Pruthi, Sandhya

6526 Background: Most patients diagnosed with breast cancer turn to the Internet to learn about their diagnosis; however, information online is often generic, challenging to navigate, and not expert-curated. To facilitate patient education and engagement in our breast clinic, we piloted the implementation of pre-visit education via brief microlearning videos organized within an online platform. Methods: Seventeen videos of 2-4 minute duration were developed by multidisciplinary content experts. Videos covered a variety of educational topics relevant to breast cancer, including treatment options. Patients received a link via email to create an account, which provided access to the platform. Aggregate viewing data and optional patient surveys (online after viewing 3 videos and at the clinical appointment) were used to assess opt-in rates, engagement, and satisfaction. Results: Between September 2018 and January 2019, 57.4% (240/418) of women with biopsy proven breast cancer who were sent an email invitation registered on the platform. On average, patients watched 11 of the 17 videos, with 93.7% of users (225/240) viewing at least one. Overall, 85% (168/198) of women recommend the microlearning format for patient education. The most-viewed video topics included types of breast cancer, breast abnormality and biopsy, understanding biopsy results, tumor markers, and staging. Seventy-eight percent (154/198) of women reported that they planned to share the videos with family or caregivers, and 67% (133/198) felt that the educational content increased their satisfaction with their overall experience. Barriers to video access were emails marked as junk, not having an email address, and difficulties with videos loading. Conclusions: The majority of patients participating in this pilot registered on the platform and watched pre-visit microlearning educational videos. These expert-curated videos contributed to high levels of satisfaction and engagement. Strategies to overcome barriers to access will be developed to expand the reach of this new valuable component of breast cancer care.

1501 Background: Despite BC risk reduction of 50-65% by preventive endocrine therapy (ET), very few at-risk women choose to take them. A woman’s perceived BC risk correlates with uptake of ET. A PRS comprised of 77 BC genetic susceptibility loci (Single Nucleotide Polymorphisms (SNP) improves the accuracy of risk prediction for BC. We examined the impact of the addition of individualized PRS BC risk prediction to standard risk calculator estimates on intent to take BC prevention medication. Methods: Eligible women had ≥5% 10 yr BC Tyrer-Cuzick risk (IBIS) or 5 year Gail score ≥3%, with no history of BC or hereditary BC syndrome. Standard BC risk estimates (IBIS or Gail) were incorporated into the counselling on BC preventive ET. A self-reported questionnaire at baseline quantified intention to take ET and explored factors associated with this decision. Blood samples were obtained and genotyped for 77 SNPs, individualized PRS were calculated then incorporated into IBIS and Gail predictions for 5 yr, 10 yr, & lifetime BC risk. At a second visit, PRS risk & prevention recommendations were revisited. Post visit questionnaires assessed change in intent to take ET. Multivariable linear regression was performed to assess impact of baseline variables on change in intent to take medication. Results: From 2016 to 2017, 151 women in Canada & USA were enrolled, median age: 56.1 (range 36-76.4), 35.6% were premenopausal, 98.7% were Caucasian. Median 5yr, 10yr, & lifetime IBIS risk estimates were 3.8% (2.0-11.5), 7.9% (5.0-23.1), and 25.3% (5.5 to 92.2). PRS increased BC risk estimates in 84 (55.6%) and reduced BC risk estimates in 67 (44%) women. After PRS risk counselling, intention to take ET significantly changed (p<0.001): 41.9% of those with increased PRS were more inclined, and 46.7% of women with decreased PRS were less inclined to take ET. On multivariable regression, increase in PRS (p<0.0001) and less concern about ET side effects (p<0.0001) were associated with greater intent to take ET. Conclusions: In high risk women, PRS significantly changed BC risk estimates & intent to take preventive ET. Further assessments of the impact of PRS scores on compliance with ET are warranted. Clinical trial information: NCT02517593.

Abstract Introduction: There is insufficient knowledge about the feasibility and effect of mind-body intervention on QOL and stress at initial diagnosis and shortly after undergoing breast cancer surgical treatment. The pre-operative and post-operative period can be stressful, distressing and anxiety provoking for many women. Mind-body interventions such as meditation, relaxation and mindfulness can offset distress and is an option to cope with the stresses of treatment. We investigated the role of wearable mindfulness based technology in patients newly diagnosed breast cancer patients. Methods: This randomized study compared the Muse EEG mindfulness sensing headset device (n=16) to a stress reduction education control group (n=13). Primary outcomes included quality of life (QOL), stress, and fatigue via validated, standardized scales/subscales: Functional Assessment of Cancer Therapies – General (FACT-G), Multidimensional Fatigue Symptom Inventory – Short Form (MFSI-SI), and the Perceived Stress Scale (PSS). Participants from an academic cancer center were randomized to the wearable device or stress education material prior to surgery. Participants completed questionnaires at initial diagnosis and at specific time points during the breast cancer surgical journey: pre-surgery, post-surgery (2 weeks), and at 3 months. Usage was directly from Muse and via written log. Was It Worth It (WIWI) survey was conducted at 3 months. Results: Mindfulness via the headset devise was feasible and worthwhile (71.4% intervention group). The scales of QOL, fatigue, and stress improved in both groups at 3 months compared to baseline (MFSI-E, MFSI-M, MFSI-V, FACT-EWB, and PSS). Participants randomized to the mindfulness headset device had improved fatigue and QOL at 2 weeks post-operatively (MFSI-E, MFSI-V, MFSI-T, FACT-PWB, FACT-EWB) and in total MFSI at 3 months. The results were not significantly different between groups. High mindfulness headset utilizers (&gt;30 sessions) compared to below average utilizers differed at the 3 month visit in fatigue and QOL (MFSI-G, MFSI-P, FACT-PWB, and FACT-Total). Conclusion: Our study demonstrated that the use of wearable mindfulness sensing headset device was feasible, simple to use, low cost, and integrated into the surgical breast cancer journey. Overall, among breast cancer patients undergoing surgery there was improvement in QOL, fatigue, and stress with mind-body interventions around surgery compared to baseline. Participants randomized to the wearable mindfulness headset device trended toward outcomes sooner (2 week follow-up) and with high utilization. Further research is needed to determine significance of these outcomes and long term impact in care of cancer survivors. Citation Format: Pruthi S, Millstine DM, Bhagra A, Nguyen M-D. Effect of wearable wellness brain sensing mindfulness-based technology in newly diagnosed surgical breast cancer patients: A randomized intervention [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-11-12.

Abstract Background: Estrogen receptor (ER)-negative tumors and human epidermal growth factor 2-Neu (HER2) positive breast cancers are known to be more clinically aggressive subtypes of breast cancer and account for 30% of all breast cancers. Women with HER2 + breast cancers, whether ER+ or ER -, require cytotoxic chemotherapy with a HER2-targeting agent, and often have adverse outcomes. Thus, preventive agents are needed to reduce the incidence of these subtypes of aggressive breast cancer. Lapatinib, a dual tyrosine kinase inhibitor, inhibits epidermal growth factor receptors (EGFR) and HER2 kinases and has shown to decrease breast cell proliferation in invasive breast cancer and adjacent premalignant lesions. Therefore, we conducted a multi-institutional randomized Phase II clinical trial to study the effects of the signal transduction inhibitor lapatinib in women with HER2-positive or EGFR-positive ductal carcinoma in situ (DCIS). Methods: Randomized participants received either lapatinib (750mg, 1000mg, or 1500mg) or placebo daily for 2-6 weeks prior to their surgery. After minimal accrual, the trial was later amended to lapatinib 1000mg or placebo. Pre-treatment breast tissue was obtained from initial diagnostic core biopsy and post-treatment breast tissue was obtained from surgical excision specimen. Blood was obtained prior to surgery to assess serum lapatinib level. Participants kept a daily symptom assessment log and had a cardiac assessment at baseline and prior to surgery. Patients were instructed to take drug up to and including the day before surgery. The dual primary endpoint for this study was change in proliferation in pre- versus post-treatment biopsies between the two treatment arms, as measured by Ki67 as well as toxicity assessment. Secondary endpoints included incidence of DCIS at surgery and modulation of tissue biomarker expression in growth factor receptors (EGFR, ErbB2); phosphorylated growth factor receptor (phospho-ErbB2); signal transduction markers (MAPK, phospho-MAPK); hormone receptors (ER, PR); and p27. Results:Twenty-two women (mean age: 51; range: 32-66) with HER2+ or EGFR+ DCIS were treated with lapatinib (1,000 or 1,500 mg) or placebo for 2–6 weeks prior to surgical excision. Ki67 expression was significantly decreased in the lapatinib treatment arms compared to placebo (p=0.0122). Diarrhea, fatigue, and skin reactions were notable adverse events that occurred predominately in the lapatinib arm compared to placebo. No grade 3 or 4 events related to the study drug were noted during the study. No changes were noted in cardiac function. DCIS was present in all surgical specimens in both arms. Invasive breast cancer was noted in 1 patient on lapatinib 1000mg and 3 patients on placebo. No statistically significant changes were noted in signal transduction biomarkers Conclusion:These results demonstrate the effectiveness of lapatinib in reducing proliferation in women with EGFR+ or HER2+ DCIS. Even low-grade toxicities can deter use of an agent in the prevention setting. This and the lack of a risk model for HER2+ and triple negative breast cancer make the development of larger scale clinical prevention trials of lapatinib for the prevention a challenge. Citation Format: Thomas PS, Contreras A, Pruthi S, Krontiras H, Rimawi M, Garber J, Wang T, Hilsenbeck SG, Vornik LA, Gilmer T, Friedman R, Heckman-Stoddard BM, Dunn B, Kuerer H, Brown PH. A phase II pre-surgical trial of lapatinib for the treatment of women with HER2 positive or EGFR positive ductal carcinoma in situ [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD3-07.

Abstract Background: MicroRNAs (miRNA) are small, noncoding RNAs with important regulatory roles in tissue development, differentiation, proliferation, and when deregulated tumor formation. The goal of this study was to characterize the miRNA profile of normal breast tissue from carriers of either BRCA1 or BRCA2 mutations, with and without a prior history of cancer, for biomarker discovery for future prevention studies in high risk patient populations. Methods: MicroRNA profiling was conducted using a panel of breast candidate miRNAs and normal ‘non-cancerous’ tissue biopsy from 15 BRCA1 mutation carriers, 15 BRCA2 mutation carriers and 15 BRCA screened mutation negative subjects from high risk families. Results: While small differences were observed for any individual miRNA between groups, the most striking observation was the presence of a clear BRCA1 miRNA signature that was distinct from that in BRCA2 subjects or in the high-risk, non-mutation carriers. The BRCA1 pattern was present in normal appearing tissue biopsy independent of previous history of cancer, treatment for cancer, age, menopausal status or oophorectomy. BRCA2 carriers and high risk, mutation negative subjects showed an overall shared miRNA expression pattern. MicroRNA species that distinguished the groups included differences in the expressed levels of let-7a, let-7b, miR-125b, miR-145, miR-15b and members of the miR-181 family. Ongoing efforts include pathway modeling to gain insight on novel targets for prevention along with RT-PCR confirmation of differentiating microRNA species as well the potential downstream targets for example of miR-181b target genes including HOXA7, HOXA9, HOXA11 and PBX3. Conclusion: The presence of a distinctive miRNA profile in normal appearing tissue of BRCA1 mutation carriers suggest a major role of BRCA1 mutation status on the normal tissue not previously reported. If corroborated, miRNA profiling studies of normal breast tissue may prove useful in both risk assessment as well as providing insight on deregulated pathways for pharmacologic intervention for risk reduction in the BRCA carrier population. Citation Format: Sandhya Pruthi, Julie Buckmeier, Christina Preese, Vera J. Suman, Rachel M. Hurley, Patricia Thompson. microRNA expression profiling in normal breast epithelium of BRCA1 and BRCA2 carriers as prevention targets. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr C47.

Abstract Purpose: BRCA1 and BRCA2 mutation carriers develop breast cancers with a tumor phenotype unique from spontaneous tumors. We surveyed documented BRCA mutation carriers to determine willingness to be contacted about participation in future breast cancer prevention research studies directed to their unique phenotype that may or may not require breast biopsies. Methods: At each of the 3 participating institutions, women at least 20 years of age with a documented germline deleterious mutation in BRCA1 or BRCA2 and no prior history of breast cancer were contacted to participate in a survey to ascertain their willingness to be contacted to participate in future prevention trials. Survey results were summarized using descriptive statistics. Results: Among 56 BRCA1 and BRCA2 mutation carriers who responded, 55.4% of women reported high or very high interest in participating in randomized control study of chemoprevention agent vs. placebo. Within this population, post-menopausal women demonstrated a higher interested in study participation (64.5%) versus pre-menopausal women (38.9%). When examining willingness to undergo breast biopsy for a chemoprevention study, women expressed near equal willingness (42.9%) and unwillingness (44.6%) for biopsy. Conclusions: BRCA1 and BRCA2 mutation carriers demonstrated significant interest in breast cancer prevention study participation involving trial agent versus placebo, and an equal expression of willingness and unwillingness to undergo breast biopsy, establishing the feasibility for future research elucidating targeted chemoprevention agents. Citation Format: Rachel M. Hurley, Vera J. Suman, Mary Daly, Funmi Olopade, Paul J. Limburg, Sandhya Pruthi. Assessment of interest for breast cancer prevention trial participation among BRCA mutation carriers. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr C01.

e12064 Background: Data on long-term cardiovascular effects and safety of aromatase inhibitors (AI) are limited and conflicting. The purpose of the current study was to evaluate the effect of AI on vascular injury as assessed by peripheral endothelial function among women with breast cancer. Methods: This is an observational, prospective study of 96 postmenopausal women with breast cancer at initiation of treatment, with or without AI. All participants underwent baseline and 6-12 months follow up non-invasive peripheral endothelial function measurement. Reactive hyperemia index (RHI) was measured using the EndoPAT test. The primary endpoint was endothelial function deterioration of at least 20% between baseline and follow-up. Results: Mean age of the study population was 66±7 years. There was no statistical difference in demographic data between the groups. Compared with the control group, more women in the treatment group demonstrated worsening of RHI (53% vs. 42%, p = 0.207) between baseline and 6-12 month follow up measurement. There was no statistical difference between the groups at baseline. When RHI deterioration was evaluated as a dichotomous variable, with a 20% cutoff, women in the AI group demonstrated higher rates of RHI deterioration (28% vs. 8%, p=0.020). The risk of AIs for endothelial dysfunction was correlated with burden of cardiovascular (CV) risk, such that in women with >3 CV risk factors, AIs were associated with increased risk of RHI deterioration (42% vs. 10%, p=0.016), whereas in women with <2 CV risk factors, rates of RHI deterioration were similar in AI and control groups (20% vs. 7%, p = 0.232). Conclusions: This study suggests that AI therapy may be associated with vascular injury as detected by deterioration in endothelial function. The effect is more pronounced among women with higher baseline CV risk factor burden. The results of this study have potentially important implications for patients with breast cancer being treated with AI and for women at increased lifetime risk of breast cancer who may use AI for breast cancer risk reduction. Clinical trial information: NCT00719966.