Clinical and pathological characteristics of Chinese patients with BRCA related breast cancer

Abstract

Breast cancers related to BRCA mutations are associated with particular biological features. Here we report the clinical and pathological characteristics of breast cancer in Chinese women with and without BRCA mutations and of carriers of BRCA1 mutations compared to BRCA2 mutations. Two hundred and 26 high-risk Hong Kong Chinese women were tested for BRCA mutations, medical information was obtained from medical records, and risk and demographic information was obtained from personal interviews. In this cohort, 28 (12.4%) women were BRCA mutation carriers and among these carriers, 39.3% were BRCA1 and 60.7% were BRCA2 mutations. Mutation carriers were more likely to have a familial history of breast and ovarian cancer, high-grade cancers, and triple negative (TN) cancers. Prevalence of TN was 48.3% in BRCA carriers and 25.6% in non-carriers and was 67.7% in BRCA1 and 35.3% in BRCA2 carriers. Estrogen receptor (ER) negative cancer was significantly associated with BRCA1 mutations, especially in those under 40 years of age. BRCA-related breast cancer in this Chinese population is associated with family history and adverse pathological/prognostic features, with BRCA2 mutations being more prevalent but BRCA1 carriers having more aggressive and TN cancers. Compared to Caucasian populations, prevalence of BRCA2 mutations and TN cancer in BRCA2 mutation carriers in Chinese population are elevated.

Prevalence and characterization of BRCA1 and BRCA2 germline mutations in Chinese women with familial breast cancer

“…Although no significant difference in the average age of onset between BRCA1 and BRCA2 carriers was observed, BRCA1 carriers tended to be younger at diagnosis of breast cancer than BRCA2 carriers. In this study, both BRCA1 and BRCA2 carriers were more likely to be triple-negative breast cancer (69.2 and 45.8%, respectively) compared with non-carriers (23.0%), the observation that BRCA1 tumors harbor a high frequent of triple-negative phenotype was consistent with previous studies [18,[31][32][33]. Although BRCA1 carriers exhibited a higher rate of triple-negative breast cancer than did BRCA2 carriers in this cohort, the BRCA2 carriers in this study exhibited a higher rate of triple-negative breast cancer than did Caucasian women who carried a BRCA2 mutation [34].…”

“…The BRCA2 mutations were 1.7-fold higher than that of BRCA1 in this cohort, the finding is consistent with a recent finding in Hong Kong Chinese women [18] and other Asian populations [19][20][21][22], in which BRCA2 mutation rate is more prevalent than BRCA1. By contrast, BRCA1 mutation is more common than BRCA2 in most Caucasian populations [23,24].…”

Novel LOVD databases for hereditary breast cancer and colorectal cancer genes in the Chinese population

“…However, no founder mutations of BRCA1 or BRCA2 genes have yet been identified in the Chinese population from this study. Two previous studies have proposed that 1081delG (c.962delG) in BRCA1 gene and c.3109C>T in BRCA2 gene are founder mutations in the Chinese population [Khoo et al, 2002;Kwong et al, 2009], but these results have not been supported by any other data. Nevertheless, some recurrent pathogenic variants were observed in our database (Tables 1 and 2).…”

BRCA1/2 mutations and triple negative breast cancers

“…For example, two studies selected participants who were known BRCA1/2 carriers [7,34], 3 studies selected patients from high risk clinics or based on a high prior probability of carrying a mutation [28,40,51], and 3 studies selected only participants with known TN breast cancer cases [18,26,52]. In 6 studies, BRCA1/2 testing was performed prospectively [18,28,30,35,51,52]. Studies that included participants who underwent BRCA1/2 testing because of established risk factors were more likely to have higher proportions of carriers, as one would expect.…”