Prior History Of Breast Cancer Research Articles

8157 Hypercalcemia To Hypocalcemia In Three Days: The Importance Of Asking The Questions

Abstract Disclosure: P. Kachhadia: None. K. Patel: None. S. Khan: None. A. Abu Limon: None. S. Aldasouqi: None. F. Akanbi: None. Z. Ul Abideen: None. Introduction: Severe hypercalcemia needing inpatient hospitalization requires very thorough history taking in order to determine etiology and treatment plan. Causes differ drastically, and misdiagnosis or mistreatment can be life threatening. Here, we present a case of symptomatic hypercalcemia secondary to milk-alkali syndrome that was treated promptly after admission with IV zoledronic acid, leading to severe symptomatic hypocalcemia and prolonged hospitalization. Case presentation: Patient is a 68 year old female with a PMH of breast cancer, osteoporosis and hiatal hernia who presented to the emergency department for fatigue, constipation and lightheadedness. On evaluation, she was found to have a creatinine of 1.54 (0.6-1.1 mg/dL), eGFR 36 (>90 mL/min/1.73 m²), Ca 18.48 (8.6-10.2 mg/dL), albumin 4.7 (3.4-5.4 g/dL), Mg1.4 (1.7-2.2 mg/dL), 25-OHD 18 (30-100), 1,25-Dihydroxy Vitamin D 7.4 (18-78 pg/mL), PTH 11.2 (15-65 pg/mL), phosphorus level 2.4 (2.5-4.5mg/dL), TSH 2.01 (0.4-4.0 mIU/L). SPEP and PTHrP were unremarkable. Due to history of prior breast cancer, imaging was done and CT showed new possible RUL pancoast tumor with RUL spiculated opacity. Patient was started on IV fluids and subsequently received IV zoledronic acid due to concern for severe hypercalcemia secondary to malignancy. By day 3 of treatment, patient's calcium decreased severely, down to a corrected calcium level of 6.4 (8.6-10.2 mg/dL). It was upon further investigation and discussion with the patient that we discovered the patient had received subcutaneous denosumab for her osteoporosis three weeks prior to admission. In addition, she was taking six tums daily (total 1 month duration) for symptoms of dyspepsia secondary her hiatal hernia. The patient’s severe hypocalcemia was treated with high dose oral calcium carbonate and vitamin D along with IV calcium gluconate. Magnesium was replaced daily. Through daily replacement, patient was kept in the hospital for a total of 10 days duration before her calcium levels were deemed safe for return home. Discussion: Hypercalcemia is a common cause of hospitalization worldwide. Testing should be comprehensive and history taking should be thorough to help navigate treatment plans. Bisphosphonates are indicated for hypercalcemia of malignancy, and its use otherwise may be the cause of severe hypocalcemia if not used in the right setting. In our case, the patient’s hypocalcemia was multifactorial from prior denosumab use and then subsequent zoledronic acid use. Additional risk factors included low vitamin D counts and disruption of high amounts of over the counter tums after being admitted to the hospital. Anchoring bias also led clinicians to believe that the hypercalcemia was secondary to malignancy. Consequently, this led to a prolonged 10 day hospitalization for persistently low calcium levels. Presentation: 6/1/2024

Artificial Intelligence Algorithm for Subclinical Breast Cancer Detection

Early breast cancer detection is associated with lower morbidity and mortality. To examine whether a commercial artificial intelligence (AI) algorithm for breast cancer detection could estimate the development of future cancer. This retrospective cohort study of 116 495 women aged 50 to 69 years with no prior history of breast cancer before they underwent at least 3 consecutive biennial screening examinations used scores from an AI algorithm (INSIGHT MMG, version 1.1.7.2; Lunit Inc; used September 28, 2022, to April 5, 2023) for breast cancer detection and screening data from multiple, consecutive rounds of mammography performed from September 13, 2004, to December 21, 2018, at 9 breast centers in Norway. The statistical analyses were performed from September 2023 to August 2024. Artificial intelligence algorithm score indicating suspicion for the presence of breast cancer. The algorithm provided a continuous cancer detection score for each examination ranging from 0 to 100, with increasing values indicating a higher likelihood of cancer being present on the current mammogram. Maximum AI algorithm score for cancer detection and absolute difference in score among breasts of women developing screening-detected cancer, women with interval cancer, and women who screened negative. The mean (SD) age at the first study round was 58.5 (4.5) years for 1265 women with screening-detected cancer in the third round, 57.4 (4.6) years for 342 women with interval cancer after 3 negative screening rounds, and 56.4 (4.9) years for 116 495 women without breast cancer all 3 screening rounds. The mean (SD) absolute differences in AI scores among breasts of women developing screening-detected cancer were 21.3 (28.1) at the first study round, 30.7 (32.5) at the second study round, and 79.0 (28.9) at the third study round. The mean (SD) differences prior to interval cancer were 19.7 (27.0) at the first study round, 21.0 (27.7) at the second study round, and 34.0 (33.6) at the third study round. The mean (SD) differences among women who did not develop breast cancer were 9.9 (17.5) at the first study round, 9.6 (17.4) at the second study round, and 9.3 (17.3) at the third study round. Areas under the receiver operating characteristic curve for the absolute difference were 0.63 (95% CI, 0.61-0.65) at the first study round, 0.72 (95% CI, 0.71-0.74) at the second study round, and 0.96 (95% CI, 0.95-0.96) at the third study round for screening-detected cancer and 0.64 (95% CI, 0.61-0.67) at the first study round, 0.65 (95% CI, 0.62-0.68) at the second study round, and 0.77 (95% CI, 0.74-0.79) at the third study round for interval cancers. In this retrospective cohort study of women undergoing screening mammography, mean absolute AI scores were higher for breasts developing vs not developing cancer 4 to 6 years before their eventual detection. These findings suggest that commercial AI algorithms developed for breast cancer detection may identify women at high risk of a future breast cancer, offering a pathway for personalized screening approaches that can lead to earlier cancer diagnosis.

Abstract B101: Knowledge, attitudes, and self-efficacy toward cancer genetic testing among Black women with and without breast cancer

Abstract Germline genetic testing for cancer risk offers opportunities for decision-making about screening and clinical risk management for individuals and their family members. Despite increasing availability of cancer genetic testing, Black individuals are still much less likely to receive or engage with testing compared to non-Hispanic white individuals. We sought to identify individual level factors influencing knowledge about and attitudes toward cancer genetic testing among Black women with and without breast cancer. Participants included 925 women from the Black Women’s Health Study who had previously provided a biospecimen for research and were invited to have their cancer genetic research findings confirmed via a CLIA-certified laboratory and learn their results as part of a randomized controlled trial. Prior to confirmation testing, all women completed a baseline questionnaire about personal and family history of cancer; prior genetic testing for hereditary cancer; and knowledge, attitudes, and confidence in one’s ability to use genetic information (genetics self-efficacy). We used linear regression to evaluate individual-level factors influencing cancer genetics knowledge, attitudes, and self-efficacy. Overall, mean knowledge score was 12.3 out of 16 (SD, 2.5); there were no differences in knowledge score between women who had a personal history of breast cancer and those who did not. While the majority of women answered most questions correctly, 20-30% of women were unable to correctly answer questions about validity of test results, clinical implications of a variant of uncertain significance, and legal protections against health insurance discrimination. Younger age, higher educational attainment, being married, and having had prior genetic testing were statistically significant predictors of higher total knowledge score. There were no differences in mean knowledge scores by first degree family history of breast cancer or personal history of breast or other cancer. Predictors of favorable attitudes and genetics self-efficacy included younger age, higher educational attainment, and being married. Women with a personal history of breast cancer had somewhat more favorable attitudes toward genetic testing compared to those with no prior history of breast cancer. In multivariable adjusted models, higher total knowledge was associated with more favorable attitudes and higher self-efficacy. In this cohort of highly educated Black women, overall cancer genetics knowledge was relatively high; however, evaluation of individual knowledge questions revealed opportunities for improvement in specific areas. Older women, those with lower educational attainment, and women who are not married or living as married may benefit from more targeted education about genetic cancer testing. Further, despite the role genetic testing currently plays in guiding cancer treatment, Black women who had breast cancer did not have higher knowledge scores than those without breast cancer and therefore may also benefit from targeted education. Citation Format: Kimberly A. Bertrand, Michelle Trevino-Talbot, Maggie Rudderman, Maureen Flynn, Howard J. Cabral, Julie R. Palmer, Catharine Wang. Knowledge, attitudes, and self-efficacy toward cancer genetic testing among Black women with and without breast cancer [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B101.

Evaluation of Sensitivity, Specificity, and Risk of Malignancy in Patients with Pleural Effusion and Prior History of Breast Cancer

Evaluation of Sensitivity, Specificity, and Risk of Malignancy in Patients with Pleural Effusion and Prior History of Breast Cancer

Racial differences in background parenchymal enhancement, a novel marker of breast cancer.

10528 Background: Breast density is a risk factor for breast cancer that can guide eligibility for supplemental screening including MRI, but Black women are less likely to qualify for supplemental screening due to having less dense breasts on average despite higher rates of breast cancer mortality. Background parenchymal enhancement (BPE), the enhancement of fibroglandular breast tissue on contrast-enhanced MRI, is a novel biomarker that has been shown to be a superior breast cancer risk marker than breast density. Women with high BPE levels have up to a four-fold increased risk of breast cancer, even after adjusting for density, but no studies have examined BPE exclusively among Black women. Methods: We identified Black and white women ages 40-74 with no prior history of breast cancer who had a mammogram and subsequent MRI as part of a screening or diagnostic work-up from 2016-2022 at our institution. BPE was qualitatively defined according to BI-RADS (Breast Imaging Reporting and Data System), with four ordinal levels of increasing enhancement: minimal, mild, moderate, and marked. We conducted a cross-sectional study to perform a logistic regression with race as the exposure and moderate or marked BPE as the outcome, using minimal and mild BPE as the reference group, adjusted for age and BI-RADS density. Results: We included 1027 Black women and 4834 white women in our analysis. Fewer Black women had extremely dense breasts compared to white women (6% vs 13%, p= 0.04), however, there was a larger proportion of high BPE (moderate or marked) in Black women compared to white women (32% vs 28%, p = 0.03) (Table). There was an inverse association between age and BPE levels (p = 0.03), and a positive association between density and BPE levels regardless of race (p< 0.01) (not shown). Black women were 39% more likely to have high BPE levels (95% CI: 1.39 [1.19, 1.63]), adjusted for age and density. Conclusions: Black women have lower density but higher BPE than white women, suggesting that BPE may improve identification of breast cancer risk for Black women. Participants [Table: see text]

Factors associated with delay in breast biopsy in a vulnerable population.

e13526 Background: Prompt diagnosis and treatment of breast cancer can improve outcomes and reduce stress and anxiety in patients. Race, socioeconomic status, and education level are associated with delays in diagnosis in breast cancer patients. 63% of Louisiana’s parishes are classified as rural, and 18.8% of the population is below the poverty line (the second highest in the country). The above factors make access to care challenging. Our study aimed to identify factors associated with delay in breast biopsy after abnormal diagnostic imaging in our patient population. Methods: A retrospective cohort study including female patients >18 years undergoing breast biopsy for abnormal diagnostic imaging findings from 1/1/2022 to 12/31/2022 at LSU Health, Shreveport, was done. Patients with a prior history of breast cancer, pregnant females, and patients with cognitive defects were excluded. Patients were followed from abnormal diagnostic imaging to biopsy. Descriptive analysis was done for baseline cohort characteristics. Univariate and multivariate logistic regression models were used to find 95% Confidence Interval and Odds ratio (ORs) for independent factors associated with time to biopsy (TTB). The study was approved by IRB. Results: 148 women (mean age [SD]: 54 [12] years) were included in the analysis. 67.5% were African American, and 25.6% lived in rural areas. The mean distance from the patient’s home to our center was 26.7 miles (Range: 3-219). The mean TTB from abnormal diagnostic imaging was 13.79 days (Range: 0-84), and 67.5% of patients had TTB of =<14 days. A TTB of more than 14 days was considered a delay in biopsy. After adjusting for age, multivariate logistic regression showed rural residence was associated with TTB of >14 days. (OR: 2.5, 95% CI: 1.15-5.67, p=0.02) (Table). A distance more than 40 miles from the hospital was associated with a higher likelihood of TTB of >14 days on a multivariate model adjusted for age and race revealed (OR: 2.2, 95% CI: 1.004-5.10, p= 0.04). Conclusions: Patients residing in rural parishes and at a distance more than 40 miles from our center have a higher likelihood of delay in time to biopsy from the diagnostic imaging. Same-day breast biopsy should be prioritized in such patients to ensure timely diagnosis and treatment. Cancer Centers serving the safety net population can conduct similar studies and implement changes to ensure equitable access to care. [Table: see text]

Abstract PO4-20-11: Excellent Response to Trastuzumab Deruxtecan in “HER-2 Low” Leptomeningeal Breast Cancer and Diagnostic and Monitoring Utility of CNSide Assay

Abstract A 72-year-old female presented to the emergency department with sudden onset of imbalance and cognitive decline. Two years ago, she was diagnosed with stage III estrogen receptor (ER) positive, progesterone receptor (PR) negative and human epidermal growth factor receptor 2 (HER2) negative (immunohistochemistry score: 0) invasive breast cancer. She subsequently underwent lumpectomy, adjuvant radiation and chemotherapy. She had been taking adjuvant letrozole at the time of presentation. Magnetic resonance imaging (MRI) of the brain showed obstructive hydrocephalus without any parenchymal lesion or leptomeningeal enhancement. MRI of spine, computerized tomography of chest/abdomen/pelvis and bone scan were unrevealing except a left adrenal mass which was equivocal for metastasis. Cerebrospinal fluid (CSF) analysis showed rare malignant cells. Based on the morphology of malignant cells and the patient’s prior history of breast cancer, the diagnosis of leptomeningeal disease with breast primary was made. There were insufficient cells for additional studies. CNSide, a microfluidic platform that uses antibody capture method to detect CSF tumor cells, showed 4678 tumor cells per milliliter (ml) of CSF. Immunocytochemistry of these cells showed that the cells were ER negative (criterion: < 2.6% ER positive cells) and programmed cell death ligand 1 (PD-L1) negative (criterion: < 3.4% PD-L1 positive cells). Fluorescence in situ hybridization (FISH) testing showed 22% of tumor cells with HER2 amplification (either HER2 to CEP17 ratio >/= 2.0 or HER2 copy number >/= 6). She underwent ventriculoperitoneal (VP) shunt placement with complete recovery of her neurological symptoms. Five weeks later, she was started on trastuzumab deruxtecan (T-DXd) mainly because of the HER2 FISH results from CNSide. She did not receive central nervous system(CNS) irradiation due to complete resolution of neurological symptoms with VP shunt placement. After two cycles of T-DXd, MRI brain showed mild leptomeningeal enhancement along bilateral superior cerebellar sulci. Positron emission tomography/computed tomography(PET/CT) scan showed a new sclerotic rib focus, thought to represent treatment response. It also showed decrease in size of the adrenal mass. The adrenal mass was hypermetabolic on PET, consistent with malignancy. CSF cytology was negative, while CSF tumor cell count significantly reduced to 6.72 cells/ml using CNSide. There were no new neurological symptoms. Despite MRI brain findings, she was continued on T-DXd given overall favorable clinical, radiological and CSF data. After 7th cycle of T-DXd, repeat CSF cytology continued to remain negative, CNSide CSF tumor cell count decreased further to 6.27 cells/ml, MRI brain showed interval resolution of prior leptomeningeal enhancement, CT scan showed further decrease in size of the adrenal mass (baseline 5.4cm to 3cm), stable rib sclerotic lesion and no additional metastatic lesion. To date, she has undergone eight cycles of T-DXd which has effectively controlled her disease for a period of seven months. She has not needed VP shunt revision and continues to do well. To our knowledge, this is the first case demonstrating the activity of T-DXd against CSF tumor cells where a small subset exhibited HER2 amplification. This case also highlights the benefits of using advanced and highly sensitive CSF assays to diagnose and surveil leptomeningeal disease and to assess HER2 signaling. This case is well-timed especially in the era of next-generation, CNS penetrating, potent HER2-directed antibody-drug conjugate like T-DXd which can mount antitumor activity even with minimal HER2 expression in tumors. Citation Format: Sarah Stanford, Zeni Kharel, Lauryn Hemminger, Tyler Schmidt, Sara Hardy, Jason Zittel, Nimish Mohile, Ajay Dhakal. Excellent Response to Trastuzumab Deruxtecan in “HER-2 Low” Leptomeningeal Breast Cancer and Diagnostic and Monitoring Utility of CNSide Assay [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-20-11.

Abstract GS01-06: Advancing Evidence of the Associations Between Specific Benign Breast Diagnoses and Future Breast Cancer RIsk

Abstract Background: Benign breast disease (BBD) is a common breast biopsy finding encompassing a diverse spectrum of diagnoses. Breast cancer risk associated with many specific BBD diagnoses and their joint associations with breast density have not been extensively studied. We estimate the future risk of invasive breast cancer associated with specific BBD diagnoses typically categorized into the broad category of proliferative lesions without atypia (PWoA) and evaluate whether associations differ by breast density or by presence of calcifications. Methods: We included 1,313,943 women ages 40-79 years who underwent 5,282,063 mammograms in the Breast Cancer Surveillance Consortium from 1996 to 2019 with no prior history of breast cancer. We fit a Cox proportional hazards model to estimate hazard ratios associated with each combination of PWoA BBD diagnoses, whether calcifications were present on biopsy, and breast density. We used classification trees to group combinations of PWoA diagnoses, breast density, age groups, and presence of calcifications with similar magnitudes of associations with 5-year risk of invasive breast cancer. Results: Compared with women with a PWoA BBD diagnosis without calcifications, presence of calcifications significantly elevated risk for breast cancer (HR=1.19, 95% CI = 1.02 to 1.41, P=0.03). Considering specific PWoA diagnoses, classification trees identified groups of women with higher and lower invasive cancer risk than expected risk for all PWoA combined. Among women ages 60-79 years with heterogeneously or extremely dense breasts, the 2.6% of women with any PWoA diagnosis, except papillomatosis, were at high invasive breast cancer risk (5-year risk >2.5%) (Table 1). Among women ages 40-59 years with dense breasts, presence of calcifications with papillomas, usual ductal hyperplasia, columnar cell hyperplasia, or PWoA NOS diagnoses put these women at high risk (5-year risk >2.5%) compared to women with the same BBD diagnoses without calcifications who were at intermediate or average risk (1-2.49%) (Table 1). Among women ages 60-79 years with non-dense breasts, the 1.6% of women with papilloma, usual ductal hyperplasia, radial scar, or PWoA NOS diagnoses were at high breast cancer risk (Table 2). Among women ages 40-59 years with non-dense breasts, presence of calcifications with usual ductal hyperplasia or PwoA NOS diagnoses put these women at intermediate risk (1.67-2.49%) compared to women with these BBD diagnoses without calcifications who were at average risk (1-1.66%) (Table 2). Women 60-79 years with fatty breasts were at intermediate 5-year risk if they had papillomas, usual ductal hyperplasia, or PWoA NOS diagnoses. Women 40-59 years with fatty breasts were at low risk of breast cancer regardless of PWoA diagnosis (Table 2). Conclusion: Specific BBD diagnoses and the presence of calcifications can change a woman’s predicted 5-year breast cancer risk compared to broad BBD categories alone. This information could be incorporated into risk prediction models to improve model accuracy. Citation Format: Olivia Sattayapiwat, Karla Kerlikowske, Donald Weaver, Alexander Borowsky, Theresa Keegan, Brian Sprague, Diana Miglioretti. Advancing Evidence of the Associations Between Specific Benign Breast Diagnoses and Future Breast Cancer RIsk [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr GS01-06.

Abstract PO4-15-01: A multi-center prospective cohort study to evaluate the presence of circulating tumor cells using the Epic Sciences platform among women with metastatic breast cancer

Abstract Background: The presence of tumor cells (or their components) in the blood of women with a history of early breast cancer has the potential to herald the development of metastatic recurrence at its earliest stages. Such early detection could potentially lead to novel prevention strategies, but it requires a sensitive assay. Objective: To use the Epic Sciences platform to detect and enumerate CTCs in blood samples from patients with an established diagnosis of metastatic breast cancer (MBC), prior to initiation of 1st line systemic therapy in the metastatic setting. Methods: We conducted a multi-center prospective cohort study to evaluate the presence of CTCs using the Epic Sciences platform among patients with a new diagnosis of MBC. Men or women age 18 to 85 were included, irrespective of breast cancer subtype. Patients with a prior or concurrent malignancy whose natural history or treatment had the potential to interfere with the detection of MBC in a liquid biopsy were excluded. A one-time blood draw was performed before patients received any local or systemic therapy in the metastatic setting. In addition, those with recurrent disease must have been off any systemic adjuvant therapy for ≥3 weeks prior to blood collection. Two 5 mL blood samples were obtained for CTC identification and enumeration. CTC identification was based on immunofluorescence analysis using Epic Sciences platform as previously described (Ueno et al 2017). The presence of CTCs was correlated with clinical and pathological features, which were abstracted from medical records and pathology reports. The association between the presence of CTCs and clinical/pathologic characteristics was tested using Fisher’s exact test for categorical variables and t-test or Wilcoxon rank sum tests for numerical variables. All analyses were performed using the R software package. Results: 100 patients were recruited between February 2021 and January 2023 at five academic oncology centres in Ontario and Quebec, Canada. 95 patients had evaluable blood for analysis and 5 did not due to blood age and/or insufficient blood volume. Six patients were excluded after providing a blood sample because tissue biopsy ultimately revealed a 2nd primary tumor (n=4) or benign tissue (n=2). Hence, 89 patients with a clinical diagnosis of MBC and with evaluable blood for CTC analyses were ultimately included in our cohort. The average age of patients was 61 years. Most patients (n=49, 55%) had a prior history of early breast cancer, 38 (43%) had de-novo metastatic disease and prior breast cancer history was unknown for 2 patients. 50 (66%) of patients had visceral metastatic disease. The most common sites of metastases included bone (62%), lung (30%), liver (29%) and lymph nodes (17%). 63 of 89 patients (71%) had detectable CTCs at baseline, prior to any local or systemic treatment in the metastatic setting. The median number of detectable CTCs per 5mL sample was 2 (IQR 8.5) and the range was 0 – 12,798. Twenty nine of 89 (33%) patients had 5 or more CTCs detected per 5ml blood. The proportion of patients with detectable CTCs was numerically highest (n=39/51, 76%) among patients with hormone receptor (HR)+/HER2-ve breast cancer, followed by HER2+ (n=16/22, 73%) and triple negative (n=8/13, 62%) disease. Associations between CTC detection with prior history of early breast cancer, sites of metastatic disease and disease burden will also be presented. Conclusions: Approximately 3 in 4 women with newly diagnosed metastatic breast cancer have detectable CTCs using the Epic Sciences platform prior to initiation of first line systemic therapy. CTCs may be a promising tool for the monitoring of breast cancer recurrence and will be investigated in an ongoing Canadian prospective observational study that aims to elucidate biomarkers of late breast cancer recurrence. Citation Format: Katarzyna Jerzak, Pamela Goodwin, Marguerite Ennis, Christine Brezden-Masley, Nathaniel Bouganim, Mark Basik, Arushi Jain, Giuseppe Di Caro, Rick Wenstrup, Nadine Hartmann, Megan Slade, Ana Elisa Lohmann. A multi-center prospective cohort study to evaluate the presence of circulating tumor cells using the Epic Sciences platform among women with metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-15-01.

Abstract PO3-16-09: Real-World Experience with Trastuzumab Deruxtecan at a Diverse NCI Comprehensive Cancer Center

Abstract Background: Trastuzumab Deruxtecan (T-DXd) is an antibody-drug conjugate originally approved for use in patients with HER2–positive metastatic breast cancer (MBC). In June 2022, data from the DESTINY-Breast04 trial revealed a near-doubling of progression-free survival (PFS) and significantly improved overall survival (OS) for patients with HER2-low MBC (immunohistochemistry [IHC] grade 1+ or IHC2+ in situ hybridization [ISH]-negative) treated with T-DXd versus standard-of-care chemotherapy. The data from this clinical trial led to the approval of T-DXd for use in patients with HER2-low MBC. However, the DESTINY-Breast studies completed to date have included < 5% black patients. This retrospective study of patients at a racially diverse NCI Comprehensive Cancer Center was designed to study whether T-DXd in a real-world population are comparable to published data. Methods: A retrospective chart review was conducted and identified 72 patients with HER2-low and HER2-positive MBC who received T-DXd between December 2019 and March 2023 at the Winship Cancer Institute at Emory University. Data collected for all patients included demographics, prior breast cancer history, T-DXd -specific and post-T-DXd treatment, and clinical outcomes where applicable. Results: Of the 103 patients who were dosed with T-DXd, 55 (53.4%) had HER2-positive disease, and 48 (46.7%) patients had HER2-low disease. 71 (68.9%) patients had hormone-receptor positive disease and 32 (31.1%) patients had hormone-receptor negative disease. The overall study population was 46% Caucasian; 38% African American; 13% Asian; 4% Unreported. The average number of cycles received was 11 (on treatment an average of 8 months). Pneumonitis occurred in 5 patients (4.9%). HER2-positive patients were typically on T-Dxd for a greater number of cycles than HER2-low patients (Table 1). Additionally, patients with brain metastases were, on average, treated with T-Dxd longer than patients without brain metastases, 14.5 versus 9 cycles. The number of cycles of T-Dxd received, the need for dose reduction, and incidence pneumonitis did not differ significantly between black and white patients. The data for this study is preliminary 48% of the patient population are still actively undergoing T-Dxd treatment. Conclusion: This study reviewed and analyzed T-Dxd treatment in a diverse population of both HER2-positive and HER2-low MBC patients, and in this study, outcomes of treatment did not differ by race. More attention to this topic is needed in future studies of larger populations, along with increased efforts to enroll diverse patient populations in clinical trials. Table 1. Citation Format: Jane Meisel, Maisey Ratcliffe. Real-World Experience with Trastuzumab Deruxtecan at a Diverse NCI Comprehensive Cancer Center [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-16-09.

Abstract B021: Influenza-induced inflammatory response reactivates and promotes dormant breast cancer cell outgrowth in lungs

Abstract Breast cancer is the most common form of cancer and the second cancer-causing death in females. Although remission rates are high if detected early, survival rates drop substantially when breast cancer becomes metastatic. Metastatic relapse can occur months to years after the initial diagnosis and treatment of the primary tumor. This relapse is mediated by awakening of dormant disseminated cancer cells (dDCCs). Studies have demonstrated that the relationship between the microenvironment and dDCCs is critical for maintaining both dormancy and for facilitating awakening to promote metastasis development. Prior studies have shown increased inflammation in the microenvironment can facilitate DCC awakening and outgrowth. Viral respiratory infections are also associated with massive inflammation and immune cell influx, typically in acute form. Respiratory infections affect millions of people worldwide, as is particularly evident in the ongoing SARS-CoV2 pandemic and variably severe annual influenza seasons. How the inflammatory response to viral respiratory infections impacts breast cancer metastasis remains unclear. Using FVB MMTV-erbB2/neu/HER2 mice as a model of breast dormancy in the lungs and influenza virus, we show that following influenza infection there is a significant increase in the number of disseminated cancer cells in the lungs of influenza infected mice with more than a 1000-fold expansion of carcinoma cells over a couple of weeks. Interestingly most of this expansion of DCCs takes place within 10 days following influenza infection. Strikingly, by 15 days post-infection, the lesions that expanded from solitary HER2+ DCCs almost homogeneously return to a quiescent state. Furthermore, we show interleukin-6 is required for the early phase of dormant cancer cells reawakening and proliferation and that CD4+ T cells are required for the maintenance of the expanded cancer cells post-infection at the late phase. Depletion of CD4 T cells (but not CD8 cells) during infection with influenza virus leads to the elimination of the expanded DCC population in the lung. Finally, single-cell RNA-seq analyses of DCC and microenvironmental cells in the lungs before and after infection reveals insight into underlying mechanisms for virus-induced awakening and reentry into dormancy. scRNA-seq analyses reveal that expanding DCC post-influenza infection reprogram CD4 and CD8 T-cells to a more immune suppressed state. These results support a model whereby pulmonary viral infections can increase the risk of metastatic relapse in the lungs for patients with a prior history of breast cancer. Thus, the immune response evolved to combat respiratory infections can be coopted and reprogrammed by dormant cancer cells to enable their expansion, thus increasing the odds of further metastatic cancer evolution. Ongoing work is currently being done to investigate this process in mouse models of SARS-CoV2 infection, as well as to examine clinical databases for epidemiological associations between respiratory viral infections and metastatic disease in the lung. Citation Format: Bryan J. Johnson, Shi Biao Chia, Vadym Zaberezhnyy, Varsha Sreekanth, Meher Boorgula, Michael Papanicolaou, James Costello, Andrew Goodspeed, Julio A. Aguirre-Ghiso, Mercedes Rincon, James V. DeGregori. Influenza-induced inflammatory response reactivates and promotes dormant breast cancer cell outgrowth in lungs [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Cancer Evolution and Data Science: The Next Frontier; 2023 Dec 3-6; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_2):Abstract nr B021.

Outcomes of High-Risk Breast MRI Screening in Women Without Prior History of Breast Cancer: Effectiveness Data from a Tertiary Care Center.

To evaluate the diagnostic performance outcomes of a breast MRI screening program in high-risk women without prior history of breast cancer. Retrospective cohort study of 1 405 consecutive screening breast MRI examinations in 681 asymptomatic women with high risk of breast cancer without prior history of breast cancer from January 1, 2015, to December 31, 2019. Outcomes (sensitivity, specificity, positive predictive value, negative predictive value, false-negative rate [FNR], cancer detection rate [CDR]) and characteristics of cancers were determined based on histopathology or 12-month follow-up. MRI examinations performed, BI-RADS assessments, pathology outcomes, and CDRs were analyzed overall and by age decade. Results in incidence screening round (MRI in last 18 months) and nonincidence round were compared. Breast MRI achieved CDR 20/1000, sensitivity 93.3% (28/30), and specificity 83.4% (1 147/1375). Twenty-eight (28/1 405, CDR 20/1000) screen-detected cancers were identified: 18 (64.3%, 18/28) invasive and 10 (35.7%, 10/28) ductal carcinoma in situ. Overall, 92.9% (26/28) of all cancers were stage 0 or 1 and 89.3% (25/28) were node negative. All 14 incidence screening round malignancies were stage 0 or 1 with N0 disease. Median size for invasive carcinoma was 8.0 mm and for ductal carcinoma in situ was 9.0 mm. There were two false-negative exams for an FNR 0.1% (2/1 405). High-risk screening breast MRI was effective at detecting early breast cancer and associated with favorable outcomes.

Secondary Breast Angiosarcoma After a Primary Diagnosis of Breast Cancer: A Retrospective Analysis of the Surveillance, Epidemiology, and End Results (SEER) Database.

Angiosarcoma is a rare complication of breast-conserving therapy. This study evaluated the change in incidence between 1992 and 2016 of secondary breast angiosarcoma (SBA) in patients with a history of breast cancer and the impact of management strategies for the original breast carcinoma on angiosarcoma treatment. Breast cancer and angiosarcoma cases were abstracted from the Surveillance, Epidemiology, and End Result (SEER) database. SBAs were defined as angiosarcomas located in the breast occurring after a prior breast cancer diagnosis. Primary breast angiosarcomas (PBAs) were defined as an angiosarcoma diagnosis listed as "one primary only." Incidence rates were estimated using a proportion of the US total population. Survival was analyzed by the Kaplan-Meier method, and Cox proportional hazard models were used to assess the association of clinicopathologic characteristics on overall survival. Between 1992 and 2016, 193 cases of SBA were reported in the SEER dataset in patients with a prior history of breast cancer. The incidence of breast angiosarcoma in patients with a prior diagnosis of breast cancer increased 3-fold from about 10 cases per 100,000 person-years to about 30 cases per 100,000 person-years over this same period ( P =0.0037). For treatment of SBA (n=193), almost all (95%) had surgery. Nine percent received radiation (compared with 35% of patients with PBA, P <0.001) and 23% received chemotherapy (vs. 45% for PBA, P =0.11). We demonstrate an increasing incidence of SBA over the study period. These data can help inform shared decision-making for optimal management of locoregional breast cancer and raise awareness of secondary angiosarcoma.

Barriers to breast cancer screening in a developing middle eastern country: A nationwide survey.

e22517 Background: Breast cancer imposes a significant global health burden not only due to being constantly ranked as the leading malignancy in females, but also due to the immense resulting morbidity and mortality. Despite the presence of screening modalities, the uptake is relatively low due to unidentified barriers in many countries and regions. The Identification of these barriers towards screening is of paramount importance to tackle the health burden imposed by breast cancer, especially in countries like Jordan, a developing middle eastern country. Methods: A self-reporting survey consisting of comprehensive questions regarding the participant’s demographics, medical history, knowledge about breast cancer and the screening modalities was distributed to females aged 25 years and above with no prior history of breast cancer who are residing across the different regions of Jordan. The first consecutive 790 participants were enrolled, and data analysis was performed to identify the key barriers. Results: The mean age of the enrolled study population was 41 ± 9 years old with the majority being married (82.8%), have underwent a higher level of education (86.5%), are non-smokers (75.2%), and are medically insured (72.4%). 209 participants (26.5%) had reported a family history of breast cancer, while 83.4% of the participants reported awareness about breast cancer screening modalities with breast self-examination being the most commonly known modality of screening in 39.2% of the participants. Only 22.4% of the participants were aware of the 3 available screening methods. The majority of the participants (57.1%) did not undergo previous screening. When the participants who did not undergo previous breast cancer screening were compared with those who did, the participants without prior screening were more likely to report the lack of knowledge towards screening modalities (27.7% vs 8.0%) (p-value &lt; 0.001), fear of the results (22.6% vs 13.9%) (p-value = 0.002), fear of pain during or after from the test (10.4% vs 5.9%) (p-value = 0.024), and feeling of embarrassment provoked by the screening test (15.7% vs 6.5%) (p-value &lt; 0.001) as key barriers. On the contrary, there was no statistically significant difference between the two groups when assessing financial aspect of screening uptake as a potential barrier (p-value = 0.860). Conclusions: Despite the considerably high percentage of participants being aware of breast cancer screening modalities, an alarmingly low rate of screening uptake was witnessed due to several barriers. The collective identification of lack of knowledge towards screening modalities and the nature of the available tests, in addition to the fear of the results and pain following the test, and feeling of embarrassment undoubtedly mandates the formulation of comprehensive awareness campaigns that effectively tackle these barriers.

Vitamin D deficiency as a risk factor for breast cancer development.

10559 Background: Previous studies and meta-analyses have suggested that women with low levels of vitamin D may be at increased risk of breast cancer development and recurrence. The relationship is suspected to be inverse, nonlinear, and predominantly present in postmenopausal women. The purpose of this study was to use the TriNetX platform to determine the magnitude of breast cancer risk increase for women with significant vitamin D deficiency and evaluate the significance of menopause on vitamin D-associated breast cancer risk. Methods: The TriNetX platform was used to generate patient cohorts via International Classification of Disease-10 (ICD-10) codes. All patients were females over 40, had no prior history of breast cancer (C50), and had been diagnosed with menopause (Z78.0). One cohort had less than 20 ng/mL of vitamin D while the other had greater than 30 ng/mL. The cohorts were balanced for age, race, and ethnicity, resulting in 73,659 patients in each arm. They were then evaluated for the future development of breast cancer (C50). Two additional cohorts were created of premenopausal patients aged 40-55 using the same vitamin D parameters and cohort balancing. Results: Postmenopausal women with vitamin D levels below 20 ng/mL had a 45% greater risk of developing breast cancer (risk ratio 1.45, 95% CI (1.38,1.52), p-value &lt;0.0001). (Table) Deficient premenopausal women were also found to be at significantly increased risk although the absolute risk difference was small (relative risk 1.18, 95% CI (1.10,1.27), p-value &lt;0.0001). Conclusions: These results confirm and also quantify the previously-suspected increased breast cancer risk for women who are deficient in vitamin D. The impact of low vitamin D levels on breast cancer risk in premenopausal patients was statistically significant but small in magnitude, while postmenopausal women were found to have approximately 45% higher risk as compared to women who were not deficient. Vitamin D supplementation for all deficient postmenopausal women should be considered. [Table: see text]

Validation of an Eastern Armenian breast cancer health belief survey.

With the fourth highest breast cancer mortality rate in the world, breast cancer prevention and early detection is a priority for Armenia. The Ministry of Health recently initiated efforts to expand access to breast cancer screening. However, little is known about the population's understanding and perception of breast cancer screening programs. This cross-sectional telephone-based study sought to develop and validate an Eastern Armenian language version of the Champion's Health Belief Model Scale (CHBMS) for future use. The English-language CHBMS survey was first rigorously translated by two Armenian nationals and evaluated for face validity. Telephone surveys were then administered to randomly-selected women of approximately screening age (35-65 years) with no prior history of breast cancer living in Armenia's capital between 2019-2020 (n = 103). The translated survey's psychometric properties were evaluated, examining (1) content equivalence, (2) test-retest reliability and (3) internal consistency. Content equivalence and test-retest reliability of the Armenian CHBMS were characterized using correlational analysis with Pearson's coefficient ranging from 0.76-0.97 (p<0.001) and 0.72-0.97 (p<0.001), respectively, for all five CHBMS domains. The translated survey's internal consistency was comparable to the original English-language CHBMS with a Cronbach's alpha greater than 0.7 for all five domains (0.75-0.94 (p<0.001). The translated Eastern Armenian version of CHBMS is a valid, internally-consistent, and reliable research tool that is ready for imminent use among screening-age women to investigate breast cancer perceptions and beliefs as the Armenian government seeks to expand screening access.

Abstract 1899: Breast density comparison of Hispanic versus Non-Hispanic patients undergoing screening mammograms: Influence of age, parity and breast-feeding

Abstract Background: Higher mammographic breast density is associated with a 4 to 6-fold increased risk of breast cancer. Some single institution retrospective studies show higher breast densities in Hispanic patients (Oppong et al. Breast J. 2018). The prevalence of breast density based on Hispanic ethnicity has not been studied in large database studies. Methods: We performed a retrospective review of women &amp;gt; 40 years undergoing screening mammograms from 2016-2022. Patients with prior history of breast cancer were excluded. We reviewed demographic variables such as race, self-reported ethnicity, body mass index (BMI), parity, breastfeeding and menopausal status. Breast density was characterized as predominantly fatty (PF), scattered fibroglandular (SF), heterogeneously dense (HD) and extremely dense (ED). We used Chi-square and Kruskal-Wallace tests to compare breast density across measured variables, and Ordinal Logistic Regression to compare breast density levels between self-declared ethnicity while adjusting for other variables. Results: 15946 patients were studied; 7317 (46%) identified as Hispanic, the rest non-Hispanic (NH). 6131 (83%) of Hispanics identified as white. Mean age on 1st screening mammogram was 57.64 (SD 7.21). Compared to NH, Hispanics had mean earlier age of 1st mammogram (56.8 vs. 58.3 years), higher BMI (30.5 vs. 28.6) and higher parity (2.53 vs. 1.71). There were significant differences in BI-RADS density categories by Hispanic vs. NH (p&amp;lt;0.001), with differences in PF (20.2% vs. 18.5%), SF (41.7% vs. 39.0%), HD (35.8% vs. 37.2%), and ED (2.3% vs. 5.3%). The ordinal logistic regression model suggests that Hispanics have 17% lower odds than NH of 1 category higher density (OR, 95% CI: 0.83, 0.78-0.88). There were also significant ethnicity differences in age at first exam, BMI, parity, and number of children breast-fed (P&amp;lt;0.001). Adjusting for these ethnicity-associated differences explained the observed differences in density between Hispanic and NH individuals (ORadj, 95% CI: 0.98, 0.92-1.04); adjusting only for BMI served to explain the observed differences in density (ORadj, 95% CI: 0.99, 0.94-1.05). Conclusions: Hispanics were observed to have a lower age of first screening mammogram, higher BMI, higher parity, and breast-fed children compared to non-Hispanics. On univariate analysis, Hispanics were noted to have lower breast density compared to non-Hispanics, these differences do not persist on multivariate analysis. This suggests that BMI likely plays a predominant role in driving the ethnicity-related differences in breast density noted here. Further research efforts should focus on the influence of BMI and other individual-level factors on mammographic density, with a view towards understanding their potential roles in describing differential ethnicity-specific breast cancer risk. Citation Format: Sangeetha Prabhakaran, Vernon S. Pankratz, Jennifer L. Saline, Emily J. Reese. Breast density comparison of Hispanic versus Non-Hispanic patients undergoing screening mammograms: Influence of age, parity and breast-feeding [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1899.

Patient Cost-Sharing and Utilization of Breast Cancer Diagnostic Imaging by Patients Undergoing Subsequent Testing After a Screening Mammogram

Out-of-pocket costs (OOPCs) have been largely eliminated for screening mammography. However, patients still face OOPCs when undergoing subsequent diagnostic tests after the initial screening, which represents a potential barrier to those who require follow-up testing after initial testing. To examine the association between the degree of patient cost-sharing and the use of diagnostic breast cancer imaging after undergoing a screening mammogram. This retrospective cohort study used medical claims from Optum's deidentified Clinformatics Data Mart Database, a commercial claims database derived from a database of administrative health claims for members of large commercial and Medicare Advantage health plans. The large commercially insured cohort included female patients aged 40 years or older with no prior history of breast cancer undergoing a screening mammogram examination. Data were collected from January 1, 2015, to December 31, 2017, and analysis was conducted from January 2021 to September 2022. A k-means clustering machine learning algorithm was used to classify patient insurance plans by dominant cost-sharing mechanism. Plan types were then ranked by OOPCs. A multivariable 2-part hurdle regression model was used to examine the association between patient OOPCs and the number and type of diagnostic breast services undergone by patients observed to undergo subsequent testing. In our sample, 230 845 women (220 023 [95.3%] aged 40 to 64 years; 16 810 [7.3%] Black, 16 398 [7.1%] Hispanic, and 164 702 [71.3%] White) underwent a screening mammogram in 2016. These patients were covered by 22 828 distinct insurance plans associated with 6 025 741 enrollees and 44 911 473 distinct medical claims. Plans dominated by coinsurance were found to have the lowest mean (SD) OOPCs ($945 [$1456]), followed by balanced plans ($1017 [$1386]), plans dominated by copays ($1020 [$1408]), and plans dominated by deductibles ($1186 [$1522]). Women underwent significantly fewer subsequent breast imaging procedures in dominantly copay (24 [95% CI, 11-37] procedures per 1000 women) and dominantly deductible (16 [95% CI, 5-28] procedures per 1000 women) plans compared with coinsurance plans. Patients from all plan types underwent fewer breast magnetic resonance imaging (MRI) scans than patients in the lowest OOPC plan (balanced, 5 [95% CI, 2-12] MRIs per 1000 women; copay, 6 [95% CI, 3-6] MRI per 100 women; deductible, 6 [95% CI, 3-9] MRIs per 1000 women. Despite policies designed to remove financial barriers to access for breast cancer screening, significant financial barriers remain for women at risk of breast cancer.

Abstract P4-03-23: Comparison of Breast Cancer vs Cardiovascular Disease Risk and Uptake of Chemoprevention vs Statins in a Cohort of Predominantly Hispanic Women Undergoing Screening Mammography

Abstract Background: Atherosclerotic cardiovascular disease (ASCVD) and breast cancer are two of the most diagnosed chronic diseases among women in the U.S. Although prevention of ASCVD with statins is widely practiced, breast cancer chemoprevention with selective estrogen receptor modulators (SERMs) or aromatase inhibitors (AIs) is underutilized in the primary care setting, despite significant evidence in randomized controlled trials demonstrating its clinical benefits. We compared the risk of ASCVD and breast cancer among predominantly Hispanic women undergoing screening mammography, as well as uptake of statins and SERMs/AIs for ASCVD and breast cancer risk reduction, respectively, among high-risk women. Methods: We conducted a retrospective cohort study among 1,655 English or Spanish-speaking women, age 40-79 years, with no prior history of breast cancer, who underwent screening mammography from 2014 to 2016 at Columbia University Irving Medical Center in New York City. Participants completed a survey collecting data on sociodemographic and breast cancer risk factors and had available data in the electronic health record (EHR) for calculating ASCVD risk, including systolic blood pressure, total and HDL cholesterol, history of diabetes, treatment for hypertension, and current smoking status. The main outcomes included 5-year and lifetime invasive breast cancer risk according to the Gail model, and 10-year and lifetime ASCVD risk score according to the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) ASCVD risk calculator. High-risk was defined as a 5-year invasive breast cancer risk 1.67% and 10-year ASCVD risk 7.5%. Secondary outcomes included uptake of chemoprevention with SERMs or AIs and statins among women at high-risk for breast cancer and ASCVD, respectively, based upon medication lists in the EHR. We compared mean lifetime risk of breast cancer vs ASCVD for the entire cohort using a paired t-test, and the proportion of high-risk women taking statins vs chemoprevention using McNemar’s test. Results: Among 1,655 evaluable women, mean age was 58 years (SD=10.1 years), with 76% Hispanic, 6% non-Hispanic White, 3% non-Hispanic Black, 2% Asian, and 13% other. About half (48%) of women met high-risk criteria for ASCVD compared to 15% who met high-risk criteria for breast cancer. Among all women, mean lifetime ASCVD risk was higher than mean lifetime breast cancer risk (10.71% vs. 5.46%, p&amp;lt; 0.001). Among women at high risk for ASCVD or breast cancer, respectively, statin uptake was higher compared to SERM/AI uptake for breast cancer chemoprevention (84% vs. 7%, p&amp;lt; 0.001). Overall, fewer Hispanic compared to non-Hispanic women met high-risk criteria for ASCVD (47% vs. 51%, respectively) and breast cancer (9% vs. 34%, respectively). Conclusions: In a population of predominantly Hispanic women undergoing screening mammography, we found that more women met high-risk criteria for ASCVD compared to breast cancer. Among women at high risk for ASCVD, statin uptake was about 12-fold higher compared to uptake of breast cancer chemoprevention among women at high risk for breast cancer. Given significant underutilization of breast cancer chemoprevention, placing this in the context of prevention of other chronic diseases, such as statins for ASCVD, may enhance uptake of SERMs or AIs in the primary care setting. Citation Format: Luisa Nilan, Mary M. McDermid, Jacquelyn N. Amenta, Julia E. McGuinness, Katherine D. Crew, Rita Kukafka. Comparison of Breast Cancer vs Cardiovascular Disease Risk and Uptake of Chemoprevention vs Statins in a Cohort of Predominantly Hispanic 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 P4-03-23.

Perceptions of Breast Cancer Risks Among Women Receiving Mammograph Screening

Breast density is an independent risk factor for breast cancer. Despite the proliferation of mandated written notifications about breast density following mammography, there is little understanding of how women perceive the relative breast cancer risk associated with breast density. To assess women's perception of breast density compared with other breast cancer risks and explore their understanding of risk reduction. This mixed-methods qualitative study used telephone surveys and semistructured interviews to investigate perceptions about breast cancer risk among a nationally representative, population-based sample of women. Eligible study participants were aged 40 to 76 years, reported having recently undergone mammography, had no history of prior breast cancer, and had heard of breast density. Survey participants who had been informed of their personal breast density were invited for a qualitative interview. Survey administration spanned July 1, 2019, to April 30, 2020, with 2306 women completing the survey. Qualitative interviews were conducted from February 1 to May 30, 2020. Respondents compared the breast cancer risk associated with breast density with 5 other risk factors. Participants qualitatively described what they thought contributed to breast cancer risk and ways to reduce risk. Of the 2306 women who completed the survey, 1858 (166 [9%] Asian, 503 [27%] Black, 268 [14%] Hispanic, 792 [43%] White, and 128 [7%] other race or ethnicity; 358 [19%] aged 40-49 years, 906 [49%] aged 50-64 years, and 594 [32%] aged ≥65 years) completed the revised risk perception questions and were included in the analysis. Half of respondents thought breast density to be a greater risk than not having children (957 [52%]), having more than 1 alcoholic drink per day (975 [53%]), or having a prior breast biopsy (867 [48%]). Most respondents felt breast density was a lesser risk than having a first-degree relative with breast cancer (1706 [93%]) or being overweight or obese (1188 [65%]). Of the 61 women who were interviewed, 6 (10%) described breast density as contributing to breast cancer risk, and 43 (70%) emphasized family history as a breast cancer risk factor. Of the interviewed women, 17 (28%) stated they did not know whether it was possible to reduce their breast cancer risk. In this qualitative study of women of breast cancer screening age, family history was perceived as the primary breast cancer risk factor. Most interviewees did not identify breast density as a risk factor and did not feel confident about actions to mitigate breast cancer risk. Comprehensive education about breast cancer risks and prevention strategies is needed.