Disparities in Genetic Referrals for Breast Cancer among the Asian Immigrant Populations: How Can We Eliminate Them?

Abstract

Despite major advances in genetic testing for breast cancer, access to genetic counseling and testing are significantly lower among immigrant and refugee populations. Both patient related barriers and provider-based factors contribute to disparities in genetic referrals and testing. Previous studies addressing genetic referral patterns among the minorities have focused on African Americans, however, there are no reports addressing disparities in genetic referrals and testing in Asian immigrant and refugee populations living in the United States (US). Given the rapid influx of these populations and increasing rates of breast cancer among Asian immigrant populations in the US, this area remains unexplored. This review addresses the current data on familial breast cancer syndromes, describe the various barriers, and attempts to provide suggestions to eliminate the disparities in genetic referral patterns. Citation: Kamaraju S, Jacquart A, Stachowiak S, Geurts J, Depas M, et al. (2019) Disparities in Genetic Referrals for Breast Cancer among the Asian Immigrant Populations: How Can We Eliminate Them?. Ann Public Health Reports 3(1):35-40 Kamaraju et al. Ann Public Health Reports 2019, 3(1):35-40 Open Access | Page 36 | acterized by early-onset breast cancer, soft tissue and bone sarcomas, leukemia, broncho-alveolar cancer, adrenocortical cancer, choroid plexus, and brain cancers. The lifetime cancer risks for individuals with LFS are significant. However, cancer-specific risks for individuals with LFS are currently unknown and are likely influenced by genotype, personal risk factors, environment, and modifier genes. The risk of developing at least one LFS-associated cancer is estimated to be 50% by age 30 and 90% by age 60 [18]. A recent study reported nine different TP53 pathogenic variants in an attempt to better determine the cancer-specific risks between Korean and Caucasian patients with LFS. Two novel frameshift pathogenic variants were reported in the TP53 gene at p.Pro98Leufs*25 and p.Pro27Leufs*17. Recurrent missense pathogenic variants were also reported at codons 31 (p.Val31I1e), 175 (p.Arg175His) and 273 (p.Arg273Cys) [19]. Individuals with LFS have a high lifetime risk of developing cancer, will often develop cancer at an early age, and may develop more than one primary cancer throughout their lifetime. Although germline TP53 pathogenic variants are rare, comprehensive hereditary cancer risk assessment needs to be performed in any individual diagnosed with breast cancer under age 31 years and in families with multiple, rare tumors occurring at early ages [18]. Cowden syndrome: Pathogenic variants in the PTEN gene are associated with PTEN hamartoma tumor syndrome (PHTS) a spectrum of highly variable conditions with overlapping features including Cowden syndrome (CS) [20]. CS is characterized by hamartomas, papillomas of the lips, mucous membranes, acral skin keratosis, and macrocephaly. Affected individuals are also at an increased risk to develop breast cancer (81-85%), endometrial cancer (28%), non-medullary thyroid cancers (35%), kidney cancer (35%), colon cancer (9%), and melanoma (6%) [21]. Germline PTEN (MMAC1) analysis was performed in 12 Japanese patients with a clinical diagnosis of CS and their relatives [22]. This study reported novel missense and nonsense mutations with their novel techniques. Previous studies also demonstrated germline mutations in PTEN/MMAC1 on chromosome 10q23 in 40-80% of the patients with CS. It was concluded that further functional and molecular epidemiologic studies need to be performed to confirm phenotype-genotype associations in patients with CS, especially those of minority groups [22]. Revised PHTS clinical diagnostic criteria were proposed after a systematic search and review of the medical literature [23]. Recommendations for germline testing were made whenever possible to confirm a clinical diagnosis in the patient and to facilitate cascade testing in subsequent family members [23]. Based on an individual’s presenting clinical manifestations, healthcare professionals may also utilize Cleveland Clinic’s online risk assessment tool to estimate a patient’s likelihood of harboring a PTEN gene pathogenic variant and recommend for referral to a genetics professional to discuss genetic testing [20]. The majority of all breast cancers, in general, are sporadic, with only 5-10% being inherited. Approximately half of women with hereditary breast cancer, defined as the inheritance of a pathogenic variant in a single cancer susceptibility gene, have pathogenic variants in the BRCA1 and BRCA2 genes, also known as hereditary breast and ovarian cancer syndrome (HBOC). The remaining proportion of hereditary breast cancer is caused by moderate-risk genes, low-penetrant genes, yet undiscovered genes, or rare syndromes [8]. Individuals with a BRCA1 or BRCA2 pathogenic variant, are estimated to have an approximate 43-87% risk of breast cancer, 15-63% risk for ovarian cancer, 16-20% for prostate cancer, 1-7% risk for male breast cancer, and in some families a 7% risk or higher for pancreatic cancer [9,10]. Multiple studies have reported the prevalence of BRCA1 and BRCA2 pathogenic variants in Asians. In an unselected cohort of 826 Chinese women with ovarian cancer, there was a reported prevalence of 20.8% for BRCA1 and 7.6% for BRCA2 in the women who underwent germline analysis [11]. In carriers of pathogenic variants, late stages of disease (III-IV) was diagnosed in 85.5% of the patients at a younger age [11]. A recent study at a tertiary hospital in an Indian subcontinent demonstrated the presence of BRCA pathogenic variant in 13 cases (54%) among 24 patients who met the criteria for HBOC syndrome, suggestive of the need for a thorough evaluation for hereditary cancer syndromes in these populations [12]. Triple negative breast cancer (TNBC), a subtype of breast cancer, has been reported to have poor outcomes in African American and Latina women. Given its impact on prognosis, the presence of BRCA pathogenic variants in TNBC patients with varied demographic factors was evaluated [13]. In this retrospective study, 450 patients had evaluable genetic test results. Authors reported 139 (30.8%) BRCA1 (n = 106) or BRCA2 (n = 32) pathogenic variants. In this report, the BRCA pathogenic variant prevalence was: African American (20.4%), Ashkenazi Jewish (50%), Asian (28.5%), Caucasian (33.3%), and Hispanic (20%). The prevalence of pathogenic variants also differed by age at diagnosis: < 40 years (43.8%), 4049 years (27.4%), 50-59 years (25.3%), 60-69 years (12.5%), and > 70 years (16.6%) [13]. A BRCA1 frameshift pathogenic variant (rs80350973) has also been reported among 125 Chinese patients with TNBC with a prevalence of (7.2%) [14]. This high prevalence may lend insight to genotype-phenotype correlations for this specific patient population. Further genetic risk evaluation for HBOC syndrome should be considered in individuals with a personal history and/or a family history of the following: Breast cancer diagnosed under or equal to age 50 years, TNBC diagnosed under or equal to age 60 years, ovarian cancer, male breast cancer, pancreatic cancer, metastatic breast cancer, metastatic prostate cancer, and multiple BRCA-associated cancers in the same person [8,15-17]. Other hereditary breast cancer syndromes among