scholarly journals Risk of Asynchronous Contralateral Breast Cancer in Noncarriers of BRCA1 and BRCA2 Mutations With a Family History of Breast Cancer: A Report From the Women's Environmental Cancer and Radiation Epidemiology Study

2013 ◽  
Vol 31 (4) ◽  
pp. 433-439 ◽  
Author(s):  
Anne S. Reiner ◽  
Esther M. John ◽  
Jennifer D. Brooks ◽  
Charles F. Lynch ◽  
Leslie Bernstein ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Young Women ◽  
Contralateral Breast Cancer ◽  
Contralateral Breast ◽  
Brca1 And Brca2 ◽  
Bilateral Disease ◽  
History Of ◽  
Brca2 Mutations ◽  
Brca1 And Brca2 Mutations

Purpose To fully characterize the risk of contralateral breast cancer (CBC) in patients with breast cancer with a family history who test negative for BRCA1 and BRCA2 mutations. Patients and Methods From our population-based case-control study comparing women with CBC to women with unilateral breast cancer (UBC), we selected women who tested negative for BRCA1 and BRCA2 mutations (594 patients with CBC/1,119 control patients with UBC). Rate ratios (RRs) and 95% CIs were estimated to examine the association between family history of breast cancer and risk of asynchronous CBC. Age- and family history–specific 10-year cumulative absolute risks of CBC were estimated. Results Family history of breast cancer was associated with increased CBC risk; risk was highest among young women (< 45 years) with first-degree relatives affected at young ages (< 45 years; RR, 2.5; 95% CI, 1.1 to 5.3) or women with first-degree relatives with bilateral disease (RR, 3.6; 95% CI, 2.0 to 6.4). Women diagnosed with UBC before age 55 years with a first-degree family history of CBC had a 10-year risk of CBC of 15.6%. Conclusion Young women with breast cancer who have a family history of breast cancer and who test negative for deleterious mutations in BRCA1 and BRCA2 are at significantly greater risk of CBC than other breast cancer survivors. This risk varies with diagnosis age, family history of CBC, and degree of relationship to an affected relative. Women with a first-degree family history of bilateral disease have risks of CBC similar to mutation carriers. This has important implications for the clinical management of patients with breast cancer with family history of the disease.

scholarly journals Clinical and pathological characteristics of Chinese patients with BRCA related breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22226-e22226
Author(s):  
A. Kwong ◽  
L. Wong ◽  
C. Wong ◽  
F. Law ◽  
E. Tang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
High Risk ◽  
Breast Cancers ◽  
Brca1 And Brca2 ◽  
Brca Mutations ◽  
Mutation Carriers ◽  
History Of ◽  
Brca2 Mutations ◽  
Brca1 And Brca2 Mutations

e22226 Background: Breast cancers due to underlying germline BRCA1 and BRCA2 mutations are associated with particular pathological features that may differ from sporadic breast cancers. We report clinical and pathologic characteristics of breast cancer in a clinical cohort of high risk Chinese women with BRCA mutations and those without mutations. Methods: 202 high risk women based on their age and family history were recruited from March 2007 to November 2008. Medical information was prospectively collected from the patients and medical records. BRCA1 and BRCA2 mutations were detected using full gene sequencing and multiplex ligation-dependent probe amplification (MLPA). Results: Of the 202 female probands tested, 25 (12.3 %) were BRCA mutation carriers of which 11 (44%) were BRCA1 and 14 (56%) were BRCA2 mutations. Breast cancer risk factors, other than family history, did not differ between carriers and non-carriers. Mutation carriers were more likely to have a familial history of breast cancer (p=0.07) and personal and family history of ovarian cancer (p=0.005; p=0.007). Other cancers found in carriers families included pancreatic, gastric, colon, lung, liver, and nasopharyngeal. 23% of women diagnosed with DCIS had BRCA mutations compared with 11.4% of those with invasive cancers. BRCA related tumors were more likely to be ER, PR and Her-2 negative (Triple negative, TN) (p= 0.006). Overall 9.6% of non-BRCA cancers were TN whereas 25.9% of BRCA cancers were TN. Prevalence of TN in BRCA1 carriers is 71% compared with 13.4% in BRCA2 carriers. BRCA1 mutation related cancers were significantly more likely to be ER negative than BRCA2 and this is only significant in those who are under 40 years of age (p=0.070). Conclusions: We have a high BRCA2 mutation rate in our cohort. BRCA related breast cancer is associated with families with increasing number of first degree relatives with breast and/or ovarian cancers and were higher for DCIS cancers. Prevalence of TN breast cancers was high compared to Caucasian cohorts. BRCA mutations were associated with pathologically, poor prognostic features (TN and high grade) especially in younger women. No significant financial relationships to disclose.

Efficacy of Contralateral Prophylactic Mastectomy in Women With a Personal and Family History of Breast Cancer

2001 ◽  
Vol 19 (19) ◽  
pp. 3938-3943 ◽  
Author(s):  
Shannon K. McDonnell ◽  
Daniel J. Schaid ◽  
Jeffrey L. Myers ◽  
Clive S. Grant ◽  
John H. Donohue ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Risk Reduction ◽  
Contralateral Breast Cancer ◽  
Prophylactic Mastectomy ◽  
Contralateral Prophylactic Mastectomy ◽  
Contralateral Breast ◽  
Breast Cancers ◽  
History Of

PURPOSE: To estimate the efficacy of contralateral prophylactic mastectomy in women with a personal and family history of breast cancer. PATIENTS AND METHODS: We followed the course of 745 women with a first breast cancer and a family history of breast and/or ovarian cancer who underwent contralateral prophylactic mastectomy at the Mayo Clinic between 1960 and 1993. Family history information and cancer follow-up information were obtained from the medical record, a study-specific questionnaire, and telephone follow-up. Life-tables for contralateral breast cancers, which consider age at first breast cancer, current age, and type of family history, were used to calculate the number of breast cancers expected in our cohort had they not had a prophylactic mastectomy. RESULTS: Of the 745 women in our cohort, 388 were premenopausal (age < 50 years) and 357 were post- menopausal. Eight women developed a contralateral breast cancer. Six events were observed among the premenopausal women, compared with 106.2 predicted, resulting in a risk reduction of 94.4% (95% confidence interval [CI], 87.7% to 97.9%). For the 357 postmenopausal women, 50.3 contralateral breast cancers were predicted, whereas only two were observed, representing a 96.0% risk reduction (95% CI, 85.6% to 99.5%). CONCLUSION: The incidence of contralateral breast cancer seems to be reduced significantly after contralateral prophylactic mastectomy in women with a personal and family history of breast cancer.

Abstract B127: Family history of breast cancer and risk of contralateral breast cancer

2010 ◽  
Author(s):  
Anne S. Reiner ◽  
Colin B. Begg ◽  
Leslie Bernstein ◽  
Robert W. Haile ◽  
Julia A. Knight ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Contralateral Breast Cancer ◽  
Contralateral Breast ◽  
History Of

scholarly journals Risk of Contralateral Breast Cancer in Women with and without Pathogenic Variants in BRCA1, BRCA2, and TP53 Genes in Women with Very Early-Onset (<36 Years) Breast Cancer

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 378 ◽  
Author(s):  
Zerin Hyder ◽  
Elaine F. Harkness ◽  
Emma R. Woodward ◽  
Naomi L. Bowers ◽  
Marta Pereira ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Contralateral Breast Cancer ◽  
Genomic Medicine ◽  
Contralateral Breast ◽  
Breast Cancers ◽  
Brca1 And Brca2 ◽  
North West ◽  
Pathogenic Variants ◽  
Brca1 Brca2

Early age at diagnosis of breast cancer is a known risk factor for hereditary predisposition and some studies show a high risk of contralateral breast cancer in BRCA1 carriers diagnosed at very young ages. However, little is published on the risk of TP53 carriers. 397 women with breast cancer diagnosed <36 years of age were obtained from three sources: (i) a population-based study of 283 women diagnosed sequentially from 1980–1997 in North-West England, (ii) referrals to the Genomic Medicine Department at St Mary’s Hospital from 1990–2018, and (iii) individuals from (i) and the Family History Clinic at Wythenshawe Hospital South Manchester who tested negative for pathogenic variants (PV) in all three genes. Sequencing of BRCA1, BRCA2, and TP53 genes was carried out alongside tests for copy number for PV on all referred women. Rates of contralateral breast cancer were censored at death, last assessment, or risk-reducing mastectomy. In total, 47 TP53, 218 BRCA1, and 132 BRCA2 PV carriers were identified with breast cancer diagnosed aged 35 years and under, as well as a representative sample of 261 not known to carry a PV in BRCA1, BRCA2, and TP53. Annual rates of contralateral breast cancer (and percentage of synchronous breast cancers) were TP53: 7.03% (4.3%), BRCA1: 3.57% (1.8%), and BRCA2: 2.63% (1.5%). In non-PV carriers, contralateral rates in isolated presumed/tested non-carrier cases with no family history were 0.56%, and for those with a family history, 0.69%. Contralateral breast cancer rates are substantial in TP53, BRCA1, and BRCA2 PV carriers diagnosed with breast cancer aged 35 and under. Women need to be advised to help make informed decisions on contralateral mastectomy, guided by life expectancy from their index tumor.

Incidence of BRCA1 and BRCA2 Mutations in Young Korean Breast Cancer Patients

2004 ◽  
Vol 22 (9) ◽  
pp. 1638-1645 ◽  
Author(s):  
Doo Ho Choi ◽  
Min Hyuk Lee ◽  
Allen E. Bale ◽  
Darryl Carter ◽  
Bruce G. Haffty
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Hormone Receptors ◽  
Young Age ◽  
Korean Women ◽  
Deleterious Mutations ◽  
Breast Cancer Patients ◽  
Brca1 And Brca2 ◽  
Brca2 Mutations ◽  
Brca1 And Brca2 Mutations

Purpose The prevalence of BRCA-associated breast carcinoma in the Korean population has not been evaluated extensively. Methods Sixty Korean women who developed breast cancer by age 40 years were studied. Lymphocyte specimens from peripheral blood were processed for BRCA1 and BRCA2 by complete sequencing. Family history through three generations was obtained. Available paraffin-embedded tissue blocks were processed for immunohistochemical staining. Results In the cohort of 60 patients, nine patients with 11 deleterious mutations (six in BRCA1 and five in BRCA2) and seven missense mutations of unknown significance were found. Two patients had deleterious mutations in both BRCA1 and BRCA2 (double mutant). One half of the mutations were novel, and no founder mutations were observed in this cohort. Most of the BRCA-associated patients had no family history of breast and/or ovarian cancer. The expression of HER-2/neu, cyclin D1, and hormone receptors was less common, and p53 overexpression was more common in BRCA-associated tumors. Conclusion The prevalence of BRCA1 and BRCA2 mutations in Korean women with breast cancer at a young age was high. However, the penetrance, as evidenced by the low frequency of breast and ovarian cancers in family members, appears to be low. These data suggest that there may be different genetic and etiologic factors affecting transmission and penetrance of the BRCA genes in Korean patients with breast cancer diagnosed at a young age.

Roles of Radiotherapy and Chemotherapy in the Development of Contralateral Breast Cancer

2008 ◽  
Vol 26 (34) ◽  
pp. 5561-5568 ◽  
Author(s):  
Maartje J. Hooning ◽  
Berthe M.P. Aleman ◽  
Michael Hauptmann ◽  
Margreet H.A. Baaijens ◽  
Jan G.M. Klijn ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Adjuvant Chemotherapy ◽  
Contralateral Breast Cancer ◽  
Positive Family History ◽  
Young Patients ◽  
Contralateral Breast ◽  
Postmastectomy Radiotherapy ◽  
Increased Risk ◽  
History Of

Purpose Few studies have examined whether modern radiotherapy and chemotherapy affect the risk of contralateral breast cancer (CBC), and results are inconclusive. Patients and Methods We assessed long-term risk of CBC in a predominantly young breast cancer (BC) population (n = 7,221), focusing on the effects of radiation dose, chemotherapy, and family history of BC. Risk of CBC was evaluated using Cox proportional hazards regression models. Results Radiotherapy-associated risk of CBC increased with decreasing age at first treatment (age < 35 years, hazard ratio [HR] = 1.78; 95% CI, 0.85 to 3.72; age > 45 years, HR = 1.09; 95% CI, 0.82 to 1.45). Postmastectomy radiotherapy using direct electron fields led to a significantly lower radiation exposure to the contralateral breast than postlumpectomy radiotherapy using tangential fields. Women treated before age 45 years with postlumpectomy radiotherapy experienced 1.5-fold increased risk of CBC compared with those who had postmastectomy radiotherapy. The joint effects of postlumpectomy radiotherapy and strong family history for BC on risk of CBC were greater than expected when individual risks were summed (HR = 3.52; 95% CI, 2.07 to 6.02; Pdeparture from additivity = .043). Treatment with adjuvant chemotherapy (cyclophosphamide, methotrexate, and fluorouracil) was associated with a nonsignificantly decreased risk of CBC in the first 5 years of follow-up but did not reduce CBC risk in subsequent years. Conclusion Young patients with BC irradiated with breast tangentials experience increased risk of CBC, especially in those with a positive family history of BC. This finding should be taken into account when advising breast radiation with tangential fields to young patients with BC. Adjuvant chemotherapy seemed to reduce the risk of CBC during the first 5 years after treatment only.

scholarly journals Analysis of BRCA1 and BRCA2 mutations in Brazilian breast cancer patients with positive family history

2005 ◽  
Vol 123 (4) ◽  
pp. 192-197 ◽  
Author(s):  
Rozany Mucha Dufloth ◽  
Sílvia Carvalho ◽  
Juliana Karina Heinrich ◽  
Júlia Yoriko Shinzato ◽  
César Cabello dos Santos ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Cancer Patients ◽  
Positive Family History ◽  
Breast Cancer Patients ◽  
Brca1 And Brca2 ◽  
Cancer Susceptibility Genes ◽  
Brca2 Mutations ◽  
Exon 11 ◽  
Brca1 And Brca2 Mutations

CONTEXT AND OBJECTIVE: BRCA1 and BRCA2 are the two principal hereditary breast cancer susceptibility genes, and the prevalence of their mutations among Brazilian women is unknown. The objective was to detect BRCA1 and BRCA2 mutations in Brazilian patients with breast cancer, so as to establish genetic profiles. DESIGN AND SETTING: Cross-sectional study, in Centro de Atenção Integral à Saúde da Mulher, Universidade Estadual de Campinas, Brazil, and Institute of Pathology and Molecular Immunology, University of Porto, Portugal. METHODS: Thirty-one breast cancer patients with positive family history (criteria from the Breast Cancer Linkage Consortium) were studied, and genomic DNA was extracted from peripheral blood. Single-strand conformation polymorphism was used for the analysis of exons 2, 3, 5, and 20 of BRCA1. Cases showing PCR products with abnormal bands were sequenced. Exon 11 of BRCA1 and exons 10 and 11 of BRCA2 were directly sequenced in both directions. RESULTS: Four mutations were detected: one in BRCA1 and three in BRCA2. The BRCA1 mutation is a frameshift located at codon 1756 of exon 20: 5382 ins C. Two BRCA2 mutations were nonsense mutations located at exon 11: S2219X and the other was an unclassified variant located at exon 11: C1290Y. CONCLUSION: The BRCA1 or BRCA2 mutation prevalence found among women with breast cancer and such family history was 13% (4/31). Larger studies are needed to establish the significance of BRCA mutations among Brazilian women and the prevalence of specific mutations.

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