BRCA1/2 Mutation Types Do Not Affect Prognosis in Ovarian Cancer Patients

Background: High grade serous ovarian carcinoma (HGSOC) is the most lethal type of epithelial ovarian cancer, with a prevalence of germline BRCA1/2 mutations as high as 20%. Our objective is to determine whether the location of mutations in the different domains of the BRCA1/2 genes affects the clinical outcome of HGSOC patients. Methods: A total of 51 women with BRCA1 or BRCA2 mutated ovarian cancer were identified. Progression-free survival (PFS) and overall survival (OS) were analyzed. Results: In our study cohort, 35 patients were carriers of germline mutations in BRCA1 and 16 in BRCA2. The median PFS time following completion of the primary therapy was 23.8 months (95% CI 20.1–27.5) and the median OS was 92.9 months (95% CI 69.8–116.1) in all BRCA carriers. After multivariate analysis, no significant association among the location or type of BRCA1/2 mutation with PFS or OS was identified. Notably, significant differences in PFS between carriers of identical mutations in the same BRCA gene were detected. Conclusions: Among HGSOC patients, BRCA1/2 carriers with mutations in different locations of the genes show no significant difference in survival outcomes, in terms of PFS and OS, suggesting the potential effect of other genetic abnormalities and co-contributing risk factors.

Case Report: Young Adults With Breast Cancer: A Case Series of Fertility Preservation Management and Literature Review

Breast cancer comprised at least 21.8% of the overall cancer among young adult (YA) women and became the leading cancer in this group in Japan, with 50% adolescent and YAs being diagnosed and 15–44-year-old women showing excellent 5-year survival. Surgical-chemoradiation therapy often results in excellent survivorship with an increased incidence of treatment-induced subfertility. Therefore, adding fertility preservation (FP) to the primary cancer treatment is necessary. Herein, we reported a series of cases of YA women with breast cancer who opted for FP, where their option was tailored accordingly. To date, the selection of oocytes, embryos and ovarian tissue is widely available as an FP treatment. PGT could reduce the risk of BRCA mutation transmission amongst BRCA carriers before pregnancy planning. Otherwise, gonadotropin-releasing hormone analog has no gonadoprotective effect and thus should not be considered as an FP option.

Characteristics of breast cancer patients tested for germline BRCA1/2 mutations by next-generation sequencing in Ramathibodi Hospital, Mahidol University

Germline mutations in BRCA1/2 are the most common cause of hereditary breast and ovarian cancer (HBOC) syndrome. A few studies have reported the prevalence of germline BRCA mutations in Asian patients with breast cancer. Here, we aimed to explore the prevalence and characteristics of breast cancers in Thai patients with germline BRCA1/2 mutations. We retrospectively reviewed breast cancer patients tested for germline BRCA1/2 mutations in our institute during 2014–2018. BRCA mutations were detected using next-generation sequencing and confirmed using Sanger sequencing. We analyzed the characteristics of patients with or without BRCA mutations, disease-free survival (DFS), and associated factors. Among the 67 included patients, 12 (18%) were BRCA1/2 carriers (6 each), 4 (6%) harbored variants of uncertain significance, and 51 (76%) were non-carriers. We discovered two novel frameshift mutations in BRCA2 (c.2380delA and c.8855dupT). Mean ages at breast cancer diagnosis in BRCA1 carriers, BRCA2 carriers, and non-carriers were 39.8, 46.2, and 42.0 years, respectively. The 12 tumors of BRCA carriers were mostly the luminal-B subtypes. Two of these tumors were HER2-positive luminal-B; however, the triple-negative subtype was not observed. After adjusting for stages and luminal subtypes, BRCA carriers experienced worse 3-year DFS than non-carriers (81.5% vs. 90.3%, HR 2.04 (0.64–6.49), P = 0.229). The stage at diagnosis was the sole factor significantly associated with 3-year DFS (100%, 84.8%, and 72.7%; stages I, II, and III, respectively). In summary, breast cancers in Thai patients with germline BRCA1/2 mutations were mostly the luminal-B subtypes and experienced a worse prognosis than those without mutations.

BRCA1/2 Mutations and Long-Term Clinical Outcomes in Egyptian Breast Cancer Patients

Introduction: Clinical findings regarding the impact of BRCA1/2 mutational status on the prognosis of breast cancer patients are still controversial. We aimed to investigate the prognostic relevance of BRCA1/ 2 mutations on recurrence and long-term survival, for the first time, in Egyptian female breast cancer patients. Patients and Methods: The study cohort comprised 103 Egyptian female breast cancer patients previously tested for BRCA1/2 mutations using HRM analysis and direct sequencing. Clinicopathological and long-term clinical follow-up data including date and site of disease progression, were retrieved from medical records until death or loss to follow-up. Outcome measures including overall survival (OS), disease-free survival (DFS), recurrence-free survival, and metastasis-free survival (MFS) were compared in all BRCA1/ 2 mutation carriers versus non-carriers at 2, 5, 10, and 15 years after diagnosis. Results: The profile of the detected variants was previously reported. The American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) guidelines were used to re-classify the variants. The median follow-up time was 6.9 years (range, 4.2-24.4 years). BRCA carriers had significantly worse DFS than non-carriers, at 2 years 86.7% vs 88.2%; at 5 years 38.1% vs 57.8%; and at 10 years 21.6% vs 34.1% ( P=0.024). Negative estrogen receptor (ER) status (HR=2.44, 95%CI=1.33-4.47) and large tumor size (HR=2.19, HR=1.21-3.98) were also significant factors for worse DFS. Recurrence-free survival was significantly worse in BRCA carriers compared to non-carriers, at 5 years: 95.2% vs 98.2%; at 10 years: 54.4% vs 79.8%; and at 15 years 34.6% vs 61.7% ( P=0.005). BRCA carriers showed poorer OS and MFS, though not statistically significant [OS in BRCA carriers and non-carriers at 5 years: 81.6% vs 89.3%; at 10 years: 59.2% vs 60.6%; and at 15 years: 36.3 vs 59.2% ( P=0.42); and MFS at 2 years 86.7% vs 88.1%; at 5 years 44.5% vs 61.1% ; and at 10 years: 25.3% vs 38.2% ( P=0.41)]. Conclusion: To our knowledge, this is the first study in the Middle East to investigate long-term survival outcome of BRCA1/2 related breast cancer. We, herein, underline the necessity of implementing BRCA screening strategies and intensive surveillance in the mainstream oncology practice in Egypt.