Rhodes, Deborah J.

Abstract Background Molecular breast imaging (MBI) has shown utility as a supplement to mammography in women with dense breasts. Background parenchymal uptake (BPU), which describes the level of Tc-99m sestamibi in fibroglandular tissue on MBI, varies among women with similar density. Higher BPU is associated with greater breast cancer risk. The goal of this work is to investigate the histological correlations of BPU that may explain this association with risk. Methods We compared histologic features of prospectively collected benign breast tissue biopsies from healthy women who had a region of dense tissue on mammography exhibiting one of the extreme categories of BPU on MBI: either photopenic or marked. Tissue composition of specimens was assessed by measuring area of epithelium, stroma, and fat and counting lobules. Lobular involution status was assessed by an expert pathologist as either none, partial, or complete. Ki-67 index and estrogen receptor-alpha expression were also assessed. Results Biopsies were performed in 48 women (mean age 54.9 years [SD 11.1 years]), including 20 with marked BPU and 28 with photopenic BPU. Women with marked BPU were younger (mean age 49.9 vs. 58.4 years, p = 0.004), had higher body mass index ( p = 0.01), and were more likely premenopausal ( p = 0.005). Marked BPU specimens had a higher proportion of epithelium (14.5% vs. 2.2%, p < 0.001), lower stromal content (44.8% vs. 84.2%, p = 0.005), similar fat (18.9% vs. 12.9%, p = 0.41), and greater lobule counts (15.5 vs. 6.3, p < 0.001) compared to photopenic specimens. Complete lobular involution was less frequent in marked tissue than in photopenic tissue (10.5% vs. 76%, p < 0.001). Ki-67 index was higher in marked BPU tissues (5.4% vs. 1.6%, p = 0.006), though the difference was attenuated after adjustment for epithelial area (p = 0.26). Estrogen receptor-alpha expression did not differ between marked and photopenic groups (25.6% vs. 28.4%, p = 0.12). Conclusions Marked BPU on MBI is associated with greater epithelial content, less lobular involution, and higher proliferative activity—features characteristic of tissue at elevated risk for malignant transformation. These findings suggest that BPU provides functional information beyond mammographic density, supporting its role as an imaging biomarker for breast cancer risk in women with dense breasts. Trial Registration: NCT01240278 and NCT01588834

In women with dense breasts, adding molecular breast imaging to digital breast tomosynthesis (DBT) increased both overall and invasive cancer detection rates, while modestly raising the recall rate compared with DBT alone.

Background: Latinas with mammographic dense breasts are at increased risk of breast cancer. This randomized controlled trial tests the effectiveness of three breast density (BD) educational approaches on adherence to subsequent mammography screening among Latinas receiving care at a Federally Qualified Health Center (FQHC). Measure(s): Adherence was ascertained using electronic health record and survey responses. Kaplan–Meier estimates of the time to subsequent mammogram were used to obtain adherence rates at 1- and 2-years post baseline mammogram. Cox modeling assessed whether adherence differed by patient characteristics or group assignment. Results: This analysis was limited to Latinas enrolled between October 27, 2016, and December 21, 2018 ( n = 946; 66.1% <50 years of age, 53.5% with dense breasts). Adherence rates at 1 year was 24.8% increasing to 51.7% by year 2. Latinas randomized to the Promotora + brochure + letter arm (hazard ratio [HR]: 1.09 [95% confidence interval [95% CI] 0.87 to 1.36]) or brochure + letter (HR: 1.03 [95% CI 0.82 to 1.29]) arm were not more likely to be adherent to subsequent mammography compared to the letter only arm ( p = 0.76) . Adjusting for age and study group, having more prior mammograms, being “extremely likely” to get an annual mammogram, and having more confidence to get an annual mammogram at baseline were significant drivers of subsequent adherence. Conclusion: Informational interventions targeting BD education alone are unlikely to significantly improve adherence to subsequent mammography among Latinas receiving care in FQHCs.

Abstract Mammographic breast density (MBD) has been shown to be a strong, independent risk factor for breast cancer (BC) irrespective of race/ethnicity. Given the risk association of MBD and its potential to mask tumors on a mammogram, state and federal laws have mandated that women receive information regarding their personal MBD in their mammography reports. However, concerns have been raised regarding the impact of MBD notification on patient anxiety, especially written information for women who experience health disparities such as racial/ethnic minorities, lower health literacy, limited English proficiency and lower socioeconomic status. We performed a randomized controlled clinical trial to examine the impact of three different written and interpersonal approaches to MBD notification on patient anxiety, BC worry, and self-perceived BC risk, among Latinas receiving routine mammography screening at a federally qualified medical center (FQHC). We hypothesized that interpersonal education would reduce anxiety and worry, relative to the written notifications alone. The study was performed at the Baseline Clinic of Mountain Park Health Center, a FQHC in Phoenix, AZ. Women between ages 40 and 74 years presenting for screening mammogram were eligible. After providing signed informed consent, participants were randomized equally to usual care (UC- mailed notification letter); enhanced care (notification letter and MBD educational brochure designed for this study): interpersonal care (notification letter, brochure, promotora education via telephone). A stratified block randomization procedure was used with age &gt; 50 years (yes vs no), ethnicity (Hispanic vs non-Hispanic), and language preference (Spanish vs. English) as strata. Study participants completed surveys at the time of enrollment/pre-intervention (T0), at two weeks to six months after intervention was delivered (T1), and about one year after randomization (T2). Anxiety state was measured using the state anxiety subscale of the State-Trait Anxiety Inventory scale (STAI-S) (range from 20-80). BC worry was probed using the question: “How frequently do you worry about getting breast cancer someday”. The self-perceived lifetime risk of BC was rated between 0% (no chance of BC) to 100% (definitely will get BC). The proportion of participants with an increase or persistence of higher level for each outcome between time points was compared between the three study groups. The study was approved by the Mayo Clinic Institutional Review Board. 1332 Latina women were enrolled and randomized between October 2016 and October 2019. All completed the baseline (T0) survey, 928 completed T1, 632 completed T2, and 516 completed both T1 and T2 surveys. At study entry, majority of the participants were young (64.1% between age 40-49 years), had no family history of breast cancer (81.0%), had less than high school education (68.8%), and were married or partnered (67.8%). At T0, the mean (SD) anxiety STAI score was 32.5 (11.1); 51.8% with moderate or severe anxiety (score &gt; 30). With regard to BC worry, 41.3% reported worrying “sometimes”, “often”, or “almost all the time”. Further, 25.4% reported a self-perceived lifetime risk of developing BC of &gt;10% while only 6.6% had a Gail model estimated lifetime risk score of &gt;10%. There was no significant difference in changes in anxiety, BC worry or self-perceived risk from T0 to either T1 or T2 surveys between the intervention groups. In summary, this study found high levels of baseline anxiety and BC worry (despite the majority being 40-49 years old and having no family history of BC) which persisted regardless of how notification and education were delivered. Future work is needed to improve the understanding of factors that could lower anxiety and BC worry and improve risk perception in this population. Citation Format: Karthik Ghosh, Sarah Jenkins, Jennifer Ridgeway, Jessica D. Austin, Bijan Borah, Bhavika K. Patel, Deborah Rhodes, Aaron Norman, Edna P. Ramos, Matt Jewett, Crystal Gonzalez, Valentina Hernandez, Davinder Singh, Vera Suman, Celine Vachon. Breast Density Notification: Impact on anxiety, breast cancer worry, and self-perceived risk among Latinas at a federally qualified medical center. [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 P6-05-38.

BackgroundThe objective of this randomized trial was to evaluate the short‐term effect of bilingual written and interpersonal education regarding mammographic breast density (MBD).MethodsLatinas aged 40 to 74 years who were presenting for screening mammography were recruited and randomized 1:1:1 to receive a letter with their mammogram and MBD results (usual care [UC]), a letter plus a brochure (enhanced care [ENH]), or a letter plus a brochure and telephonic promotora education (interpersonal care [INT]). Surveys were administered at enrollment (T0) and 2 weeks to 6 months after intervention delivery (T1). Differences were assessed with χ2, Kruskal‐Wallis, and McNemar tests and pairwise comparisons as appropriate. INT metrics and audio recordings were analyzed with descriptive statistics and qualitative content analysis.ResultsBetween October 2016 and October 2019, 943 of 1108 Latina participants (85%) completed both surveys. At T1, INT participants were more likely (P < .001) to report seeing their MBD results in the letter (70.2%) than UC (53.1%) or ENH participants (55.1%). The percentage of INT women who reported speaking with a provider about MBD (29.0%) was significantly greater (P < .001) than the percentage of UC (14.7%) or ENH participants (15.6%). All groups saw significant (P < .001) but nondifferential improvements in their knowledge of MBD as a masking and risk factor. In the INT group, the promotora delivered education to 77.1% of the 446 participants randomized to INT and answered questions at 28.3% of the encounters for an average of $4.70 per participant.ConclusionsAmong Latinas in a low‐resource setting, MBD knowledge may increase with written or interpersonal education, but with modest investment, interpersonal education may better improve MBD awareness and prompt patient‐provider discussions.

Abstract Background: Hereditary factors play a key role in the risk of developing breast cancers. Identification of a germline predisposition can have important implications for treatment decisions, risk-reducing interventions, cancer screening, and testing for family members. Aim: To determine the prevalence of pathogenic or likely pathogenic germline mutations (P/LP) using a “universal” testing approach and uptake of no-cost cascade family testing in patients with breast cancer. Methods: We undertook a prospective multi-site study of germline genetic alterations among breast cancer patients receiving care at Mayo Clinic cancer centers in Rochester, MN; Eau Claire, WI; Jacksonville, FL and Phoenix, AZ between April 1, 2018 and March 31, 2020. Patients with a new or active breast cancer diagnosis (all stages) irrespective of cancer family history were tested with a &gt;80-gene next generation sequencing panel.Results: Of 390 patients, the median age was 58 years (SD 12.3), 1% were male, 85% were white and 28% had advanced (stage 3-4) disease. P/LP were found in 12.1% (n=47) of patients, including 29 in moderate and high penetrance cancer susceptibility genes. 13 (3.3%) patients had mutations in BRCA1 or 2, while 33 (8.4%) had mutations in BRCAness (ATM, BAP1, BARD1, BLM, BRCA1, BRCA2, BRIP1, CHEK2, NBN, PALB2, RAD50, RAD51C, RAD51D, WRN) associated genes. Of the P/LP findings the most frequent aberrations were in BRCA2 (13.5%), BRCA1 (11.5%), CHEK2 (11.5%), MUTYH (11.5%), and WRN (9.6%). Variants of uncertain significance were found in 209 (53.6%) including 26 (6.6%) with concurrent P/LP and VUS. 37 (9.4%) patients had mutations associated with published management recommendations, precision therapies and/or clinical trial eligibility. 10 (2.6%) patients had P/LP that would not have met current screening guidelines, including 4 with moderate or high penetrance mutations. Patients with younger age of diagnosis were less likely than patients with older age of diagnosis to have a P/LP mutation (OR= 0.47, 95%CI: 0.25-0.90 p = 0.020). Only 10 (21%) patients with P/LP had family members undergo familial site- specific testing at no cost.Conclusions: In this prospective multi-center study of unselected breast cancer patients, universal multi-gene panel testing found that 1 in 8 patients harbor P/LP germline variants. Current guidelines were able to identify the majority of patients with P/LP mutations. Familial site specific testing is greatly under-utilized even when cost is not a barrier. Multigene panels impact cancer patient care by identifying precision medicine treatment interventions, and guiding long-term medical management and preventive surveillance. Citation Format: Brenda Ernst, Natalie Ertz-Archambault, Deborah J Rhodes, Donald W Northfelt, Myra Wick, Douglas L Riegert-Johnson, Scott Okuno, Katie Kunze, Michael Golafshar, Cindy M Azevedo, PLS Uson Junior, ED Esplin, Robert Nussbaum, Margaret Klint, Sarah Mantia, Megan Hager, Keith Stewart, Niloy Jewel Samadder. Universal genetic testing in breast cancer patients: A multi-center prospective study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD10-05.

Abstract Purpose: Among a Latina population in a low resource healthcare setting, to test the effectiveness of bilingual (Spanish/English) written and interpersonal educational interventions in increasing breast density (BD) awareness, knowledge, and conversations with healthcare providers, which are goals of BD notification mandates. Procedures: This randomized trial was conducted at a Federally Qualified Health Center (FQHC) in an urban community of the Southwest U.S. Women ages 40- 74 presenting for screening mammography were recruited and randomized 1:1:1 to usual care (mailed letter with mammogram and BD results), enhanced care (letter plus BD educational brochure), or interpersonal care (letter, brochure, and telephonic promotora education). The baseline survey was administered in person at enrollment prior to the mammogram. Follow-up surveys were by phone or mail after the mammography results letter was mailed and promotora delivery was complete (median days from baseline to follow-up survey = 97 days). Differences between groups at baseline or follow-up were assessed with chi-square tests. Logistic regression using generalized estimating equations to account for repeated data was used to assess differences by time (baseline to follow-up) within group, including a time-by-group interaction. Results: Between October 2016 and October 2019, 1377 women were enrolled. Of these, 1085 (79%) self-identified Latinas completed baseline and follow-up surveys. Median age was 47 years. Most (91%) reported speaking mostly Spanish, and 69.1% had less than a high school degree. At baseline, only 20.9% reported having heard of BD, and only 30.5% of those knew their personal BD category. At follow-up, women in the interpersonal group were more likely to report seeing their BD results in the notification letter compared to the usual care and enhanced groups (70.4% vs. 52.9% and 54.3%, p &lt; 0.001) and to report having spoken with a provider about their BD (27.3% vs. 14.2% and 15.7%, p &lt; 0.001). They also reported higher mean understanding of BD (7.7 on a 0-10 scale vs. 6.3 and 6.6, p &lt; 0.001). There were no significant differences on these outcomes between the usual care and enhanced groups. All groups saw significant improvement in correct responses from baseline to follow-up for questions on the ability of BD to mask tumors on a mammogram and BD as a breast cancer risk factor (p &lt; 0.001 all groups), but the degree of improvement in masking knowledge was significantly higher for the interpersonal vs usual care group [OR for a correct response in follow-up vs baseline: 6.4 (interpersonal) vs 3.7 (usual care), p=0.01]. Conclusion: Among a Latina population in a FQHC, telephonic promotora education was more effective than written notification alone or a mailed brochure on key goals of notification mandates. Adding a brochure does not appear to be more effective than sending a letter alone on key outcomes, but the interpersonal nature of promotora education may prompt attention to mailed information and provide an opportunity for questions. Citation Format: Jennifer L. Ridgeway, Sarah M. Jenkins, Deborah J. Rhodes, Bhavika K. Patel, Edna Ramos, Bijan Borah, Karthik Ghosh, Vera J. Suman, Aaron Norman, Davinder Singh, Celine M. Vachon. Evaluating educational interventions to increase breast density awareness among Latinas: A randomized clinical trial in a Federally Qualified Health Center [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-245.

Abstract Objective: Breast density notification laws aim to increase women’s awareness and knowledge about breast density (BD). This study’s aim was to compare BD knowledge and awareness in two Hispanic populations: a safety-net clinic serving Latina population in Maricopa County, Arizona (AZ) and a national sample of Hispanic women participating in an online research panel. Materials/Methods: Women ages 40-74 were recruited at the AZ clinic from 2016-2019 at a screening mammography appointment as part of a larger clinical trial (AZ cohort). Surveys were completed in person (English or Spanish) at enrollment to assess awareness of BD, understanding of BD risk, and mammography history. The same questions were asked in a nationally representative online panel survey conducted in 2017. All data from the national survey were weighted to adjust for probability of selection into the panel and post-stratified to match known U.S. Hispanic population distributions (NS cohort). Univariate comparisons between the clinic and the national panel were performed using Rao-Scott chi-square tests. Associations with awareness and correct knowledge were examined with multivariable logistic regression. All summaries and analyses are weighted, and were performed with SAS version 9.4 SURVEY procedures (SAS Institute Inc., Cary, NC). Results: The analysis included 1332 Hispanic women from the AZ clinic and 152 Hispanic women who completed the national survey. The AZ cohort was younger (mean age: 48.5 vs 52.8), had less education (less than high school: 68.7% vs 34.8% less than high school), more likely to prefer Spanish (92.3% vs 53.1%) and less likely to have had a prior mammogram as compared NS cohort (82.8% vs 90.4%) (all p≤ 0.03). NS cohort was more likely to have awareness of BD (32.6% vs 20.7%); correct understanding of the masking effect of BD, (67.8% vs 37.0%,) and breast cancer risk (72.2% vs 32.6%,), compared to the AZ cohort (all p &lt; 0.004). When adjusted for differences in education, age, language, and screening mammography history, BD awareness was similar between the two cohorts (adjusted odds ratio [ORadj] 0.95, p=0.83). Awareness was positively associated with more education, previous mammogram history, and English language. However, differences in BD knowledge remained (ORadj=2.8 [p=0.03] and 7.2 [P&lt;0.001] for knowledge of masking and risk, respectively). Conclusions: There were significant differences in BD awareness and knowledge between a nationally-representative sample of Latinas and Latinas in a low-resource setting. The differences in BD awareness, but not knowledge, could be explained by education, screening history and preferred language. These findings suggest that a one-size-fits-all approach to raising BD awareness and knowledge will not work. To ensure equitable dissemination of health care to Latina women undergoing screening mammography, future work should be aimed at developing effective tools and resources for educating Spanish-speaking women about BD and risk-based screening. Citation Format: Jillian Leaver, Bhavika K. Patel, Jennifer L. Ridgeway, Sarah Jenkins, Vera Suman, Deborah J. Rhodes, Aaron Norman, Karthik Ghosh, Bijan Borah, Carrie Hruska, Edna Ramos, Davinder Singh, Matt Jewett, Carmen Radecki-Breitkof, Celine Vachon. Breast density knowledge and awareness among Latinas in a low-resource setting: A comparison nationally-representative sample of Latinas [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-238.