Ruddy, Kathryn J.

e23081 Background: Anthracycline-induced cardiotoxicity (AIC) is a well-known phenomenon, but the true incidence is poorly defined, and definitions of AIC in the literature are variable. We performed a systematic review and meta-analysis to elucidate AIC definitions and the incidence of clinical heart failure (HF) and subclinical AIC reported in adult breast cancer and lymphoma patients after anthracycline (AC) therapy. Methods: 3,428 abstract and titles were identified via PubMed search. Inclusion criteria for full text review included minimum of 100 adult patients receiving ACs; median/mean follow up of at least 12 months; and specified evaluation of left ventricular ejection fraction. Outcomes were divided into clinical HF and subclinical AIC. Meta-analysis was performed with MedCalc software with random effects model. Results: 366 full text articles were reviewed. 24 studies, including a total of 11,065 patients, reported clinical HF findings; 21 studies, including a total of 8,098 patients, reported subclinical AIC findings. Meta-analysis showed an overall incidence of clinical HF of 3.1% (range 0 to 29%, CI 1.9 to 4.6%, I2= 93.9%); an incidence of 2.0% (CI 0.9 to 3.6%, I2 = 91.6%) in breast cancer patients receiving AC; and 4.8% in lymphoma patients receiving AC (CI 2.1 to 8.6%, I2 = 93.6%). Subclinical AIC was seen in 13.8% overall patients (range 2 to 45%, CI 10.4 to 17.7%, I2= 95.3%); 10.3% of breast cancer patients (CI 7.0 to 14.3%, I2= 95.0%); and 19.8% of lymphoma patients (CI 12.3 to 28.6%, I2= 94.4%). Incidence of HF correlated with increasing age (r = 0.51, p = 0.06) and cumulative dose (r = 0.51 , p = 0.19). There was notable heterogeneity of AIC definitions between studies (Table). Conclusions: Cardiotoxicity is not uncommon among patients who receive AC, particularly at doses given for the treatment of lymphoma. However, there was considerable heterogeneity in HF incidences. More uniform criteria and precise estimates are needed to inform clinical practice and trials. [Table: see text]

6575 Background: Delays in diagnosis (dx) and treatment (tx) affect breast cancer (BC) outcomes. We sought to identify factors associated with delays among young women, who do not undergo routine screening and often have pregnancy or breastfeeding-related breast changes that may mask a BC. Methods: The Young Women’s Breast Cancer Study is a multicenter, prospective cohort that enrolled 1302 women with newly dx BC age ≤40 between 2006-2016. Women reported the method and timing of cancer detection on the baseline survey. 231 were ineligible or excluded due to missing information. Among those reporting self-detected cancers, using multivariable regression we evaluated factors associated with delays ≥90 days (d) from symptom to presentation (self delay) and presentation to dx (care delay); in stage 0-III BC we evaluated delays ≥60d from dx to tx (tx delay). Results: 1071 eligible women had median age at dx of 37 yrs (17-40) and 74% reported self-detected cancers. Self delay or care delay ≥90d was reported in 17% and 13%, respectively. Factors inversely associated with self delay included pregnancy at dx (vs nulliparous, OR 0.10, CI 0.01-0.78) and perceived financial comfort (vs not, OR 0.62, CI 0.41-0.93). Women dx ≤1 year post-partum who breastfed (vs nulliparous, OR 2.60, CI 1.14-5.93) and those with a family history of breast/ovarian cancer (vs none, OR 1.79, CI 1.00-3.19) were more likely to have a care delay. Age was inversely associated with care delays (OR 0.94, CI 0.89-0.99). Tx delay was reported by 10% (105/1015), and associated with being single (vs partnered, OR 1.61, CI 1.02-2.56 ), non-white (vs white, OR 1.85, CI 1.09-3.13) and having Stage 0 BC (vs stage 1, OR: 3.08, CI 1.65-5.77); women with stage 3 BC (vs stage 1, OR 0.13, CI 0.03-0.56) were less likely to have a tx delay. Conclusions: In this cohort, most young women with BC underwent timely dx and tx initiation. Women dx ≤1 year post-partum who breastfed were more likely to experience a care delay, likely because lactational changes may mask BC signs and symptoms. The associations of perceived financial status with self delay and non-white race with tx delay underscore the need for additional support to ensure timely care for underserved populations with the goal of eliminating disparities in outcomes.

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.

554 Background: HER2+ breast cancer (BC) is particularly common in young women. Genomic features of HER2+ tumors before and after H-based therapy have not been described in a population of young women and may point to clinically targetable mechanisms of resistance. Methods: From a large prospective cohort of women diagnosed with BC age ≤40 years, we identified those with HER2+ BC and tumor tissue available for sequencing before and after chemo+H. Whole exome sequencing (WES) was performed on each tumor and on germline DNA from blood. Tumor-normal pairs were analyzed for mutations and copy number (CN) changes. Evolutionary analysis was performed for patients with both pre- and post-treatment (tx) samples. Results: 22 women had successful WES samples from at least one timepoint; 13 of these had paired sequencing results both before and after chemo+H. For the majority of women, post-tx sample was following neoadjuvant chemo + H, though post-tx timepoint for other women represented locoregional or distant metastasis (Table). TP53 was the only gene that was significantly recurrently mutated in both pre- and post-tx samples. Comparison of matched pre-tx and post-tx samples demonstrated that large changes in HER2 CN over the course of tx were uncommon, only 2/13 pts had > 2-fold change in HER2 CN. Other clonal and subclonal genomic alterations were found to be acquired in the post-tx sample compared to the pre-tx sample. One patient acquired a putative activating mutation in ERBB2. Another patient acquired a clonal hotpsot mutation in TP53. MYC gene amplification was observed in 4 post-tx tumors. NOTCH2 alterations were found in post-tx biopsies from 2 different patients, and mutations in STIL were also found in post-tx biopsies from 2 patients, though the function of these mutations is not known. Conclusions: HER2+ breast tumors in young women display genomic evolution following tx with chemo+H. HER2 CN changes are uncommon, but we identified several genes that warrant exploration as potential mechanisms of resistance to therapy in this population.[Table: see text]

Background Young age is a known factor associated with suboptimal adherence to endocrine therapy (ET) for adjuvant breast cancer (BC) treatment. This study was aimed at assessing nonadherent behaviors and associated factors among young women with early‐stage hormone receptor–positive BC. Methods As part of a multicenter, prospective cohort of women with a diagnosis of BC at or under the age of 40 years, participants were surveyed 30 months after their diagnosis about adherent behaviors. Among those who reported taking ET, adherence was measured with a 3‐item Likert‐type scale: Do you ever forget to take your ET? If you feel worse when you take your ET, do you stop taking it? Did you take your ET exactly as directed by your doctor over the last 3 months? Women reporting at least 1 nonadherent behavior were classified as nonadherers. Variables with a P value <.20 were included in a multivariable logistic model. Results Among 384 women, 194 (51%) were classified as nonadherers. Univariate factors that retained significance in the multivariable model included educational level (odds ratio [OR], 0.50 for high vs low; P = .04), level of social support according to the Medical Outcome Study Social Support Survey (OR, 0.98 per 1 point; P = .01), and confidence with the decision regarding ET measured on a 0 to 10 numerical scale (OR, 0.63 for high vs low; P = .04). Conclusions Findings from this study could help to identify young patients at higher risk for nonadherence. Interventions adapted to the level of education and aimed at reinforcing support and patients' confidence in their decision to take ET could improve adherence and associated outcomes in this population.