Testing For Breast Cancer Research Articles

BRCA testing and management of BRCA-mutated early-stage breast cancer: a comprehensive statement by expert group from GCC region.

BReast CAncer (BRCA)1 and BRCA2 gene pathogenic variants account for most hereditary breast cancers (BC). Identification of BRCA mutations can significantly influence both prognosis and treatment outcomes. Furthermore, it enables the identification of individuals who are at heightened risk of developing BC due to inherited genetic mutations. Many developing countries rely on western guidelines for BRCA testing and BC management; however, there exist wide disparities in the prevalence of risk factors, availability of medical resources, and practice patterns. Guidelines tailored to specific regions can help mitigate healthcare variations, promote consistency in treatment, and aid healthcare providers in identifying effective therapies for improving patient outcomes. Hence, oncologists from the Gulf Cooperation Council (GCC) congregated virtually in March 2023 and reviewed existing data on the epidemiology of BC, BRCA mutations, practices and challenges associated with BRCA testing and management of BRCA mutated early-stage BC in the GCC region. They also provided insights on the real-world diagnostic and treatment practices and challenges in the GCC region in the BRCA-mutated early-stage BC domain and suggested some variations to international guidelines to aid their uptake in this region.

Additional prognostic value of the BCT score in patients with ER+HER2- breast cancer receiving 21-gene assay–guided adjuvant treatments.

548 Background: In early estrogen receptor (ER)+HER2- breast cancer, a 21-gene expression assay-guided decision-making for adjuvant treatments has been widely utilized as a standard-of-care. The GenesWell BCT is a multigene assay that is designed to predict the risk of distant recurrence (DR) in patients with ER+HER2- breast cancer. This assay consists of nine genes, which are used to generate a risk score that can help guide treatment decisions. We addressed an additional value of the GenesWell Breast Cancer Test (BCT) score using the cohort of ER+HER2- breast cancer patients receiving a 21-gene assay-guided adjuvant treatments, focusing the chemotherapy untreated subset with low 21-gene recurrence score (RS). Methods: This multicentre, observational follow-up study was done in 4 academic institutions in South Korea. Patients with ER+HER2- breast cancer who received RS-guided adjuvant treatments were enrolled. A total of 705 patients were included. Of these, the rate of women with node-positive disease was 21.6% (152/705), and the rate of women with younger than 50 years old was 61.4% (433/705). The BCT score was obtained using the specimens which were previously analyzed for RS. The primary endpoint was recurrence-free survival (RFS), and the secondary endpoint was distant recurrence-free survival (DRFS). Results: Among the 705 patients, the RS assigned 110 (15.6%) as high risk (≥26), whereas the BCT score assigned 239 (33.9%) as high risk (≥4). The agreement between two tests was noted in 494 (70.1%); concordances were made in 69 for high and in 425 for low, respectively. At a median follow up of 85 months, 80 had tumor recurrences, 38 had distant recurrences, and the 7-year RFS was 90.0% (95% CI, 87.6%-92.5%). In the 595 patients with low RS, 556 (93.4%) did not receive adjuvant chemotherapy. Within the 556 chemotherapy-untreated patients with low RS, the RFS differed significantly according to the BCT score ( p= .014); the 7-year RFS was 92.9% in the BCT-low, while it was 85.7% in the BCT-high. Within the group, the BCT score was demonstrated as an independent prognostic factor for both RFS and DRFS adjustment of tumor size, nodal stage, and histologic grade. In addition, the RFS of the low-BCT score group was superior to that of the high-BCT group in either women younger than 50 years of age with an RS of 21 to 25 or all women with an RS of 21 to 25. Conclusions: We found that the BCT score was useful in stratifying the risk of relapse in chemotherapy-untreated patients with a low recurrence score (RS). This indicates that the BCT score could provide additional clinical value in identifying patients with a long-term risk of relapse, particularly in young women with an RS of 21 to 25.

Improving Rates of Germline BRCA Mutation Testing for Patients With Ovarian Cancer in Vancouver Island, British Columbia, Canada.

Despite more than a decade of endorsement from multiple international cancer authorities advocating all women with ovarian cancer be offered germline breast cancer (BRCA) gene testing, British Columbia Cancer Victoria was not meeting this target. A quality improvement project was undertaken with the aim of increasing completed BRCA testing rates for all eligible patients seen at British Columbia Cancer Victoria to > 90% by 1 year from April 2016. A current state analysis was completed, and multiple change ideas were developed, including education of medical oncologists, referral process update, initiating a group consenting seminar, and engagement of a nurse practitioner to lead the seminar. We used a retrospective chart audit from December 2014 to February 2018. On April 15, 2016, we initiated our Plan, Do, Study, Act (PDSA) cycles and completed them on February 28, 2018. We evaluated sustainability through an additional retrospective chart audit from January 2021 to August 2021. Patients with completed germline BRCA genetic testing climbed from an average of 58%-89% per month. Before our project, patients waited on average 243 days (± 214) for their genetic test results. After implementation, patients received results within 118 days (± 98). This was sustained with an average of 83% of patients per month having completed germline BRCA testing almost 3 years after project completion. Our quality improvement initiative resulted in a sustained increase in germline BRCA test completion for eligible patients with ovarian cancer.

Barriers to BRCA, HRD, and HRRm testing despite increased utilization: U.S. physician survey results.

380 Background: Despite increasing use of breast cancer (BRCA) gene and homologous recombination deficiency/ homologous recombination repair gene mutation(s) (HRD/HRRm) testing, barriers to uniform adoption of these tests to inform patient management remain. The purpose of this study was to identify potential barriers to BRCA, HRD, and HRRm testing from the physician’s perspective. Methods: A cross-sectional online survey was sent to a US representative sample of primary care providers, medical oncologists, urologists, and surgeons, including both users and non-users of the tests. Physician demographics, practice characteristics, barriers (reimbursement, knowledge, logistical), and strategies to alleviate barriers were collected. Descriptive analysis was conducted via SASv9.4. Results: Three hundred physicians participated in this survey (49.7 years of age and 17.9 years in clinical practice on average). Most respondents (94.3%) reported at least 1 barrier to test use (BRCA 94.0%, HRD 91.3%, HRRm 90.3%). The most common barrier was the challenge in obtaining prior authorizations (BRCA 74.0%, HRD 80.0%, HRRm 83.5%). Other commonly reported barriers included test not being covered by insurance (BRCA 64.8%, HRD 61.8%, HRRm 67.6%), insurance policies restricting certain genomic tests to a particular lab/test provider (BRCA 64.0%, HRD 66.5%, HRRm 67.4%), and unclear/inconsistent payer policies for test coverage (BRCA 63.6%, HRD 63.6%, HRRm 66.7%). Physicians were more likely to report barriers to HRD/HRRm testing compared to BRCA testing. More reimbursement-related barriers were reported by primary care providers vs. other physicians. Physician/patient education, collaboration with specialists, standardization in test guidelines, and improvement in test interpretation were reported as key strategies to improving further test adoption in patient management. Conclusions: The results highlight that physicians have concerns about reimbursement-related, knowledge-related, and logistical barriers that may impact clinical optimization. Addressing these barriers to improve oncology care is of utmost importance.[Table: see text]

Predicting the Response of Neoadjuvant Chemotherapy in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer With Axillary Lymph Node Metastasis by Multigene Assay.

The GenesWell™ breast cancer test (BCT) is a recently developed multigene assay that predicts the risk of distant recurrence in patients with hormone receptor-positive (HR+) and human epidermal growth factor-2 negative (HER2-) early breast cancer (BC). The ability of this assay to predict the response to neoadjuvant chemotherapy (NACT) has not been established to date. Biopsy specimens from HR+/HER2- BC patients with axillary lymph node (LN) metastasis who underwent NACT were analyzed using the BCT score. The modified BCT score was developed and patients classified into high-and low-response groups. A total of 88 patients were available for the BCT score among the 108 eligible patients. The median follow-up duration was 35.9 (7.8-128.5) months. Among them, 61 (65.1%) had cN1 and 53 (60.2%) had cT1 or cT2 disease. The BCT score was low in 25 (28.4%) patients and high in 63 (71.6%). Among the 50 patients with pathologic complete response or partial response, 41 (82.0%) were in the high BCT score group and 9 (18.0%) were in the low BCT score group. Among the 38 patients with stable or progressive disease, 22 (57.9%) were in the high BCT score group and 16 (42.1%) were in the low BCT score group (p = 0.025). Ki-67 before NACT was a significant factor for predicting tumor response (p = 0.006; 3.81 [1.50-10.16]). The BCT score showed a significant response to NACT (p = 0.016; 4.18 [1.34-14.28]). Distant metastasis-free survival was significantly different between the high- and low-response groups (p = 0.004). We demonstrated that the BCT score predicts NACT responsiveness in HR+/HER2- BC with LN metastasis and might help determine whether NACT should be performed. Further studies are required to validate these results.

Incorporating of telementoring (Project ECHO) into practice: Efficacy of Point Of Service Testing-Breast Cancer (ePOST-BC).

113 Background: An estimated 327,630 breast cancers (BC) will be diagnosed in the US in 2020, and as high as 14% (45,868) may be related to a hereditary cancer syndrome. Testing eligible patients in clinical practice is hindered by multiple barriers including time, available workforce, cost, lack of organizational pathways, provider knowledge, as well as health disparities. To address some of these barriers, our team provided a telementoring and process improvement intervention for cancer care programs primarily serving rural patients across Kansas and Western Missouri using Project ECHO. We aimed to improve the process surrounding access to genetic education and testing for patients with BC. Methods: Rural and community cancer care teams were invited by the Masonic Cancer Alliance, the outreach arm of the University of Kansas Cancer Center, to participate in ePOST-BC. Five 1-hour Project ECHO sessions (community building, didactic, and case-based learning) covered topics included: 1) essential elements of HCS and genetic testing, 2) guidelines for genetic testing in BC 3) enhanced understanding of risk, screening, and management including precision medicine in HCS, and 4) overcoming barriers to genetic testing and management in low resource settings. Provider and practice readiness was assessed using the Organizational Readiness for Implementing Change survey. A REDCap database was used for registration, surveys and data collection. Results: Ten practices (6 = metro; 4 = rural) participated in the telementoring sessions and five practices participated in the optional process improvement intervention. Provider and clinic interest and participation was high and readiness was varied. Improvements were identified in knowledge, readiness, and patient access to genetic education and testing. The level of engagement in process improvement was impacted by an identified champion (either MD and/or APP), organizational commitment, and motivator (i.e., accreditation standard, business development). Conclusions: Rural and community oncology providers are interested and willing to engage in telementoring to improve implementation of point of service genetic education and testing. This improves provider knowledge, readiness and implementation of testing. Demonstrating a change in testing completion for eligible patients is difficult in a community setting without intensive data collection. Next steps include the incorporation of technology and standardized tools into practice to address provider and care team burden.

Trends in access to female cancer screening in Brazil, 2007-16.

This study aims to analyse changes in the prevalence of cervical cancer (CCa) and breast cancer (BCa) screening among women in the Brazilian capitals and Federal District in the last decade (2007-16). Data from the surveillance system of risk and protective factors for chronic diseases through telephone interviews (n=267 949) were used. Adequate screening consisted of, at least, one Pap test triennially, for women aged between 25 and 64years, and mammography exam biannually, for women aged between 50 and 69years. The prevalence of adequate screening was investigated for each type of cancer isolated and combined (women aged between 50 and 64years). The prevalence of adequate screening was estimated for the total population and according to socioeconomic variables. Linear regression models were used. The prevalence of adequate screening test for CCa remained stable, around 82%, while the screening test for BCa increased from 71 to 78% between 2007 and 2016. Higher increases were observed among women with low schooling and from less developed regions. The percentage of adequate screening (considering both types), for women aged between 25 and 69years, remained stable, close to 78%. Screening for BCa increased significantly. Smaller coverage rates are verified among women with low schooling and from less developed regions.

Comparison of GenesWell BCT Score With Oncotype DX Recurrence Score for Risk Classification in Asian Women With Hormone Receptor-Positive, HER2-Negative Early Breast Cancer.

Introduction: The GenesWell Breast Cancer Test (BCT) is a recently developed multigene assay that predicts the risk of distant recurrence in patients with early breast cancer. Here, we analyzed the concordance of the BCT score with the Oncotype DX recurrence score (RS) for risk stratification in Asian patients with pN0-N1, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer.Methods: Formalin-fixed, paraffin-embedded breast cancer tissues previously analyzed using the Oncotype DX test were assessed using the GenesWell BCT test. The risk stratification by the two tests was then compared.Results: A total of 771 patients from five institutions in Korea were analyzed. According to the BCT score, 527 (68.4%) patients were classified as low risk, and 244 (31.6%) as high risk. Meanwhile, 134 (17.4%), 516 (66.9%), and 121 (15.7%) patients were categorized into the low-, intermediate-, and high-risk groups, respectively, according to the RS ranges used in the TAILORx. The BCT high-risk group was significantly associated with advanced lymph node status, whereas no association between RS risk groups and nodal status was observed. The concordance between the two risk stratification methods in the overall population was 71.9% when the RS low-risk, and intermediate-risk groups were combined into one group. However, poor concordance was observed in patients aged ≤50 years and in those with lymph node-positive breast cancer.Conclusions: The concordance between the BCT score and RS was low in women aged ≤50 years or with lymph node-positive breast cancer. Further studies are necessary to identify more accurate tests for predicting prognosis and chemotherapy benefit in this subpopulation.

Mainstreaming genetic counseling for BRCA testing into oncology clinics - Indian perspective.

BReastCAncer (BRCA) susceptibility genes BRCA1 and BRCA2 are mainly associated with hereditary breast and ovarian cancer (HBOC) syndrome and present an estimated 45%-65% cumulative lifetime risk of developing breast cancer and an 11%-39% risk of ovarian cancer. HBOC is also linked to triple-negative breast cancer (TNBC). BRCA1 mutations in TNBC are observed in 36% of women age <40 years and 27% of women age <50 years. In India, the prevalence of BRCA1/2 mutation varies from 2.9% to 38% among families with genetic predisposition toward hereditary cancers. With HBOC being linked to early-onset breast cancer and increased susceptibility to other cancers, early screening for BRCA mutations has become a pressing need. Though genetic counseling (GC) for BRCA mutation testing is common in most of the developed countries, India still faces several challenges in mainstreaming the same. Many barriers to effective GC for BRCA testing are unique to India. There is a dearth of trained geneticists which puts the pressure on oncologists to give GC for which they neither have the time or training. Presence of multiethnic/linguistic population acts as a major hindrance along the way toward development of robust predictive and effective GC models for BRCA testing. The current review discusses the need and benefits of GC in breast cancer prevention, through BRCA testing, from an Indian perspective. The functional framework of GC and the role of genetic counselors are discussed in detail. In addition, importance of GC training and role of a multidisciplinary team approach for mainstreaming pre- and post-BRCA test GC is highlighted.

BCT score predicts chemotherapy benefit in Asian patients with hormone receptor-positive, HER2-negative, lymph node-negative breast cancer.

The Breast Cancer Test (BCT) score has been validated for its ability to predict the risk of distant metastasis in hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer. This study aimed to examine the value of the BCT score for predicting the benefit of adjuvant chemotherapy for Korean women with hormone receptor-positive, HER2-negative, lymph node-negative breast cancer. The study included 346 patients treated with either hormone therapy alone (n = 203) or hormone therapy plus chemotherapy (n = 143), and compared patient survival between the two treatment groups. The effect of BCT score on patient survival by treatment group was assessed using Cox proportional hazards models. Based on the results, the BCT score was prognostic for distant metastasis-free survival and breast cancer-specific survival in the hormone therapy alone group. There was no significant difference between the treatment groups in terms of 10-year distant metastasis-free survival in the overall patient population. However, when patients were classified as low risk (n = 266) and high risk (n = 80) according to the BCT score, addition of adjuvant chemotherapy to hormone therapy for patients classified as BCT high-risk group led to a significant improvement in 10-year distant metastasis-free survival, from 65.4% to 91.9% (hazard ratio, 0.18; 95% confidence interval, 0.05–0.64; P = 0.003); in contrast, there was no benefit for the BCT low-risk group. The stratification of patients according to the BCT score also identified clinically high-risk patients who may not benefit from chemotherapy. Results were similar for breast cancer-specific survival. In conclusion, the BCT score was not only of prognostic value but was also a predictor of chemotherapy benefit for Korean patients with hormone receptor-positive, HER2-negative, lymph node-negative breast cancer.

Diagnostic value of circulating microRNAs as biomarkers for breast cancer: a meta-analysis study

Recent studies have provided new insights into the diagnostic value of circulating microRNAs (miRNAs) for breast cancer (BCa). However, the inconsistent results between studies have prevented the widespread usage of miRNAs in clinics. To systematically assess the potential diagnostic value of circulating miRNAs in BCa, we performed a comprehensive meta-analysis. Eligible studies were retrieved by searching electronic databases. The quality of the studies was assessed on the basis of quality assessment for studies of diagnostic accuracy (QUADAS) criteria. The bivariate meta-analysis model was employed to summarize the diagnostic indices and plot the summary receiver operator characteristic (SROC) curve. A total of 15 studies were included in this meta-analysis, involving 1368 BCa patients and 849 healthy controls. Our bivariate random effects meta-analysis yielded an area under curve (AUC) value of 0.9217, with a sensitivity of 0.82 (95 % confidence interval (CI) 0.80-0.83) and specificity of 0.82 (95% CI 0.80-0.85) for the use of miRNAs in differentiating BCa patients from healthy controls. Notably, our subgroup analysis suggested that a combination of multiple miRNAs (AUC, sensitivity, and specificity of 0.9518, 0.87, and 0.88, respectively) seemed to harbor higher accuracy than single miRNA-based assays (AUC, sensitivity, and specificity of 0.8923, 0.79, and 0.77, respectively). Altogether, our data indicate that circulating miRNA profiling has a potential to be used as a screening test for BCa, among which, the detection of a combined multiple miRNAs may be a more comprehensive indicator than individual miRNA.

Surgical and Financial Implications of Genetic Counseling and Requests for Concurrent Prophylactic Mastectomy

Risk assessment evaluation and breast cancer (BRCA) testing can occur in situations where a woman considers herself to be at increased risk for developing breast cancer or her physicians, either during routine evaluation or after diagnosis of unilateral breast cancer, consider her to be at risk for harboring a genetic predisposition to breast malignancy. This study examined the impact of risk assessment counseling on trends in breast surgery and cost of care. A retrospective chart review was performed from January 1, 1999 to December 31, 2008 for women older than 18 years who underwent breast surgery for malignancy or prophylaxis, had at least 1-year follow-up, and underwent genetic counseling. From the total number of women treated at our institution who underwent unilateral or bilateral mastectomy, we identified 102 women who underwent genetic counseling and selected 199 patients who did not undergo counseling to create a 4:1 retrospective case-control study. Patients who underwent BRCA gene testing and/or counseling were compared with patients who did not (controls). The study was powered at 70%, and alpha was set at 0.05. Counseled patients were >9 times more likely to undergo bilateral mastectomies (odds ratio = 9.18). They were younger (46.4 vs. 61.8) and incurred higher total costs ($10,810 vs. $7,266) (P < 0.002). The same trend was observed in each group. In counseled and control groups, younger women chose bilateral mastectomies (mean 44.4; 55.5), whereas older women chose unilateral procedures (mean 49.8; 63.02) (P < 0.014). Total cost for bilateral mastectomies was greater than unilateral mastectomies for both groups. Of 55 counseled patients undergoing mastectomies (85 breasts), 78 (92%) breasts were reconstructed, whereas 113 (49%) of 230 breasts were reconstructed in the control group. There was a statistically significant association between counseling with BRCA testing and decision to undergo bilateral as opposed to unilateral mastectomies. Younger women were also more likely to choose bilateral mastectomies whether or not they underwent counseling. Furthermore, a greater proportion of counseled women who underwent reconstruction opted to have bilateral implants. At our institution, younger women tend to choose costlier options.

LEUCOCYTE-ADHERENCE-INHIBITION TEST IN BREAST CANCER

LEUCOCYTE-ADHERENCE-INHIBITION TEST IN BREAST CANCER