraction of hereditary breast cancer cases (0.7% to 1.1%). The next step to increase the practical value of the detected alterations should be the analysis of biological characteristics of tumors in carriers of these mutations that can potentially become a target for chemotherapy.
37
Huang, Kai-Ling, Yu-Ling Liu, Ya-Ying Hsu, and Wen-Ling Kuo. "Retrospective Analysis of Clinicopathological Features and Familial Cancer History of Synchronous Bilateral Breast Cancer." Healthcare 9, no. 9 (September 13, 2021): 1203. http://dx.doi.org/10.3390/healthcare9091203.
Full textAbstract:
Bilateral breast cancer is a strong predictor of BRCA 1/2 mutation and hence one criterion indicated for hereditary genetic testing. The purpose of this study is to assess the characteristics of synchronous bilateral breast cancer (SBBC) and its association with personal and familial cancer traits. Patients diagnosed with SBBC in our institute between 1992 and 2018 were retrospectively reviewed, and the information of clinicopathological features, personal and family cancer history were analyzed. Of the 307 SBBCs enrolled, the growing case number generally aligned with the regional breast cancer incidence after the era of population-based mammography screening. SBBC patients had similar cancer stages but worse survival outcomes than those in the standard scenario. A total of 42.0% had mixed pathological diagnoses, and 22.8% had discordant immunohistochemistry (IHC) subtypes from both sides, which contributed to treatment challenges. The correlation of SBBC with hereditary breast and ovarian cancer (HBOC) syndrome was strongly implied, as 20.7% of our SBBC patients with known familial cancer histories had HOBC-related familial cancers (breast, ovarian, or prostate cancers). These findings highlight the need for genetic counseling and germline mutation testing in patients with SBBC. Early PARP inhibitor treatment should also be considered in high-risk cases for outcome improvement.
38
Kapoor, Nimmi S., Jennifer Swisher, Rachel E. McFarland, Mychael Patrick, and Lisa D. Curcio. "Impact of hereditary multigene panel testing for cancer survivors." Journal of Clinical Oncology 34, no. 3_suppl (January 20, 2016): 261. http://dx.doi.org/10.1200/jco.2016.34.3_suppl.261.
Full textAbstract:
261 Background: Recently, genetic testing for hereditary cancer syndromes has seen numerous advances in testing spectrum, capability, and efficiency. This may have important implications for cancer survivors and their families. The purpose of this study is to evaluate the impact of reflex genetic testing with newer multi-gene panels on patients with prior negative BRCA1/2 tests. Methods: Data was collected retrospectively from patients who underwent multi-gene panel testing at one of three sites from a single institution between 8/2013-6/2015. Those with a personal history of breast or ovarian cancer and a prior negative BRCA1/2 test were included. Results: Of 914 patients who underwent multi-gene panel tests, 187 met study inclusion criteria. Ten patients (5.3%) were found to carry 11 pathogenic mutations, including 6 patients with mutations in CHEK2, 2 patients with mutations in PTEN, and 1 patient each with mutations in the following genes: BARD1, NF1, and RAD51C. One patient had two pathogenic mutations identified—CHEK2 and BARD1. Of 10 patients with mutations, 9 had a personal history of breast cancer diagnosed at a median age of 43 (range 35-52) and 1 had ovarian cancer diagnosed at age 65. A majority of mutation carriers underwent panel testing years after their cancer diagnosis (median 6 years, range 0.5-32 years) and none with delayed testing had undergone prophylactic contralateral mastectomy prior to the discovery of their gene mutation. All patients with mutations had a family history of at least one cancer, with most having a variety of cancer diagnoses in multiple relatives. Positive panel testing results altered clinical management in most patients, including addition of breast MRI, colonoscopy, or thyroid ultrasound depending on the gene mutation. After discovery of a PTEN mutation 19 years after her initial cancer treatment, one woman underwent bilateral prophylactic mastectomy and was found to have occult ductal carcinoma in situ. Conclusions: Cancer survivorship must incorporate advances in technology that may be beneficial even years after treatment has ended. Multi-gene panel testing can be applied in survivorship settings as a useful tool to guide screening recommendations.
39
Castro, Michael, Koah Vierkoetter, Douglas Prager, Shasta Montgomery, and Kristin Sedgwick. "Synchronous Onset of Breast and Pancreatic Cancers: Results of Germline and Somatic Genetic Analysis." Case Reports in Oncology 9, no. 2 (July 21, 2016): 387–94. http://dx.doi.org/10.1159/000447348.
Full textAbstract:
Background: Synchronous cancers have occasionally been detected at initial diagnosis among patients with breast and ovarian cancer. However, simultaneous coexistence and diagnosis of breast and pancreas cancer has not previously been reported. Case Report: Paternal transmission of a germline BRCA2 mutation to a patient who was diagnosed at age 40 with locally advanced breast and pancreas cancer is presented. Somatic genomic analysis of both cancers with next-generation DNA sequencing confirmed the germline result and reported a variety of variants of unknown significance alterations, of which two were present in both the breast and pancreas cancers. Discussion: The possibility that genomic alterations could have been responsible for modulating the phenotypic or clinical expression of this rare presentation is considered. The authors call attention to the practice of privatizing the clinicogenetic information gained from genetic testing and call for health policy that will facilitate sharing in order to advance the outcomes of patients diagnosed with hereditary cancers.
40
Van Thuan, Tran, Nguyen Van Chu, Pham Hong Khoa, Nguyen Tien Quang, Dao Van Tu, Nguyen Thi Quynh Tho, Phung Thi Huyen, et al. "A Novel BRCA1 Gene Mutation Detected With Breast Cancer in a Vietnamese Family by Targeted Next-Generation Sequencing: A Case Report." Breast Cancer: Basic and Clinical Research 14 (January 2020): 117822342090155. http://dx.doi.org/10.1177/1178223420901555.
Full textAbstract:
Hereditary breast cancer is an inherited genetic condition, mainly caused by BRCA1 and BRCA2 gene mutations. These genetic changes can increase the risks of breast and ovarian cancers in women, while prostate and breast cancers in men. Especially, mutations in either BRCA1 or BRCA2 genes take important roles in early-onset breast cancer. The present study focused on a 47-year-old Vietnamese woman with breast cancer by applying targeted next-generation sequencing technique. A novel BRCA1 gene mutation, namely NM_007294.3 (BRCA1): c.4998insA (p. Tyr1666Terfs), was identified both in this patient and in some of the members in her family proved the fact that the mutated genes passed down through generations. This change may exponentially initiate breast cancer risks and become a valuable marker for exact clinical prognosis and treatment.
41
Melbarde-Gorkusa, Inga, Ilze Strumfa, Andrejs Vanags, Genadijs Trofimovics, and Janis Gardovskis. "Pathological Features of BRCA1/BRCA2 Mutation-Associated Breast Cancer: Implications for Diagnostics and Treatment." Acta Chirurgica Latviensis 11, no. 1 (January 1, 2011): 114–21. http://dx.doi.org/10.2478/v10163-012-0022-8.
Full textAbstract:
Pathological Features ofBRCA1/BRCA2Mutation-Associated Breast Cancer: Implications for Diagnostics and TreatmentBRCA1andBRCA2gene mutations are responsible for significant hereditary breast cancer burden.BRCA1/2mutation-associated breast cancers (furtherBRCA1orBRCA2cancers) are distinctive not only by family history but also by the biological features of the tumour influencing both diagnostic possibilities and response to different treatment modalities. Distinctive morphology and immunohistochemical phenotype of hereditary breast cancers may help to identify patients who are likely to carry germ line mutations inBRCA1orBRCA2gene. The efficacy of specific treatment options can be predicted as well. Additionally,BRCA1carcinomas have different histopathological manifestations fromBRCA2cancers. The cellular and molecular characteristics ofBRCA1/2breast cancer can explain the clinical data and provide prognostic and predictive information. Here, we discuss the peculiarities of breast cancer inBRCA1/2mutation carriers having significant implications in the diagnostics, surgical approach and overall planning of treatment.
42
Khan, Manzoor, Sameen Bin Naeem, Shazia Asim, Mussadique Ali Jhattial, and Neelam Siddiqui. "Outcomes of Hereditary Breast-Ovarian Cancer Syndrome: A single center experience." Pakistan Journal of Medical and Health Sciences 16, no. 6 (June 22, 2022): 114–15. http://dx.doi.org/10.53350/pjmhs22166114.
Full textAbstract:
Aim: To assess the survival and progression patterns of Hereditary Breast and Ovarian Cancer (HBOC) at our hospital. Methods: We did retrospective cohort study of thirty patients presenting with hereditary breast ovarian and cancer diagnosed and treated at Shaukat Khanum Memorial Cancer Hospital and Research Center (SKMCH&RC), Lahore, Pakistan from 1994 to 2012. Patient’s demographics, clinical and histopathology data was obtained from cancer registry department of SKMCH&RC hospital. Chi-square test and independent sample T-test were used to analyze the data to find the association between variables i.e. age, comorbidities, BMI and progression free survival. Result: All patients except two received chemotherapy and surgery as per guidelines. Of the thirty patients, thirteen patients had shown progression free survival (PFS) out of which one patient died whereas progression of disease was observed in seventeen patients of HBOC out of which six patients were expired. Comorbidities and family history of cancer did not show statistically significant results for the mortality (P > 0.05). Metastasis and presence of ascites indicated statistically significant influence on PFS having P value < 0.05. CA-125 at presentation, chemotherapy usage and adjuvant therapy did not show significant impact on PFS (P > 0.05). Conclusion: Seven cases of diagnosed HBOC died. We identified that there were 43.33% cases of diagnosed HOBC who met progression free survival and rest developed the progression. Metastasis and presence of ascites showed significant impact for the progression of disease. Keywords: Progression free survival (PFS), BRCA mutation; Hereditary Breast and Ovarian cancer (HBOC).
43
Gervas, P. A., A. Yu Molokov, E. V. Panpherova, L. Ph Pisareva, and N. V. Cherdyntseva. "Ethnic aspects of hereditary breast cancer." Siberian journal of oncology 18, no. 2 (April 26, 2019): 102–8. http://dx.doi.org/10.21294/1814-4861-2019-18-2-102-108.
Full textAbstract:
This studyaimed to reveal the spectrum of BRca1 and BRca2 genes mutation in various ethnic groups of the Russian Federation. asystematic literature search includes data for the past 10 years and was conducted by using electronic databases of pubmed, eliBRaRY and ect.Material and methods.The review includes research data on the frequency of mutations of breast cancer-associated genes in various ethnic groups of the Russian Federation.Results.For «slavic» patients with a family history, the BRca1/2 mutation testing is the standard of care. in addition, the development of new antitumour drugs has resulted in improved survival rates. more than 1000 mutations of the BRca1 gene have been identified. Recent research is focused on the confirmation the beneficial effect of identified mutations. For the indigenous population (mongoloid ethnic groups), there are no standards for the treatment of inherited breast cancer. thus, the advances in molecular oncology for the treatment of hereditary breast cancer are not available for the indigenous population of the Russian Federation.Conclusion.In this context, the search for markers of early cancer detection and the development of criteria for therapy response are relevant for indigenous people. the development of new predictive and prognostic criteria of breast cancer among mongoloid ethnic groups with a family history will allow the innovative strategies for personalized molecular therapy to be developed.
44
Selvakumar, Veda Padma Priya, Shubha Garg, Jatinder Kaur, Geeta Kadayaprath, Nitesh Rohatgi, Meenu Walia, Ranga Rao Rangaraju, Pramod Kumar Julka, Harit Kumar Chaturvedi, and Amit Verma. "Genetic testing for hereditary breast and ovarian cancer in Indian population: A single institutional study." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): e13153-e13153. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e13153.
Full textAbstract:
e13153 Background: Women with Hereditary breast ovarian cancer have an increased lifetime risk of developing breast, ovarian and other second primary cancers . A number of genes including BRCA 1 & 2 have been implicated in Hereditary Breast Ovarian Cancer. In this background we sought to analyze the genetic pattern of patients who underwent genetic testing as per the NCCN criteria for hereditary breast ovarian cancer syndrome. Methods: All consecutive patients who fit into the NCCN criteria for genetic testing for Hereditary Breast Ovarian Cancer from 2016 to 2018 were referred to our genetic clinic. The data of all the patients who underwent further genetic testing after counselling were collected and analyzed. Results: Out of 155 patients who underwent genetic testing ,131 patients were found eligible for the study.127 were female and 4 were male. There were 27 pathogenic mutations identified while 32 were variants of unknown significance . The remaining 72 were negative for any of the known mutations. 22 were pathogenic for BRCA 1 Mutation , two pathogenic for BRCA 2 and one for TP53 ,PALB2 and ATM each. Out of the 32 VUS, 9 were BRCA 2, 4 in CDH 1, 2 in BRCA1, CHEK2 ,MSH2 and BRIP1 and one each in MLH1, MLH3, ATM, APC, RAD51D, XRCC3, NBN, TP53.Three patients had double VUS reported. BRCA 1 is the most common pathogenic mutation ( 16.79% ) found while BRCA 2 is the most common VUS reported ( 28 %). Conclusions: 20.6 % of eligible patients had pathogenic mutations which is much higher than the western literature. However the VUS rates in Indian population are high 22% owing to a paucity of genetic data of Indian population. Multigene testing helps in identifying other genes asscociated with the Hereditary breast ovarian cancer criteria in addition to BRCA 1 & 2.
45
Infante, Mar, Mónica Arranz-Ledo, Enrique Lastra, Luis Enrique Abella, Raquel Ferreira, Marta Orozco, Lara Hernández, Noemí Martínez, and Mercedes Durán. "Increased Co-Occurrence of Pathogenic Variants in Hereditary Breast and Ovarian Cancer and Lynch Syndromes: A Consequence of Multigene Panel Genetic Testing?" International Journal of Molecular Sciences 23, no. 19 (September 29, 2022): 11499. http://dx.doi.org/10.3390/ijms231911499.
Full textAbstract:
The probability of carrying two pathogenic variants (PVs) in dominant cancer-predisposing genes for hereditary breast and ovarian cancer and lynch syndromes in the same patient is uncommon, except in populations where founder effects exist. Two breast cancer women that are double heterozygotes (DH) for both BRCA1/BRCA2, one ovarian cancer case DH for BRCA1/RAD51C, and another breast and colorectal cancer who is DH for BRCA2/PMS2 were identified in our cohort. Ages at diagnosis and severity of disease in BRCA1/BRCA2 DH resembled BRCA1 single-carrier features. Similarly, the co-existence of the BRCA2 and PMS2 mutations prompted the development of breast and colorectal cancer in the same patient. The first BRCA1/BRCA2 DH was identified by HA-based and Sanger sequencing (1 of 623 families with BRCA PVs). However, this ratio has increased up to 2.9% (1 DH carrier vs. 103 single PV carriers) since using a custom 35-cancer gene on-demand panel. The type of cancer developed in each DH patient was consistent with the independently inherited condition, and the clinical outcome was no worse than in patients with single BRCA1 mutations. Therefore, the clinical impact, especially in patients with two hereditary syndromes, lies in genetic counseling tailor-made for each family based on the clinical guidelines for each syndrome. The number of DH is expected to be increased in the future as a result of next generation sequencing routines.
46
Laptiev, S. A., M. A. Korzhenevskaia, A. P. Sokolenko, A. G. Iyevleva, and E. N. Imyanitov. "MEDICAL AND GENETIC COUNSELING OF HEREDITARY BREAST AND OVARIAN CANCER." Scientific Notes of the I. P. Pavlov St. Petersburg State Medical University 25, no. 2 (September 5, 2018): 7–18. http://dx.doi.org/10.24884/1607-4181-2018-25-2-7-18.
Full textAbstract:
Hereditary breast and ovarian cancer is one of the most common genetic pathology. Medical and genetic counseling of patients with hereditary breast and ovarian cancer and their families plays the important role in cancer care, as it helps to develop the set of diagnostic, preventive and therapeutic measures aimed at monitoring healthy individuals and to create personalized approaches to the treatment of patients.
47
Slavin, Thomas P., Kimberly C. Banks, Darya Chudova, Geoffrey R. Oxnard, Justin I. Odegaard, Rebecca J. Nagy, Kar Wing Kevin Tsang, et al. "Identification of Incidental Germline Mutations in Patients With Advanced Solid Tumors Who Underwent Cell-Free Circulating Tumor DNA Sequencing." Journal of Clinical Oncology 36, no. 35 (December 10, 2018): 3459–65. http://dx.doi.org/10.1200/jco.18.00328.
Full textAbstract:
Purpose To determine the potential for detection of incidental germline cancer predisposition mutations through cell-free DNA (cfDNA) analyses in patients who underwent solid tumor somatic mutation evaluation. Patients and Methods Data were evaluated from 10,888 unselected patients with advanced (stage III/IV) cancer who underwent Guardant360 testing between November 2015 and December 2016. The main outcome was prevalence of putative germline mutations identified among 16 actionable hereditary cancer predisposition genes. Results More than 50 cancer types were studied, including lung (41%), breast (19%), colorectal (8%), prostate (6%), pancreatic (3%), and ovarian (2%). Average patient age was 63.5 years (range, 18 to 95 years); 43% were male. One hundred and fifty-six individuals (1.4%) had suspected hereditary cancer mutations in 11 genes. Putative germline mutations were more frequent in individuals younger than 50 years versus those 50 years and older (3.0% v 1.2%, respectively; P < .001). Highest yields of putative germline findings were in patients with ovarian (8.13%), prostate (3.46%), pancreatic (3.34%), and breast (2.2%) cancer. Putative germline mutation identification was consistent among 12 individuals with multiple samples. Patients with circulating tumor DNA copy number variation and/or reversion mutations suggestive of functional loss of the wild-type allele in the tumor DNA also are described. Conclusion Detection of putative germline mutations from cfDNA is feasible across multiple genes and cancer types without prior mutation knowledge. Many mutations were found in cancers without clear guidelines for hereditary cancer genetic counseling/testing. Given the clinical significance of identifying hereditary cancer predisposition for patients and their families as well as targetable germline alterations such as in BRCA1 or BRCA2, research on the best way to validate and return potential germline results from cfDNA analysis to clinicians and patients is needed.
48
Yap, Timothy A., Arya Ashok, Jessica Stoll, Anna Ewa Schwarzbach, Kimberly L. Blackwell, Tianhong Li, Hyunseok Kang, Judy Ellen Garber, and Funda Meric-Bernstam. "Rate of incidental germline findings detected by tumor-normal matched sequencing in cancer types lacking hereditary cancer testing guidelines." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 10582. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.10582.
Full textAbstract:
10582 Background: Up to 10% of all cancers are associated with hereditary cancer syndromes; however, guidelines for germline testing are currently limited to patients and families with specific cancer types (ovarian, breast, prostate, pancreatic, etc.). Although germline alterations have been shown in genes associated with cancers such as bile-duct, head & neck, brain, bladder, esophageal, and lung cancers, genetic testing is not routinely offered (PMID: 28873162). In such cancers, a guidelines-based approach may fail to detect cancer risk variants found by tumor-normal (T/N) matched sequencing. Here, we report the prevalence of incidental germline findings in patients with the aforementioned 6 cancer types and highlight frequently mutated genes by cancer type. Methods: We retrospectively analyzed next-generation sequencing data from de-identified records of 19,630 patients tested using Tempus|xT T/N matched assay. Incidental germline findings (i.e., single nucleotide variants and small insertions/deletions) detected in 50 hereditary cancer genes were determined for: bile duct (n = 466), head & neck (n = 673), esophageal (n = 395), brain (n = 1,391), bladder (n = 810), and lung (n = 5,544), where n = total patients. For comparison, we also included 4 cancer types that frequently undergo germline testing: ovarian (n = 2,042), breast (n = 3,542), prostate (n = 2,146), and pancreatic (n = 2,621). Results: We detected incidental pathogenic/likely pathogenic germline variants (P/LPV) in 6.5% (601/9,279) of patients diagnosed with the 6 selected cancer types lacking hereditary cancer testing guidelines. The highest prevalence of P/LPV was identified in patients with bladder (8%), brain (6.9%), and lung (6.5%) cancers. Frequently mutated genes (Table) include ATM (n = 62), BRCA2 (n = 60), BRCA1 (n = 33), APC (n = 27), and CHEK2 (n = 21). Of note, the Ashkenazi Jewish variant (p.I1307K) was the most frequent mutation in APC. For cancer types where patients frequently undergo germline testing, the rates of incidental germline findings in descending order were ovarian (15%), breast (12%), prostate (9.4%), and pancreatic (8.5%) cancers. Conclusions: In addition to enhanced variant calling, T/N matched sequencing may identify germline variants missed by a guidelines-based approach to testing. The identification of such germline findings may have clinical implications for the patient, as well as at-risk family members, thereby resulting in the opportunity for genetic counseling and risk-stratified intervention.[Table: see text]
49
Kurian, Allison W., Emily E. Hare, Meredith Mills, Lisa McPherson, Kerry Kingham, Alice S. Whittemore, Valerie McGuire, et al. "Evaluation of a cancer gene sequencing panel in a hereditary risk assessment clinic." Journal of Clinical Oncology 31, no. 26_suppl (September 10, 2013): 7. http://dx.doi.org/10.1200/jco.2013.31.26_suppl.7.
Full textAbstract:
7 Background: Multiple-gene sequencing panels are entering clinical practice. We report on research testing with a custom sequencing panel comprising 43 genes and 32 cancer-associated variants among patients referred for assessment of hereditary breast and ovarian cancer risk. Methods: Patients referred to the Stanford Cancer Genetics Program for clinical BRCA1 and BRCA2 (BRCA1/2) mutation testing from 2002-2012 were invited to donate a blood sample for research on an Institutional Review Board-approved protocol. Blood samples were frozen at -80 degrees, and DNA extracted after <1-10 years. The entire coding region, exon-intron boundaries (+/- 10bp) and all known pathogenic variants in other regions were sequenced for 43 genes that have published associations with risk of breast, ovarian and other cancers. An additional 32 cancer-associated variants were also sequenced. Clinically significant results were disclosed to patients. Results: Germline DNA samples were sequenced from 199 women: 141 had breast cancer, and 57 carried known BRCA1/2 mutations. Analytic results for BRCA1/2 sequencing and pathogenicity interpretations were concordant with prior clinical testing for all patients. Twenty variants designated as pathogenic, either based on published literature or due to a novel truncating or splice donor/acceptor effect, were observed in genes other than BRCA1/2, including ATM, BLM, CDH1, CDKN2A, MUTYH, MLH1, NBN, PRSS1, and SLX4. Thirteen patients had pathogenic variants warranting a change in cancer screening or risk reduction based on practice guidelines; they were invited for confirmatory clinical testing and counseling. One 53-year old patient with a personal history of breast and endometrial cancers was found to carry a pathogenic MLH1 mutation; she underwent risk-reducing salpingo-oophorectomy and colonoscopy, with removal of a tubular adenoma. Conclusions: Among patients referred for BRCA1/2 mutation testing, a comprehensive sequencing assay identified 20 [10.1%, 95% confidence interval (CI) 6.5%-15.1%] pathogenic mutations in other genes, of which 13 (6.5%, CI 3.8%-11%) prompted a change in care. Disclosure of research results to participants was feasible and well-tolerated.
50
Garber, Haven, Akshara Singareeka Raghavendra, Kenneth R. Hess, Banu Arun, and Nuhad K. Ibrahim. "Brain metastasis in patients with hereditary BRCA-mutated invasive breast cancer." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): 1074. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.1074.
Full textAbstract:
1074 Background: In the past six months, two poly(ADP-ribose) polymerase (PARP) inhibitors have been approved for the treatment of patients with metastatic breast cancer and germline pathogenic variants in BRCA1 or BRCA2 ( gBRCA). In addition, recent data from the IMpassion 130 trial lends support for the role of immunotherapy in a subset of patients with triple negative breast cancer (TNBC). Approximately 60% of patients with gBRCA1 have TNBC. There is evidence that both PARP inhibitors and checkpoint inhibitors cross the blood-brain barrier and both classes of agents have entered clinical trials for patients with brain metastases in other tumor types. We studied the clinical course of breast cancer patients with gBRCA and brain metastasis at our institution to inform clinical trial design for this group of patients with poor outcomes. Methods: Patients with stage I to III invasive breast cancer, gBRCA, and eventual development of brain metastasis were identified from clinical databases. Data analyzed included breast cancer subtype and stage at diagnosis, treatment, time to distant recurrence and to discovery of brain metastasis, and overall survival from time of development of brain metastasis. Results: Patients in our cohort (n = 24, to date) were diagnosed at a young age (median age 39) and primarily had TNBC (21/24, 87.5%) with infiltrating ductal carcinoma histology. Nineteen patients had gBRCA1 and 4 patients had gBRCA2. All but 1 patient received anthracycline-based chemotherapy in the neoadjuvant/adjuvant setting. Median time to distant metastasis was 2 years (range: 0.8 – 15) and the brain was the first site of recurrence in 5 of 24 (21%) patients. Median time from diagnosis to development of brain metastasis was 2.6 years (range: 1.2 – 19) and most patients (18/25, 72%) had multiple brain metastases discovered on the initial brain MRI. Median overall survival (OS) was 3.7 years (range: 1.8 – 24) and median OS from the time of brain metastasis was 7 months (range: 1 month – 13 years). Conclusions: Breast cancer patients with germline pathogenic variants in BRCA1/2 who develop brain metastasis have a dismal prognosis. These patients may benefit from an agent with intracranial activity at the time of first distant recurrence.