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. 2018 Aug 21:9:909.
doi: 10.3389/fphar.2018.00909. eCollection 2018.

Association Between BRCA Status and Triple-Negative Breast Cancer: A Meta-Analysis

Haixia Chen  1 , Jianming Wu  1 , Zhihong Zhang  2 , Yong Tang  1 , Xiaoxuan Li  1 , Shuangqing Liu  2 , Shousong Cao  1 , Xianzhu Li  2
Affiliations

Association Between BRCA Status and Triple-Negative Breast Cancer: A Meta-Analysis

Haixia Chen et al. Front Pharmacol. .

Abstract

Triple-negative breast cancer (TNBC) is a subtype of aggressive breast cancer and characterized by a lack of the expression of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2. BRCA genes are tumor-suppressor genes that are involved in DNA damage repair and mutations of BRCA genes may increase the risk of developing breast cancer and/or ovarian cancer due to defective DNA repair mechanisms. However, the relationship between BRCA status and TNBC needs to be further investigated and validated. The aim of this meta-analysis was to evaluate the association between BRCA status and TNBC. We systematically searched the electronic databases of MEDLINE (PubMed), Embase, and Cochrane Library to identify relevant publications from April, 1959 to November, 2017. The data from the studies were examined by a meta-analysis using STATA software to calculate the odds ratio (OR) with 95% confidence interval (CI) by fixed-effect and random-effect models. We identified 16 qualified studies from 527 publications with 46,870 breast cancer patients including 868 BRCA1 mutations (BRCA1Mut ) carriers, 739 BRCA2 mutations (BRCA2Mut ) carriers, and 45,263 non-carriers. The results showed that breast cancer patients with BRCA1Mut carriers were more likely to have TNBC than those of BRCA2Mut carriers (OR: 3.292; 95% CI: 2.773-3.909) or non-carriers (OR: 8.889; 95% CI: 6.925-11.410). Furthermore, high expression of nuclear grade and large tumor burden (>2 cm) were significantly more common in breast cancer patients with BRCA1Mut carriers than those of BRCA2Mut carriers (OR: 2.663; 95% CI: 1.731-4.097; P = 0.211) or non-carriers (OR: 1.577; 95% CI: 1.067-2.331; P = 0.157). The data suggest that breast cancer patients with BRCA1Mut are more likely to have TNBC, high nuclear grade, and larger tumor burden.

Keywords: BRCA1; BRCA2; Triple-negative breast cancer (TNBC); meta-analysis; mutation.

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Figures

Figure 1
Figure 1
Flow chart for study selection.
Figure 2
Figure 2
The odds ratio (OR) of BRCA1 mutations vs. BRCA2 mutations in patients with TNBC by Forest Plot.
Figure 3
Figure 3
The odds ratio (OR) of BRCA1 mutations vs. non-carriers in patients with TNBC by Forest Plot.
Figure 4
Figure 4
The odds ratio of BRCA2 mutations vs. non-carriers in patients with TNBC by Forest Plot.
Figure 5
Figure 5
Indication of publication bias for the association between BRCA1 mutations and BRCA2 mutations by Begg's Funnel Plot with pseudo 95% confidence limits. The data indicate that there was no obvious indication of publication bias.
Figure 6
Figure 6
Indication of publication bias for the association between BRCA1 mutations and non-carriers by Begg's Funnel Plot with pseudo 95% confidence limits. The data indicate that there was no obvious indication of publication bias.
See this image and copyright information in PMC

References

    1. Aleskandarany M., Caracappa D., Nolan C. C., Macmillan R. D., Ellis I. O., Rakha E. A., et al. . (2015). DNA damage response markers are differentially expressed in BRCA-mutated breast cancers. Breast Cancer Res. Treat. 150, 81–90. 10.1007/s10549-015-3306-6 - DOI - PMC - PubMed
    1. Arun B., Bayraktar S., Liu D. D., Gutierrez Barrera A. M., Atchley D., Pusztai L., et al. . (2011). Response to neoadjuvant systemic therapy for breast cancer in BRCA mutation carriers and noncarriers: a single-institution experience. J. Clin. Oncol. 29, 3739–3746. 10.1200/JCO.2011.35.2682 - DOI - PMC - PubMed
    1. Atchley D. P., Albarracin C. T., Lopez A., Valero V., Amos C. I., Gonzalez-Angulo A. M., et al. . (2008). Clinical and pathologic characteristics of patients with BRCA-positive and BRCA-negative breast cancer. J. Clin. Oncol. 26, 4282–4288. 10.1200/JCO.2008.16.6231 - DOI - PMC - PubMed
    1. Baldassarre G., Battista S., Belletti B., Thakur S., Pentimalli F., Trapasso F., et al. . (2003). Negative regulation of BRCA1 gene expression by HMGA1 proteins accounts for the reduced BRCA1 protein levels in sporadic breast carcinoma. Mol. Cell Biol. 23, 2225–2238. 10.1128/MCB.23.7.2225-2238.2003 - DOI - PMC - PubMed
    1. Boyle B. (2012). Triple-negative breast cancer: epidemiological considerations and recommendations. Ann. Oncol. 6, 7–12. 10.1093/annonc/mds187 - DOI - PubMed