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

Abstract

e22226 Background: Breast cancers due to underlying germline BRCA1 and BRCA2 mutations are associated with particular pathological features that may differ from sporadic breast cancers. We report clinical and pathologic characteristics of breast cancer in a clinical cohort of high risk Chinese women with BRCA mutations and those without mutations. Methods: 202 high risk women based on their age and family history were recruited from March 2007 to November 2008. Medical information was prospectively collected from the patients and medical records. BRCA1 and BRCA2 mutations were detected using full gene sequencing and multiplex ligation-dependent probe amplification (MLPA). Results: Of the 202 female probands tested, 25 (12.3 %) were BRCA mutation carriers of which 11 (44%) were BRCA1 and 14 (56%) were BRCA2 mutations. Breast cancer risk factors, other than family history, did not differ between carriers and non-carriers. Mutation carriers were more likely to have a familial history of breast cancer (p=0.07) and personal and family history of ovarian cancer (p=0.005; p=0.007). Other cancers found in carriers families included pancreatic, gastric, colon, lung, liver, and nasopharyngeal. 23% of women diagnosed with DCIS had BRCA mutations compared with 11.4% of those with invasive cancers. BRCA related tumors were more likely to be ER, PR and Her-2 negative (Triple negative, TN) (p= 0.006). Overall 9.6% of non-BRCA cancers were TN whereas 25.9% of BRCA cancers were TN. Prevalence of TN in BRCA1 carriers is 71% compared with 13.4% in BRCA2 carriers. BRCA1 mutation related cancers were significantly more likely to be ER negative than BRCA2 and this is only significant in those who are under 40 years of age (p=0.070). Conclusions: We have a high BRCA2 mutation rate in our cohort. BRCA related breast cancer is associated with families with increasing number of first degree relatives with breast and/or ovarian cancers and were higher for DCIS cancers. Prevalence of TN breast cancers was high compared to Caucasian cohorts. BRCA mutations were associated with pathologically, poor prognostic features (TN and high grade) especially in younger women. No significant financial relationships to disclose.

Germline mutations in Chinese ovarian cancer with or without breast cancer

“…Interestingly, the BRCA1/2 ‐positive rate was similar among different age groups in the OV cohort, which was different from the BROV cohort, as well as the BRCA ‐positive breast cancer patients in our previous study (Kwong et al, 2009). The majority of these two groups of cancer patients were diagnosed at the age between 20 and 44 or later (Table S3a).…”

Mutations of TP53 and genes related to homologous recombination repair in breast cancer with germline BRCA1/2 mutations

“…Clinical and genetic characteristics of breast cancer patients with pathogenic gBRCA1/2 mutations were investigated in the present study. In consistence with previous reports, about half of our patients were diagnosed before age 40, and majority were premenopausal [4,39]. These patients also presented with other high risk features, such as family history of breast cancer, co-occurrence of contralateral breast or ovarian cancer, and high Ki-67 index [5,7,40].…”

Predicting the Likelihood of Carrying a BRCA1 or BRCA2 Mutation in Asian Patients With Breast Cancer

“…In multivariable regression analyses, we found that the risk factors significantly associated with BRCA PV carrier status in this study were consistent with previously published findings from Asian countries, including younger age of diagnosis, bilateral breast cancer, ER-negative status, HER2negative status, higher grade, and presence of first-degree family history of breast cancer or ovarian cancer. 20,22,[30][31][32][33][34][35][36][37][38] We found that all the BRCA carrier prediction models and the MCC were more sensitive (sensitivity/detection rate) and accurate (discrimination) for BRCA1 than BRCA2, which is likely to be driven by the stronger association between BRCA1 and the ER-negative status, TNBC subtype, and ovarian cancer family history. [39][40][41][42][43] Indeed, several studies have previously demonstrated that the use of pathologic characteristics, namely ER and TNBC, improved the sensitivity and discrimination for BRCA1 when selecting individuals for germline genetic testing in high-risk breast cancer patients.…”

“…In multivariable regression analyses, we found that the risk factors significantly associated with BRCA PV carrier status in this study were consistent with previously published findings from Asian countries, including younger age of diagnosis, bilateral breast cancer, ER-negative status, HER2-negative status, higher grade, and presence of first-degree family history of breast cancer or ovarian cancer. 20,22,30-38…”