BACKGROUND: BRCA1/2 mutated breast cancer accounts for 3 to 12% of all women with breast cancer and significantly increases the lifetime risk of breast cancer. However, the optimal local treatment for breast cancer with BRCA germline mutation remains controversial. Here we present a meta-analysis to evaluate the impact of breast-conserving therapy (BCT) on the prognosis of breast cancer with BRCA mutation.
METHODS: Two independent reviewers searched Pubmed, Embase and Cochrane Central Register of Controlled Trials databases for relevant studies on BCT and BRCA mutated breast cancer. Fixed or random effect models were used for meta-analyses based on whether significant heterogeneity existed among included studies. Funnel plot and Begg's test were employed for the evaluation of publication bias.
RESULTS: Totally, four studies with five cohorts and a totally 1254 patients were included for meta-analyses. The BCT group involved more T0/T1 (BCT 63.7% Vs. M 48.9%, p < 0.001), N0 (BCT 70.5% Vs. M 56.2%, p < 0.001) and ER negative (BCT 58.8% Vs. M 49.3% p < 0.01) tumors than M group. Patients who received M tended to have prophylactic contralateral mastectomy (BCT 16.5% Vs. M 35.8%, p < 0.001). BCT had a significant higher risk for local recurrence than M (HR 3.838, 95% CI = 2.376-6.201, p < 0.001). The pooled results revealed no significant impact of BCT on disease-free survival (DFS), metastasis-free survival (MFS), breast cancer-specific survival (BCSS) and overall survival (OS).
CONCLUSIONS: The present meta-analysis suggested that BCT had increasing local recurrence risk, but did not significantly impact patient survival in terms of DFS, MFS, BCSS and OS. BCT may serve as a safe alternative to mastectomy for breast cancer with BRCA mutation. Further high-quality randomized control trials are warranted to explore the optimal surgical management for BRCA mutation carriers.
BACKGROUND: Unilateral breast cancer (UBC) patients with germline pathogenic BRCA1/2 variants have a higher risk of developing contralateral breast cancer (CBC) and need contralateral risk-reducing local treatments, including contralateral risk-reducing mastectomy (CRRM) and prophylactic irradiation (CPI). The aim of our study was to systematically explore the efficacy of CRRM and CPI in reducing CBC risk and increasing survival.
METHODS: A search was done, and eligible randomized trials and cohort studies should include and compare UBC patients with germline pathogenic BRCA1/2 variants who have and have not received contralateral risk-reducing local treatment. Random-effects meta-analysis was used in this study. Primary outcomes of the studies included overall survival (OS) and the incidence of contralateral breast cancer (CBC), and secondary outcomes included breast cancer-specific survival (BCSS).
RESULTS: A total of five studies with 1769 UBC patients with germline pathogenic BRCA1/2 variants were enrolled in our meta-analysis. CRRM was correlated with a lower risk of CBC in UBC patients with germline pathogenic BRCA1/2 variants (summary RR = 0.07; 95%CI 0.03-0.13, I2 = 3%), a significantly increased OS (summary RR, 1.15; 95%CI 1.04-1.26, I2 = 26%) and a significantly increased BCSS (summary RR, 1.18; 95%CI 1.07-1.31, I2 = 64%) compared with surveillance. CPI also decreased the risk of CBC (RR 0.02; 95%CI 0.05-0.88) but did not significantly improve OS (RR 0.97; 95%CI 0.90-1.05) and BCSS (RR 0.97; 95%CI 0.90-1.05) compared with surveillance.
CONCLUSIONS: CRRM reduces CBC risk and increases OS and BCSS in UBC patients with germline pathogenic BRCA1/2 variants, and could be offered as a risk-reducing local treatment. For those who oppose CRRM, CPI could be offered for CBC-risk reduction, while its survival benefit is still uncertain.
BACKGROUND: Studies evaluating role of BRCA mutations on the survival outcomes in breast cancer (BC) patients have given confounding results and hence, in this meta-analysis, we assessed the impact of BRCA mutations on survival in BC patients.
METHODS: Studies comparing survival outcomes of BC patients having BRCA mutations against wildtype BRCA phenotype were retrieved from PubMed, EMBASE, and Cochrane Library. Overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and breast cancer-specific survival (BCCS) were the outcomes. Hazard ratio (HR) with 95% confidence interval (CI) was used for analysis. Subgroup analysis was performed for survival based on triple negative breast cancer (TNBC) and follow-up durations. The meta-analysis was performed as per PRISMA guidelines.
RESULTS: Altogether, 30 articles with 35,972 patients (mean age 45.6 years) were included. Patients with BRCA 1 mutation had significantly lower OS (HR [95% CI] 1.2 [1.08, 1.33]; P < 0.001), BRCA 2 mutation had significantly lower DFS (HR [95% CI] 1.35 [1.1, 1.67]; P = 0.0049) and BCSS (HR [95%CI] 1.46 [1.26, 1.7]; P < 0.0001), and TNBC patients with BRCA 1 mutation had significantly poor DFS (HR [95% CI] 1.65 [1.08, 2.54]; P = 0.0216). Based on follow-up duration, the OS in BRCA 1-mutated patients revealed significantly poorer outcomes in studies with ≤ 5 years (HR 1.48) and > 5 years (HR 1.14) of follow-up. In BRCA 2 -mutated patients, the OS was significantly poorer in studies with > 5 years of follow-up (HR 1.39, P < 0.05).
CONCLUSION: BC patients with BRCA 1 or BRCA 2 mutations had poor survival outcomes and hence screening patients with BC for BRCA mutations might help in strategizing their treatment and improving their survival.
BACKGROUND: Recent progress in understanding the genetic basis of breast cancer and widely publicized reports of celebrities undergoing risk-reducing mastectomy (RRM) have increased interest in RRM as a method of preventing breast cancer. This is an update of a Cochrane Review first published in 2004 and previously updated in 2006 and 2010.
OBJECTIVES: (i) To determine whether risk-reducing mastectomy reduces death rates from any cause in women who have never had breast cancer and in women who have a history of breast cancer in one breast, and (ii) to examine the effect of risk-reducing mastectomy on other endpoints, including breast cancer incidence, breast cancer mortality, disease-free survival, physical morbidity, and psychosocial outcomes.
SEARCH METHODS: For this Review update, we searched Cochrane Breast Cancer's Specialized Register, MEDLINE, Embase and the WHO International Clinical Trials Registry Platform (ICTRP) on 9 July 2016. We included studies in English.
SELECTION CRITERIA: Participants included women at risk for breast cancer in at least one breast. Interventions included all types of mastectomy performed for the purpose of preventing breast cancer.
DATA COLLECTION AND ANALYSIS: At least two review authors independently abstracted data from each report. We summarized data descriptively; quantitative meta-analysis was not feasible due to heterogeneity of study designs and insufficient reporting. We analyzed data separately for bilateral risk-reducing mastectomy (BRRM) and contralateral risk-reducing mastectomy (CRRM). Four review authors assessed the methodological quality to determine whether or not the methods used sufficiently minimized selection bias, performance bias, detection bias, and attrition bias.
MAIN RESULTS: All 61 included studies were observational studies with some methodological limitations; randomized trials were absent. The studies presented data on 15,077 women with a wide range of risk factors for breast cancer, who underwent RRM.Twenty-one BRRM studies looking at the incidence of breast cancer or disease-specific mortality, or both, reported reductions after BRRM, particularly for those women with BRCA1/2 mutations. Twenty-six CRRM studies consistently reported reductions in incidence of contralateral breast cancer but were inconsistent about improvements in disease-specific survival. Seven studies attempted to control for multiple differences between intervention groups and showed no overall survival advantage for CRRM. Another study showed significantly improved survival following CRRM, but after adjusting for bilateral risk-reducing salpingo-oophorectomy (BRRSO), the CRRM effect on all-cause mortality was no longer significant.Twenty studies assessed psychosocial measures; most reported high levels of satisfaction with the decision to have RRM but greater variation in satisfaction with cosmetic results. Worry over breast cancer was significantly reduced after BRRM when compared both to baseline worry levels and to the groups who opted for surveillance rather than BRRM, but there was diminished satisfaction with body image and sexual feelings.Seventeen case series reporting on adverse events from RRM with or without reconstruction reported rates of unanticipated reoperations from 4% in those without reconstruction to 64% in participants with reconstruction.In women who have had cancer in one breast, removing the other breast may reduce the incidence of cancer in that other breast, but there is insufficient evidence that this improves survival because of the continuing risk of recurrence or metastases from the original cancer. Additionally, thought should be given to other options to reduce breast cancer risk, such as BRRSO and chemoprevention, when considering RRM.
AUTHORS' CONCLUSIONS: While published observational studies demonstrated that BRRM was effective in reducing both the incidence of, and death from, breast cancer, more rigorous prospective studies are suggested. BRRM should be considered only among those at high risk of disease, for example, BRCA1/2 carriers. CRRM was shown to reduce the incidence of contralateral breast cancer, but there is insufficient evidence that CRRM improves survival, and studies that control for multiple confounding variables are recommended. It is possible that selection bias in terms of healthier, younger women being recommended for or choosing CRRM produces better overall survival numbers for CRRM. Given the number of women who may be over-treated with BRRM/CRRM, it is critical that women and clinicians understand the true risk for each individual woman before considering surgery. Additionally, thought should be given to other options to reduce breast cancer risk, such as BRRSO and chemoprevention when considering RRM.
Mutaciones de BRCA ocurren con frecuencia en el cáncer de mama (BC), pero su impacto pronóstico en los resultados de BC no se ha determinado. Se realizó un metanálisis actualizado sobre la asociación entre las mutaciones BRCA y la supervivencia en pacientes con BC. Se realizaron búsquedas en bases de datos electrónicas. La medida de resultado primaria fue la supervivencia global (SG) y las medidas de resultado secundarias incluyeron la supervivencia específica del cáncer de mama (BCSS) y la supervivencia libre de eventos (EFS). Las relaciones de riesgo (HR) y el intervalo de confianza (IC) del 95% se extrajeron y se agruparon con modelos de efectos aleatorios. Los datos de 297, 402 pacientes con BC fueron agrupados de 34 estudios. La mediana de las tasas de prevalencia de BRCA1 y BRCA2 mutaciones fueron 14,5% y 8,3%, respectivamente. Las mutaciones de BRCA se asociaron con un peor OS (BRCA1: HR = 1,69, IC del 95%, 1,35 a 2,12, p <0,001, BRCA2: HR = 1,50, IC del 95%: 1,03 a 2,19, p = 0,034). (BRCA1: HR = 1,14, IC 95%, 0,81 a 1,16, p = 0,448, BRCA2: HR = 1,16, IC del 95%: 0,82 a 1,66, p = 0,401) o EFS (BRCA1: HR = 1,10, IC del 95%, 0,86 a 1,41, p = 0,438, BRCA2: HR = 1,09, IC del 95%: 0,81 a 1,47, p = 0,558). Varios estudios analizaron las mutaciones BRCA1 y BRCA2 juntas y no encontraron ningún impacto en el SO (HR = 1,21, IC del 95%, 0,73 a 2,00, p = 0,454) o EFS (HR = 0,94, IC del 95%, 0,60 a 1,48, p = 0,787) . Las mutaciones BRCA1 y BRCA2 se asociaron con un OS deficiente en pacientes con BC, pero no tuvieron un impacto significativo en BCSS o EFS. Se observó una supervivencia mejorada en pacientes con BC que tuvieron mutación BRCA1 y tratados con endocrinoterapia. Los resultados pueden tener implicaciones terapéuticas y pronósticas importantes para los portadores de mutación BRCA con BC.
AIMS: BRCA1/2 mutation carriers show reduced apoptotic response to ionising radiation leading to recent debate about the safety of wide local excision and radiotherapy. The aim of the current study was to determine if BRCA1/2 mutation carriers with breast cancer undergoing wide local excision and radiotherapy show increased ipsilateral and contralateral breast tumour recurrence and reduced survival compared with unilateral mastectomy.
MATERIALS AND METHODS: Following a detailed literature search, the methodology, populations, biases and outcomes of ipsilateral breast tumour recurrence, contralateral breast tumour recurrence and survival were evaluated for 25 articles.
RESULTS: No differences in outcomes were found between wide local excision and mastectomy. BRCA1/2 mutation status was predictive of contralateral breast cancer only. Radiotherapy reduces the risk of ipsilateral recurrence and confers no increase in contralateral recurrence.
CONCLUSION: BRCA1/2 mutation status does not preclude treatment with wide local excision and radiotherapy. Given the retrospective studies with inherent flaws and small patient numbers, further large prospective trials are required.
Portadores de mutaciones BRCA1 / 2 se encuentran en un mayor riesgo de cáncer de mama y de cáncer de mama contralateral posterior (CBC). Este estudio tiene como objetivo evaluar la evidencia del efecto de los genes BRCA1 / 2 de portador en CBC riesgo acumulado en pacientes con cáncer de mama femenino. La literatura se buscó en PubMed y Embase hasta junio de 2013 para los estudios sobre el riesgo de CBC después de un primer cáncer de mama invasivo primario en los portadores de mutaciones BRCA1 / 2 femeninas. Una síntesis cualitativa se llevó a cabo y la calidad metodológica de los estudios evaluados. Riesgos acumulativos de CBC después de 5, 10 y 15 años desde el primer diagnóstico de cáncer de mama se agruparon por estado BRCA1 2 mutación /. Un total de 20 artículos, de 1324 recuperado a través de la búsqueda, se reunieron los criterios de inclusión: 18 retrospectiva y 2 estudios prospectivos de cohorte. Se agruparon los riesgos acumulados de hasta cinco estudios. El acumulado de 5 años el riesgo de CBC para BRCA1 y BRCA2 mutación transportistas fue del 15% (IC del 95%: 9,5% a 20%) y 9% (IC del 95%: 5% -14%), respectivamente. Este riesgo aumenta con el tiempo transcurrido desde el diagnóstico del primer cáncer de mama; el de 10 años el riesgo aumenta hasta un 27% y 19%, respectivamente. Los 5 años de riesgo acumulado fue notablemente menor en los transportistas no BRCA (3%; IC del 95%: 2% -5%) y se mantuvo así durante los años siguientes (5%; IC del 95%: 3% -7%). En conclusión, el riesgo de aumentos de cooperación transfronteriza con la longitud de tiempo después del primer diagnóstico de cáncer de mama en portadoras de BRCA1 / 2 mutación. Los estudios que abordan el impacto de los factores relacionados con el tratamiento y las características clínicas de la primera el cáncer de mama en este riesgo están garantizados.
OBJETIVO: Para examinar si la mastectomía profiláctica contralateral (CPM) se asocia con una mejor supervivencia, la incidencia de cáncer de mama contralateral (CBC), y la recurrencia en pacientes con cáncer de mama unilateral (UBC).
ANTECEDENTES: A pesar de los datos contradictorios, las tasas de CPM siguen aumentando. Aquí presentamos el primer meta-análisis para evaluar los resultados post-CPM en las mujeres con UBC.
MÉTODOS: Se realizaron búsquedas en bases de datos y se recuperan 5 bibliografías papeles 'para los estudios relevantes publicados hasta marzo de 2012. De efectos fijos y aleatorios meta-análisis se realizaron sobre la base de pruebas de la heterogeneidad de los estudios. Examinamos posibles factores de confusión a través de la estratificación y la meta-regresión. Se presenta riesgos agrupados relativos (RR) y diferencias de riesgo (DR) con 95% de intervalo de confianza (IC) en P 2 colas <0,05.
Resultados: De los 93 estudios revisados, 14 fueron incluidos en el metanálisis. En comparación con los no receptores, los receptores de CPM tuvieron mayores tasas de supervivencia general [OS; RR (IC del 95%: 1,06, 1,11) = 1,09] y menores tasas de mortalidad específica por cáncer de mama [BCM; RR (IC del 95%: 0,56, 0,85) = 0,69], pero no vio ninguna reducción absoluta del riesgo de CBC metacrónico (MCBC). Entre los pacientes con elevado riesgo familiar / genética (FGR, es decir, el estado de portador de BRCA y / o antecedentes familiares de cáncer de mama), tanto los riesgos relativos y absolutos de MCBC se redujo significativamente entre los receptores de CPM [RR = 0,04 IC (95%: 0,02, 0,09); RD (IC del 95%: -35,6%, -12,4%) = -24,0%], pero no hubo mejoría en la SG o BCM.
CONCLUSIONES: CPM se asocia con una disminución de la incidencia MCBC pero no mejoró la supervivencia de los pacientes con FGR elevada. Los resultados superiores observadas al comparar los destinatarios de CPM con quienes no las reciben en la población general no son probablemente atribuible a una disminución de la RPC-derivado de la incidencia MCBC. Pacientes UBC sin FGR conocido no debe aconsejar a someterse a la RPC.
INTRODUCCIÓN: El manejo clínico óptimo de cáncer de mama (CM) que surjan en BRCA1 / 2 mutaciones portadores es un tema difícil complicado por el riesgo de neoplasias malignas subsiguientes y por las posibles diferencias en la respuesta a los tratamientos locales y sistémicos.
OBJETIVO: Revisar sistemáticamente la diferencia en el resultado después de la terapia de conservación del seno (BCT) y la mastectomía uni o bilateral en BRCA1 / 2 aC relacionados.
Material y métodos: Se seleccionaron 20 estudios, para los que se evaluó la metodología, las características de las poblaciones, los sesgos de confusión, los factores de riesgo y los resultados.
RESULTADOS: Todos los estudios son retrospectivos, que entraña numerosos sesgos. Se variaron con respecto al número de los pacientes, la selección y factores de confusión. Pacientes con CM hereditarias llevaron a un aumento del riesgo de recurrencia ipsilateral en 5/17 estudios, una peor supervivencia en 4/14, un mayor riesgo de BC contralateral en 14/16.
CONCLUSIÓN: A excepción de riesgo contralateral, la presencia de una mutación BRCA no parece ofrecer información pronóstica adicional. Ensayos prospectivos grandes, estratificados para las estrategias de reducción de riesgos están garantizados.
BRCA1/2 mutated breast cancer accounts for 3 to 12% of all women with breast cancer and significantly increases the lifetime risk of breast cancer. However, the optimal local treatment for breast cancer with BRCA germline mutation remains controversial. Here we present a meta-analysis to evaluate the impact of breast-conserving therapy (BCT) on the prognosis of breast cancer with BRCA mutation.
METHODS:
Two independent reviewers searched Pubmed, Embase and Cochrane Central Register of Controlled Trials databases for relevant studies on BCT and BRCA mutated breast cancer. Fixed or random effect models were used for meta-analyses based on whether significant heterogeneity existed among included studies. Funnel plot and Begg's test were employed for the evaluation of publication bias.
RESULTS:
Totally, four studies with five cohorts and a totally 1254 patients were included for meta-analyses. The BCT group involved more T0/T1 (BCT 63.7% Vs. M 48.9%, p < 0.001), N0 (BCT 70.5% Vs. M 56.2%, p < 0.001) and ER negative (BCT 58.8% Vs. M 49.3% p < 0.01) tumors than M group. Patients who received M tended to have prophylactic contralateral mastectomy (BCT 16.5% Vs. M 35.8%, p < 0.001). BCT had a significant higher risk for local recurrence than M (HR 3.838, 95% CI = 2.376-6.201, p < 0.001). The pooled results revealed no significant impact of BCT on disease-free survival (DFS), metastasis-free survival (MFS), breast cancer-specific survival (BCSS) and overall survival (OS).
CONCLUSIONS:
The present meta-analysis suggested that BCT had increasing local recurrence risk, but did not significantly impact patient survival in terms of DFS, MFS, BCSS and OS. BCT may serve as a safe alternative to mastectomy for breast cancer with BRCA mutation. Further high-quality randomized control trials are warranted to explore the optimal surgical management for BRCA mutation carriers.
