Germline BRCA mutations (gBRCAmut) on breast cancer (BC) outcomes: A large meta-analysis.

AbstractBreast cancer is the most common cancer in women, and its high mortality has become one of the biggest health problems globally. Several studies have reported an association between breast cancer and ATM gene variants. This study aimed to demonstrate and analyze the relationship between ATM gene polymorphisms and breast cancer prevalence rate. A systematic literature review was undertaken using the following databases: Medline (PubMed), Web of sciences, Scopus, EMBASE, Cochrane, Ovid, and CINHAL to retrieve all cross-sectional studies between January 1990 and January 2020, which had reported the frequency of ATM variants in patients with breast cancer. A random-effects model was applied to calculate the pooled prevalence with a 95% confidence interval. The pooled prevalence of ATM variants in patients with breast cancer was 7% (95% CI: 5−8%). Also, the pooled estimate based on type of variants was 6% (95% CI: 4−8%; I square: 94%; P: 0.00) for total variants¸ 0% (95% CI: 0−1%; I square: 0%; P: 0.59) for deletion variants, 12% (95% CI: 7−18%; I square: 99%; P: 0.00) for substitution variants, and 2% (95% CI: 4−9%; I square: 67%; P: 0.08) for insertion variants. This meta-analysis showed that there is a significant relationship between ATM variants in breast cancer patients. Further studies are required to determine which of the variants of the ATM gene are associated with BRCA mutations.

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Effect and Safety of Therapeutic Regimens for Patients With Germline BRCA Mutation-Associated Breast Cancer: A Network Meta-Analysis

Frontiers in Oncology ◽

10.3389/fonc.2021.718761 ◽

2021 ◽

Vol 11 ◽

Author(s):

Ying Jiang ◽

Xiang-Yu Meng ◽

Ning-Ning Deng ◽

Chen Meng ◽

Lu-Hui Li ◽

...

Keyword(s):

Breast Cancer ◽

Brca Mutation ◽

Meta Analysis ◽

Objective Response ◽

Pathologic Complete Response ◽

Progression Free Survival ◽

Complete Response ◽

Cancer Type ◽

Brca Mutations ◽

Better Than

PurposeBreast 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.MethodsPublic 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.ResultsSeventeen 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.ConclusionThe 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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Breast-conserving therapy for breast cancer with BRCA mutations: a meta-analysis

Breast Cancer ◽

10.1007/s12282-021-01312-2 ◽

2021 ◽

Author(s):

Changjun Wang ◽

Yan Lin ◽

Hanjiang Zhu ◽

Yidong Zhou ◽

Feng Mao ◽

...

Keyword(s):

Breast Cancer ◽

Meta Analysis ◽

Breast Conserving Therapy ◽

Brca Mutations

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Platinum-Based Neoadjuvant Chemotherapy for Breast Cancer With BRCA Mutations: A Meta-Analysis

Frontiers in Oncology ◽

10.3389/fonc.2020.592998 ◽

2020 ◽

Vol 10 ◽

Author(s):

Chang-Jun Wang ◽

Ying Xu ◽

Yan Lin ◽

Han-Jiang Zhu ◽

Yi-Dong Zhou ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Meta Analysis ◽

Brca Mutations

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BRCA mutations and survival in breast cancer: an updated systematic review and meta-analysis

Oncotarget ◽

10.18632/oncotarget.12158 ◽

2016 ◽

Vol 7 (43) ◽

pp. 70113-70127 ◽

Cited By ~ 16

Author(s):

Yaning Zhu ◽

Jian Wu ◽

Chengwan Zhang ◽

Suan Sun ◽

Jian Zhang ◽

...

Keyword(s):

Breast Cancer ◽

Systematic Review ◽

Meta Analysis ◽

Brca Mutations

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Deep exploration of PARP inhibitors in breast cancer: monotherapy and combination therapy

Journal of International Medical Research ◽

10.1177/0300060521991019 ◽

2021 ◽

Vol 49 (2) ◽

pp. 030006052199101

Author(s):

Zheling Chen ◽

Xiao Wang ◽

Xiao Li ◽

Yucheng Zhou ◽

Ke Chen

Keyword(s):

Breast Cancer ◽

Advanced Breast Cancer ◽

Meta Analysis ◽

Treatment Options ◽

Metastatic Breast ◽

Progression Free Survival ◽

Advanced Breast ◽

Systemic Review ◽

Brca Mutations ◽

Free Survival

Objective Nearly 5% of patients with breast cancer carry germline BRCA mutations, which are more common in triple-negative breast cancer (TNBC). Previous clinical trials demonstrated the therapeutic efficacy of poly (ADP-ribose) polymerase inhibitors (PARPis) against BRCA-mutated metastatic breast cancer. The current study conducted a systemic review and meta-analysis of the clinical efficiency and safety of PARPis, either alone or combined with chemotherapy, in patients with TNBC. Methods We searched PubMed, EMBASE, and ClinicalTrials.gov to identify randomized controlled trials comparing PARPi therapy with chemotherapy, and comparisons of chemotherapy plus PARPis with chemotherapy alone were included. The study endpoints included the clinical response, progression-free survival, and adverse event rates. Results PARPi therapy was revealed to improve progression-free survival in patients with advanced breast cancer, either alone or in combination with chemotherapy. Subgroup analysis illustrated that patients with mutant BRCA1 and mutant BRCA2 and those who had not been treated with platinum-based agents could specifically benefit from PARPis. Conclusion PARPi monotherapy can significantly improve clinical outcomes in patients with advanced breast cancer, especially those with TNBC, those who had not previously received platinum therapy, and those with mutant BRCA1/2. PARPis combined with chemotherapy represent new treatment options for patients with advanced cancer.

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Screening BRCA1 and BRCA2 Mutation Carriers for Breast Cancer

Cancers ◽

10.3390/cancers10120477 ◽

2018 ◽

Vol 10 (12) ◽

pp. 477 ◽

Cited By ~ 14

Author(s):

Ellen Warner

Keyword(s):

Breast Cancer ◽

Observational Studies ◽

Meta Analysis ◽

Brca2 Mutation ◽

Great Majority ◽

Clinical Breast Examination ◽

Brca1 And Brca2 ◽

Brca Mutations ◽

Highly Sensitive

Women with BRCA mutations, who choose to decline or defer risk-reducing mastectomy, require a highly sensitive breast screening regimen they can begin by age 25 or 30. Meta-analysis of multiple observational studies, in which both mammography and magnetic resonance imaging (MRI) were performed annually, demonstrated a combined sensitivity of 94% for MRI plus mammography compared to 39% for mammography alone. There was negligible benefit from adding screening ultrasound or clinical breast examination to the other two modalities. The great majority of cancers detected were non-invasive or stage I. While the addition of MRI to mammography lowered the specificity from 95% to 77%, the specificity improved significantly after the first round of screening. The median follow-up of women with screen-detected breast cancer in the above observational studies now exceeds 10 years, and the long-term breast cancer-free survival in most of these studies is 90% to 95%. However, ongoing follow-up of these study patients, as well of women screened and treated more recently, is necessary. Advances in imaging technology will make highly sensitive screening accessible to a greater number of high-risk women.

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