Detecting prostate cancer in BRCA1 and BRCA2 mutation carriers: A role for EN2?

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4653-4653
Author(s):  
Emma Killick ◽  
Richard Morgan ◽  
Francesca Launchbury ◽  
Nicola E. Annels ◽  
Elizabeth Bancroft ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Risk Group ◽  
Brca Mutation ◽  
Brca2 Mutation ◽  
Digital Rectal Examination ◽  
Brca1 And Brca2 ◽  
Mutation Carriers ◽  
Increased Risk ◽  
Brca Mutation Carriers ◽  
The Impact

4653 Background: EN2 is part of the HOX gene family and plays a role in foetal development. More recently a potential oncogenic role for the protein has been postulated and its utility as a cancer biomarker has been explored in prostate cancer (PrCa) and breast cancer. Carriers of mutations in the BRCA1 and BRCA2 genes have an increased risk of PrCa (1.8-fold and 5-fold respectively) and their tumours tend to be more aggressive and advanced than sporadic cases. Currently there is no national screening program for BRCA mutation carriers in the UK, and the IMPACT study was set up to evaluate PSA screening in this particular group. Here we analyse the efficacy of the urinary EN2 protein as a marker of early cancer detection within this higher risk group. Methods: First pass urine (without preceding digital rectal examination) was collected as part of the IMPACT screening study which enrolled individuals aged between 40 and 69 who were unaffected by PrCa at time of enrolment into the study (n= 418). All participants were from families harbouring a BRCA1 or BRCA2 mutation and were either BRCA mutation carriers themselves or controls with a negative predictive BRCA genetic test. They underwent annual PSA test with a PSA of > 3.0 ng/ml triggering a diagnostic biopsy. EN2 protein was measured in the urine using an ELISA; (positive = > 42.5ng/ml). Results: Our initial results demonstrated urinary EN2 had a sensitivity of 66.67% and a specificity of 89.29% when discriminating which men had been diagnosed with PrCa; the ROC AUC was 0.816. The difference in EN2 level between those diagnosed with cancer and those who were not was significant (p = <0.001). There was trend towards higher EN2 levels in those with more aggressive tumours (median EN2 84.5ng/mL in Gleason ≤3+4 vs 111ng/mL in Gleason ≥4+3), however this was not statistically significant. In one PrCa case EN2 rise preceded PSA rise by 2 years. Further samples are in the process of being analysed, results from these will be included. Conclusions: Urinary EN2 protein measurement warrants further investigation as a PrCa biomarker in this higher risk group with genetic predisposition to PrCa.

How to manage BRCA mutation carriers?

2020 ◽  
Vol 41 (3) ◽  
Author(s):  
Laura Sabiani ◽  
Julien Barrou ◽  
Jérome Mathis ◽  
Francois Eisinger ◽  
Marie Bannier ◽  
...  
Keyword(s):  
Brca Mutation ◽  
Brca1 Mutation ◽  
Brca2 Mutation ◽  
Immediate Breast Reconstruction ◽  
Bilateral Mastectomy ◽  
Brca1 And Brca2 ◽  
Mutation Carriers ◽  
Brca Mutation Carriers ◽  
The Impact ◽  
Risk Reducing

AbstractInherited mutations in BRCA1 and BRCA2 genes increase the risk of development of cancer in organs especially in breast and ovary. Prevention and screening in BRCA mutation carriers are of high importance. Prophylactic surgeries are possible but are still insufficiently performed because they require surgical procedures in healthy patients. Guidelines for the management of BRCA mutations carriers must absolutely be part of the standard practice of all those involved in the management of these patients to increase the impact of the implementation of these preventive measures. There is no screening recommended for ovarian cancer. A risk-reducing bilateral salpingo-oophorectomy should be performed from age 35 to 40 years for BRCA1 mutation carriers and 40 to 45 years for BRCA2 mutation carriers. A screening for breast cancer should be performed annually from 30 years old by breast MRI and mammography. A risk-reducing bilateral mastectomy is recommended with nipple sparing mastectomy and immediate breast reconstruction from 30 years and before 40 years. A multidisciplinary care must be implemented for these patients with an important psychological support.

scholarly journals Management Options after Prophylactic Surgeries in Women with BRCA Mutations: A Review

2007 ◽  
Vol 14 (4) ◽  
pp. 330-337 ◽  
Author(s):  
Dawn C. Allain ◽  
Kevin Sweet ◽  
Doreen M. Agnese
Keyword(s):  
Medical Management ◽  
Cancer Susceptibility ◽  
Brca Mutation ◽  
Brca2 Gene ◽  
Brca1 And Brca2 ◽  
Management Options ◽  
Cancer Susceptibility Genes ◽  
Mutation Carriers ◽  
Increased Risk ◽  
Brca Mutation Carriers

Background Although breast cancer is relatively common, only about 5% of cases are due to inheritance of highly penetrant cancer susceptibility genes. The majority of these are caused by mutations in the BRCA1 and BRCA2 genes, which are also associated with an increased risk of ovarian cancer. Increased surveillance, chemoprevention, and prophylactic surgeries are standard options for the effective medical management of mutation carriers. However, optimal management of female carriers who choose to undergo prophylactic surgeries is still poorly understood. Methods The authors provide an overview of the current literature regarding medical management options for women carriers of BRCA1 and BRCA2 gene mutations and the implications for those individuals who have chosen to undergo prophylactic surgeries. Results BRCA mutation carriers who opt for prophylactic surgeries are still at risk for development of malignancy, and appropriate monitoring is warranted. Conclusions There are limited data on the appropriate medical management for BRCA mutation carriers after prophylactic surgeries. However, a management plan can be extrapolated from the general management recommendations for surveillance and other risk-reducing strategies in BRCA-positive individuals.

An exploratory study to determine if BRCA1 and BRCA2 mutation carriers have higher risk of cardiac toxicity.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1585-1585 ◽  
Author(s):  
Roohi Ismail-Khan ◽  
Monique Sajjad ◽  
Weihong Sun ◽  
Hatem Hussein Soliman ◽  
Hyo S. Han ◽  
...  
Keyword(s):  
Breast Cancer ◽  
General Population ◽  
Exploratory Study ◽  
Online Survey ◽  
Cardiac Toxicity ◽  
Brca Mutation ◽  
Brca2 Mutation ◽  
Mutation Carriers ◽  
Increased Risk ◽  
Brca Mutation Carriers

1585 Background: Anthracycline related cardiac toxicity (CT) is a concern in treating women with breast cancer. The prevalence of heart failure (HF) affects 2% of the population, less so in women. Patients receiving anthracycline based therapy (ABT) have a dose-dependent risk of reduction in ejection fraction. Recent work by Dr. Verma suggests that BRCA-deficient mice manifest increased levels of cardiac failure. We sought to explore the risk for CT and evaluate the association between ABT and HF in female BRCA mutation carriers. Methods: An online survey was developed to collect information about breast cancer treatment (including HF) in BRCA mutation carriers through the national BRCA patient advocacy organization FORCE via their 2011 conference and their website as well as the Moffitt-based Inherited Cancer Registry (ICARE). The prevalence of CT and HF was calculated in both BRCA 1 and 2 breast cancer patients and compared to general population risks. Data from those that received ABT was compared to published HF rates from ABT. Results: Our sample included 227 BRCA1 carriers and 164 BRCA2 carriers in whom 6.4% reported cardiac toxicity (i.e., either HF and/or CT). This included similar proportions in BRCA1 vs BRCA2 carriers (i.e., 6.6% and 6.1%, respectively). These proportions are significantly higher than the published rate of 2% (all p-values < 0.001). Specifically regarding ABT, 112 mutation carriers had doxorubicin (Adriamycin) for treatment of whom 8% reported HF, similar to the 11 who had Epirubicin (11 patients), of whom 9% reported HF. Conclusions: Our data suggests that BRCA mutation carriers may have an increased risk of CT compared to the general population. In particular, women with BRCA mutations treated with ABT also appear to have a higher risk of developing CT and/or HF. This exploratory study provides the basis upon which larger retrospective and prospective studies are currently being planned. The high percentage of CT observed in this study requires confirmation as they could inform recommendation for cardiac screening and review of the current standard for ABT use in this population.

scholarly journals Update on chemoprevention in BRCA1 and BRCA2 mutation carriers

2005 ◽  
Vol 8 (9) ◽  
Author(s):  
M. Stumacher ◽  
S. M. Domchek
Keyword(s):  
Breast Cancer ◽  
Prophylactic Mastectomy ◽  
Brca Mutation ◽  
Brca2 Mutation ◽  
Breast Cancers ◽  
Brca1 And Brca2 ◽  
Prophylactic Oophorectomy ◽  
Estrogen Exposure ◽  
Mutation Carriers ◽  
Increased Risk

Chemoprevention with tamoxifen and oophorectomy are thought to be effective in decreasing the incidence of breast cancer in women at increased risk for the disease. There is mounting data supporting the idea that hormonal interventions that reduce estrogen exposure to breast epithelium, such as prophylactic oophorectomy and tamoxifen, are effective in breast cancer prevention in both BRCA1 and BRCA2 mutations carriers. Several recent studies directly address the protective effect of tamoxifen and oophorectomy in BRCA mutation carriers and suggest that these endocrine manipulations decrease the risk of primary and secondary breast cancers. Ongoing studies aim to better define the effect of tamoxifen in these very high-risk women and determining whether factors, such as earlier age of use or prior prophylactic oophorectomy, impact tamoxifen's effect. Based on existing data, we recommend that women with deleterious mutations in BRCA1 or BRCA2 be informed of the beneficial effect of oophorectomy on breast cancer risk and that women who choose breast cancer screening instead of prophylactic mastectomy be offered tamoxifen as a prevention option.

Is mammography adequate for screening BRCA mutation carriers with low breast density?

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10014-10014 ◽  
Author(s):  
R. Bigenwald ◽  
E. Warner ◽  
A. Gunasekara ◽  
K. Hill ◽  
P. Causer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Density ◽  
Brca Mutation ◽  
Brca1 Mutation ◽  
Brca2 Mutation ◽  
Brca1 And Brca2 ◽  
Younger Women ◽  
Mutation Carriers ◽  
Brca Mutation Carriers

10014 Background: Several large observational studies have demonstrated that magnetic resonance imaging (MRI) is much more sensitive than M (sensitivity 71–96% vs. 28–43%) for screening women > age 25 at high risk for hereditary breast cancer. However, MRI is much more costly and less specific than M. The extent to which the low sensitivity of M in these studies is due to the greater average breast density of younger women is unknown. Accordingly, we sought to determine the sensitivity of M and MRI according to breast density for the detection of breast cancer in a screening study of BRCA mutation carriers. Methods: Breast density was measured on the screening mammogram of the contralateral breast for all women who developed in-situ or invasive breast cancer on study. Density was measured in 2 ways: qualitatively according to the four categories characterized by the BIRADS system: 1) mostly fatty, 2) scattered fibroglandular tissue, 3) heterogeneously dense, 4) extremely dense; and semi-quantitatively using computer-aided techniques with subsequent classification as: A) ≤10%, B) 11–25%, C) 26%-50%, or D) >50% density. Results: Between 11/97 and 06/05 a total of 39 cases (12 in-situ and 27 invasive) were found in 36 mutation carriers (19 BRCA1 and 17 BRCA2). Mean age of the women with cancer was 48 (range 34 to 64). Average semi-quantitative breast density for BRCA1 mutation carriers was 28% and for BRCA2 was 27%. Sensitivity of M vs. MRI for in-situ cases was 25% vs. 83%, and for invasive cases was 30% vs. 93%. Sensitivities for BRCA1 and BRCA2 mutation carriers were similar. For BIRADS 1 to 4 respectively M detected 1/3 (33%), 5/11 (45%), 4/22 (18%), and 1/3 (33%) of cases; and for density groups A to D respectively detected 2/6 (33%), 7/15 (47%), 1/11 (9%) and, 1/7 (14%). Conclusion: Although there was a trend towards decreasing mammographic sensitivity with increasing density, even among BRCA mutation carriers with low breast density mammography is an inadequate screening tool. No significant financial relationships to disclose.

scholarly journals Targeted Prostate Cancer Screening in BRCA1 and BRCA2 Mutation Carriers: Results from the Initial Screening Round of the IMPACT Study

2014 ◽  
Vol 66 (3) ◽  
pp. 489-499 ◽  
Author(s):  
Elizabeth K. Bancroft ◽  
Elizabeth C. Page ◽  
Elena Castro ◽  
Hans Lilja ◽  
Andrew Vickers ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Screening ◽  
Prostate Cancer Screening ◽  
Brca2 Mutation ◽  
Impact Study ◽  
Initial Screening ◽  
Brca1 And Brca2 ◽  
Mutation Carriers ◽  
The Impact

Increased risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers after breast-conserving therapy compared to mastectomy

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1512-1512
Author(s):  
R. K. Schmutzler ◽  
M. K. Graeser ◽  
K. Rhiem ◽  
B. Schlehe ◽  
W. Hofmann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Contralateral Breast Cancer ◽  
Brca Mutation ◽  
Brca2 Mutation ◽  
Breast Conserving Therapy ◽  
Contralateral Breast ◽  
Cox Regression Analysis ◽  
Mutation Carriers ◽  
Increased Risk ◽  
Brca Mutation Carriers

1512 Background: BRCA mutation carriers affected by breast cancer face an elevated risk of contralateral breast cancer (clBrCa). We here aimed at estimating the influence of breast conserving therapy (BCT) versus mastectomy (MXT) on the rik of clBrCa. Methods: We conducted a retrospective cohort study in 3810 index patients (pts) collected within the CHBOC. Deleterious BRCA1 or BRCA2 mutations were detected in 921 pts and medical records were obtained from 532 pts (344 BRCA1, 184 BRCA2 mutation carriers, 4 both) of whom 261 (49%) underwent BCT and 271 (51%) MXT. Pts were followed from the initial diagnosis of breast cancer until clBrCa or censored at time of prophylactic contralateral mastectomy, oophorectomy, death, or date of last visit. Median age at first diagnosis was 39.9 years (range 17.5 to 79.0) and median follow up 48.84 months (3413 person years). The hazard ratio (HR) was estimated using multivariate Cox regression analysis adjusting for conduct of radiotherapy, age at first breast cancer, and affected BRCA gene. Results: In the univariate analysis the risk of clBrCa was 12.2% (95% CI 7.6 to 16.8) at 5 years and 24.9% (95% CI 18.0 to 31.9) at 10 years for pts treated with MXT and 25.9% (95% CI 18.8 to 33.1) at 5 years and 45.7% (95% CI 35.0 to 56.5) at 10 years for pts treated with BCT. In the multivariate analysis, the HR was 1.8 for BCT versus MXT (95% CI 1.2 to 2.7). Neither age at diagnosis of the first primary nor BRCA mutation status were significantly predictive. A subgroup analysis comparing BCT plus radiotherapy with MXT minus radiotherapy revealed a HR of 1.6 (95% CI 1.02 to 2.56) for the BCT group. Conclusions: We report for the first time a 1.8-fold increased risk of clBrCa in BRCA mutation carriers undergoing BCT versus MXT. Scattered radiation is the most probable causation. Although results from further studies such as the WECARE study should be awaited, our results provide evidence that recommendations for primary brCa treatment of BRCA mutation carriers must to be reconsidered. No significant financial relationships to disclose.

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