Abstract
Introduction
Genetic testing for hereditary cancer syndromes, particularly BRCA1 and BRCA2 (BRCA) germline pathogenic or likely pathogenic variants (GPVs), is critical in informing surgical decisions for women with breast cancer. Young Black women are historically underrepresented in genetic testing and research, making it essential to understand how testing timing influences treatment choices. We evaluated how the timing of BRCA testing affected surgical management among young Black women with breast cancer.
Methods
Participants were drawn from a population-based cohort of Black women diagnosed with invasive breast cancer at age 50 or younger, recruited via Florida and Tennessee cancer registries. Data were collected through structured questionnaires, electronic health records, and lab reports, including information on genetic testing, BRCA status, and treatment. Participants were categorized by timing of BRCA testing (pre-surgical vs post-surgical) and GPV status. Chi-squared tests assessed associations between testing timing, BRCA status, and surgical treatment.
Results
Among 633 participants, people with a BRCA GPV who were tested before surgery (n = 29) were significantly more likely to undergo bilateral mastectomy (82.8%) than those tested after surgery (40%). Timing of testing and BRCA status were both strongly associated with surgery received (P < 0.0001).
Conclusion
BRCA testing at diagnosis and prior to surgery is significantly associated with surgical management in young Black women with breast cancer. These findings highlight the importance of timely genetic testing, especially in populations with historically lower testing rates.
Plain Language Summary
Many women with breast cancer receive genetic testing to find out if they have inherited mutations that increase their risk for future cancers. This information can help guide decisions about surgery, such as whether to remove one or both breasts. However, young Black women are less likely to receive genetic testing early in their treatment. This study examined how the timing of genetic testing affected surgical choices in young Black women with breast cancer. We found that women who received testing before surgery were more likely to choose a more aggressive surgery that could lower their future cancer risk. These findings suggest that offering genetic testing earlier in the treatment process may help women make more informed decisions. This research highlights the need to improve access to timely genetic testing, especially for Black women who have historically faced barriers in cancer care.
Introduction
Breast cancer is the most commonly diagnosed cancer among women in the United States, with over 297 000 cases expected in 2023. 1 Approximately 5% of unselected breast cancers are attributed to germline pathogenic or likely pathogenic variants (GPVs) in high-penetrance inherited susceptibility genes, primarily occurring in the BRCA1 and BRCA2 (BRCA) genes.2-5 The prevalence of BRCA GPVs in specific high-risk subgroups including women diagnosed with breast cancer under age 50 and women with triple negative breast cancer (TNBC) is estimated to range from 10-30%.6-9 Importantly, identifying BRCA GPVs at the time of breast cancer diagnosis can impact treatment decisions, particularly regarding surgical choices. 10 Current guidelines through the American Society for Clinical Oncology and the National Comprehensive Cancer Network include germline testing for high penetrance breast cancer susceptibility genes, including the BRCA genes, as a consideration for any patient diagnosed with breast cancer under the age of 65, and testing is recommended for those diagnosed under the age of 50 or having TNBC.11,12
Among people with a BRCA GPV, the risk of developing a second primary breast cancer is significantly higher than in the general population, with younger age at diagnosis linked to even greater risk.13,14 For women diagnosed with premenopausal breast cancer with a BRCA GPV, the risk of developing contralateral breast cancer is estimated to be between 30 to 40%.15,16 Consequently, BRCA status may greatly influence surgical decision-making, including the choice of risk-reducing bilateral mastectomy (RRM), which has been associated with a reduction of risk of contralateral breast cancer.17,18 Rates of RRM among people with BRCA GPVs vary from 18% to 42% with limited data about variation between racial and ethnic groups.17,19
Although Black women have disproportionately higher rates of early-onset breast cancer and TNBC, studies indicate that they are less likely to receive testing compared to White women.6,18 This racial disparity is influenced by a combination of systemic, socioeconomic, and cultural factors. 20 Understanding how the timing of genetic testing affects surgical decision-making among Black women with breast cancer is essential to address this gap and improve outcomes. Critically, prior research involving a population-based sample of Black women diagnosed with breast cancer at or below the age of 50 found that 12.4% of participants had a BRCA GPV, an estimate considerably higher than estimates in general unselected predominantly White breast cancer patients. 21
Medical mistrust and concerns regarding the use of genetic data may contribute to the underutilization of genetic testing among Black women.6,22 However, evidence suggests that when genetic testing is offered, Black women are just as likely to be interested in and act on the information as other groups. 18 Despite this, there remains limited data on how genetic testing impacts surgical decision-making for young Black women. Our study aimed to assess the association between the timing of BRCA testing and surgical management among young Black women with breast cancer.
Materials and Methods
Study Population
The study population was derived from the Black Women with Breast Cancer: Etiology, Survival, and Treatment Outcomes (BEST) study, a population-based longitudinal cohort of self-identified Black women diagnosed with invasive breast cancer at or below age 50 between 2005 and 2018. 23 Women were recruited through state cancer registries in Florida and Tennessee, spoke English, and were alive at the time of recruitment. Participants completed written informed consent, a baseline questionnaire including information on their breast cancer treatment received, and provided access to medical records. All participants provided written informed consent prior to their inclusion in the study. The consent process included a detailed explanation of the study’s purpose, procedures, potential risks, and benefits. Participants were informed of their right to withdraw from the study at any time without penalty.
All participants completed their initial curative intent treatment prior to their enrollment into the BEST study. Additionally, usual care prior to study enrollment could include genetic testing as part of their clinical care. For those participants who received germline genetic testing prior to study entry, test reports were requested to confirm results of genetic testing. Regardless of the participants’ prior receipt of genetic testing, all women were offered genetic testing through a mailed saliva kit to extract DNA and conduct multigene panel testing for inherited cancer predisposition through the research study. All participants were offered education about inherited cancer through the study, and those identified with a GPV were offered counseling under the supervision of a board-certified genetics professional. Additional details of study recruitment have been described elsewhere. 24
For the present retrospective cohort analysis, of the 785 BEST participants in the parent study, we excluded women missing data on stage at diagnosis (n = 30), those with stage IV disease at diagnosis (n = 27), with bilateral breast cancer (n = 36), those missing timing of genetic testing (n = 45), or missing timing of surgery (n = 14) yielding a final analytic sample of 633. The median time between breast cancer diagnosis and enrollment into the BEST study was 2.5 years with an Interquartile range of 1.4 to 5.5 years. Of the analytic sample, 44% (n = 280) received cancer germline testing prior to entering the BEST cohort. For this retrospective cohort analysis, participants were classified into one of four groups based on the timing of genetic testing and BRCA carrier status: (1) Tested prior to surgery, BRCA GPV; (2) Tested prior to surgery, no BRCA GPV; (3) Tested after surgery, BRCA GPV; and (4) Tested after surgery, no BRCA GPV. Genetic testing results and BRCA status were confirmed via medical records or test reports. The primary outcome of interest was the type of breast surgery received. Surgical treatment was categorized as either Contralateral Prophylactic Mastectomy (RRM) or unilateral surgery, which included mastectomy or breast-conserving surgery. Treatment data were harmonized from medical records, cancer registry files, and patient-reported data, prioritizing medical records when available. All direct patient identifiers are removed for this analysis as is always done to protect patient confidentiality, and results are reported in aggregate thus identity of any individual participant cannot be ascertained.
Statistical Analysis
Bivariate chi-squared tests were performed to assess the relationship between the timing of genetic testing and the type of surgical treatment received. All analyses were carried out in SAS version 9.4.
Ethical Considerations
This study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board (or Ethics Committee) of Vanderbilt University Medical Center (IRB# 170 233) with original approval on 2/23/2017 and most recent continuing review approval on 1/15/2025, as well as the Florida Department of Health (Study Number: 2011-05-VBU) and the Tennessee Department of Health IRBs (Study Number: TDHIRB-2019-0139) with most recent continuing review approvals on 2/12/2025 and 6/2/2025, respectively. This investigation followed the Strengthening the Reporting of Observational Studies in Epidemiology Guidelines. 25
Results
Characteristics of the Study Population
A total of 180 (28.4%) participants underwent genetic testing before surgery, of whom 29 (16.1%) had BRCA GPV and 151 (83.9%) did not. Among the 453 (71.6%) tested after surgery, 40 (8.8%) had BRCA GPV and 413 (91.2%) did not. Overall, 32.7% (n = 207) of participants received a RRM. This proportion varied markedly by BRCA status and timing of testing (P < 0.0001). Among participants with a BRCA GPV tested before surgery (n = 29), 82.8% (n = 24) received a RRM. In contrast, only 40% (n = 16) women with a BRCA GPV tested after surgery (n = 40) underwent RRM (Figure 1). Among participants who were tested before surgery but did not have a BRCA GPV (n = 151), 37.7% (n = 57) received a RRM. Among participants with a BRCA GPV tested prior to surgery (n = 29), 75.9% (n = 22) had TNBC (P < 0.0001). Study population flow diagram
Discussion
Our study provides important insights into how the timing of BRCA genetic testing influences surgical management among young Black women with breast cancer, a population historically underrepresented in genetic research and clinical trials. We found that women who were aware of their BRCA GPV status prior to surgery were significantly more likely to undergo bilateral mastectomy, a pattern consistent with prior studies conducted in predominantly White populations.26-30
The association between preoperative BRCA knowledge and increased rates of RRM has been well-documented. In a single-institution study of people with a BRCA GPV with breast cancer, 68% of women tested at diagnosis received bilateral mastectomy compared to only 8% of those tested after completing treatment. 26 Similarly, a U.K.-based study found rates of 88% vs 39% for testing before vs after surgery, respectively. 27 In the United States, Chiba et al (2016) reported that 82.5% of people with a BRCA GPV who knew their BRCA GPV status before surgery opted for RRM, compared to only 29% of those who learned their status postoperatively. 30 Additionally, Yadav et al (2017) found that 76.4% of women aware of their BRCA status before surgery chose contralateral prophylactic mastectomy, compared to just 14.7% of those unaware. 29 In a commercially insured population in the United States, 86.5% people with a BRCA GPV tested before surgery underwent bilateral mastectomy compared to 43.8% who were tested after. 28 Taken together, these findings are consistent with our study findings, where 82.8% of people with a BRCA GPV tested before surgery underwent bilateral mastectomy, compared to 40% of those tested after surgery. All prior studies had limited representation of Black participants, and none conducted subgroup analyses. Consequently, our findings extend this evidence base to young Black women, highlighting similar patterns in surgical decision-making.
Importantly, there was a greater percentage of participants with a BRCA GPV tested before surgery, than after surgery, potentially suggesting a level of patient activation among a subset of high-risk women. There remain critical gaps in reaching eligible individuals who were not tested prior to surgical treatment. Potential reasons for not testing involve a lack of provider recommendation, lack of knowledge about patient eligibility, or limited perceived utility of germline testing following curative intent treatment.18,31-34 Additionally, for the case of women tested after surgery, it is possible that women tested after all curative intent treatment has been received are less willing to undergo further treatment, underscoring the importance of optimal timing. Our study is strengthened by the inclusion of young Black women across multiple healthcare systems and insurance types, allowing for a broader perspective on care delivery patterns in a population disproportionately affected by cancer care inequities.
Notably, we observed that a substantial proportion (37.7%) of women tested before surgery who did not have a BRCA GPV also underwent bilateral mastectomy. This may reflect heightened anxiety, misperceptions of risk, or provider influence and highlights the need for nuanced pre-test counseling to ensure informed decision-making.35,36 Prior research has shown that even in the absence of a GPV, some women choose bilateral due to family history or perceived risk. 37 Surgical decision-making for breast cancer is influenced by many clinical and non-clinical factors, including access to health care, concerns for cancer recurrence breast density, tumor characteristics such as size of tumor and location, aesthetics and symmetry, as well as the impact of surgery on body image and sexuality.35,36,38-44
Another key finding is the high prevalence of triple-negative breast cancer among women with BRCA GPVs tested before surgery (75.9%). TNBC is more common in people with BRCA1 GPVs and in Black women, and is associated with more aggressive disease and fewer targeted treatment options. 45 This may further motivate patients and providers to consider bilateral mastectomy as a risk-reducing strategy. 27
Many studies have explored different ways to increase timely genetic testing among guideline recommended populations. Some of these interventions have been at the health system level including reflex testing, the automatic testing of eligible individuals, expansion of telegenetics programs, and multi-gene panel testing.46-48 Other efforts have involved more community-based outreach to improve trust and healthcare system engagement among marginalized populations.34,49 At the policy level, there has been expanded coverage of cancer genetic testing including by state Medicaid programs thereby improving access.50,51 To continue to improve timely genetic testing requires multi-factorial individual, system-level, and policy approaches in order to fully maximize the clinical benefit for all populations.
Our study has several strengths, including the utilization of a population-based cohort of young Black women treated across both academic and community health centers with diverse socioeconomic backgrounds. Another strength is that all participants were offered genetic testing, either as part of routine standard of care or as part of the research study, which has enabled us to evaluate how timing of genetic testing affects surgical management. A limitation of this study is that the overall sample of germline BRCA GPVs was relatively small, limiting our ability to conduct regression analyses. Further, breast cancer surgical decision-making is influenced by a wide variety of non-clinical factors including patient preference. We did not have additional patient-level context that may be relevant to surgical decision-making. Additionally, due to the population-based recruitment employed in this study, and the diverse healthcare settings from which participants have been treated, we do not have precise treatment timing information to calculate exact days between testing and surgery. However, understanding the relative testing timing, whether it happened before or after surgery, provides critical insight into the cancer care delivery of this population.
Conclusions
Our findings suggest that young Black women with breast cancer who are aware of their germline BRCA carrier status before surgery are significantly more likely to undergo bilateral mastectomy. As genetic testing becomes more widely recommended and accessible, ensuring timely germline testing among populations particularly burdened by cancer disparities will be critical to supporting informed treatment decision-making and equitable cancer care.
Footnotes
Ethical Consideration
The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board (or Ethics Committee) of Vanderbilt University Medical Center (IRB# 170 233) with original approval on 2/23/2017 and most recent continuing review approval on 1/15/2025, as well as the Florida Department of Health (Study Number: 2011-05-VBU) and the Tennessee Department of Health IRBs (Study Number: TDHIRB-2019-0139) with most recent continuing review approvals on 2/12/2025 and 6/2/2025, respectively.
Consent to Participate
All participants provided written informed consent prior to their inclusion in the study. The consent process included a detailed explanation of the study’s purpose, procedures, potential risks, and benefits. Participants were informed of their right to withdraw from the study at any time without penalty.
Consent for Publication
Not applicable. All data included in this publication was pooled with no individual-level data.
Author Contributions
Conceptualization, MLR, KM, TP, SR; methodology, MLR; software, MLR; formal analysis, MLR; investigation, All Authors; resources, MLR, TP; data curation, MLR, AW, LV; writing—original draft preparation, MLR, JAB; writing—review and editing, All Authors; visualization, MLR, TP; supervision, TP; project administration, AW; funding acquisition, MLR, TP. All authors have read and agreed to the published version of the manuscript.
Funding
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work has been supported in part by NCI grant R01CA204819 (TP), Susan G. Komen SAC210105 (TP), and NCATS UL1 TR000445. MLR is funded by the American Association for Cancer Research in Partnership with Victoria’s Secret and Pelotonia Career Development Award (22-20-73-ROBE), Breast Cancer Research Foundation grant HEI-25-011 (TP and SR).
Declaration of Conflicting Interests
The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: MLR receives consulting fees from the National Committee for Quality Assurance, Outside the scope of the submitted work. MLR receives research grant support paid to her institution by Gilead Sciences outside the scope of the submitted work. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.
Data Availability Statement
The data that support the findings of this study are not publicly available due to their highly identifiable nature and the sensitive information they contain. Access to the data may be granted upon completion of all required data use agreements and institutional approvals upon reasonable request. Interested researchers should contact the corresponding author for further information.