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.
Highlights
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with a higher risk of both local and distant recurrence and poor overall prognosis and it accounts for about 10–20% of all cases of breast cancer (Foulkes et al, 2010; Ovcaricek et al, 2011; Boyle, 2012)
The included studies were conducted in eight countries or regions as USA 5, Korea 3, China 2, Hong Kong 1, UK 1, Germany 1, France 1, and Spain 2, the published date was between 2006 and 2017. 45,870 patients were included in the studies, with the median age ranged from 32.0 to 57.1 years, 868 BRCA1Mut carriers, 739 BRCA2Mut carriers, and 45,263 noncarriers (Table 1)
We found that BRCA1Mut carriers were more likely to have TNBC than those of BRCA2Mut carriers (OR: 3.292; 95% confidence interval (CI): 2.773–3.909) or non-carriers (OR: 8.889; 95% CI: 6.925–11.410) among the patients with breast cancer (Figure 2)
Summary
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with a higher risk of both local and distant recurrence and poor overall prognosis and it accounts for about 10–20% of all cases of breast cancer (Foulkes et al, 2010; Ovcaricek et al, 2011; Boyle, 2012). BRCA and Triple-Negative Breast Cancer targets for treatment (Onitilo et al, 2009). Mutations in BRCA genes induce defective DNA repair mechanisms, which are associated with the risk of development of breast and/or ovarian cancers (Peng et al, 2016). Some studies showed that BRCA1 mutation (BRCA1Mut) carriers were more likely to have ER-negative/PR-negative breast cancer (Musolino et al, 2007; Byrski et al, 2008; Kirk, 2010). Comen et al (2011) found that the association between TNBC and BRCA mutations was limited to BRCA1, and a significant proportion of women with TNBC had BRCA2Mut. Currently, the relationship between the status of BRCA mutation and the statuses of ER, PR, HER2/neu and P53 have been inconsistent (Maegawa and Tang, 2010; Wu et al, 2010). The exact relationship between BRCA status and TNBC needs to be further investigated and validated
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