Uptake of genetic testing for germline BRCA1/2 pathogenic variants in a predominantly Hispanic population

Abstract

Background

Genetic counseling is under-utilized in women who meet family history criteria for BRCA1 and BRCA2 (BRCA1/2) testing, particularly among racial/ethnic minorities. We evaluated the uptake of BRCA1/2 genetic testing among women presenting for screening mammography in a predominantly Hispanic, low-income population of Washington Heights in New York City.

Methods

We administered the Six-Point Scale (SPS) to women presenting for screening mammography at Columbia University Irving Medical Center (CUIMC) in the Washington Heights neighborhood of New York, NY. The SPS is a family history screener to determine eligibility for BRCA1/2 genetic testing based upon U.S. Preventive Services Task Force (USPSTF) guidelines that has been validated in low-income, multiethnic populations.

Results

Among women who underwent screening mammography at CUIMC between November 2014 and June 2016, 3,055 completed the SPS family history screener. Participants were predominantly Hispanic (76.7%), and 12% met family history criteria for BRCA1/2 testing, of whom <5% had previously undergone testing.

Conclusions

In a multiethnic population, a significant proportion met family history criteria for BRCA1/2 testing, but uptake of genetic testing was low. Such underutilization of BRCA1/2 genetic testing among minorities further underscores the need to develop programs to engage high-risk women from underrepresented populations in genetic testing services.

Introduction

The majority of hereditary breast and ovarian cancers (HBOC) result from pathogenic variants in the BRCA1 and BRCA2 genes. Women with germline BRCA1/2 mutations have estimated risks of 40–87% and 18–88% for breast cancer, respectively [1]. The U.S. Preventive Services Task Force (USPSTF) recommends that women whose family history may be associated with an increased risk of BRCA1/2 pathogenic variants undergo genetic counseling and/or testing [2]. However, uptake of genetic counseling for women at high risk for HBOC remains low, even among women with breast cancer [3]. Barriers to genetic counseling include patients’ lack of knowledge of personal medical history and cancer risk, inaccuracies and inconsistencies in documentation of family history of cancer [4–7], and failure of primary care providers and cancer specialists to obtain adequate family cancer histories in order to refer patients at risk for hereditary cancer to genetic counselors [8–10].

Minority populations are even less likely to undergo genetic counseling/testing for HBOC. Among women diagnosed with breast cancer or with a family history of breast and/or ovarian cancer, Hispanic and black women are less likely than white women to undergo testing for BRCA1/2 pathogenic variants, with odds ratios as low as 0.22 [11–13]. Factors that contribute to lower utilization of genetic counseling among minorities include poor understanding of genetic testing, low perception of personal cancer risk, and decreased frequency of reporting of family history compared to whites [14–17]. Despite these limitations, when provided with information about hereditary cancer, Hispanic women express high levels of interest in undergoing genetic counseling/testing, and when offered BRCA1/2 testing based on eligibility, high proportions complete testing [14, 18].

We evaluated the uptake of BRCA1/2 genetic testing among women presenting for screening mammography in a predominantly Hispanic, low-income population of Washington Heights in New York City.

Materials and Methods

We conducted a prospective study called the Know Your Risk: Assessment at Screening (KYRAS)[19]. Women were approached for enrollment during routine screening mammography at the Avon Breast Imaging Center at Columbia University Irving Medical Center (CUIMC) in the Washington Heights neighborhood of New York, NY, and provided written informed consent to complete a baseline survey and to allow access to their electronic health record (EHR). The inclusion criteria included: 1) women age ≥18 years, 2) English or Spanish-speaking, 3) no previous diagnosis of breast cancer. The study was approved by the Institutional Review Board at CUIMC.

We administered a questionnaire collecting information about sociodemographic characteristics, breast cancer risk factors, and prior BRCA1/2 genetic testing. The Gail model was used to estimate 5-year risk of invasive breast cancer [20]. The questionnaire included the Six-Point Scale (SPS), a family history screener to determine eligibility for BRCA1/2 genetic testing based upon USPSTF guidelines that has been validated in populations of low income, multiethnic women [21, 22]. The SPS is a simplified questionnaire that can be administered in a low-cost, efficient manner, consisting of ten questions that assess eligibility for HBOC genetic testing based upon USPSTF guidelines. The SPS includes questions regarding personal history of breast or ovarian cancer, as well as Jewish ancestry, family history of male breast cancer or ovarian cancer, and history of breast cancer among first- and second-degree female relatives. A score of six or higher on this scale indicates eligibility for HBOC genetic counseling and/or testing.

Results

Of 18,502 women who underwent screening mammography at CUIMC between November 2014 and June 2016, 3,558 (19.2%) were approached for participation, 3,055 (85.9% of total approached) completed the SPS family history screener, and 503 (14.1% of total approached) refused participation (Figure 1). The baseline characteristics of women eligible for genetic testing are presented in Table 1. The median age was 58 years (range 29 to 91). Over two-thirds (N = 253) were Hispanic, approximately 11% (N = 39) reported being of Ashkenazi Jewish descent, and about half (N = 190) had a high school education or less. These demographic characteristics were similar to those among the 9,514 of the 18,502 women for whom ethnicity data was available by questionnaire or by EHR data, as published previously [23]. Over 75% of women reported a family history of breast cancer and over 40% a family history of ovarian cancer. About 12% (N=369) women were eligible for genetic testing by the SPS, but only 4.6% (N=17) of eligible women had previously undergone BRCA1/2 genetic testing based upon self-report and EHR review. Fourteen women not eligible for genetic testing by the SPS had undergone genetic testing.

Figure 1.

Flow diagram for the population approached at screening mammography for participation and completion of questionnaire, with responses to questions regarding previous testing for BRCA1/2 pathogenic variants.

Table 1.

Baseline characteristics of women who completed the Six-Point Scale (SPS) family history screener, stratified by eligibility for BRCA1/2 genetic counseling and/or testing.

Characteristic	Eligible (n=369)	Ineligible (n=2686)	Total (n=3055)
Median age, years (range)	58(29 – 91)	59 (33 – 99)	59 (29 – 99)
Race/Ethnicity, N (%)
Hispanic	249 (67.5)	2093 (77.9)	2342 (76.7)
White, Non-Hispanic	74 (20.1)	245 (9.1)	319 (10.4)
Black, Non-Hispanic	33 (8.9)	257 (9.6)	290 (9.5)
Asian	7 (1.9)	48 (1.8)	55 (1.8)
Other	6 (1.6)	43 (1.6)	49 (1.6)
Ashkenazi Jewish descent, N (%)	42 (11.4)	44 (1.6)	86 (2.8)
Highest level of education, N (%)
High school diploma, GED, or less	185 (50.1)	1666 (62.0)	1851 (60.6)
Vocational, technical, or military	5 (1.4)	38 (1.4)	43 (1.4)
Some college or university	56 (15.2)	342 (12.7)	398 (13.0)
Associate’s or bachelor’s degree	56 (15.2)	390 (14.5)	446 (14.6)
Graduate or professional degree	67 (18.2)	247 (9.2)	314 (10.3)
Unknown		3 (0.1)	3 (0.1)
Family history of breast cancer, N (%)	292 (79.1)	527 (19.6)	819 (26.8)
Family history of ovarian cancer, N (%)	149 (40.4)	141 (5.2)	290 (9.5)
Reported prior BRCA1/2 testing, N (%)	17 (4.6)	14 (0.5)	31 (1.0)
Negative genetic test result	13 (3.5)	11 (0.4)	12 (0.4)
Pathogenic variant in BRCA1/2	2 (0.5)	0 (0.0)	1 (0.0)
Unknown result	2 (0.5)	3 (0.1)	4 (0.1)

Discussion

We found that in our multiethnic, predominantly Hispanic population presenting for screening mammography, genetic testing for HBOC was significantly underutilized. While 12% of the women who completed the SPS family history screener were eligible for HBOC genetic counseling/testing, less than 5% of those eligible reported previous testing for BRCA1/2 pathogenic variants. This finding of underutilization of HBOC genetic testing among minorities is in agreement with previous studies [11–13].

Such underutilization of HBOC genetic testing among minorities further underscores the need to develop programs to effectively engage high-risk women from underrepresented populations in genetic testing services. Efforts to increase education about and uptake of HBOC genetic counseling/testing have increasingly focused on the use of computer-based decision aids (DAs) for both patients and providers, including online family pedigree tools such as iPrevent, Pedigree Assessment Tool (PAT), OPERA, and Cancer in the Family [24–27]. A recent systematic review of decision aids for cancer care decisions, including genetic testing, found that the use of decision aids resulted in improved patient knowledge and accuracy of risk perception, decreased decisional conflict, reduced clinician-directed decision making, and fewer patients being indecisive[28]. Our research group has developed a web-based decision aid for patients and an EHR-embedded breast cancer risk navigation tool for primary care providers. We are currently evaluating their effectiveness in increasing appropriate uptake of BRCA1/2 genetic counseling in a randomized controlled trial [29]. Our goals are to better integrate HBOC risk assessment into primary care and expand access to BRCA1/2 testing to a broader population of high-risk women.

Another challenge to expanding access to genetic testing and counseling for hereditary breast and ovarian cancer is that current guidelines for eligibility have the potential to miss women with pathogenic variants, including in BRCA1/2. Recently, an analysis of nearly 1,000 women with a diagnosis of breast cancer who had not previously undergone single- or multigene testing found that approximately half of the women did not meet National Comprehensive Cancer Network (NCCN) guidelines for genetic testing; however, when these women subsequently underwent multigene panel testing, the percentage who were found to have pathogenic or likely pathogenic variants was similar between the groups of women meeting and not meeting NCCN guidelines (9.4% vs. 7.9%, respectively, with p=0.4241) [30]. These findings highlight the limitations of current family history guidelines in identifying women who would benefit from genetic counseling and testing services for HBOC, even among patients already diagnosed with breast cancer. There has been discussion not only about modifying current guidelines to refer all women diagnosed with breast cancer for genetic testing regardless of family history, but also about implementing universal screening in the general population. A decision-analytic model evaluating the cost-effectiveness of family history-based BRCA1/2 testing compared to population-based multigene panel testing for BRCA1/2 and other moderaterisk pathogenic variants associated with HBOC in the U.S. and U.K. found that population-based testing was more cost-effective and was projected to prevent 1.86% of breast cancers in the U.K. and 1.91% in the U.S.[31]. However, the penetrance of breast and ovarian cancer in carriers of non-BRCA1/2 pathogenic variants is less well-defined, and variants of unknown significance (VUS) can be discovered as part of a multi-gene analysis, leading to potential clinical confusion and unnecessary testing, procedures, anxiety, and costs. As such, the challenge going forward in adopting broader screening guidelines for HBOC is to balance the benefits of identifying women with pathogenic variants who might benefit from additional screening and cancer prevention with the potential harms of over-testing.

The strengths of our study are the multiethnic, predominantly Hispanic population, which is underrepresented in research on HBOC genetic testing. Potential limitations include the recruitment of participants from a single institution at an urban academic medical center and from a population already actively engaged in screening mammography and potentially more likely to have access to the medical system.

In summary, our study identified significant underutilization of genetic counseling/testing for hereditary breast and ovarian cancer in a multiethnic, predominantly Hispanic and less educated population. Further efforts should be made to develop programs to effectively engage high-risk women from underrepresented populations in genetic testing services, as well as to explore potential limitations to current guidelines for HBOC screening that might further contribute to poor uptake of these services.