Largest study of BRCA1 and BRCA2 carriers refines estimates of cancer risk in Asian population

Largest study of BRCA1 and BRCA2 carriers refines estimates of cancer risk in Asian population

A team of clinical scientists and researchers from the University of Nottingham (Malaysia Campus), National Cancer Center Singapore (NCCS), Cancer Research Malaysia, Nanyang Technological University, Singapore (NTU Singapore), University of Malaya, University of Cambridge, A* STAR's Genome Institute of Singapore (GIS) and other institutions have conducted the largest study to date of BRCA1 and BRCA2 (BReast CAncer Genes 1 and 2) carriers in an Asian population and the Breast and ovarian cancer risk estimates refined for this population. The results, published inThe Lancet Regional Health – Western Pacificwill better guide the clinical treatment of Asian patients with BRCA1 and BRCA2 mutations.

Breast cancer is the most common and common cause of cancer death among women in Singapore, while ovarian cancer ranks sixth in incidence and mortality in the same group. A 2022 study conducted under Singapore's National Precision Medicine Program showed that genetic mutations linked to hereditary breast and ovarian cancer affect nearly 1 in 150 people in Singapore. Global estimates suggest that 3-5% of breast cancers and 10-15% of ovarian cancers are caused by mutations in these genes. BRCA1 and BRCA2 genes are the most commonly affected genes in hereditary breast and ovarian cancers, and carriers have an increased risk of developing these cancers.

However, large-scale studies of BRCA1 and BRCA2 carriers have only been conducted in populations of predominantly European ancestry. Because other genes and lifestyle factors also influence cancer risk in BRCA carriers and these are different in Asians than in Europeans, there was considerable uncertainty regarding the cancer risk in Asian BRCA carriers. The clinical management of BRCA1 and BRCA2 carriers in Asia can be improved as only four small studies have been conducted on this cohort to date. More information is needed for proactive care and monitoring of BRCA1 and BRCA2 carriers of Asian descent.

To address this urgent clinical need, a multidisciplinary team of clinicians, scientists and genetic counselors examined the clinical data of 572 families in Singapore and Malaysia with BRCA1 and BRCA2 mutations. The family members were aged 20 to 79 and of Chinese, Indian and Malay descent. Of the 1,121 BRCA1 carriers, 144 and 65 were diagnosed with breast and ovarian cancer, respectively. Of the 1,275 BRCA2 152 carriers were diagnosed with breast cancer and 19 with ovarian cancer. Statistical analyzes were used to estimate the risk that carriers had of developing breast and ovarian cancer. They were also compared based on ethnicity, location and birth cohort.

Key findings

The results showed that penetrance, or the likelihood of these carriers developing breast cancer, has increased over time, with the largest increase occurring among people born after 1960. This increase is likely due to urbanization and changes in reproductive patterns. The estimated breast cancer incidence for all ethnic groups in the study was highest at age 55 and decreased thereafter.

The study also showed that cancer incidence among BRCA1 and BRCA2 carriers in Singapore is comparable to that in the Western population. The blue line, blue circle and blue square represent the cumulative risk of Asians in the United States, Malaysian Chinese and Singaporean Chinese, while the orange line, orange circle and orange square represent Asians in the United Kingdom, Malaysian Indians and Singaporean Indians. respectively.

The cumulative risk of breast and ovarian cancer among Chinese BRCA1 and BRCA2 carriers in Singapore was similar to that of Asians in the United States (approximately 37% of East Asians in the United States), but higher compared to Chinese in Malaysia. The cumulative risks of Indian BRCA1 and BRCA2 carriers in Singapore were similar to Asians in the UK (with approximately 47% South Asians in the UK), but higher compared to Indians from Malaysia.

Implications for clinical management

The results of this study provide an important new framework for estimating cancer risk in Asian carriers and enable a more individualized approach to the clinical management of this population. This is supported by an editorial in the February 2024 issue ofJAMA Oncology, that advances in technology have enabled easier and more cost-effective identification of BRCA1 and BRCA2 carriers and enabled the implementation of cancer risk management strategies outlined by the National Comprehensive Cancer Network (a coalition of 33 cancer centers in the United States). These include clinical breast examination and breast MRI at age 25, mammography at age 30, risk-reducing surgeries, and therapeutic interventions. In the same issue, a study of 2,488 women in North America and Europe suggested that MRI monitoring was associated with a significant reduction in breast cancer mortality in female BRCA1 carriers compared to no MRI monitoring. A second study of 4,332 women who were BRCA1 or BRCA2 carriers found that oophorectomy was associated with a significant reduction in all-cause mortality.

Early interventions for BRCA1 and BRCA2 carriers include screening options based on individual risk to detect cancer at its earliest and most treatable stage, as well as risk-reducing measures such as therapeutic interventions (antiestrogen therapy, tamoxifen, etc.) and prophylactic surgeries (mastectomy, salpingectomy). and oophorectomy).

Recent studies have shown that BRCA1 and BRCA2 gene carriers are more common than previously thought, while this study shows that carriers' risk of developing breast and ovarian cancer is as high in Singapore as in Western countries. Genetic testing should be considered to identify carriers early so that care planning can be personalized and early interventions such as regular monitoring and risk-reducing measures can be implemented.”

Joanne Ngeow, co-senior author, associate professor of genomic medicine at NTU Singapore's Lee Kong Chian School of Medicine and head of the Cancer Genetics Service at NCCS

This research is supported by the National Medical Research Council (NMRC), Ministry of Health, Singapore under the Clinician Scientist Award – Investigator (MOH-000654).

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