High-risk Breast Cancer Screening Research Articles

Performance of breast MRI for high-risk screening during lactation.

To assess the diagnostic performance of breast MRI during lactation in the setting of high-risk breast cancer screening. Screening breast MRIs performed between April 2008 and March 2024 were retrospectively reviewed. Background parenchymal enhancement (BPE) grade was compared between lactating patients and patients who recently stopped lactating using the Mann-Whitney test. Breast Imaging Reporting and Data System (BI-RADS) scores prevalence rates were compared between lactating patients and controls encompassing young non-lactating patients using the Chi-square test. Diagnostic performance was calculated for patients with a biopsy reference or a 1-year radiologic follow-up. One-hundred forty-two screening breast MRIs were performed in lactating patients (n = 104, median age, 36.0 ± 6.0 years). Marked BPE appeared in 82% of cases (116/142), with a higher BPE grade in exams performed during lactation as compared with those performed in patients who had recently ceased lactating (p < 0.001). Screening MRIs performed during lactation had a higher rate of BI-RADS 3 scores (40/142, 28% vs. 683/8922, 7%, p < 0.001) and a lower rate of BI-RADS 1/2 scores (88/142, 62% vs. 7549/8922, 84.6%, p = 0.002) compared with those performed in controls (n = 8922). One pregnancy-associated breast cancer was detected, and one interval-cancer occurred. All MRI-guided biopsies were negative (n = 13). Screening breast MRI during lactation had 50% sensitivity (1/2), 60% specificity (72/120), 2.0% positive predictive value (1/49), and 98.6% negative predictive value (71/82). The efficacy of breast MRI for high-risk screening during lactation is limited by prominent BPE, leading to an increased rate of BI-RADS 3 categorization and diminished overall specificity. Question Studies on breast MRI during lactation were solely focused on studies conducted in patients with known cancer but not in the screening setting. Findings Screening breast MRI during lactation usually results in marked background parenchymal enhancement, negatively impacting its diagnostic performance. Clinical relevance Despite the lower performance, and amidst the significant risk of pregnancy-associated breast cancer, this screening approach remains relevant for lactating patients with high-risk profiles, such as BReast Cancer (BRCA) carriers. Radiologists should be familiar with the normal appearance of breast MRI duringlactation.

Prospective Study of Supplemental Screening With Contrast-Enhanced Mammography in Women With Elevated Risk of Breast Cancer: Results of the Prevalence Round.

Contrast-enhanced mammography (CEM) and magnetic resonance imaging (MRI) have shown similar diagnostic performance in detection of breast cancer. Limited CEM data are available for high-risk breast cancer screening. The purpose of the study was to prospectively investigate the efficacy of supplemental screening CEM in elevated risk patients. A prospective, single-institution, institutional review board-approved observational study was conducted in asymptomatic elevated risk women age 35 years or older who had a negative conventional two-dimensional digital breast tomosynthesis screening mammography (MG) and no additional supplemental screening within the prior 12 months. Four hundred sixty women were enrolled from February 2019 to April 2021. The median age was 56.8 (range, 35.0-79.2) years; 408 of 460 (88.7%) were mammographically dense. Biopsy revealed benign changes in 22 women (22/37, 59%), high-risk lesions in four women (4/37, 11%), and breast cancer in 11 women (11/37, 30%). Fourteen cancers (10 invasive, tumor size range 4-15 mm, median 9 mm) were diagnosed in 11 women. The overall supplemental cancer detection rate was 23.9 per 1,000 patients, 95% CI (12.0 to 42.4). All cancers were grade 1 or 2, ER+ ERBB2-, and node negative. CEM imaging screening offered high specificity (0.875 [95% CI, 0.844 to 0.906]), high NPV (0.998 [95% CI, 0.993 to 1.000), moderate PPV1 (0.164 [95% CI, 0.076 to 0.253), moderate PPV3 (0.275 [95% CI, 0.137 to 0.413]), and high sensitivity (0.917 [95% CI, 0.760 to 1.000]). At least 1 year of imaging follow-up was available on all patients, and one interval cancer was detected on breast MRI 4 months after negative screening CEM. A pilot trial demonstrates a supplemental cancer detection rate of 23.9 per 1,000 in women at an elevated risk for breast cancer. Larger, multi-institutional, multiyear CEM trials in patients at elevated risk are needed for validation.

Deep learning for predicting future lesion emergence in high-risk breast MRI screening: a feasibility study

BackgroundInternational societies have issued guidelines for high-risk breast cancer (BC) screening, recommending contrast-enhanced magnetic resonance imaging (CE-MRI) of the breast as a supplemental diagnostic tool. In our study, we tested the applicability of deep learning-based anomaly detection to identify anomalous changes in negative breast CE-MRI screens associated with future lesion emergence.MethodsIn this prospective study, we trained a generative adversarial network on dynamic CE-MRI of 33 high-risk women who participated in a screening program but did not develop BC. We defined an anomaly score as the deviation of an observed CE-MRI scan from the model of normal breast tissue variability. We evaluated the anomaly score’s association with future lesion emergence on the level of local image patches (104,531 normal patches, 455 patches of future lesion location) and entire CE-MRI exams (21 normal, 20 with future lesion). Associations were analyzed by receiver operating characteristic (ROC) curves on the patch level and logistic regression on the examination level.ResultsThe local anomaly score on image patches was a good predictor for future lesion emergence (area under the ROC curve 0.804). An exam-level summary score was significantly associated with the emergence of lesions at any location at a later time point (p = 0.045).ConclusionsBreast cancer lesions are associated with anomalous appearance changes in breast CE-MRI occurring before the lesion emerges in high-risk women. These early image signatures are detectable and may be a basis for adjusting individual BC risk and personalized screening.Relevance statementAnomalies in screening MRI preceding lesion emergence in women at high-risk of breast cancer may inform individualized screening and intervention strategies.Key points• Breast lesions are associated with preceding anomalies in CE-MRI of high-risk women.• Deep learning-based anomaly detection can help to adjust risk assessment for future lesions.• An appearance anomaly score may be used for adjusting screening interval times.Graphical

Cost-effectiveness evaluation of risk-based breast cancer screening in Urban Hebei Province

To evaluate the implementations of Cancer Screening Program in Urban Hebei and to model the cost-effectiveness of a risk-based breast Cancer Screening Program. Women aged 40–74 years were invited to participate the Cancer Screening Program in Urban Hebei form 2016 to 2020 by completing questionnaires to collect information about breast cancer exposure. Clinical screening including ultrasound and mammography examination were performed. We developed a Markov model to estimate the lifetime costs and benefits, in terms of quality-adjusted life years (QALY), of a high-risk breast Cancer Screening Program. Nine screening strategies and no screening were included in the study. The age-specific incidence, transition probability data and lifetime treatment costs were derived and adopted from other researches. Average cost-effectiveness ratios (ACERs) were estimated as the ratios of the additional costs of the screening strategies to the QLYG compared to no screening. Incremental cost-effectiveness ratios (ICERs) were calculated based on the comparison of a lower cost strategies to the next more expensive and effective strategies after excluding dominated strategies and extendedly dominated strategies. ICERs were used to compare with a willingness-to-pay (WTP) threshold. Sensitivity analysis was explored the influence factors. A total of 84,029 women completed a risk assessment questionnaire, from which 20,655 high-risk breast cancer females were evaluated, with a high-risk rate of 24.58%. There were 13,392 high-risk females completed the screening program, with participation rate was 64.84%. Undergoing ultrasound, mammography and combined screening, the suspicious positive detection rates were 15.00%, 9.20% and 19.30%, and the positive detection rates were 2.11%, 2.76% and 3.83%, respectively. According to the results by Markov model, at the end of 45 cycle, the early diagnosis rates were 55.53%, 60.68% and 62.47% underwent the annual screening by ultrasound, mammography and combined, the proportion of advanced cancer were 17.20%, 15.85% and 15.36%, respectively. Different screening method and interval yield varied. In the exploration of various scenarios, annual ultrasound screening is the most cost-effective strategy with the ICER of ¥116,176.15/QALY. Sensitivity analyses demonstrated that the results are robust. Although it was not cost effective, combined ultrasound and mammography screening was an effective strategy for higher positive detection rate of breast cancer. High-risk population-based breast cancer screening by ultrasound annually was the most cost-effective strategy in Urban Hebei Province.

Feasibility Study and Clinical Impact of Incorporating Breast Tissue Density in High-Risk Breast Cancer Screening Assessment.

Breast tissue density (BTD) is known to increase the risk of breast cancer but is not routinely used in the risk assessment of the population-based High-Risk Ontario Breast Screening Program (HROBSP). This prospective, IRB-approved study assessed the feasibility and impact of incorporating breast tissue density (BTD) into the risk assessment of women referred to HROBSP who were not genetic mutation carriers. All consecutive women aged 40-69 years who met criteria for HROBSP assessment and referred to Genetics from 1 December 2020 to 31 July 2021 had their lifetime risk calculated with and without BTD using Tyrer-Cuzick model version 8 (IBISv8) to gauge overall impact. McNemar's test was performed to compare eligibility with and without density. 140 women were referred, and 1 was excluded (BRCA gene mutation carrier and automatically eligible). Eight of 139 (5.8%) never had a mammogram, while 17/131 (13%) did not have BTD reported on their mammogram and required radiologist review. Of 131 patients, 22 (16.8%) were clinically impacted by incorporation of BTD: 9/131 (6.9%) became eligible for HROBSP, while 13/131 (9.9%) became ineligible (p = 0.394). It was feasible for the Genetics clinic to incorporate BTD for better risk stratification of eligible women. This did not significantly impact the number of eligible women while optimizing the use of high-risk supplemental MRI screening.

Impact of COVID-19 and Socioeconomic Factors on Delays in High-Risk MRI Breast Cancer Screening.

The purpose of this study is to investigate if there was a delay in high-risk MRI breast cancer screening in our local region, if this delay is ongoing despite COVID-19 vaccinations, and if demographic and socioeconomic factors are associated with these delays. Six-hundred and sixty-five high-risk breast patients from 23 January 2018–30 September 2021 were included. Delays were determined by comparing the time in between each patients’ MRI screening exams prior to the COVID-19 pandemic to the time in between MRI screening exams during the height of the COVID-19 pandemic as well as the time in between exams when our patients started receiving vaccinations. Delays were analyzed via logistical regression with demographic and socioeconomic factors to determine if there was an association between these factors and delays. Significant time delays in between MRI screening exams were found between the pre-COVID timeframe compared to during the height of COVID. Significant time delays also persisted during the timeframe after patients started getting vaccinations. There were no associations with delays and socioeconomic or demographic factors. Significant time delays were found in between MRI high-risk breast cancer screening examinations due to the COVID-19 pandemic. These delays were not exacerbated by demographic or socioeconomic factors.

High Risk Breast Cancer Screening is a Double Edged Sword: A Qualitative Study of Patient Perspectives on the Ontario High Risk Breast Cancer Screening Program

BackgroundMRI-based breast cancer screening for high-risk women has been associated with false positives. This study explored the benefits and drawbacks of MRI-based screening using in-depth patient interviews. MethodsThis was a qualitative study of interviews with women participating in the High Risk Ontario Breast Screening Program. Women enrolled at two centers who had completed at least one round of screening were invited to participate. Recruitment was suspended when thematic saturation was reached. Semi-structured telephone interviews were conducted and transcribed verbatim. Emergent themes were identified and a coding framework established. Results21 women (median age 41 years) participated in telephone interviews. Women had been in the program a median of 4 years (IQR 1-5), and 71% had experienced at least one abnormal screen. Eight participants (38%) had undergone biopsies. Six women (29%) were BRCA mutation carriers. MRIs were described as intimidating, uncomfortable, and claustrophobic. Participants were concerned about long-term exposure to gadolinium contrast. Compared to MRI, mammography alone was viewed as painful, less sensitive, and a “useless…waste of time.” MRI provided a “psychological safety net” that outweighed the distress associated with abnormal screens. Many women accepted this trade-off as a “two-edged sword” that was “worth it” and provided a sense of control. Suggestions for improvement included more information regarding the risks of MRI, and access to counselling. ConclusionsWomen participating in MRI-based screening strongly value reassurance from a highly sensitive screening test. This outweighed the distress of abnormal screens. There are areas for improvement around patient communication and psychosocial support.

Abstract P3-04-01: Information availability about screening for high-risk breast cancer on cancer center websites

Abstract Background: Radiology and oncology clinical guidelines recommend that people with high-risk of breast cancer should be offered screening with magnetic resonance imaging (MRI). Rates of appropriate screening remain low, which could also be related to patient awareness and knowledge about optimal screening modalities/schedules. Appropriate screening is even more critical for African-American women, in whom there are higher rates of genetic mutations (e.g., BRCA) conferring a greater risk of high-risk breast cancer. Southern United States (US) states have a higher proportion of African-American women. We sought to explore the availability of information on high-risk breast cancer screening using breast MRI across the websites of the top 20 cancer centers in the US (as per US News data) as well as the top US News cancer center in each of 5 representative southern US states where the average annual breast cancer-related death rate is greater than 20 per 100,000 people, age adjusted to the 2000 US standard population. Methods:We utilized publicly available data from the 2020-2021 US News website to identify top 20 cancer centers. We performed a google search using two separate keyword phrases (“high-risk breast cancer screening” and “breast MRI”), and the name of the cancer center. US News 2020-21 online ranking data was also used to identify the top cancer center in each of the five representative US states (Alabama, Georgia, Louisiana, Mississippi and South Carolina) and a similar search methodology was adopted for these five cancer centers. We then reviewed each cancer center’s website(s) and webpages to ascertain the availability of information regarding the availability of specific high-risk breast cancer clinic/programs and specific information on screening with breast MRI. Results: Of the top 20 US cancer centers, 15 (75%) have an established high-risk breast cancer clinic/program per their website. Two (2/15) of these cancer centers only had a general high-risk cancer assessment/genetics clinic and two (2/15) had no additional information available about the high-risk clinics. Information on high-risk factors was available on 12/20 (60%) websites. Seventeen centers (85%) included information on breast MRI, but only 8 (40%) had patient-centered detailed information on breast MRI for high-risk patients and 4 (20%) centers included an online, personalized, risk assessment tool. Among the top cancer center in each of the 5 representative Southern states, only 1 (20%) had information regarding a high-risk breast cancer evaluation program. While 4 (80%) had information on breast MRI information, there was no specific information available for high risk screening. Conclusions: These findings underscore the unmet need of easy access to online information from the websites of the top cancer centers nationally as well as the top state level cancer centers in the five representative southern US states for women with high risk of developing breast cancer. These limitations are particularly relevant for African-American women living in the South. Limitations of this study include the cross-sectional assessment of online data and that discrepancies may exist between websites and actual availability of clinical services. Citation Format: Jaspreet Singh Batra, Elizabeth Park, Arjun Gupta. Information availability about screening for high-risk breast cancer on cancer center websites [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-04-01.

Tackling Health Disparities in Radiology: A Practical Conceptual Framework.

Tackling Health Disparities in Radiology: A Practical Conceptual Framework.

"High-Risk Breast Cancer Screening in BRCA1/2 Carriers Leads to Early Detection and Improved Survival After a Breast Cancer Diagnosis".

BackgroundGermline BRCA1/2 pathogenic variant (PV) carriers have high lifetime risk of developing breast cancer and therefore subjected to intense lifetime screening. However, solid data on the effectiveness of high-risk screening of the BRCA1/2 carrier population is limited.Patients and MethodsRetrospectively, we analyzed 346 women diagnosed with breast tumors. Patients were divided according to the timing of BRCA1/2 PVrecognition, before (BRCA-preDx awareness, N = 62) or after (BRCA-postDx awareness group, N = 284) cancer diagnosis.ResultsMedian follow-up times were 131.42 and 93.77 months in the BRCA-preDx awareness and BRCA-postDx awareness groups, respectively. In the BRCA-preDx awareness group, 78.7% of the patients had invasive tumors and 21.3% were diagnosed with pure ductal carcinoma in situ. In contrast, in the BRCA-postDx awareness group over 93% of women were diagnosed with invasive cancer and only 6.4% had in situ disease. The mode of tumor detection differed significantly between the groups: 71.9% in the BRCA-postDx awareness group and 26.2% in the BRCA-preDx awareness group were diagnosed after personally palpating a lump. Tumor size and nodal involvement were significantly more favorable in the BRCA-preDx awareness group. T stage was significantly lower in the BRCA-preDx awareness group: 54.84% at T1 and 20.96% at Tis. In the BRCA-postDx awareness group, only 37.54% were at T1 and 6.49% at Tis. The N stage was also significantly lower in the BRCA-preDx awareness group: 71% had no lymph node metastases, compared with 56.1% in the BRCA-postDx awareness group. Additionally, therapeutic procedures varied between the groups: BRCA-preDx awareness group patients underwent more breast conserving surgeries. Axillary lymph node dissection was done in 38% of women in the BRCA-postDx awareness group and in only 8.7% of the BRCA-preDx awareness group patients. Interestingly, improved survival was found among patients who underwent high-risk screening (hazard ratio=0.34).ConclusionsHigh-risk screening might facilitate downstaging of detected breast tumor among BRCA1/2 carrier population.

Impact of Launching A High-Risk Breast Cancer Screening Program Using the Tyrer-Cuzick Model.

Impact of Launching A High-Risk Breast Cancer Screening Program Using the Tyrer-Cuzick Model.

Breast cancer screening implications of risk modeling among female relatives of ATM and CHEK2 carriers.

With the increasing use of multigene panel tests, pathogenic and likely pathogenic (P/LP) variants are identified more frequently in the moderate-penetrance breast cancer genes ATM and CHEK2. Lifetime breast cancer risk among women with P/LP variants in these genes generally exceeds 20%, meeting the threshold at which high-risk breast cancer screening through breast magnetic resonance imaging (MRI) is recommended. Among a registry-based sample of 56 ATM and 69 CHEK2 carriers, the authors sought to determine the percentage of relatives in whom a P/LP variant would impact breast cancer surveillance. Lifetime breast cancer risks for unaffected, female first-degree and second-degree relatives were estimated using the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA). Among first-degree relatives of ATM and CHEK2 carriers, only 22.6% and 14.9%, respectively, were found to have lifetime breast cancer risks of ≥20% based on family cancer history alone; however, when including the proband's P/LP variant in the model, these percentages increased significantly to 56.6% and 55.3%, respectively (P<.0001 and P<.0001, respectively). Similar increases in lifetime breast cancer risks were found among second-degree relatives. The results of the current study suggest that the majority of female first-degree and second-degree relatives of ATM and CHEK2 carriers do not qualify for breast MRI based on family cancer history alone. Therefore, testing for these genes, as well as awareness of positive moderate-penetrance breast cancer gene results in the family, may impact MRI eligibility. These findings highlight the potential usefulness of and need for breast cancer risk models that incorporate moderate-penetrance gene positivity to inform screening recommendations among at-risk family members.

Evaluation of 3.0-T MRI Brain Signal after Exposure to Gadoterate Meglumine in Women with High Breast Cancer Risk and Screening Breast MRI.

Background Otherwise healthy women at high risk for breast cancer undergo annual contrast agent-enhanced breast MRI screening examinations, resulting in high cumulative doses of gadolinium-based contrast agents (GBCAs). Whereas the majority of studies showed no T1 signal ratio increase in deep brain nuclei after more than six doses of macrocyclic GBCA, this has not been explored in a healthy study population. Purpose To assess whether women who are administered large cumulative doses of macrocyclic GBCA with breast MRI at high-risk breast cancer screening exhibit T1 alterations in deep brain nuclei. Materials and Methods In this prospective study from November 2017 to March 2018, healthy women who were either exposed (because of high-risk breast cancer screening) or unexposed to only gadoterate meglumine underwent 3.0-T brain MRI with a dedicated head coil, including T1 mapping and magnetization-prepared rapid gradient-echo sequences. T1 times and T1 signal intensities were measured in the dentate nucleus (DN), globus pallidus (GP), crus anterior of capsula interna (CA), and pons. Ratios of DN to pons and GP to CA were calculated, and univariable Pearson correlation coefficients were calculated. Multivariable analysis included partial regression analysis. Results This study evaluated 25 women (mean age, 51 years ± 11 [standard deviation]) who were exposed to a mean GBCA dose of 129 mL (median 112 mL; range, 70-302 mL) and 16 women (mean age, 37 years ± 10) who were never exposed to any GBCA. Infratentorially, no correlation between cumulative GBCA dose and T1 times or signal intensity ratios was detected (P = .66 and .55, respectively). In partial correlation analysis by considering age as a confounder, there was a moderate negative correlation between GP-to-CA ratio and GBCA dose (r = -0.40; P = .01) but not for GP T1 times (r = 0.19; P = .24). Conclusion After administration of relatively large cumulative doses of gadoterate dimeglumine, healthy women at high risk for breast cancer who underwent annual contrast-enhanced breast MRI screening did not exhibit T1 signal increase in deep brain nuclei at 3.0-T MRI. © RSNA, 2019.

NF1 Patients Receiving Breast Cancer Screening: Insights from The Ontario High Risk Breast Screening Program.

Neurofibromatosis Type I (NF1) is caused by variants in neurofibromin (NF1). NF1 predisposes to a variety of benign and malignant tumor types, including breast cancer. Women with NF1 <50 years of age possess an up to five-fold increased risk of developing breast cancer compared with the general population. Impaired emotional functioning is reported as a comorbidity that may influence the participation of NF1 patients in regular clinical surveillance despite their increased risk of breast and other cancers. Despite emphasis on breast cancer surveillance in women with NF1, the uptake and feasibility of high-risk screening programs in this population remains unclear. A retrospective chart review between 2014–2018 of female NF1 patients seen at the Elizabeth Raab Neurofibromatosis Clinic (ERNC) in Ontario was conducted to examine the uptake of high-risk breast cancer screening, radiologic findings, and breast cancer characteristics. 61 women with pathogenic variants in NF1 enrolled in the high-risk Ontario breast screening program (HR-OBSP); 95% completed at least one high-risk breast screening modality, and four were diagnosed with invasive breast cancer. Our findings support the integration of a formal breast screening programs in clinical management of NF1 patients.

Breast Cancer Screening in High-Risk Patients during Pregnancy and Breastfeeding: A Systematic Review of the Literature.

There are currently no clear guidelines for high-risk breast cancer screening during the pregnancy and breastfeeding periods. The objective of this systematic review (SR) was to assess the available evidence pertaining to breast cancer screening recommendations in this population with the aim of supporting future guidelines. We performed a SR of the literature using the electronic databases MEDLINE and Embase. Predetermined inclusion and exclusion criteria were used during the abstract screening and full-text data extraction phases. We retrieved 2,274 abstracts after removal of duplicates, from which 16 studies were included based on predetermined eligibility criteria. Most of the studies found were narrative reviews and expert opinions. Clinical breast exam (CBE) was recommended by 12 studies during pregnancy and by 6 studies in the breastfeeding period. Mammography was recommended in the breastfeeding period by 2 studies. Magnetic resonance imaging was recommended in the breastfeeding period by 2 studies. Ultrasound was considered not appropriate for screening in this population. The information extracted from this SR is based primarily on expert opinion and anecdotal evidence, which explains the lack of standardized guidelines for high-risk breast cancer screening in this population. However, expert opinion may be a surrogate outcome for high-risk breast cancer screening recommendations in this subset of patients, and as such, may justify the clinical management to be tailored accordingly. This SR summarizes the evidence pertaining to high-risk breast cancer screening during pregnancy and breastfeeding, which could serve as a catalyst for future research on the topic.

Abstract P1-10-06: High participation of African-American women veterans in high risk breast cancer screening pilot program

Abstract SPECIFIC AIMS: To assess breast cancer risk in Women Veterans. BACKGROUND/RATIONALE: Women are the fastest growing segment of patients numbering over 2 million and breast cancer incidence has more than tripled from 1995 to 2012 within the Veterans Health Administration (VHA). Preliminary data suggest that Women Veterans may be at an increased breast cancer risk based on unique service-related exposures (e.g., burn pits, depleted uranium) and Post Traumatic Stress Disorder (PTSD). Historically, breast cancer rates among African Americans (AA) are lower than those seen in the general population (8.2-13.3%). METHODS: A pilot study was conducted at Bronx, NY and Washington, DC Veterans Affairs Medical Centers. Participants were enrolled at their regular visit to Women's Health Clinics or at breast cancer education and awareness events. 5-year and lifetime risks of developing invasive breast cancer were calculated using the Gail Breast Cancer Risk Assessment Tool (BCRAT). Demographics, PTSD status, eligibility for chemoprevention and genetic counseling using the Breast Cancer Genetics Referral Screening Tool (B-RST), were also determined. ELIGIBILITY CRITERIA: Women Veterans age ≥ 35 years with no personal history of breast cancer. RESULTS: A total of 99 Women Veterans with an average age of 54 years participated between 2015 and 2018; 60% African American (AA); 13% Hispanic; 14% non-Hispanic White and 13% as other. In total, 35% (35/99) were considered high risk with a 5-year BCRAT of &amp;gt;1.66% and of these, 51% were AA; 14% Hispanic and 17 % were other. Prior breast biopsies were performed in only 22% (22/99) of our entire Veteran population; 57% (56/99) having a family history positive for breast cancer. Comparatively, in our high risk AA alone, 33% (6/18) had prior breast biopsies with 94% (17/18) having a positive family history. High risk patients were referred for chemoprevention; 5 (19%) accepted; and 13/35 (37%) patients were referred for genetic counseling. PTSD was present in 29% overall and in 31% of the high risk subgroup. IMPLICATIONS: The VHA, which leads the nation in mammogram compliance, is an untapped potential resource for the study of breast cancer. To our knowledge, this is the only study with 60% AA Women Veterans. High participation rates among AA in this pilot study have uncovered the potential for further inquiry into this population, which is otherwise dramatically under-represented in research. Over half (51%) of AA in this pilot study had a high risk score, likely linked to a high rate of prior breast biopsies and family history. Limitations of this study include the small sample size, exclusively urban population, geography and self-selection for screening due to a higher level of concern for breast cancer. If Women Veterans are at higher risk of breast cancer, it has been assumed that this would be related to service-related exposures, PTSD and other factors. However this pilot study, which was not designed or powered to do more than raise questions, suggests the additional possibility of an innate or genetic risk, especially in AAs. Future directions include the evaluation of genetic and molecular mutations in high risk AA Women Veterans, possibly even a role for PTSD epigenetic changes and tumorigenesis. Citation Format: Park Y-HA, Keller AT, Bidassie B, Venne VL, Heron BB, Hoffman-Hōgg L, Hawley DK, Hsu T-CM, Colonna SV, Aggarwal A. High participation of African-American women veterans in high risk breast cancer screening pilot program [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-10-06.

Behind every mammo there's an MRI: Evaluation of high-risk breast cancer screening strategies in BRCA mutation carriers

Objective: Recent data suggest that BRCA mutation carriers younger than 40 years may not benefit from mammography in addition to MRI screening. Our objective was to evaluate screening modalities utilized in a high-risk population with regard to abnormalities and outcomes.

American College of Radiology-Compliant Short Protocol Breast MRI for High-Risk Breast Cancer Screening: A Prospective Feasibility Study.

The purpose of this study was to assess the feasibility of a short protocol for screening breast MRI that is noninferior to standard-of-care (SOC) MRI in image quality that complies with American College of Radiology accreditation requirements. In a prospective feasibility trial, 23 women at high risk underwent both an initial SOC MRI examination that included axial iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) and T1-weighted volume imaging for breast assessment (VIBRANT) dynamic contrast-enhanced sequences and a separate short breast MRI protocol comprising a fast spin-echo (FSE) triple-echo Dixon T2 sequence for T2-weighted imaging and a 3D dual-echo fast spoiled gradient-echo two-point Dixon sequence for dynamic contrast-enhanced imaging from October 1, 2015, through May 2, 2016. Image quality assessment was performed by three radiologists, who scored the images for fat saturation, artifact severity, and quality of normal anatomic structures. Enhancing lesions were evaluated according to BI-RADS MRI features. Quantitative analysis was performed by measuring the signal intensity of anatomic areas in each patient. The mean acquisition time for short-protocol breast MRI was 9.42 minutes and for SOC MRI was 22.09 minutes (p < 0.0001). The mean table times were 13.92 and 35.87 minutes (p < 0.0001). Compared with the FSE triple-echo Dixon T2 short-protocol breast MRI sequence, the IDEAL SOC MRI sequence had significantly worse motion artifact (p < 0.01) and fat saturation (p = 0.04). The other parameters did not differ significantly. Quantitative analysis showed that the FSE triple-echo Dixon T2 sequence had more effective fat saturation and higher tissue contrast. All five lesions were given the same assessments by the readers, and at BI-RADS lesion morphologic ranking, identical high image quality scores were assigned to both the VIBRANT and 3D dual-echo fast spoiled gradient-echo 2-point Dixon sequences. Short-protocol breast MRI comprising a T2-weighted sequence and a fast dynamic sequence with less than 10-minute acquisition time is feasible and has image quality at least equivalent to that of an SOC MRI protocol with a > 20-minute mean acquisition time. Larger studies comparing the cancer detection rate, sensitivity, and specificity of each imaging protocol are needed to determine whether short-protocol breast MRI can replace SOC MRI to screen patients at high breast cancer risk.

Breast density estimation from high spectral and spatial resolution MRI.

A three-dimensional breast density estimation method is presented for high spectral and spatial resolution (HiSS) MR imaging. Twenty-two patients were recruited (under an Institutional Review Board--approved Health Insurance Portability and Accountability Act-compliant protocol) for high-risk breast cancer screening. Each patient received standard-of-care clinical digital x-ray mammograms and MR scans, as well as HiSS scans. The algorithm for breast density estimation includes breast mask generating, breast skin removal, and breast percentage density calculation. The inter- and intra-user variabilities of the HiSS-based density estimation were determined using correlation analysis and limits of agreement. Correlation analysis was also performed between the HiSS-based density estimation and radiologists' breast imaging-reporting and data system (BI-RADS) density ratings. A correlation coefficient of 0.91 ([Formula: see text]) was obtained between left and right breast density estimations. An interclass correlation coefficient of 0.99 ([Formula: see text]) indicated high reliability for the inter-user variability of the HiSS-based breast density estimations. A moderate correlation coefficient of 0.55 ([Formula: see text]) was observed between HiSS-based breast density estimations and radiologists' BI-RADS. In summary, an objective density estimation method using HiSS spectral data from breast MRI was developed. The high reproducibility with low inter- and low intra-user variabilities shown in this preliminary study suggest that such a HiSS-based density metric may be potentially beneficial in programs requiring breast density such as in breast cancer risk assessment and monitoring effects of therapy.

Increased Identification of Candidates for High-Risk Breast Cancer Screening Through Expanded Genetic Testing

PurposeBreast MRI screening is recommended for women with a >20% lifetime risk for breast cancer on the basis of estimates derived from risk models dependent largely on family history. Alternatively, a >20% lifetime risk can be established through genetic testing of BRCA1 and BRCA2, as well as a growing selection of other genes associated with inherited breast cancer risk. The aim of this study was to quantify the impact of testing for genes other than BRCA1/2 and the extent to which mutation carriers in these genes would have been identified as candidates for enhanced screening on the basis of family history alone. MethodsWomen were tested with a 25-gene hereditary cancer panel including BRCA1/2 and 7 additional genes known to be associated with a >20% lifetime risk for breast cancer (ATM, CHEK2, PALB2, TP53, PTEN, CDH1, and STK11). Women found to carry pathogenic variants (PVs) were evaluated with the Claus model to assess whether they would have been found to be at >20% lifetime risk on the basis of family history. ResultsIn total, 9,751 PVs in the selected breast cancer risk genes were identified in 9,641 women. BRCA1/2 accounted for 59.1% of the PVs, and 38.8% were in ATM, CHEK2, or PALB2. Only 24.7% of all women with PVs found in any gene reached the >20% lifetime risk threshold using the Claus model. ConclusionsExpanding genetic testing beyond BRCA1/2 significantly increases the number of women who are candidates for breast MRI and other risk reduction measures, most of whom would not have been identified through family history assessment.