Triple-negative breast cancer in Hispanic patients: high prevalence, poor prognosis, and association with menopausal status, body mass index, and parity.
ABSTRACT Triple-negative breast cancer (TNBC) is defined as breast cancer that is negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. TNBC represents 15% of all invasive breast cancers, but some studies have suggested that its prevalence differs between races. To the authors' knowledge, no previous studies have determined the prevalence of TNBC and its risk factors among Hispanic women.
The authors identified 2074 Hispanic women with breast cancer who attended the National Cancer Institute in Mexico City from 1998 to 2008. All histopathologic and immunohistochemical diagnoses were rereviewed by a breast cancer pathologist. The prevalence of TNBC, its association with clinicopathologic characteristics, and its prognostic impact were determined.
The median patient age at diagnosis (±standard deviation) was 50 ± 12 years. The overall prevalence of TNBC was 23.1%. Younger age (P < .001), premenopausal status (P = .002), increased parity (P = .029), hormonal contraceptive use (P = .04) high histologic grade (P < .001), and advanced disease (P < .001) were associated independently with TNBC. Postmenopausal patients who had a body mass index (BMI) <25 kg/m(2) (P = .027) or <30 kg/m(2) (P < .001) were more likely to have TNBC. In multivariate analysis, patients with TNBC had a higher risk of locoregional recurrence (LRR), lower disease-free survival (DFS) (hazard ratio, 1.62; 95% confidence interval, 1.13-2.32; P = .009), and a lower cancer-specific survival (CSS) rate (hazard ratio, 1.66; 95% confidence interval, 1.20-2.30; P = .002) than patients with non-TNBC.
The median age at diagnosis of Hispanic women with breast cancer was 11 years younger than the average age reported in the United States. The prevalence of TNBC in this study population was higher than that reported in white women with breast cancer. TNBC was associated with a higher risk of LRR and with lower DFS and CSS than those in patients with non-TNBC.
Full-textDOI: · Available from: Oscar Arrieta, Jun 05, 2014
SourceAvailable from: Miguel Santibáñez[Show abstract] [Hide abstract]
ABSTRACT: BACKGROUND Frequent recurrent mutations in the breast and ovarian cancer susceptibility (BRCA) genes BRCA1 and BRCA2 among Hispanics, including a large rearrangement Mexican founder mutation (BRCA1 exon 9-12 deletion [ex9-12del]), suggest that an ancestry-informed BRCA-testing strategy could reduce disparities and promote cancer prevention by enabling economic screening for hereditary breast and ovarian cancer in Mexico.METHODS In a multistage approach, 188 patients with cancer who were unselected for family cancer history (92 with ovarian cancer and 96 with breast cancer) were screened for BRCA mutations using a Hispanic mutation panel (HISPANEL) of 115 recurrent mutations in a multiplex assay (114 were screened on a mass spectroscopy platform, and a polymerase chain reaction assay was used to screen for the BRCA1 ex9-12del mutation). This was followed by sequencing of all BRCA exons and adjacent intronic regions and a BRCA1 multiplex ligation-dependent probe amplification assay (MLPA) for HISPANEL-negative patients. BRCA mutation prevalence was calculated and correlated with histology and tumor receptor status, and HISPANEL sensitivity was estimated.RESULTSBRCA mutations were detected in 26 of 92 patients (28%) with ovarian cancer, in 14 of 96 patients (15%) with breast cancer overall, and in 9 of 33 patients (27%) who had tumors that were negative for estrogen receptor, progesterone receptor, and human epithelial growth factor 2 (triple-negative breast cancer). Most patients with breast cancer were diagnosed with locally advanced disease. The Mexican founder mutation (BRCA1 ex9-12del) accounted for 35% of BRCA-associated ovarian cancers and 29% of BRCA-associated breast cancers. At 2% of the sequencing and MLPA cost, HISPANEL detected 68% of all BRCA mutations.CONCLUSIONS In this study, a remarkably high prevalence of BRCA mutations was observed among patients with ovarian cancer and breast cancer who were not selected for family history, and the BRCA1 ex9-12del mutation explained 33% of the total. The remarkable frequency of BRCA1 ex9-12del in Mexico City supports a nearby origin of this Mexican founder mutation and may constitute a regional public health problem. The HISPANEL mutation panel presents a translational opportunity for cost-effective genetic testing to enable breast and ovarian cancer prevention. Cancer 2014. © 2014 American Cancer Society.Cancer 09/2014; 121(3). DOI:10.1002/cncr.29058 · 4.90 Impact Factor
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ABSTRACT: Triple negative breast cancer (TNBC) is one type of breast cancer (BC), which is defined as negative for estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (Her2). Its origins and development seem to be elusive. And for now, drugs like tamoxifen or trastuzumab which specifically apply to ER, PR or Her2 positive BC seem unforeseeable in TNBC clinical treatment. Due to its extreme malignancy, high recurrence rate and poor prognosis, a lot of work on the research of TNBC is needed. This review aims to summarize the latest findings in TNBC in risk factors, possible therapeutic targets and possible prognostic makers.09/2014; 6(9):1329-1335. DOI:10.3978/j.issn.2072-1439.2014.08.13
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ABSTRACT: Hispanics in El Paso, TX, a large American-Mexican border city constitute 85% of the population. Limited cancer research has been conducted in this population. We sought to study the prevalence of BRCA mutations among Hispanic patients of Mexican origin, identify reported Mexican founder or recurrent mutations, and study the breast cancer characteristics in mutation carriers. Hispanic women of Mexican descent with a personal history of breast cancer, who presented consecutively for genetic cancer risk assessment, were enrolled in an Institutional Review Board-approved registry and underwent BRCA testing based on national guidelines. The characteristics of tumors and patients with positive BRCA mutation were analyzed. 88 patients were screened; 18 patients (20%) were BRCA carriers. Among BRCA carriers, 72% were diagnosed with breast cancer at younger than 50 years, 61% had "Triple negative disease". BRCA carriers had a significantly higher Body Mass Index (BMI) than non-carriers. Thirteen patients had BRCA1 mutations and five had BRCA2 mutations. A total of 17 deleterious BRCA Mutations were observed. Seven have been previously reported as specific genes from Mexico as country of origin. Five new mutations in BRCA carriers of Mexican descent were identified. Hispanic breast cancer patients of Mexican origin present at a younger age, and have predominantly triple negative tumors and high BMI. We identified 5 new mutations not reported previously in Hispanic BRCA carriers of Mexican descent. Interestingly, 41% of BRCA mutations identified have been reported as recurrent mutations in Hispanic individuals from Mexico as the country of origin. A more cost-effective approach to initial screening of Hispanic individuals based on country of origin is desirable and would potentially decrease the number of cases requiring complete sequencing.