scholarly journals Germline PALB2 Mutation in High-Risk Chinese Breast and/or Ovarian Cancer Patients

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4195
Author(s):  
Ava Kwong ◽  
Vivian Y. Shin ◽  
Cecilia Y. S. Ho ◽  
Aleena Khalid ◽  
Chun Hang Au ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Cancer Patients ◽  
Ductal Carcinoma ◽  
Familial Aggregation ◽  
Mutation Carriers ◽  
Gene Test ◽  
History Of ◽  
Palb2 Mutation ◽  
Brca1 Brca2

The prevalence of the PALB2 mutation in breast cancer varies across different ethnic groups; hence, it is of intense interest to evaluate the cancer risk and clinical association of the PALB2 mutation in Chinese breast and/or ovarian cancer patients. We performed sequencing with a 6-gene test panel (BRCA1, BRCA2, TP53, PTEN, PALB2, and CDH1) to identify the prevalence of the PALB2 germline mutation among 2631 patients with breast and/or ovarian cancer. In this cohort, 39 mutations were identified with 24 types of mutation variants, where the majority of the mutations were frame-shift mutations and resulted in early termination. We also identified seven novel PALB2 mutations. Most of the PALB2 mutation carriers had breast cancer (36, 92.3%) and were more likely to have family history of breast cancer (19, 48.7%). The majority of the breast tumors were invasive ductal carcinoma (NOS type) (34, 81.0%) and hormonal positive (ER: 32, 84.2%; PR: 23, 60.5%). Pathogenic mutations of PALB2 were found in 39 probands with a mutation frequency of 1.6% and 1% in breast cancer and ovarian cancer patients, respectively. PALB2 mutation carriers were more likely have hormonal positive tumors and were likely to have familial aggregation of breast cancer.

scholarly journals Novel and Recurrent BRCA1/BRCA2 Germline Mutations in Patients with Breast /Ovarian Cancer: A Series from the South of Tunisia

2020 ◽  
Author(s):  
Dorra Ben Ayed-Guerfali ◽  
Wala Ben Kridis-Rejab ◽  
Nihel Ammous-Boukhris ◽  
Wajdi Ayadi ◽  
Slim Charfi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
High Risk ◽  
Germline Mutations ◽  
Brca Mutations ◽  
Mutation Carriers ◽  
Counseling And Testing ◽  
Recurrent Mutations ◽  
Tunisian Patients ◽  
History Of ◽  
Brca1 Brca2

Abstract Background: The incidence of breast/ovarian cancer is increasing in Tunisia especially in young women and mostly those with family history. However, the spectrum of BRCA mutations remains little explored in Tunisian patients in particular in the southern region. Methods: We sequenced the entire coding regions of BRCA1and BRCA2 genes using Next Generation Sequencing (NGS) in 134 selected patients with breast/ovarian cancer. Results: Among the 134 patients, 19 (14.17%) carried pathogenic mutations (10 are BRCA1 mutation carriers and 9 are BRCA2 mutation carriers) that are mainly frameshisft indel (76.9%). Interestingly, 5 out of the 13 variants (38.46%) were found at least twice in unrelated patients, as the c.1310-1313 delAAGA in BRCA2 and the c.5030_5033 delCTAA that has been identified in 4/98 BC patients and in 3/15 OC patients from unrelated families with strong history of cancer. Besides recurrent mutations, 6 variant (4 in BRCA1 and 2 in BRCA2) were not reported previously. Furthermore, 3 unrelated patients carried the VUS c.9976A>T, (K3326*) in BRCA2 exon 27. BRCA carriers correlated significantly with tumor site (p=0.029) and TNBC cases (p=0.008). In the groups of patients (31-40 y and 41-50 y), BRCA1 mutations occurred more frequently in patients with OC than those with BC, and conversely BRCA2 carriers are mostly affected with BC (p=0.001 and p=0.044 respectively).Conclusions: The overall frequency of the BRCA germline mutations was 14.17% in patients with high risk of breast /ovarian cancer. We identified recurrent mutations as the c.1310_1313 delAAGA in BRCA2 gene and the c.5030_5033 delCTAA in BRCA1 gene that were found in 4% and 20% of familial BC and OC respectively. Our data will contribute in the implementation of genetic counseling and testing for families with high-risk of breast/ovarian cancer.

scholarly journals Effects of BRCA Germline Mutations on Triple-Negative Breast Cancer Prognosis

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Katarzyna Pogoda ◽  
Anna Niwińska ◽  
Elżbieta Sarnowska ◽  
Dorota Nowakowska ◽  
Agnieszka Jagiełło-Gruszfeld ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Cancer Prognosis ◽  
Entire Group ◽  
Prognostic Impact ◽  
Breast Cancer Patients ◽  
Mutation Carriers ◽  
Significant Difference ◽  
History Of

Germline BRCA1 and BRCA2 mutations confer an increased lifetime risk for breast cancer and ovarian cancer. Several studies have investigated prognosis among BRCA1/2 mutation carriers and noncarriers, but the prognostic impact on outcomes of breast cancer patients has not been determined. The aim of this study was to determine the prognosis of TNBC patients with and without BRCA1/2 germline mutation. Among 502 patients diagnosed with TNBC between 2005 and 2008, 124 patients with a strong family history of breast cancer or ovarian cancer as well as TNBC patients diagnosed under 45 years were referred to the Genetic Counseling Unit for genetic counselling and genetic tests. In 30 (24%) of them, the BRCA1/2 mutation was detected (the most common 5382insC in 18 (60%) patients). The median follow-up of the entire group was 60 months. BRCA1/2 mutation carriers were statistically significantly younger at TNBC diagnosis compared with nonmutation patients (41 vs 47 years, respectively). Patients with the BRCA1/2 mutation had smaller tumors (stage I: 47% vs 24.5% in noncarriers), but there was no significant difference in the regional nodal status (58.5–63% with cN0). Contralateral breast cancer developed in 26.5% of BRCA1/2 mutation carriers and in 14% of noncarriers. Other primary cancers were also slightly more common in BRCA1/2 mutation carriers (16.5% vs 9.5%). The performed analysis did not show any significant differences between the groups in recurrence-free survival (p=0.312). There was no significant difference between patients with or without BRCA1/2 mutation as regards overall survival (p=0.649) and the risk of TNBC death (p=0.333). The survival from detection of metastases was similar in two groups (p=0.865). Our study demonstrated that the BRCA1 mutation does not affect TNBC patients’ outcomes.

Practical assessment of psychosocial concerns associated with genetic testing in ovarian cancer patients using the MICRA questionnaire.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9569-9569
Author(s):  
Merete Bjørnslett ◽  
Alv A. Dahl ◽  
Øystein Sørebø ◽  
Anne Dørum
Keyword(s):  
Ovarian Cancer ◽  
Genetic Testing ◽  
Cancer Patients ◽  
Brca Mutation ◽  
Mutation Carriers ◽  
Brca Mutation Carriers ◽  
History Of ◽  
Positive Experiences ◽  
Explained Variance

9569 Background: Ten to 15% of ovarian cancer patients are BRCA mutation carriers. By offering genetic testing, families at risk and healthy female mutation carriers will be identified and offered clinical follow-up. The MICRA questionnaire was developed as a brief, practical, and targeted assessment of concerns and psychosocial issues associated with genetic testing. This study evaluates the practical and psychometric properties of the MICRA (Norwegian translation) in tested ovarian cancer patient. Methods: Since 2002, ovarian cancer patients at Oslo University Hospital, Norwegian Radium Hospital are offered genetic counseling and testing. By the end of 2009, 1,032 were included. The 530 (51%) patients still alive, were mailed the MICRA and three other instruments relevant for mental distress. 354 (67%) patients responded. Among them 9% were BRCA mutation carriers, 7% had a personal history of breast cancer, 29% had a family history of breast and/or ovarian cancer, and 55% had no such family history. Results: In the BRCA mutation carrier group, the total MICRA score and its subscale scores of distress, uncertainty, and positive experiences were all significantly higher than in the other groups. Confirmatory factor analyses of the three subscales of MICRA showed inadequate fit indices, while a four factors solution including the new factor of Support from family (items #18 and #19), showed adequate fit. The Positive Experiences subscale showed a maximum of 4% explained variance in relation to the Hospital Anxiety and Depression Scale total score, the Impact of Event Avoidance and Intrusion scores, and the Eysenck’s Neuroticism score. The subscales of Distress and Uncertainty showed maximum 12% and 41% explained variance, respectively, while the total MICRA score showed 22% explained variance. Conclusions: Our study supports the feasibility of the MICRA in ovarian cancer patients. Frail women may be identified for closer follow-up by using MICRA. Discrimant, content and construct validities of the MICRA were supported, while the factor structure still is open to further investigation.

BRCA1/2 mutation prevalence in triple-negative breast cancer patients without family history of breast and ovarian cancer.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 1090-1090 ◽  
Author(s):  
Kerstin Rhiem ◽  
Christoph Engel ◽  
Jutta Engel ◽  
Dieter Niederacher ◽  
Christian Sutter ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Family History ◽  
Cancer Patients ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Breast Cancer Patients ◽  
Breast And Ovarian Cancer ◽  
History Of

Risk of ovarian cancer in breast-cancer patients with a family history of breast or ovarian cancer: a population-based cohort study

The Lancet ◽  
2002 ◽  
Vol 360 (9337) ◽  
pp. 891-894 ◽  
Author(s):  
Kjell Bergfeldt ◽  
Bosse Rydh ◽  
Fredrik Granath ◽  
Henrik Grönberg ◽  
Lukman Thalib ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Cohort Study ◽  
Family History ◽  
Cancer Patients ◽  
Population Based ◽  
Breast Cancer Patients ◽  
History Of

Lumpectomy and Breast Radiotherapy in Breast Cancer Patients with a Family History of Breast Cancer, Ovarian Cancer, or Both

2002 ◽  
Vol 8 (3) ◽  
pp. 154-161 ◽  
Author(s):  
Charles E. Leonard ◽  
Scot Sedlacek ◽  
Howard Shapiro ◽  
Diana Hey ◽  
Xiolan Liang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Family History ◽  
Cancer Patients ◽  
Breast Cancer Patients ◽  
Breast Radiotherapy ◽  
History Of

Oral Contraceptives and Risk of Ovarian Cancer and Breast Cancer Among High-Risk Women: A Systematic Review and Meta-Analysis

2013 ◽  
Vol 31 (33) ◽  
pp. 4188-4198 ◽  
Author(s):  
Patricia G. Moorman ◽  
Laura J. Havrilesky ◽  
Jennifer M. Gierisch ◽  
Remy R. Coeytaux ◽  
William J. Lowery ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Family History ◽  
Cancer Risk ◽  
Meta Analysis ◽  
Brca2 Mutation ◽  
Ovarian Cancer Risk ◽  
Mutation Carriers ◽  
History Of ◽  
Meta Analyses

Purpose To estimate the risks of ovarian cancer and breast cancer associated with oral contraceptive (OC) use among women at elevated risk owing to mutations in BRCA1/2 or a strong family history. Methods We searched PubMed, Embase, the Cochrane Database of Systematic Reviews, and ClinicalTrials.gov for studies published 2000 to 2012 that evaluated associations between OC use and breast or ovarian cancer among women who are carriers of a BRCA1/2 mutation or have a family history of breast or ovarian cancer. Results From 6,476 unique citations, we identified six studies examining ovarian cancer risk in BRCA1/2 mutation carriers and eight studies examining breast cancer risk in BRCA1/2 mutation carriers. For BRCA1/2 mutation carriers combined, meta-analysis showed an inverse association between OC use and ovarian cancer (odds ratio [OR], 0.58; 95% CI, 0.46 to 0.73) and a nonstatistically significant association with breast cancer (OR, 1.21; 95% CI, 0.93 to 1.58). Findings were similar when examining BRCA1 and BRCA2 mutation carriers separately. Data were inadequate to perform meta-analyses examining duration or timing of use. For women with a family history of ovarian or breast cancer, we identified four studies examining risk for ovarian cancer and three for breast cancer, but differences between studies precluded combining the data for meta-analyses, and no overall pattern could be discerned. Conclusion Our analyses suggest that associations between ever use of OCs and ovarian and breast cancer among women who are BRCA1 or BRCA2 mutation carriers are similar to those reported for the general population.

Breast cancer as seen at the Nairobi Hospital.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12514-e12514
Author(s):  
Nicholas Anthony Othieno-Abinya ◽  
Gladwell Wanjiru Kamere Kiarie ◽  
Alice Musibi ◽  
Amina Habib Kidee ◽  
Tom Nyaboga ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Triple Negative ◽  
Ductal Carcinoma ◽  
Hormonal Contraceptives ◽  
Excision Biopsy ◽  
Breast Cancer Patients ◽  
Younger Patients ◽  
History Of ◽  
History Of Cancer

e12514 Background: Breast cancer is the most common cancer and the second leading cause of death among women globally. The Nairobi Hospital has a comprehensive cancer centre, with various practitioners treating cancer patients individually. To document breast cancer diagnosis, treatment and outcome at the Nairobi Hospital. Methods: A retrospective cohort study involving records of breast cancer patients between Jan 2014 and Dec 2019 inclusive. Details included, demographic details, comorbidities, pathology, stage, treatment and outcome. The study was approved by the hospital’s Ethics and Research Committee. Results: 591 patients; 580 (98.1%) women and 11(1.9%) men. Age group 41-60 years had 330 patients(57.2%). Mean parity was 3. Fifteen (2.5%) were smokers, 73 (12.4%) took alcohol, 159 (12.4%) used hormonal contraceptives, 4(0.7%) had been exposed to iatrogenic radiation. Family history of cancer was present in 112 (19%), 25 (4.2%) had personal history of cancer, breast cancer in 8 (1.4%). Diagnosis was by core needle biopsy in 301 (50.9%), excision biopsy in 238 (40.3%), and fine needle aspiration cytology in 52 (8.8%). Pathology was invasive ductal carcinoma in 502(84.9%), invasive lobular in 12(2%). Oestrogen receptors were expressed in 329 (55.7%), progesterone receptors in 264 (44.7%), and Her2 in 129(21.8%). Triple negative were 86( 18%). T1 tumors were 84 (14.2%), T2 were 197 (33.3%), T3 were 126 (15.9%,) and T4 in 94 (15.9%), 126 (21.3%) had distant metastases. Neoadjuvant combination of doxorubicin and cyclophosphamide (AC) was in 109(18.4%) of patients, a taxane following AC (AC-T) in 79 (13.4), and 5-FU with doxorubicin and cyclophosphamide (CAF) in 105 (17.8%). Adjuvant AC was administered to 59 (10%), AC-T to 65 (11%), and CAF to 105 (17.8%), adjuvant tamoxifen to 160 (27.1%). Overall 93 patients (15.7%) received trastuzumab. Adjuvant radiotherapy was completed in 367 (62.1%). At a median follow-up of 36 months, patients 33 (5.6%) were recorded dead. The younger patients had worse survival. Conclusions: Ductal carcinoma constituted 85% of cases and metastatic disease was in 21.3 %. Triple negative cancer were 18%. Younger patients had higher risk of early death.

Rethinking breast cancer surveillance in women with BRCA-associated ovarian cancer in the post-solo trial era.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5565-5565
Author(s):  
Catherine S. John ◽  
Farin F. Amersi ◽  
Abigail Fong ◽  
Jessica Gillen ◽  
Kathleen N. Moore ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Ductal Carcinoma ◽  
Brca2 Mutation ◽  
Breast Cancer Incidence ◽  
Cancer Surveillance ◽  
Advanced Stage ◽  
Free Survival ◽  
Mutation Carriers ◽  
Increased Risk

5565 Background: Patients with BRCA mutations are at increased risk of developing both breast (BC) and epithelial ovarian cancer (EOC). Optimal breast cancer surveillance guidelines for BRCA mutation carriers following EOC has not been defined due to high risk of EOC recurrence. The recent SOLO-1 trial demonstrated a survival benefit of olaparib maintenance therapy for newly diagnosed women with advanced stage EOC. Olaparib reduced the risk of disease-progression or death by 70% compared to placebo with a median progression-free survival (PFS) of 36 months. Methods: An IRB-approved, multi-institutional study retrospective chart review was performed. Patients had BRCA-associated EOC diagnosed between 1990-2015 without a history of prior BC or mastectomy. All women received combination chemotherapy for EOC. The observed breast cancer free survival was adjusted to reflect the enhanced 3-year PFS observed in olaparib-treated women from the SOLO-1 trial. Kaplan-Meier survival curves were performed. Results: 191 patients with BRCA-associated EOC were included (135 BRCA1, 55 BRCA2, 1 BRCA1 and BRCA2). Median age was 53 years. Most women had advanced stage, high-grade serous EOC (75%). The median overall survival was 7.7 years for BRCA 1, and 9.7 years for BRCA2 mutation carriers. Annual mammography and MRI were performed in 43% and 34% of women, respectively, with a median of 4 mammograms and 3 MRI per patient. 16 women (8.3%) were diagnosed with BC over a median follow up of 80 months: 7 (44%) DCIS and 9 (56%) invasive ductal carcinoma. 14 (88%) women had early stage (0-2) BC. 28 (15%) of women had risk-reducing mastectomy performed an average of 2.1 years following their EOC diagnosis. The incidence of BC increased from 5.6% to 11% at 5- and 10-years post EOC, and in the predicted model with olaparib, from 10% to 17% at 5- and 10-years, assuming olaparib does not impact breast cancer incidence. Conclusions: The risk of metachronous BC following BRCA-associated EOC increases over time. In the post SOLO trial era, BC surveillance strategies in women with EOC should be optimized to reflect improved outcome. [Table: see text]

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