Preferences for breast cancer prevention among BRCA mutation carriers

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 17018-17018
Author(s):  
J. Jacobson ◽  
P. Patel ◽  
A. Bharthuar ◽  
D. Hershman ◽  
K. Hill ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Regression Models ◽  
Pairwise Comparisons ◽  
Carrier Status ◽  
Health States ◽  
Mutation Status ◽  
Logistic Regression Models ◽  
Mutation Carriers ◽  
Brca 1

17018 Purpose: Breast cancer screening with MRI is a new option available to patients with BRCA 1/2 mutations. We analyzed preferences for this modality and 10 other breast cancer- related health states and preventive measures among women without cancer or known high risk and women with BRCA mutations. Methods: Following IRB approval, we administered a time trade-off questionnaire to mutation carriers and to women without breast cancer or known high risk. We used Kruskal-Wallis test to compare the two groups with respect to continuous variables, chi-square tests to compare proportions, and the Wilcoxon signed rank test for pairwise comparisons. We then developed logistic regression models to analyze the association of mutation carrier status and demographic factors with willingness to trade time for each of the 11 health states. Results: Two-hundred-four women (44 mutation carriers and 160 without breast cancer or known high risk) responded to the questionnaire. Both groups assigned the highest preference rating to mammography and the next-highest to MRI, but the differences in ratings were not statistically significant. Both groups assigned the lowest preference ratings to having a child with a mutation and the next lowest to ovarian cancer. In pairwise comparisons, both groups ranked oophorectomy higher than ovarian cancer (p <0.01), but mutation carriers did not rank prophylactic mastectomy significantly differently from breast cancer (p=0.38). In the logistic regression models, mutation carrier status was not a statistically significant predictor of willingness to trade time for any health state, but younger age, lower income, and nonwhite race/ethnicity were associated with willingness to trade time for certain health states. Conclusion: Our data indicate that MRI is as acceptable as mammography to respondents, and that the preferences of BRCA 1/2 mutation carriers are similar to those of other women. Age and other demographic factors may be more important than mutation status in determining preferences. The preference ratings of individuals should not be inferred from demographic characteristics or mutation status. However, such ratings can help to clarify the quality of life implications of clinical decision-making and health care policy regarding breast cancer prevention. No significant financial relationships to disclose.

BRCA1 and BRCA2 germline mutation carriers have a lower breast density compared to high risk women without such mutations

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1517-1517
Author(s):  
P. Sharma ◽  
J. R. Klemp ◽  
B. F. Kimler ◽  
Q. J. Khan ◽  
E. J. Smith ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
High Risk ◽  
Breast Density ◽  
Genetic Factors ◽  
Mammographic Breast Density ◽  
Mutation Status ◽  
High Risk Women ◽  
Mutation Carriers ◽  
Chi Square Analysis

1517 Background: High mammographic breast density, a known risk factor for breast cancer is influenced by both genetic and non genetic factors. It is not clear if there are differences in breast densities between BRCA1/2 mutation carriers and high-risk non carriers. The aim of this study was to compare breast density in high-risk women with and without BRCA1/2 mutation. Methods: Women at high risk for development of breast cancer (based on family history, prior precancerous disease or prior breast cancer) who underwent genetic testing at the University of Kansas Breast Cancer Prevention Center between 1998 and 2005 were identified under an IRB approved protocol. BRCA1/2 full sequencing was performed at Myriad Genetic Laboratories. The earliest digitized mammogram of these subjects was identified from a preexisting mammogram database. All mammograms had to be prior to/at least one year from any chemoprevention intervention. For subjects with prior breast cancer, mammogram of the uninvolved breast was used. Breast density was assessed on the left craniocaudal mammographic view by computer assisted method, Cumulus. Frequencies of categorical variables were assessed using chi-square analysis. Continuous variables were assessed using Mann-Whitney non parametric test. Multiple regression analysis was used to investigate whether differences are due to variables other than mutation status. Results: The study population consisted of 284 high-risk women who underwent BRCA1/2 testing and for whom a mammogram was available. 30 (11%) had BRCA1 and/or 2 deleterious mutation. There was no difference between mutation carriers and non-carriers for BMI, 5 year Gail risk, parity, menopausal status and HRT use. Mutation carriers were younger (median age 42 vs. 46, p=0.020) and more likely to have a positive family history (100% vs. 85%, p=0.020). Older age (p<0.001), higher BMI (p<0.001) and having a BRCA1/2 mutation (p=0.025) were significantly associated with a lower breast density. Conclusion: Among high risk women, possession of a deleterious BRCA1/2 mutation is associated with lower breast density after adjusting for factors known to affect breast density. This suggests that breast density may be governed by genetic factors other than BRCA1/2 mutation status. No significant financial relationships to disclose.

scholarly journals Male Breast Cancer: Surgical and Genetic Features and a Multidisciplinary Management Strategy

Breast Care ◽  
2019 ◽  
Vol 15 (1) ◽  
pp. 14-21 ◽  
Author(s):  
Francesca Pellini ◽  
Eleonora Granuzzo ◽  
Silvia Urbani ◽  
Sara Mirandola ◽  
Marina Caldana ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
High Risk ◽  
Male Breast Cancer ◽  
Brca2 Mutation ◽  
Positive Family History ◽  
Male Breast ◽  
Mutation Carriers ◽  
History Of ◽  
Clinical Records

Background: Male breast cancer (MBC) is a rare disease with a rising incidence trend. The major risk factors related to MBC are a positive family history of breast cancer (BC) and BRCA1/2 mutations, which indicate a relevant genetic role. Methods: In this retrospective series, we enrolled 69 male patients presenting with male breast cancer (MBC) between 01/01/1992 and 31/12/2018, and 26 high-risk not-affected men presenting between 01/01/2016 and 31/12/2018. Participants’ electronic clinical records were reviewed. Patients’ data reported age at diagnosis, tumor characteristics, therapeutic management, and BRCA1/2 status as well as a family history of breast, ovarian, or prostate cancer (PCa) in first-degree relatives. Results: We analyzed 69 MBC patients. Median age was 64 years. The majority of tumors diagnosed were of an early TNM stage. The most frequent histological subtype was invasive ductal carcinoma (76.7%). Hormone receptors were positive in >90% of MBC cases. Nearly all patients underwent modified radical mastectomy or total mastectomy. Adjuvant endocrine therapy was delivered in 59.4%. Among MBC-affected patients, we recorded a high percentage of a positive family history of BC. Mutational analysis for the BRCA1/2 genes was performed in 17 MBC patients; 11.8% were carriers of BRCA2 pathogenic mutations. Among 26 healthy high-risk subjects included in this case series, 4 were BRCA1 mutation carriers and 9 were BRCA2 mutation carriers. Discussion: We evaluated the distribution of clinicopathological characteristics in MBC subjects and assessed the frequency of mutations in the BRCA genes in affected patients and healthy high-risk subjects, with the aim of proposing a surveillance program for BC and PCa.

scholarly journals A Simple Clinical Tool for Stratifying Risk of Clinically Significant CKD after Nephrectomy: Development and Multinational Validation

2020 ◽  
Vol 31 (5) ◽  
pp. 1107-1117 ◽  
Author(s):  
Robert J. Ellis ◽  
Sharon J. Del Vecchio ◽  
Kevin M.J. Gallagher ◽  
Danielle N. Aliano ◽  
Neil Barber ◽  
...  
Keyword(s):  
High Risk ◽  
Kidney Cancer ◽  
Regression Models ◽  
Population Based ◽  
Risk Category ◽  
Shared Decision ◽  
Clinical Tool ◽  
Kidney Tumors ◽  
Logistic Regression Models ◽  
Clinically Significant

BackgroundClinically significant CKD following surgery for kidney cancer is associated with increased morbidity and mortality, but identifying patients at increased CKD risk remains difficult. Simple methods to stratify risk of clinically significant CKD after nephrectomy are needed.MethodsTo develop a tool for stratifying patients’ risk of CKD arising after surgery for kidney cancer, we tested models in a population-based cohort of 699 patients with kidney cancer in Queensland, Australia (2012–2013). We validated these models in a population-based cohort of 423 patients from Victoria, Australia, and in patient cohorts from single centers in Queensland, Scotland, and England. Eligible patients had two functioning kidneys and a preoperative eGFR ≥60 ml/min per 1.73 m2. The main outcome was incident eGFR <45 ml/min per 1.73 m2 at 12 months postnephrectomy. We used prespecified predictors—age ≥65 years old, diabetes mellitus, preoperative eGFR, and nephrectomy type (partial/radical)—to fit logistic regression models and grouped patients according to degree of risk of clinically significant CKD (negligible, low, moderate, or high risk).ResultsAbsolute risks of stage 3b or higher CKD were <2%, 3% to 14%, 21% to 26%, and 46% to 69% across the four strata of negligible, low, moderate, and high risk, respectively. The negative predictive value of the negligible risk category was 98.9% for clinically significant CKD. The c statistic for this score ranged from 0.84 to 0.88 across derivation and validation cohorts.ConclusionsOur simple scoring system can reproducibly stratify postnephrectomy CKD risk on the basis of readily available parameters. This clinical tool’s quantitative assessment of CKD risk may be weighed against other considerations when planning management of kidney tumors and help inform shared decision making between clinicians and patients.

BRCA 1/2 mutations by next-generation sequencing testing in 200 Romanian high-risk patients with breast cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e13116-e13116
Author(s):  
Alexandru E. Eniu ◽  
Nicoleta Zenovia Antone ◽  
Andrei Stoian ◽  
Eleonora Dronca ◽  
Ramona DOINA Matei ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Prospective Study ◽  
Cancer Patients ◽  
Breast Cancer Patients ◽  
Brca 1 ◽  
Brca1 Brca2 ◽  
High Risk Breast Cancer ◽  
High Risk Breast ◽  
Risk Breast Cancer

e13116 Background: To determine types and frequencies of BRCA 1 (B1) or BRCA2 (B2) mutations in high-risk Romanian breast cancer patients, as there is no data published in this population. Methods: This prospective study evaluates the germline BRCA1/BRCA2 mutations in 200 Romanian high-risk breast cancer patients tested between February 2015-January 2017 at IOCN. Inclusion criteria selected patients diagnosed with breast cancer before 40 years, triple negative breast cancer under the age of 50, or having conventional family history criteria. All patients signed an informed consent. BRCA1/BRCA2 testing was performed using an AmpliSeq-based sequencing analysis, on the Ion Torrent Personal Genome Machine (Life Technologies) at RCFG. The pathogenic mutations were validated using Sanger technology. MLPA was performed for all 200 patients. Results: We analyzed 200 high-risk breast cancer patients and found 32 (16%) patients with pathogenic mutations, 23 (11.5%) patients with B1 and 9 (4.5%) patients with B2 mutations. The majority of patients (99.5%) presented normal MLPA results; only one sample (0.5%) presented a deletion at CHEK2-9(10). The frequency of class 5 mutations identified in B1 gene were c.1687C > T (1%), c.181T > G (2%), c.3607C > T (3.5%), c.4218delG (0.5%), c.5329_5330insC (c.5266dupC) (4.5%) and for the B2 gene c.1528G > T (0.5%), c.4022C > G (0.5%), c.7007G > A (0.5%), c.8695C > T (0.5%), c.9253 delA (0.5%), c.9371A > T (2%). Conclusions: Frequency of deleterious BRCA mutations in our cohort was 11.5% for BRCA1 and 4.5% for BRCA2. This prospective study presents the first extensive results on frequency and types of germline BRCA1/2 mutations in Romanian high-risk breast cancer patients. Clinical trial information: NCT02317120. [Table: see text]

Ten-Year Multi-Institutional Results of Breast-Conserving Surgery and Radiotherapy in BRCA1/2-Associated Stage I/II Breast Cancer

2006 ◽  
Vol 24 (16) ◽  
pp. 2437-2443 ◽  
Author(s):  
Lori J. Pierce ◽  
Albert M. Levin ◽  
Timothy R. Rebbeck ◽  
Merav A. Ben-David ◽  
Eitan Friedman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Conservation ◽  
Breast Conserving Surgery ◽  
Breast Conservation Surgery ◽  
Breast Cancers ◽  
Mutation Status ◽  
High Risk Women ◽  
Mutation Carriers ◽  
Significant Difference

Purpose We compared the outcome of breast-conserving surgery and radiotherapy in BRCA1/2 mutation carriers with breast cancer versus that of matched sporadic controls. Methods A total of 160 BRCA1/2 mutation carriers with breast cancer were matched with 445 controls with sporadic breast cancer. Primary end points were rates of in-breast tumor recurrence (IBTR) and contralateral breast cancers (CBCs). Median follow-up was 7.9 years for mutation carriers and 6.7 years for controls. Results There was no significant difference in IBTR overall between carriers and controls; 10- and 15-year estimates were 12% and 24% for carriers and 9% and 17% for controls, respectively (hazard ratio [HR], 1.37; P = .19). Multivariate analyses for IBTR found BRCA1/2 mutation status to be an independent predictor of IBTR when carriers who had undergone oophorectomy were removed from analysis (HR, 1.99; P = .04); the incidence of IBTR in carriers who had undergone oophorectomy was not significantly different from that in sporadic controls (P = .37). CBCs were significantly greater in carriers versus controls, with 10- and 15-year estimates of 26% and 39% for carriers and 3% and 7% for controls, respectively (HR, 10.43; P < .0001). Tamoxifen use significantly reduced risk of CBCs in mutation carriers (HR, 0.31; P = .05). Conclusion IBTR risk at 10 years is similar in BRCA1/2 carriers treated with breast conservation surgery who undergo oophorectomy versus sporadic controls. As expected, CBCs are significantly increased in carriers. Although the incidence of CBCs was significantly reduced in mutation carriers who received tamoxifen, this rate remained significantly greater than in controls. Additional strategies are needed to reduce contralateral cancers in these high-risk women.

scholarly journals Aromatase Inhibitors and Contralateral Breast Cancer in BRCA Mutation Carriers: A long-term Follow-up

2021 ◽  
Author(s):  
Maryam Nemati Shafaee ◽  
Kristina Goutsouliak ◽  
Heather Lin ◽  
Therese B Bevers ◽  
Angelica Gutierrez-Barrera ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Aromatase Inhibitors ◽  
Prophylactic Mastectomy ◽  
Brca Mutation ◽  
Brca1 Mutation ◽  
Brca2 Mutation ◽  
Mutation Status ◽  
Mutation Carriers ◽  
Brca Mutation Carriers

Abstract Background: Deleterious BRCA mutations confer a significant lifetime risk of breast cancer (BC) as well as contralateral BC (CBC) in patients who do not undergo prophylactic mastectomy. Prior reports have suggested that tamoxifen reduces the risk of CBC in BRCA mutation carriers. Whether aromatase inhibitors (AI) have the same effect is unknown. Methods: This is a retrospective review of patients diagnosed with non-metastatic ER+ BC between 2004-2014 with known BRCA mutation status. Patients were followed from primary diagnosis until CBC diagnosis or death. Median follow up was 11.5 years. Risk of CBC was evaluated as time to event. Results: 935 subjects were included in this analysis, with 53 BRCA1 mutation carriers, and 94 BRCA2 mutation carriers. Median age at diagnosis was 42.7 years. Seventy-two percent (676) received tamoxifen and 43% (405) received AI. A total of 66 CBCs occurred, of which 10% (15/147) occurred in BRCA mutation carriers vs %6.5 (51/788) in BRCA wild type. Multivariate analyses indicated that BRCA status and AI use were significantly associated with CBC risk. AI use resulted in a significant reduction in risk of CBC (HR 0.44, p=0.004) regardless of the BRCA mutation status. Tamoxifen use was not associated with reduced risk of CBC. Conclusions: This is the first report showing that AIs reduce the risk of CBC in BRCA mutation carriers. The potential role of AIs as chemoprevention should be validated in larger independent cohorts.

Germline mutation status and therapy response in high-risk early breast cancer: Results of the GeparOcto study (NCT02125344).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 573-573 ◽  
Author(s):  
Esther Pohl-Rescigno ◽  
Jan Hauke ◽  
Kerstin Rhiem ◽  
Volker Möbus ◽  
Jenny Furlanetto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Early Breast Cancer ◽  
Germline Mutation ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Pegylated Liposomal Doxorubicin ◽  
Therapy Response ◽  
Mutation Status ◽  
Predisposition Genes

573 Background: GeparOcto compared the efficacy of two neoadjuvant treatment (NAT) regimens in high-risk early breast cancer (BC): Sequential intense dose-dense epirubicin, paclitaxel, and cyclophosphamide (iddEPC) and weekly paclitaxel plus non-pegylated liposomal doxorubicin (PM), plus carboplatin (PMCb) in triple-negative BC (TNBC). There was no difference in pathologic complete response (pCR) rates (Schneeweiss et al. Eur J Cancer 2019). Here, we stratified pCR rates according to germline mutation status. Methods: Germline (g) mutation analysis of BRCA1/2 and 16 further BC predisposition genes in 914 patients (pts) enrolled (393 pts with TNBC, iddEPC n = 194, PMCb n = 199; 156 pts with HER2-/HR+ BC, iddEPC n = 75, PM n = 81; and 365 pts with HER2+ BC, iddEPC n = 182, PM n = 183). Results: The gBRCA1/2 mutation prevalence was 17.6% in TNBC, 14.1% in HER2-/HR+ BC and 1.4% in HER2+ BC. Overall, pts with gBRCA1/2 mutations achieved higher pCR rates than gBRCA1/2 wildtype pts (60.4% vs 46.7%, OR 1.74, P = 0.012), with more pronounced effects in the PM(Cb) arm (68.1% vs 45.7%, OR 2.53, P = 0.005). Among gBRCA1/2 wildtype pts, 76 carried mutations in non- BRCA1/2 predisposition genes. pCR rates were similar to those observed in pts without any mutation. Conclusions: Pts with gBRCA1/2 mutations benefitted most from NAT with highest pCR rates achieved in the gBRCA1/2 TNBC / PMCb group. The role of Cb for NAT of gBRCA1/2 TNBC should be further explored. Clinical trial information: NCT02125344. [Table: see text]

Omitting chemotherapy in more patients with early breast cancer in the post-TAILORx era.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12534-e12534
Author(s):  
Christos Markopoulos ◽  
Zoi Andromahi Sariyanni ◽  
Dimitrios C. Ziogas ◽  
Zoh Antonopoulou ◽  
Nikolaos Tsoulos
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Regression Models ◽  
Recurrence Score ◽  
Treatment Decisions ◽  
Oncotype Dx ◽  
Logistic Regression Models ◽  
Previously Treated ◽  
High Clinical Risk

e12534 Background: The purpose of this analysis is to evaluate how many patients previously treated according to OncotypeDX Recurrence Score (RS) could have been spared of Chemotherapy if the TAILORx RS data had been taken into account in the clinical treatment decisions. Methods: A series of 182 patients, 34-74 years of age with early breast cancer, treated in our Breast Unit during the last 10 years, for whom treatment decisions were based on OncotypeDX RS. The Recurrence Scores of all these patients were obtained and the actual treatment decisions that were made based on the pre-TAILORx cut-offs of RS 18 and 31 were recorded. These decisions were then re-evaluated based on the after TAILORx cut-off scores, by taking also into consideration the patients’ age. Descriptive statistics were used as well as logistic regression models to estimate the potential change in treatment decisions based on the new Oncotype Dx cut-offs. Results: In the cohort of patients we analyzed that underwent Oncotype Dx testing, 34.1% (62/182) received Chemotherapy, based on the initial pre-TAILORX cut-offs of the RS. When utilizing the new cut-offs (after TAILORx results) in combination with age, we have estimated that, for the patients > 50 years of age, a 12.7% was potentially over-treated and for those ≤50 years old, 9.1% was potentially over-treated since they have received chemotherapy with a RS below 16; additionally, 30.8% of the patients of that age that have RS between 16 and 20 have received chemotherapy even though the average chemotherapy benefit for this group is 1.6% and can go up to 6.7% if they have a high clinical risk as it was defined by the investigators of the TAILORx trial. Finally, 84,6% of patients ≤50 years old with RS between 21-25 received chemotherapy with a 6.5% potential benefit demonstrated in the TAILORx trial. Conclusions: Our analysis suggests that, by using the cut-offs of TAILORx trial, adjuvant chemotherapy could had been omitted in at least a further 11.5% of patients with early breast cancer, reassuring their quality of life without declining their prognosis.

Sign in / Sign up

Export Citation Format

Share Document