Perception of screening and risk reduction surgeries in patients tested for a BRCA deleterious mutation
Jennifer K. LittonShannon N. WestinKaylene ReadyCharlotte C. SunSusan K. PetersonFunda Meric‐BernstamAna M. Gonzalez‐AnguloDiane C. BodurkaKaren H. LuGabriel N. HortobágyiBanu K. Arun
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Abstract BACKGROUND: Women at a high risk for breast cancer are offered choices for screening or prophylactic surgeries. The aim of this study was to evaluate opinions regarding screening and surgical strategies in high‐risk women. METHODS: Women at the authors' institution who received BRCA1 of 2 testing before July 2005 were sent a follow‐up patient survey. The authors compared responses of women who tested positive for a deleterious mutation with those who tested negative. For those who expressed an opinion (agree vs disagree), a 2‐sided Fisher exact test was used to compare responses. RESULTS: A total of 540 surveys were sent, and 312 were returned (58%). Of these, 217 had breast cancer, and 86 women tested positive for a mutation. No BRCA + women felt mammograms were difficult to get because of discomfort, whereas 5.4% of the BRCA − group did ( P = .039). Seventy percent of BRCA + women agreed that prophylactic mastectomy (PM) is the most effective means for reducing risk, compared with 40% of BRCA − women ( P < .001). PM was felt to be the only way to reduce worry in 64.7% of BRCA + and in 34.4% of BRCA − women ( P < .001). PM was felt to be too drastic for 36.1% of BRCA + and 40.5% of BRCA − women ( P = .562). Difficulty in deciding between screening and PM occurred in 23.9% of BRCA + and 12.5% of BRCA − women ( P = .046). After excluding women with bilateral breast cancers, 81.0% of women who agreed that PM was best to reduce risk underwent a PM versus 19.1% of those who disagreed ( P < .001). Of women who felt PM was the only way to reduce worry, 84.2% underwent PM. Only 15.8% of women who did not believe that it was the only way to decrease worry underwent PM ( P < .001). CONCLUSIONS: BRCA mutation carriers were more likely to believe PM to be the best way to reduce both risk and worry of breast cancer. High‐risk women who agreed that PM was more likely to reduce risk and worry of breast cancer were more likely to proceed with this intervention. Cancer 2009. © 2009 American Cancer Society.Keywords:
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The issues of mutual perception of persons holding positions in the hierarchical organizational structure engaged in (some) operational activities are considered. Theoretical concepts have been introduced and provisions have been formulated that reveal the interconnections of the individual perception of each other by persons. Aspects (sides) of perception are established, scales of measurement and potential values of aspects of perception are defined. The significance of aspects of perception is revealed depending on the relative positioning of the positions of the perceiving and perceived persons in the hierarchy. The basic statement of the concept is formulated: the essential content of perception by person A of person B is completely exhausted by three aspects: personal (personal) perception, social perception and professional perception. These aspects are not reducible to each other.
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Triple-negative breast cancer (TNBC) is characterized by earlier recurrence and shorter survival compared with other types of breast cancer. Moreover, approximately 15 to 25% of all TNBC patients harbor germline BRCA (gBRCA) 1/2 mutations, which confer a more aggressive phenotype. However, TNBC seems to be particularly sensitive to chemotherapy, the so-called 'triple negative paradox'. Therefore, Neoadjuvant chemotherapy (NACT) is currently considered the preferred approach for early-stage TNBC. BRCA status has also been studied as a predictive biomarker of response to platinum compounds. Although several randomized trials investigated the addition of carboplatin to standard NACT in early-stage TNBC, the role of BRCA status remains unclear. In this retrospective analysis, we evaluated data from 136 consecutive patients with Stage I-III TNBC who received standard NACT with or without the addition of carboplatin, in order to define clinical features and outcomes in BRCA 1/2 mutation carriers and non-carrier controls. Between January 2013 and February 2021, 67 (51.3%) out of 136 patients received a standard anthracyclines/taxane regimen and 69 (50.7%) patients received a platinum-containing chemotherapy regimen. Deleterious germline BRCA1 or BRCA2 mutations were identified in 39 (28.7%) patients. Overall, patients with deleterious gBRCA1/2 mutation have significantly higher pCR rate than non-carrier patients (23 [59%] of 39 vs. 33 [34%] of 97; p = 0.008). The benefit of harboring a gBRCA mutation was confirmed only in the subset of patients who received a platinum-based NACT (17 [65.4%] of 26 vs. 13 [30.2%] of 43; p = 0.005) while no differences were found in the platinum-free subgroup. Patients who achieved pCR after NACT had significantly better EFS (OR 4.5; 95% CI 1.9-10.7; p = 0.001) and OS (OR 3.3; 95% CI 1.3-8.9; p = 0.01) than patients who did not, regardless of BRCA1/2 mutation status and type of NACT received. Our results based on real-world evidence show that TNBC patients with the gBRCA1/2 mutation who received platinum-based NACT have a higher pCR rate than non-carrier patients, supporting the use of this chemotherapy regimen in this patient population. Long-term follow-up analyses are needed to further define the role of gBRCA mutation status on clinical outcomes in patients with early-TNBC.
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Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer and the major phenotype of BRCA related hereditary breast cancer. Platinum is a promising chemotherapeutic agent for TNBC. However, its efficacy for breast cancer with BRCA germline mutation remains inconclusive. Here we present a meta-analysis to evaluate the effect of platinum agents for breast cancer patients with BRCA mutation in neoadjuvant setting.Pubmed, Embase, and Cochrane Central Register of Controlled Trials databases were searched for relevant studies on neoadjuvant platinum treatment and BRCA related breast cancer. Fixed- and random-effect models were adopted for meta-analyses. Heterogeneity investigation was conducted by sensitivity and subgroup analyses. Publication bias was evaluated by funnel plot and Begg's test.In all, five studies with 363 patients were included for meta-analysis. The pooled pathological complete response (pCR) rates were 43.4% (59/136) and 33.9% (77/227) for platinum and control groups, respectively. Adding platinum to neoadjuvant regimen did not significantly improved pCR rate (odds ratio [OR]: 1.340, 95% confidence interval [CI] = 0.677-2.653, p = 0.400). Sensitivity analyses also revealed platinum did not significantly increase pCR rate in either TNBC or HER2- patients (TNBC subgroup: OR: 1.028, 95% CI = 0.779-1.356, p = 0.846; HER2- subgroup: OR: 0.935, 95% CI = 0.716-1.221, p = 0.622).Our meta-analysis suggested that the addition of platinum to neoadjuvant chemotherapy did not significantly improve pCR rate for patients with BRCA mutations. Further large-scale randomized control trial with survival data may provide more robust evidence on therapeutic value of platinum for breast cancer neoadjuvant treatment.
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A straightforward way of thinking about perception is in terms of perceptual representation. Perception is the construction of perceptual representations that represent the world correctly or incorrectly. This way of thinking about perception has been questioned recently by those who deny that there are perceptual representations. This article examines some reasons for and against the concept of perceptual representation and explores some potential ways of resolving this debate. Then it analyzes what perceptual representations may be: if they attribute properties to entities, what are these attributed properties, and what are the entities they are attributed to.
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Effects of BRCA1- and BRCA2-Related Mutations on Ovarian and Breast Cancer Survival: A Meta-analysis
Abstract Purpose: To estimate the effects of BRCA1 and BRCA2 mutations on ovarian cancer and breast cancer survival. Experimental Design: We searched PubMed and EMBASE for studies that evaluated the associations between BRCA mutations and ovarian or breast cancer survival. Meta-analysis was conducted to generate combined HRs with 95% confidence intervals (CI) for overall survival (OS) and progression-free survival (PFS). Results: From 1,201 unique citations, we identified 27 articles that compared prognosis between BRCA mutation carriers and noncarriers in patients with ovarian or breast cancer. Fourteen studies examined ovarian cancer survival and 13 studies examined breast cancer survival. For ovarian cancer, meta-analysis demonstrated that both BRCA1 and BRCA2 mutation carriers had better OS (HR, 0.76; 95% CI, 0.70–0.83 for BRCA1 mutation carriers; HR, 0.58; 95% CI, 0.50–0.66 for BRCA2 mutation carriers) and PFS (HR, 0.65; 95% CI, 0.52–0.81 for BRCA1 mutation carriers; HR, 0.61; 95% CI, 0.47–0.80 for BRCA2 mutation carriers) than noncarriers, regardless of tumor stage, grade, or histologic subtype. Among patients with breast cancer, BRCA1 mutation carriers had worse OS (HR, 1.50; 95% CI, 1.11–2.04) than noncarriers but were not significantly different from noncarriers in PFS. BRCA2 mutation was not associated with breast cancer prognosis. Conclusions: Our analyses suggest that BRCA mutations are robust predictors of outcomes in both ovarian and breast cancers and these mutations should be taken into account when devising appropriate therapeutic strategies. Clin Cancer Res; 21(1); 211–20. ©2014 AACR.
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Breast cancer type 1 susceptibility (BRCA) mutations not only increase breast cancer (BC) risk but also result in poor survival and prognosis for BC patients. This study will analyze the effect and safety of therapeutic regimens for the treatment of BC patients with germline BRCA (gBRCA) mutations by network meta-analysis.Public databases were searched from inception to 29 April 2021. Frequentist network meta-analysis was conducted to analyze the benefit of chemotherapy and targeted drug-related strategies.Seventeen articles were included in the analysis. For progression-free survival (PFS), olaparib (hazard ratio (HR): 0.58; 95% confidence interval (CI): 0.43 - 0.79), platinum (HR: 0.45; 95% CI: 0.22 - 0.89), and talazoparib (HR: 0.54; 95% CI: 0.41 - 0.71) were significantly better than platinum-free chemotherapy (Chemo). The results based on indirect comparisons showed that veliparib (Vel) + platinum + Chemo was also significantly better than Chemo (HR: 0.37; 95% CI: 0.20 - 0.69). For overall survival (OS), olaparib was significantly better than Chemo only in the population who did not receive prior chemotherapy. For pathologic complete response (pCR), bevacizumab+Chemo had a significant advantage over platinum agents (OR: 3.64; 95% CI: 1.07 - 12.39). Olaparib and talazoparib both showed significantly higher objective response rates (ORRs) than Chemo.The PFS results suggested that olaparib, talazoparib, and Vel+platinum agent+Chemo were ideal regimens for overall, TNBC, and advanced BC patients with gBRCA mutations. Whether PARPis are suitable for patients with gBRCA mutations who have received prior platinum therapy still needs to be clarified.
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HER2-positive breast cancers are rare amongst BRCA mutation carriers. No data exist regarding clinicopathological characteristics and prognosis of this subgroup of patients.Using a retrospective matched cohort design, we collected data from 700 women who were diagnosed with operable invasive breast cancer from January 2006 to December 2016 and were screened for germline BRCA mutations. Clinicopathological features and survival rates were analyzed by BRCA and HER2 status.One hundred and fifteen HER2-positive/BRCA mutated cases were evaluated in comparison to the three control groups: HER2-positive/BRCA wild type (n = 129), HER2-negative/BRCA mutated (n = 222), HER2-negative/BRCA wild type (n = 234). HER2-positive breast cancers were more likely to have high histologic grade and high proliferation rate than HER2-negative neoplasms, regardless of BRCA mutation status. An interaction between BRCA mutations and HER2-positive status was found to correlate with worse survival after adjusting for prognostic variables (HR = 3.4; 95% CI: 1.3-16.7).Co-occurrence of BRCA mutations and HER2-positive status is a poor prognostic factor in patients with early or locally advanced breast cancer. This finding may be a proof of concept that a combined pharmacological intervention directed to these targets could be synergistic.
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