Breast Cancer Surveillance Research Articles

0973 HGNS Sensing Lead Damage After 3D Mammogram Requiring HGNS IPG and Lead Re-Implantation

Abstract Introduction Obstructive sleep apnea (OSA) is associated with excessive daytime sleepiness, nocturnal hypoxemia, and daytime fatigue. Standard therapy is with positive airway pressure (PAP) therapy. If this is unsuccessful or poorly tolerated, a hypoglossal nerve stimulator (HGNS) can be surgically implanted for treatment. The goal of HGNS treatment is to advance the tongue with each respiration during sleep to relieve oropharyngeal obstruction causing OSA. This therapy has been shown to be efficacious and well tolerated for moderate to severe sleep apnea with a low complication rate. Report of case(s) A 61 year-old female with history of obesity and severe OSA presented to the sleep clinic with complaint of excessive daytime sleepiness and persistently elevated apnea-hypopnea index (AHI) of 42 events/hour despite adequate usage of CPAP therapy. She underwent an HGNS placement for treatment. Following HGNS activation she used it nightly and three months after implantation underwent an HGNS titration study which was successful (AHI 5.7) and the patient was started on optimal treatment settings with resulting resolution of OSA symptoms. After a period of successful device usage, she presented for follow up and reported complaints of excessive fatigue and sleepiness that was sudden. She attributed these changes to a 3D mammography study she underwent for breast cancer surveillance. Repeat home sleep apnea testing showed sudden worsening of her AHI to 50.6. During a thorough investigation of her device, HGNS sensing waveforms indicated possible sensing lead fracture. The patient was taken to the operating room for implanted pulse generator removal and replacement with new sensing and stimulation leads. Intra-operatively, it was noted that the distal sensing lead had several tears of the polyurethane insulation near the hub of the sensor. Following successful re-implantation sensing returned to normal and she has continued HGNS treatment. Conclusion We present a case of an unusual complication of HGNS sensing lead damage following a 3D mammography study. This led to surgical exploration with removal of a torn sensing lead and re-implantation of the HGNS generator and leads. Attention should be brought to patients and providers in the future regarding this rare, but potentially serious complication. Support (if any)

Comparison of Diagnostic Performance between MRI and Mammogram with Ultrasound in Surveillance for Local Recurrent Breast Cancer after BCT

Objective: To compare the diagnostic performance of breast magnetic resonance imaging (MRI) and mammography with ultrasonography for detection of local recurrent breast cancer among female patients with post-breast conserving therapy (BCT). Materials and Methods: The authors retrospectively enrolled 190 post-BCT female patients who underwent post-operative surveillance by breast MRI and mammography with ultrasonography at King Chulalongkorn Memorial Hospital between January 1, 2008 and July 1, 2019. Two radiologists reviewed the images from the two surveillance modalities, independently. The information including radiological and histopathological data were blinded during the review process. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were then estimated to reflect the diagnostic performance of the two modalities for detection of local recurrent breast cancer. Results: Of the 190 patients, 52 (27.4%) were diagnosed as local recurrent breast cancer. Sensitivity, specificity, PPV, and NPV were 98.1%, 92%, 82.3%, 99.2%, respectively, for breast MRI, and 88.5%, 62.3%, 46.9%, 93.5%, respectively, for mammography with ultrasonography. The findings that could be better evaluated by breast MRI than by mammography with ultrasonography included post-operative change and benign mass (p<0.001), suspicious mass (p<0.001), and suspicious calcification (p<0.003). Conclusion: Breast MRI is superior to mammography with ultrasonography for detection of local recurrent breast cancer after BCT. Furthermore, MRI can help clinicians avoid unnecessary biopsy and surgical interventions due to its ability to differentiate post-treatment change from local recurrent breast cancer. Keywords: Breast conserving therapy; Magnetic resonance imaging; Breast MRI; Mammography with ultrasonography; Local recurrent breast cancer

National Performance Benchmarks for Screening Digital Breast Tomosynthesis: Update from the Breast Cancer Surveillance Consortium.

Background It is important to establish screening mammography performance benchmarks for quality improvement efforts. Purpose To establish performance benchmarks for digital breast tomosynthesis (DBT) screening and evaluate performance trends over time in U.S. community practice. Materials and Methods In this retrospective study, DBT screening examinations were collected from five Breast Cancer Surveillance Consortium (BCSC) registries between 2011 and 2018. Performance measures included abnormal interpretation rate (AIR), cancer detection rate (CDR), sensitivity, specificity, and false-negative rate (FNR) and were calculated based on the American College of Radiology Breast Imaging Reporting and Data System, fifth edition, and compared with concurrent BCSC DM screening examinations, previously published BCSC and National Mammography Database benchmarks, and expert opinion acceptable performance ranges. Benchmarks were derived from the distribution of performance measures across radiologists (n = 84 or n = 73 depending on metric) and were presented as percentiles. Results A total of 896 101 women undergoing 2 301 766 screening examinations (458 175 DBT examinations [median age, 58 years; age range, 18-111 years] and 1 843 591 DM examinations [median age, 58 years; age range, 18-109 years]) were included in this study. DBT screening performance measures were as follows: AIR, 8.3% (95% CI: 7.5, 9.3); CDR per 1000 screens, 5.8 (95% CI: 5.4, 6.1); sensitivity, 87.4% (95% CI: 85.2, 89.4); specificity, 92.2% (95% CI: 91.3, 93.0); and FNR per 1000 screens, 0.8 (95% CI: 0.7, 1.0). When compared with BCSC DM screening examinations from the same time period and previously published BCSC and National Mammography Database performance benchmarks, all performance measures were higher for DBT except sensitivity and FNR, which were similar to concurrent and prior DM performance measures. The following proportions of radiologists achieved acceptable performance ranges with DBT: 97.6% for CDR, 91.8% for sensitivity, 75.0% for AIR, and 74.0% for specificity. Conclusion In U.S. community practice, large proportions of radiologists met acceptable performance ranges for screening performance metrics with DBT. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Lee and Moy in this issue.

Enhancement of immune surveillance in breast cancer by targeting hypoxic tumor endothelium: Can it be an immunological switch point?

Breast cancer ranks second among the causes of cancer-related deaths in women. In spite of the recent advances achieved in the diagnosis and treatment of breast cancer, further study is required to overcome the risk of cancer resistance to treatment and thereby improve the prognosis of individuals with advanced-stage breast cancer. The existence of a hypoxic microenvironment is a well-known event in the development of mutagenesis and rapid proliferation of cancer cells. Tumor cells, purposefully cause local hypoxia in order to induce angiogenesis and growth factors that promote tumor growth and metastatic characteristics, while healthy tissue surrounding the tumor suffers damage or mutate. It has been found that these settings with low oxygen levels cause immunosuppression and a lack of immune surveillance by reducing the activation and recruitment of tumor infiltrating leukocytes (TILs). The immune system is further suppressed by hypoxic tumor endothelium through a variety of ways, which creates an immunosuppressive milieu in the tumor microenvironment. Non responsiveness of tumor endothelium to inflammatory signals or endothelial anergy exclude effector T cells from the tumor milieu. Expression of endothelial specific antigens and immunoinhibitory molecules like Programmed death ligand 1,2 (PDL-1, 2) and T cell immunoglobulin and mucin-domain containing-3 (TIM-3) by tumor endothelium adds fuel to the fire by inhibiting T lymphocytes while promoting regulatory T cells. The hypoxic microenvironment in turn recruits Myeloid Derived Suppressor Cells (MDSCs), Tumor Associated Macrophages (TAMs) and T regulatory cells (Treg). The structure and function of newly generated blood vessels within tumors, on the other hand, are aberrant, lacking the specific organization of normal tissue vasculature. Vascular normalisation may work for a variety of tumour types and show to be an advantageous complement to immunotherapy for improving tumour access. By enhancing immune response in the hypoxic tumor microenvironment, via immune-herbal therapeutic and immune-nutraceuticals based approaches that leverage immunological evasion of tumor, will be briefly reviewed in this article. Whether these tactics may be the game changer for emerging immunological switch point to attenuate the breast cancer growth and prevent metastatic cell division, is the key concern of the current study.

Contrast enhanced mammography in breast cancer surveillance

PurposeMammography (MG) is the standard imaging in surveillance of women with a personal history of breast cancer or DCIS (PHBC), supplemented with ultrasound. Contrast Enhanced Mammography (CEM) has higher sensitivity than MG and US. We report the performance of CEM compared with MG ± US.MethodsA retrospective study of patients undergoing their first surveillance CEM in an Australian hospital setting between June 2006 and October 2020. Cases where a patient was recalled for assessment were identified, recording radiology, pathology and treatment details. Blinded re-reading of recalled cases was performed to determine the contribution of contrast. Use of surveillance US across the board was assessed for the period.Results73/1191 (6.1%) patients were recalled. 35 (48%) were true positives (TP), with 26 invasive cancers and 9 cases of DCIS, while 38 (52%) were false positive (FP) with a positive predictive value (PPV) 47.9%. 32/73 were recalled due to MG findings, while 41/73 were only recalled due to Contrast. 14/73 had ‘minimal signs’ with a lesion identifiable on MG with knowledge of the contrast finding, while 27/73 were visible only with contrast. 41% (17/41) recalled due to contrast were TP. Contrast-only TPs were found with low and high mammographic density (MD). Screening breast US reduced by 55% in the year after CEM was implemented.ConclusionCompared to MG, CEM as a single surveillance modality for those with PHBC has higher sensitivity and comparable specificity, identifying additional malignant lesions that are clinically significant. Investigation of interval cancer and subsequent round outcomes is warranted.

Contrast Enhanced Mammography In Breast Cancer Surveillance

Contrast Enhanced Mammography In Breast Cancer Surveillance

Abstract P5-12-02: Germline variants detected by next-generation sequencing-based multigene panel testing in patients with suspected hereditary breast cancer at a University Hospital in Japan

Abstract Background: The usefulness of prophylactic surgery and surveillance for hereditary breast cancer has been demonstrated, and germline testing for BRCA1 and BRCA2 had been covered by insurance since 2020 in Japan. In addition to BRCA1 and BRCA2, several other genes are also associated with an increased risk of developing breast cancer, such as PALB2, ATM, BARD1, CHEK2, PTEN, and TP53. Next-generation sequencing-enabled multigene panel tensing provides information about these gene variants at the same time, and at a low cost. Although germline testing of BRCA1 and BRCA2 has become widespread in Japan, multi-panel gene testing for germline variants has been conducted only in a limited number of facilities, partly due to the difficulty associated with dealing with the gene variant information obtained from the test. The aim of this study was to clarify the current status of multigene panel testing in our institute, and reveal the characteristics of the variants detected in patients with, or predisposed to, hereditary breast cancer. Methods: This retrospective study included 37 individuals who underwent next-generation sequencing-based multigene panel testing in order to investigate any inherited genetic variants due to a suspicion of hereditary breast cancer. Eighteen patients had a diagnosis of breast cancer with a family history of breast and/or ovarian cancer, nine patients had a diagnosis of breast cancer without family history of breast or ovarian cancer, and 10 patients had a family history of breast cancer but had not developed breast cancer themselves. Results: Utilizing mutigene panel testing, at least one alteration was found in 24 genes, and a total of 39 variants were found in the 37 patients. Of these 37 patients, nine (24.3%) had a pathogenic/likely pathogenic variant with or without other variants of uncertain significance (VUS), 15 (40.5%) had VUS, and 13 (35.1%) had negative genetic test results. Among the nine patients with pathogenic/likely pathogenic variants, seven had variants in either BRCA1 or BRCA2 (one BRCA1 pathogenic variant, five BRCA2 pathogenic variants, and one BRCA2 likely pathogenic variant), while the remaining positive results were attributed to other genes (one MLH1 pathogenic variant, and one SDHB pathogenic variant). VUS included BRCA1 and BRCA2, as well as other breast cancer-associated genes, such as ATM (n=2), CDH1 (n=2), NF1 (n=2), PALB2 (n=1), CHEK2 (n=1), NBN (n=1), and RAD51D (n=1). VUS also included other cancer syndrome-related genes, such as MLH1 (n=2), MUTYH (n=2), APC (n=1), and RET (n=1). Conclusion: Multigene panel tests in our institute revealed pathogenic/likely pathogenic variants in 24.3% of individuals who suspected hereditary breast cancer. As expected, multigene panel tests also revealed more VUS than pathogenic variants and 40.5% individuals were detected with VUS, which included many genes associated with hereditary breast cancer and other cancer syndromes, in addition to BRCA1 and BRCA2. Individuals with VUS will need to cope with new information if the interpretation of the variant changes in the future. We need to be aware of the characteristics and limitations of this type of panel testing, and to properly utilize the test results and information obtained for good quality patient care. Citation Format: Yusa Atake, Masayuki Nagahashi, Haruka Kanaoka, Akira Hattori, Ayako Bun, Reiko Fukui, Hiromi Ozawa, Yukie Fujimoto, Tomoko Higuchi, Michiko Imamura, Keiko Murase, Yuichi Takatsuka, Mina Kashima, Chiho Okada, Chinatsu Kinjo, Mikako Miyata, Ayako Miyazaki, Mako Ueda, Hiroshi Tsubamoto, Hideaki Sawai, Yasuo Miyoshi. Germline variants detected by next-generation sequencing-based multigene panel testing in patients with suspected hereditary breast cancer at a University Hospital in Japan [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-12-02.

Abstract P2-06-04: Effects of BMI velocity on outcomes in patients with metastatic breast cancer in the Dallas Metastatic Breast Cancer Study

Abstract BACKGROUND: The Dallas Metastatic Breast Cancer Study (DMBCS) is a clinical database that was established in 2021 at a single academic medical system to track patient demographics, associated pathology, treatments, and other variables that are not widely available in the Surveillance, Epidemiology, and End Results (SEER) Program for metastatic breast cancer (MBC). One of many ongoing studies as part of the DMBCS is to investigate how weight loss after diagnosis affects outcomes in MBC patients. Although previous studies have shown that significant weight loss is associated with poorer outcomes in certain cancer types, little is known about its role in breast cancer. METHODS: 139 patients who were diagnosed with MBC between 2009-2021 were included in this data collection. BMI at the time of diagnosis of MBC and within 6 months of death or last follow-up were recorded. BMI velocity was calculated by dividing the difference between BMI at diagnosis and BMI at time of death (or last follow-up) by the number of months between initial diagnosis and time of death (or last follow-up). The BMI velocity represents the rate at which patients lost or gained weight during their disease course. A negative BMI velocity indicates weight loss, and a positive BMI velocity indicates weight gain over the defined period. The absolute value of the BMI velocity indicates how rapidly someone gains or loses weight. The association of BMI velocity on the primary outcome (overall survival (OS) and progression-free survival (PFS)) was assessed using Cox proportional hazard (PH) model. Adjusted hazard ratios (HR) with 95% confidence intervals were computed using the multivariable Cox PH model. RESULTS: At the time of diagnosis of MBC, 40% were obese and 33% were overweight. At the time of death or last follow-up, 27% were obese and 31% were overweight. The mean BMI velocity was -0.13 per month. Contrary to previous studies that have shown a negative effect of obesity on OS, we found that obesity at the time of diagnosis of MBC did not statistically worsen OS and PFS. However, compared to patients who had negative BMI velocities, improved OS (lower hazard ratio) was noted for patients with stable or increasing BMI velocities (HR = 0.53; 95% CI = 0.32-0.88, p = 0.014). A greater rate of weight loss was also associated with worse OS (HR = 0.23; 95% CI = 0.12 - 0.47, p < 0.001) and PFS (HR = 0.29; 95% CI = 0.16 - 0.52, p < 0.001). Improved PFS was seen for patients with stable or increasing BMI velocities in the unadjusted analysis (HR = 0.65; 95% CI = 0.42 - 0.99, p = 0.047). CONCLUSION: Our study found that contrary to previously published results in patients with early-stage breast cancer, obesity did not statistically worsen OS or PFS. However, the rate of weight loss, which we defined as BMI velocity, is associated with higher mortality in MBC. Our findings can be applied to clinical practice when advising MBC patients regarding healthy changes in weight during their disease course. BMI velocity could be used as a prognostic indicator to predict outcomes in patients with MBC. In future studies, we aim to quantify the amount of weight loss that is associated with worse outcomes. Citation Format: Mir Lim, Mona Pathak, Meng Cao, Anna Moscowitz, Jonathan Ladner, Sangeetha Reddy, Isaac Chan. Effects of BMI velocity on outcomes in patients with metastatic breast cancer in the Dallas Metastatic Breast Cancer Study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-06-04.

Abstract P1-05-04: Physician Practice Patterns of Breast Imaging After Treatment: Survey of Real-World Practice

Abstract Introduction: Mammography is the cornerstone of breast cancer screening, diagnosis, and surveillance. After definitive treatment for breast cancer, mammograms are continued for surveillance. The current recommendations regarding surveillance after definitive treatment (surgery and radiation) lack consensus amongst various societies. There are no clear guidelines in regards to the type of mammogram recommended: diagnostic or screening mammogram or if a diagnostic mammogram is used, when to return to routine screening protocols. Current practice patterns are driven by physician’s preference. We conducted a survey to evaluate physicians’ preferences in ordering breast imaging post- breast cancer diagnosis and treatment. Methods: This survey was approved by University of Arizona institutional review board. This survey was conducted through American Society of Clinical Oncology (ASCO) voluntary opt-in Research Survey Pool (RSP). ASCO sent out this survey to 1000 randomly selected members between 10/19/2021-11/22/2021. Weekly reminders to participate were sent through the ASCO RSP for 5 weeks. Participants clicked the link to the survey platform where upon consent they completed the survey. Results: The survey was completed by 244 healthcare professionals through the ASCO RSP. Most respondents were physicians (n=228), primarily medical oncologists (n=174) and practiced in an academic environment in the United States (n=132). After definitive treatment, majority (58%) ordered first imaging at 6 months post-surgery/radiation, and it was primarily a diagnostic mammogram (68%). Interestingly, for patients at age 80 or above, screening mammogram was used for surveillance after definitive treatment by most respondents (59%). After first post-surgery/radiation mammogram there is an almost even spilt (50%) on continuing with diagnostic versus screening mammograms for follow up. Of those who order diagnostic mammograms, majority (38%) do it for 3-5 years with an additional 30% continuing it beyond 5 years. Almost 65% of respondents reported they do not stop screening mammograms at any age for patients with a history of early-stage breast cancer as long as they are healthy. Conclusions: The practice patterns of healthcare professionals as it relates to the type and frequency of breast imaging varies significantly. Despite having the same imaging quality there is a significant difference in the cost of screening and diagnostic mammograms. In addition, in clinical practice, most routine screening care is covered by insurances without co-pays or out of pocket costs for patients. Diagnostic imaging does not fall under routine screening care and frequently requires out of pocket expenses for patients. As insurance companies start to decline certain imaging modalities used for cancer detection due to lack of data supporting the use of these expensive studies, specific imaging guidelines for follow up in post-treatment setting for patients with breast cancer are needed. Citation Format: Meredith Whittaker, Kiah Farr, Preethika Potluri, Nova Foster, Jennifer Erdrich, Jennifer Segar, Sima Ehsani, Sao Jiralerspong, Denise Roe, Pavani Chalasani. Physician Practice Patterns of Breast Imaging After Treatment: Survey of Real-World Practice [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-05-04.

Abstract PD16-02: Factors Associated with Receipt of Digital Breast Tomosynthesis Among Racially/Ethnically Diverse Women Undergoing Screening Mammography

Abstract Introduction: Digital breast tomosynthesis (DBT) is increasingly utilized in breast cancer screening, including among women at high risk for breast cancer. While there is a lack of rigorous data from randomized controlled trials demonstrating superior efficacy compared to two-dimensional (2D) digital mammography, observational studies suggest that DBT might have lower rates of false-positive results and increased detection of invasive cancer than 2D mammography. However, uptake of DBT might be lower among racial/ethnic minorities, which could contribute to breast cancer disparities. We evaluated whether sociodemographic and breast cancer risk factors were associated with receipt of DBT vs. 2D mammography among a racially/ethnically diverse population of women undergoing screening mammography. Methods: We conducted a respective cohort study among women, age 40-74 years, who underwent screening mammography at Columbia University Irving Medical Center (CUIMC) in New York, NY, from February 2020 to January 2022. We extracted data from the electronic health record (EHR) on age, race/ethnicity, first-degree family history of breast cancer (yes/no), prior breast biopsies (yes/no), and mammographic breast density (high vs. low), and calculated individual 5-year risks of invasive breast cancer according to the Breast Cancer Surveillance Consortium (BCSC) model. High risk was defined as a 5-year invasive breast cancer risk 1.67%. Our primary outcome was receipt of at least one DBT screening examination from 2020-2022 (yes/no). We conducted multivariable logistic regression analyses to assess the association between demographic/clinical factors and receipt of DBT. Results: Among 5617 evaluable women, mean age was 55.4 years (SD, 9.5 years) and 56% identified as non-Hispanic White, 10% as non-Hispanic Black, 17% as Hispanic, 8% as Asian, and 9% other/unknown. Over 60% of women had high breast density, and 34% met high-risk criteria. Seventy percent of women had at least one DBT from 2020-2022. In multivariable analyses (Table 1), women with high vs. low breast density were 2.5 times more likely to receive DBT (odds ratio [OR]=2.51, 95% confidence interval [CI]=2.19-2.88), while first-degree family history of breast cancer, prior breast biopsy, and age were inversely associated with DBT. Racial/ethnic minorities were less than half as likely to undergo DBT compared to non-Hispanic Whites; for example, Hispanic women were over 85% less likely to receive DBT (OR=0.14, 95% CI=0.11-0.16). Overall, there was no association between breast cancer risk status (high vs. low/average) and receipt of DBT (OR=1.00, 95% CI 0.92-1.08). Conclusion: We observed that the majority of women undergoing screening mammography at CUIMC from 2020-2022 received DBT for breast cancer screening. However, racial/ethnic minorities, including non-Hispanic Blacks and Hispanics, were significantly less likely than non-Hispanic Whites to have received DBT. Breast cancer risk according the BCSC model was also not associated with receipt of DBT. Future studies should determine which subsets of women are more likely to benefit from DBT. Citation Format: Julia E. McGuinness, Gargi Patel, Jacquelyn N. Amenta, Rita Kukafka, Katherine D. Crew. Factors Associated with Receipt of Digital Breast Tomosynthesis Among Racially/Ethnically Diverse Women Undergoing Screening Mammography [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD16-02.

Abstract P3-03-14: Comparing risk of breast cancer and cardiovascular disease and uptake of chemoprevention and statins among racially/ethnically diverse women with atypical hyperplasia or lobular carcinoma in situ

Abstract Background: Chemoprevention with selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs) has been shown in randomized controlled trials to decrease breast cancer incidence by 50-65% among women at high risk for breast cancer. However, chemoprevention uptake remains low among high-risk women. Women with atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS) derive the greatest benefit from SERMs and AIs for breast cancer risk reduction. A potential barrier to chemoprevention uptake is competing comorbidities, including atherosclerotic cardiovascular disease (ASCVD). We calculated risk of breast cancer and ASCVD among women with AH or LCIS and assessed uptake of chemoprevention and statins among women who met high-risk criteria for both breast cancer and ASCVD. Methods: We conducted a retrospective cohort study among women, age 40-74 years, with AH or LCIS diagnosed in 2007-2015 at Columbia University Irving Medical Center (CUIMC) in New York City. Eligible women had sufficient data in the electronic health record (EHR) to calculate 5 and 10-year invasive breast cancer risk according to the Breast Cancer Surveillance Consortium (BCSC) risk calculator, including age, race/ethnicity, first-degree family history of breast cancer, breast biopsy results, and mammographic density. We calculated 10-year ASCVD risk using the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) ASCVD risk calculator using additional EHR data, including systolic blood pressure, total and HDL cholesterol, history of diabetes, treatment for hypertension, and current smoking status. High-risk criteria to determine eligibility for SERMs/AIs and statins was defined as a 5-year invasive breast cancer risk 1.67% and 10-year ASCVD risk 7.5%, respectively. We compared mean 10-year risk of breast cancer vs. ASCVD using a paired t-test and uptake of SERMs/AIs vs. statins among women at high risk for breast cancer and ASCVD, respectively, using McNemar’s test. Results: Among 298 evaluable women, mean age was 58.2 years (standard deviation [SD], 8.34), with 33% non-Hispanic White, 41% Hispanic, 9% non-Hispanic Black, 6% Asian, and 11% other/unknown race/ethnicity. About 98% of women met high-risk criteria for breast cancer and 30% were high risk for ASCVD. Mean 10-year risk of breast cancer was higher than mean 10-year risk of ASCVD (9.14% vs. 6.69%, p< 0.001). Among women who met high-risk criteria for both breast cancer and ASCVD, uptake of statins was higher compared to SERMs/AIs (58% vs. 21%, p< 0.001). Comparing non-Hispanic Whites vs. racial/ethnic minorities, mean 10-year breast cancer risk was higher (12.12% vs. 7.71%, p< 0.001), but there were no statistically significant differences in ASCVD risk or uptake of chemoprevention or statins. Conclusions: Among women with AH or LCIS, mean absolute risk of breast cancer was higher compared to risk of ASCVD, however, uptake of statins was higher compared to chemoprevention with SERMs or AIs. To address under-utilization of chemoprevention among high-risk women, use of SERMs or AIs should be placed in the context of medications used for other chronic diseases, such as statins for ASCVD. Citation Format: Luisa Nilan, Jacquelyn N. Amenta, Julia E. McGuinness, Rita Kukafka, Katherine D. Crew, Kehinde Lawal. Comparing risk of breast cancer and cardiovascular disease and uptake of chemoprevention and statins among racially/ethnically diverse women with atypical hyperplasia or lobular carcinoma in situ [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-03-14.

Abstract PD14-07: PD14-07 Associations of Breast Cancer Risk Level and Prediction of Tumor Aggressiveness in the Athena Breast Health Network

Abstract Background: The Athena Breast Health Network (Athena) is a University of California (UC) initiative integrating clinical care and research to drive improvements in breast cancer screening. Through standardized, self-reported clinical intake forms, a patient’s breast health status and information regarding their breast cancer risk is captured before each mammography appointment. Breast cancer risk models provide a level of risk to develop breast cancer but do not take into account aggressiveness of breast cancer. Here, we evaluated outcome data of a large screening cohort for association between risk level and aggressiveness at diagnosis. Methods: We calculated Breast Cancer Surveillance Consortium (BCSC) risk scores for a cohort of 8,923 consented UCSF Athena participants from the years 2012-2018 with a median follow-up of 5-years. To identify those who developed invasive breast cancer on or after completing an Athena intake form, we performed a cancer linkage with the San Francisco Mammography Registry (SFMR), a local registry that regularly collects cancer data from the California Cancer Registry. We classified tumors as aggressive if they met one or more of the following criteria: hormone receptor (HR)-negative, HER2-positive, grade 3. All other tumors were classified as non-aggressive. We used student’s t-tests to examine associations between BCSC 5-year risk score, the development of invasive breast cancer, and tumor aggressiveness among cases. To account for the association between older age and higher BCSC risk score (as well as HR-positive subtypes), we stratified by percentiles of BCSC risk by age (top 2.5% vs. bottom 97.5%). The top 2.5% by age threshold consistently identifies women with lifetime risk of 23–28% and was chosen as high-risk threshold to trigger annual screening in the WISDOM study (Dreher: PMID34843026). Results: Of 8,923 participants, 170 (2%) developed breast cancer during the follow-up period. The average 5-year BCSC risk score for women with breast cancer was 1.81% and 1.47% for those without (p< 0.001). Among women with breast cancer, 123 (72%) developed non-aggressive cancers and 47 (28%) developed aggressive cancers. The average 5-year BCSC risk score for women with non-aggressive and aggressive cancers was 1.89% and 1.60%, respectively (p=0.13). In analyses stratified by percentile of BCSC risk by age, 521 (6%) participants had a BCSC 5-year risk score in the top 2.5% by age and 8,402 (94%) participants had a BCSC 5-year risk score in the bottom 97.5%. A higher percentage of women with non-aggressive cancers vs healthy women (controls) were in the top 2.5% by age (p = 0.001), but the percentage of aggressive cancers vs healthy women in the top 2.5% by age was similar (p = 0.61). Conclusion: Through this study we confirmed that higher 5-year BCSC risk scores are associated with higher overall breast cancer development. Interestingly, participants with the highest 5-year BCSC risk scores (top 2.5% by age), are more likely to develop cancers with non-aggressive features (low grade, hormone positive). This suggests that the BCSC model may preferentially predict less aggressive tumors, and those with the highest 5-year BCSC risk may be more likely to benefit from endocrine risk reduction therapy. There remains a gap in our ability to identity those at risk for aggressive cancers. Our findings highlight the need for screening programs to better understand who is at risk for what type of breast cancer. Current work is focused on developing models tailored to risk prediction of aggressive cancers. Citation Format: Katherine Leggat-Barr, Tomiyuri Lewis, Rosalyn Sayaman, Paige Warner, Kathy Malvin, Leah Sabacan, Elene Tsopurashvili, WISDOM Study and Athena Breast Health Network Investigators and Advocate Partners, Allison Stover Fiscalini, Jeffrey Tice, Karla Kerlikowske, Yiwey Shieh, Laura J. Esserman, Laura Van ’t Veer. PD14-07 Associations of Breast Cancer Risk Level and Prediction of Tumor Aggressiveness in the Athena Breast Health Network [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD14-07.

Abstract P6-02-04: Use of breast surveillance between women with pathogenic variants and variants of uncertain significance in breast cancer susceptibility genes

Abstract Background: Surveillance is a fundamental tool in the early detection and secondary prevention of many cancers. For women at increased genetic risk of breast cancer, mammography and breast magnetic resonance imaging (MRI) serve as the standard screening modalities. Use of surveillance mammography and MRI has been understudied among women with variant of uncertain significance (VUS) compared to pathogenic and likely pathogenic variants (P/LP). To address this gap, we examined the use of breast cancer surveillance and breast surgery in women who underwent multiple gene sequencing in a multicenter cohort of patients. We also expanded the surveillance literature by assessing correlates of breast MRI and mammography among women with VUS and investigating how rates of imaging changed over time after genetic testing. Methods: Using data from two cancer settings, we calculated use of risk reducing mastectomy (RRM) and surveillance for all women at genetically elevated risk of breast cancer, regardless of their personal history of breast cancer, with VUS or P/LP variants in a breast cancer susceptibility gene of high penetrance (BRCA1, BRCA2, PALB2, PTEN, TP53) and moderate penetrance (ATM, CDH1, CHEK2, NBN, NF1, STK11). The primary outcome was longitudinal use of surveillance mammography and breast MRI for women during the 13-month span after genetic testing, and each subsequent 13-month period up to 6 years afterwards. Results: Of 889 women, those with and without personal history of breast cancer were similar with regards to race/ethnicity, marital status, and high- or average-risk status. However, women with a personal history of breast cancer were on average older (54.1 vs 48.2 years), had longer follow-up time since genetic testing (3.4 vs 3.0 years), and were more likely to have VUS (62.5% vs 37.7%) compared to those without personal history of breast cancer. VUS carriers were less likely to undergo RRM compared to those with P/LP (HR=0.17, p=< 0.001) and high-risk women were more likely to undergo RRM than average-risk women (HR=3.91, p=0.005). Longitudinally, surveillance use among unaffected women decreased from 49.8% in the first year to 31.2% in the sixth year after genetic testing. In comparison, a greater proportion of women with a personal history of breast cancer underwent surveillance, which increased from 59.3% in the first year to 63.6% in the sixth year after genetic testing. Mammography rates did not differ between women with P/LP and VUS within the first 13 months after genetic testing and up to 4 years afterwards. Over the first four years after genetic testing, women with VUS were less likely to undergo annual MRIs compared to P/LP. This observation was true for women without a personal history of breast cancer (OR=0.34, p=0.003; OR=0.37, p=0.03; OR=0.19, p=0.004 for years 1, 2, and 3 respectively) as well as for women with a personal history of breast cancer (OR=0.31, p<=0.001; OR=0.33, p=0.002; OR=0.37, p=0.012; OR=0.3, p=0.14 for years 1, 2, 3, and 4 respectively). Conclusion: In this study of surveillance mammography and breast MRI use among women at elevated risk of breast cancer, we found that women with P/LP variants in breast cancer susceptibility genes are more likely to undergo annual breast MRI compared to those with VUS, whereas there was no difference between the groups in their use of annual surveillance mammography. This study is one of the first to examine maintenance of breast surveillance in a sample of women at elevated risk of breast cancer with non-negative genetic test results in BRCA1/2 as well as non-BRCA1/2 genes, while adjusting for personal and family history of cancer. In addition, we found that VUS, whether in high or moderate penetrance breast cancer susceptibility genes, was associated with lower use of annual breast MRI compared to P/LP variants, and equivalent use of annual mammography. These results add important evidence to dispel the myth of VUS-associated mismanagement of care. Citation Format: Sukh Makhnoon, Minxing Chen, Brooke Levin, Megan Ensinger, Kristin Mattie, Generosa Grana, Sanjay Shete, Banu K. Arun, Susan K. Peterson. Use of breast surveillance between women with pathogenic variants and variants of uncertain significance in breast cancer susceptibility genes [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-02-04.

Abstract P4-03-03: Elevated Risk of Breast Cancer Diagnosis in Women with Dense Breasts reflects a similarly Elevated Risk of Breast Cancer Onset that is Robust to the Effect of Density on Mammography Sensitivity

Abstract Dense breasts are associated with a higher risk of breast cancer diagnosis, which has impacted risk prediction tools and patient notification policies. However, given that mammography is less sensitive for women with dense breasts and these women may be subject to different confirmation testing pathways, the true association between breast density and cancer risk is unknown. We investigated the relationship between breast density and onset using a natural history model that accounts for differential sensitivity and rates of exams by breast density. Data consisted of Breast Cancer Surveillance Consortium mammogram and cancer outcomes among women aged 40-54 with a first digital mammogram between 2000-2018 (N=33,542). Of these, 15,092 had non-dense (almost entirely fatty or scattered fibroglandular densities) and18,450 had dense (heterogeneously dense or extremely dense) breasts. We estimated the empirical sensitivity of mammograms in dense and non-dense breasts (fraction of diagnosed cancers that were screen detected) and examined rates of mammograms by density. We estimated the relative risk of breast cancer diagnosis five years after the first exam using Kaplan Meier methods and the relative risk of breast cancer onset from a natural history model, assuming density-specific sensitivity was equal to the empirical sensitivity. Empirical sensitivity was .88 in women with non-dense and .78 in women with dense breasts. Mammogram utilization was somewhat higher in women with dense breasts (HR for subsequent mammograms 1.10 (95% CI [1.07, 1.12]). The relative risk of diagnosis for dense versus non-dense breasts was 1.80 (95% CI [1.46,2.57]); based on the natural history model the relative risk of onset was 1.73 [1.43,2.25]. The estimated relative risk of onset ranged from 1.67 to 2.03 under assumptions that the relative sensitivity of the screening episode for dense versus non-dense breasts was 1.0 to 0.4. In conclusion, the association of risk of breast cancer onset with breast density is robust to assumptions about the relative sensitivity in dense and non-dense breasts. Citation Format: Jane M. Lange, Charlotte Gard, Ellen O’meara, Ruth Etzioni. Elevated Risk of Breast Cancer Diagnosis in Women with Dense Breasts reflects a similarly Elevated Risk of Breast Cancer Onset that is Robust to the Effect of Density on Mammography Sensitivity [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-03-03.

Cumulative 6-Year Risk of Screen-Detected Ductal Carcinoma In Situ by Screening Frequency

Detection of ductal carcinoma in situ (DCIS) by mammography screening is a controversial outcome with potential benefits and harms. The association of mammography screening interval and woman's risk factors with the likelihood of DCIS detection after multiple screening rounds is poorly understood. To develop a 6-year risk prediction model for screen-detected DCIS according to mammography screening interval and women's risk factors. This Breast Cancer Surveillance Consortium cohort study assessed women aged 40 to 74 years undergoing mammography screening (digital mammography or digital breast tomosynthesis) from January 1, 2005, to December 31, 2020, at breast imaging facilities within 6 geographically diverse registries of the consortium. Data were analyzed between February and June 2022. Screening interval (annual, biennial, or triennial), age, menopausal status, race and ethnicity, family history of breast cancer, benign breast biopsy history, breast density, body mass index, age at first birth, and false-positive mammography history. Screen-detected DCIS defined as a DCIS diagnosis within 12 months after a positive screening mammography result, with no concurrent invasive disease. A total of 916 931 women (median [IQR] age at baseline, 54 [46-62] years; 12% Asian, 9% Black, 5% Hispanic/Latina, 69% White, 2% other or multiple races, and 4% missing) met the eligibility criteria, with 3757 screen-detected DCIS diagnoses. Screening round-specific risk estimates from multivariable logistic regression were well calibrated (expected-observed ratio, 1.00; 95% CI, 0.97-1.03) with a cross-validated area under the receiver operating characteristic curve of 0.639 (95% CI, 0.630-0.648). Cumulative 6-year risk of screen-detected DCIS estimated from screening round-specific risk estimates, accounting for competing risks of death and invasive cancer, varied widely by all included risk factors. Cumulative 6-year screen-detected DCIS risk increased with age and shorter screening interval. Among women aged 40 to 49 years, the mean 6-year screen-detected DCIS risk was 0.30% (IQR, 0.21%-0.37%) for annual screening, 0.21% (IQR, 0.14%-0.26%) for biennial screening, and 0.17% (IQR, 0.12%-0.22%) for triennial screening. Among women aged 70 to 74 years, the mean cumulative risks were 0.58% (IQR, 0.41%-0.69%) after 6 annual screens, 0.40% (IQR, 0.28%-0.48%) for 3 biennial screens, and 0.33% (IQR, 0.23%-0.39%) after 2 triennial screens. In this cohort study, 6-year screen-detected DCIS risk was higher with annual screening compared with biennial or triennial screening intervals. Estimates from the prediction model, along with risk estimates of other screening benefits and harms, could help inform policy makers' discussions of screening strategies.

Variation in second breast cancer risk after primary invasive cancer by time since primary cancer diagnosis and estrogen receptor status.

In women with previously treated breast cancer, occurrence and timing of second breast cancers have implications for surveillance. The authors examined the timing of second breast cancers by primary cancer estrogen receptor (ER) status in the Breast Cancer Surveillance Consortium. Women who were diagnosed with American Joint Commission on Cancer stage I-III breast cancer were identified within six Breast Cancer Surveillance Consortium registries from 2000 to 2017. Characteristics collected at primary breast cancer diagnosis included demographics, ER status, and treatment. Second breast cancer events included subsequent ipsilateral or contralateral breast cancers diagnosed >6months after primary diagnosis. The authors examined cumulative incidence and second breast cancer rates by primary cancer ER status during 1-5 versus 6-10years after diagnosis. At 10years, the cumulative second breast cancer incidence was 11.8% (95% confidence interval [CI], 10.7%-13.1%) for women with ER-negative disease and 7.5% (95% CI, 7.0%-8.0%) for those with ER-positive disease. Women with ER-negative cancer had higher second breast cancer rates than those with ER-positive cancer during the first 5 years of follow-up (16.0 per 1000 person-years [PY]; 95% CI, 14.2-17.9 per 1000 PY; vs. 7.8 per 1000 PY; 95% CI, 7.3-8.4 per 1000 PY, respectively). After 5 years, second breast cancer rates were similar for women with ER-negative versus ER-positive breast cancer (12.1 per 1000 PY; 95% CI, 9.9-14.7; vs. 9.3 per 1000 PY; 95% CI, 8.4-10.3 per 1000 PY, respectively). ER-negative primary breast cancers are associated with a higher risk of second breast cancers than ER-positive cancers during the first 5 years after diagnosis. Further study is needed to examine the potential benefit of more intensive surveillance targeting these women in the early postdiagnosis period.

Association of self-compassion and body image disturbance among young breast cancer patients: Mediating effect of body surveillance and body shame

ObjectiveTo examine whether body surveillance and body shame mediated the association between self-compassion and body image disturbance among young breast cancer patients. MethodsIn this cross-sectional descriptive study, a total of 310 young women with breast cancer were recruited by convenience sampling. All of them completed self-report measurements of demographic and clinical characteristics, self-compassion scale, body image self-rating questionnaire for breast cancer and body surveillance scale, and body shame scale between September and December 2021 ​at a tertiary cancer hospital in Tianjin, China. Data analysis was performed with correlation analysis and structural equation modeling to verify relationships between key variables. ResultsLess self-compassion was significantly associated with greater body image disturbance, while a positive correlation was found between body image disturbance, body surveillance, and body shame. Self-compassion indirectly negative predicted body image disturbance via the chain mediation of body surveillance and body shame. ConclusionsThe links of self-compassion and body image disturbance were mediated by body surveillance and body shame. Reducing patients’ excessive body surveillance and body shame by improving their ability of self-compassion may be an effective measure to reduce body image disturbance.

Diagnosis and the practices of patienthood: How diagnostic journeys shape illness experiences.

Sociologists have a rich history of studying the process of diagnosis and how people experience illness. Yet, the sociology of diagnosis and illness experience literatures have seldom been fully integrated. Instead,theseliteratureshighlight one element of the illness journey, wherein scholars either primarily study diagnostic processes and categories or people's illness experiences. Drawing on empirical studies that examine diagnosis and experiences of illness in varied settings (diagnosis during breast cancer surveillance, diagnosis and experience of autoimmune illness and incarcerated women's experiences of diagnoses and illness), in this article we build on our concept of regimes of patienthood to explain how diagnostic journeys, and the relations and power dynamics that manifest during this time, shape the illness experience and practices of patienthood. We construct a classification of diagnostic processes grounded in our empirical research that span (1) sudden diagnoses, (2) long, changing diagnostic journeys and (3) diagnostic journeys marked by disbelief and denial of care. Our findings demonstrate how diagnostic journeys and illness experiences are intertwined, with different diagnostic pathways impacting how illness is experienced. Analysing these categories collectively demonstrates that diagnostic journeys, while heterogenous, shape the practices that patients develop to manage health conditions and navigate unequal health-care encounters.

Performance of Statistical and Machine Learning Risk Prediction Models for Surveillance Benefits and Failures in Breast Cancer Survivors.

Machine learning (ML) approaches facilitate risk prediction model development using high-dimensional predictors and higher-order interactions at the cost of model interpretability and transparency. We compared the relative predictive performance of statistical and ML models to guide modeling strategy selection for surveillance mammography outcomes in women with a personal history of breast cancer (PHBC). We cross-validated seven risk prediction models for two surveillance outcomes, failure (breast cancer within 12 months of a negative surveillance mammogram) and benefit (surveillance-detected breast cancer). We included 9,447 mammograms (495 failures, 1,414 benefits, and 7,538 nonevents) from years 1996 to 2017 using a 1:4 matched case-control samples of women with PHBC in the Breast Cancer Surveillance Consortium. We assessed model performance of conventional regression, regularized regressions (LASSO and elastic-net), and ML methods (random forests and gradient boosting machines) by evaluating their calibration and, among well-calibrated models, comparing the area under the receiver operating characteristic curve (AUC) and 95% confidence intervals (CI). LASSO and elastic-net consistently provided well-calibrated predicted risks for surveillance failure and benefit. The AUCs of LASSO and elastic-net were both 0.63 (95% CI, 0.60-0.66) for surveillance failure and 0.66 (95% CI, 0.64-0.68) for surveillance benefit, the highest among well-calibrated models. For predicting breast cancer surveillance mammography outcomes, regularized regression outperformed other modeling approaches and balanced the trade-off between model flexibility and interpretability. Regularized regression may be preferred for developing risk prediction models in other contexts with rare outcomes, similar training sample sizes, and low-dimensional features.

Tackling bias in the data for breast cancer prediction using machine learning-based decision support

In this study, a machine learning (ML)-based decision support approach was developed to identify breast cancer likelihood in patients, based on their background and physiological data. Two ML models, Naïve Bayes and Logistic Regression were used to evaluate the Breast Cancer Surveillance Consortium dataset that had about 9:1 ratio of non-cancer cases (‘Class 0’) to cancer cases (‘Class 1’). We manually built both balanced and unbalanced training datasets and a non-overlapping testing dataset using a stratified sampling method. For each model, we partitioned the prediction results on testing set into two groups, the ‘Agree’ group included cases where balanced and unbalanced ML predictions agreed, and the remaining cases come under ‘Disagree’ group. Sensitivity and Positive Predictive Value were used as the prediction performance measures. For Naïve Bayes, the sensitivity of Class 1 in regular versus ‘Agree’ group increased from 0.687 to 0.936 and for Logistic Regression, it increased from 0.358 to 0.8306. This indicates the ‘Agree’ group predictions were more accurate and could be labeled as high-confidence ML predictions. The ‘Agree’ group consisted of 89% cases in the testing set, so the improved prediction performance was applicable for a large portion of the testing dataset.