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Purpose In the genomic era, more women with low-risk breast cancer will forego chemotherapy and rely on adjuvant endocrine therapy (AET) to prevent metastatic recurrence. However, some of these patients will unfortunately relapse. We sought to understand this outcome. Preliminary work suggested that early discontinuation of AET, also known as non-persistence, may play an important role. A retrospective analysis exploring factors related to our breast cancer patients’ non-persistence with AET was performed. Methods Women who underwent Oncotype-DX® testing between 2011 and 2014 with minimum 5 years follow-up were included. ‘Low risk’ was defined as Oncotype score Results We identified six cases of distant recurrence among low-risk patients with a median follow-up of 7.7 years. Among them, five of six patients (83%) were non-persistent with AET. The non-persistence rate in our cohort regardless of recurrence was 57/228 (25%). Non-persistent patients reported more severe side effects compared with persistent patients (p = 0.002) and were more likely to be offered a switch in endocrine therapy, rather than symptom-relief (p = 0.006). In contrast, persistent patients were 10.3 times more likely to have been offered symptom-alleviating medications compared with non-persistent patients (p p = 0.028). Conclusion Metastatic recurrence in low-risk breast cancer patients may be primarily due to non-persistence with endocrine therapy. Further work is needed to optimize care for patients who struggle with side effects. To our knowledge, these are the first published data suggesting that Oncotype-DX® score may influence persistence with AET.

Purpose: Strategies to implement estrogen therapy for advanced estrogen receptor (ER)-positive breast cancer are under-developed. Preclinical data suggest that cycling treatment with 17b-estradiol followed by estrogen deprivation can control tumor growth long-term. Experimental Design: Post-menopausal women with advanced ER+/HER2- breast cancer with recurrence or progression on ≥1 anti-estrogen- or aromatase inhibitor (AI)-based therapy were eligible. Patients received 17b-estradiol (2 mg orally TID) for 8 weeks followed by AI (physician’s choice) for 16 weeks, alternating treatments on an 8-week/16-week schedule until disease progression. Patients then optionally received continuous single-agent treatment until a second instance of disease progression. Endpoints included 24-week clinical benefit and objective response per RECIST, and tumor genetic alterations. Results: Of 19 evaluable patients, clinical benefit rate was 42.1% (95% CI: 23.1-63.9%) and objective response rate was 15.8% (95% CI: 5.7-37.9%). One subject experienced a grade 3 adverse event related to 17b-estradiol. Among patients who received continuous single-agent treatment until a second instance of disease progression, clinical benefit was observed in 5/12 (41.7%) cases. Tumor ER (ESR1) mutations were found by whole-exome profiling in 4/7 (57.1%) vs. 2/9 (22.2%) patients who did vs. did not experience clinical benefit from alternating 17b-estradiol/AI therapy. The only two patients to experience objective responses to initial 17b-estradiol had tumor ESR1 mutations. Conclusions: Alternating 17b-estradiol/aromatase inhibitor therapy may be a promising treatment for endocrine-refractory ER+ breast cancer, including following progression on CDK4/6 inhibitors or everolimus. Further study is warranted to determine whether the anti-tumor activity of 17b-estradiol differs according to ESR1 mutation status.

Supplemental Figure 1: CONSORT Diagram

Supplemental Table 1: Clinical and tumor characteristics of long-term responders

Purpose:Metaplastic breast cancer (MpBC) is a rare aggressive subtype that responds poorly to cytotoxics. Median survival is approximately 8 months for metastatic disease. We report results for advanced MpBC treated with ipilimumab + nivolumab, a cohort of S1609 for rare cancers (DART: NCT02834013).Patients and Methods:Prospective, open-label, multicenter phase II (two-stage) trial of ipilimumab (1 mg/kg i.v. every 6 weeks) plus nivolumab (240 mg i.v. every 2 weeks) for advanced MpBC. Primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity.Results:Overall, 17 evaluable patients enrolled. Median age was 60 years (26–85); median number of prior therapy lines was 2 (0–5). ORR was 18%; 3 of 17 patients achieved objective responses (1 complete, 2 partial responses; 2 spindle cell, 1 chondromyxoid histology), which are ongoing at 28+, 33+, and 34+ months, respectively. Median PFS and OS were 2 and 12 months, respectively. Altogether, 11 patients (65%) experienced adverse events (AE), including one grade 5 AE. Eight patients (47%) developed an immune-related AE (irAE), with adrenal insufficiency observed in all 3 responders. Responses occurred in tumors with low tumor mutational burden, low PD-L1, and absent tumor-infiltrating lymphocytes.Conclusions:The ipilimumab and nivolumab combination showed no new safety signals and met its primary endpoint with 18% ORR in advanced, chemotherapy-refractory MpBC. All responses are ongoing at >2 to almost 3 years later. The effect of ipilimumab and nivolumab was associated with exceptional responses in a subset of patients versus no activity. This combination warrants further investigation in MpBC, with special attention to understanding mechanism of action, and carefully designed to weigh against the significant risks of irAEs.

Purpose: In the genomic era, more women with low-risk breast cancer will forego chemotherapy and rely on adjuvant endocrine therapy (AET) to prevent metastatic recurrence. However, some of these patients will unfortunately relapse. We sought to understand this outcome. Preliminary work suggested that early discontinuation of AET, also known as non-persistence, may play an important role. A retrospective analysis exploring factors related to our breast cancer patients’ non-persistence with AET was performed. Methods: Women who underwent Oncotype DX® testing between 2011-2014 with minimum 5-year follow-up were included. ‘Low risk’ was defined as Oncotype score < 26. Outcomes of recurrence and persistence were determined by chart review. Patient, tumor and treatment factors were collected, and persistent vs non-persistent groups compared using multivariable ANOVA and Fisher Chi square exact test. Results: We identified 6 cases of distant recurrence among low-risk patients with a median follow-up of 7.7 years. Among them, 5 of 6 patients (83%) were non-persistent with AET. The non-persistence rate in our cohort regardless of recurrence was 57/228 (25%). Non-persistent patients reported more severe side effects compared with persistent patients (p=0.002) andwere more likely to be offered a switch in endocrine therapy, rather than symptom-relief (p=0.006). In contrast, persistent patients were 10.3 times more likely to have been offeredsymptom-alleviating medications compared with non-persistent patients (pConclusions: Metastatic recurrence in low-risk breast cancer patients may be primarily due to non-persistence with endocrine therapy. Further work is needed to optimize care for patients who struggle with side effects. To our knowledge, these are the first published data suggesting that Oncotype-DX® score may influence persistence with AET.

In the genomic era, more women with low-risk breast cancer will forego chemotherapy and rely on adjuvant endocrine therapy (AET) to prevent metastatic recurrence. However, some of these patients will unfortunately relapse. We sought to understand this outcome. Preliminary work suggested that early discontinuation of AET, also known as non-persistence, may play an important role. A retrospective analysis exploring factors related to our breast cancer patients' non-persistence with AET was performed.Women who underwent Oncotype-DX® testing between 2011 and 2014 with minimum 5 years follow-up were included. 'Low risk' was defined as Oncotype score 26. Outcomes of recurrence and persistence were determined by chart review. Patient, tumor and treatment factors were collected, and persistent versus non-persistent groups compared using multivariable ANOVA and Fisher Chi square exact test.We identified six cases of distant recurrence among low-risk patients with a median follow-up of 7.7 years. Among them, five of six patients (83%) were non-persistent with AET. The non-persistence rate in our cohort regardless of recurrence was 57/228 (25%). Non-persistent patients reported more severe side effects compared with persistent patients (p = 0.002) and were more likely to be offered a switch in endocrine therapy, rather than symptom-relief (p = 0.006). In contrast, persistent patients were 10.3 times more likely to have been offered symptom-alleviating medications compared with non-persistent patients (p 0.001). A subset analysis revealed that patients who persisted with therapy had a higher Oncotype-DX® score than patients who discontinued early (p = 0.028).Metastatic recurrence in low-risk breast cancer patients may be primarily due to non-persistence with endocrine therapy. Further work is needed to optimize care for patients who struggle with side effects. To our knowledge, these are the first published data suggesting that Oncotype-DX® score may influence persistence with AET.

Background Drivers behind the adoption of gene expression profiling in breast cancer oncology have been shown to include exposure to physician colleagues’ use of a given genomic test. We examined adoption of the Oncotype DX 21‐gene breast cancer recurrence score assay (ODX) in the United States after its incorporation into clinical guidelines. The influence of patient‐sharing ties and co‐location with prior adopters and the role of these potential exposures across medical specialties on peers’ adoption of the test were examined. Methods We conducted a retrospective cohort study of women with incident breast cancer using a 100% sample of fee‐for‐service Medicare enrollee claims over 2008–2011. Peer networks connecting medical oncologists and surgeons treating these patients were constructed using patient‐sharing and geographic co‐location. The impact of peer connections on the adoption of ODX by physicians and testing of patients was modeled with multivariable hierarchical regression. Results Altogether, 156,229 women identified with incident breast cancer met criteria for cohort inclusion. A total of 7689 ODX prescribing physicians were identified. Co‐location with medical oncologists who adopted the test in the early period (2008–2009) was associated with a 1.38‐fold increase in the odds of a medical oncologist adopting ODX in 2010–2011 (95% CI = 1.04–1.83), as was co‐location with early‐adopting surgeons (odds ratio [OR] = 1.25, 95% CI = 1.00–1.58). Patients whose primary medical oncologist was linked to an early‐adopting surgeon through co‐location (OR = 1.17, 95% CI = 1.04–1.32) or both patient‐sharing and co‐location (OR = 1.17, 95% CI = 1.03–1.34) were more likely to receive ODX. Conclusions Exposure to surgeon early adopters through peer networks and co‐location was predictive of ODX uptake by medical oncologists and testing of patients. Interventions focused on the role of surgeons in molecular testing may improve the implementation of best practices in breast cancer care., Surgeons have been engaged in the development of clinical algorithms involving postoperative molecular testing criteria for breast cancer patients, though promotion efforts and research into the dissemination of these technologies has primarily been focused on medical oncologists. This study demonstrates that peer influence from both early‐adopting surgeons and medical oncologists may have facilitated the uptake of the Oncotype DX recurrence score assay by their medical oncologist peers. Initiatives aimed at improving efficient and equitable incorporation of genomic and molecular innovations into breast cancer care would benefit from engaging surgeons as well as medical oncologists.

Objective The aryl hydrocarbon receptor (AHR) plays a key role in obesity. In vitro studies revealed that the tryptophan metabolite kynurenine (Kyn) activates AHR signaling in cultured hepatocytes. The objective of this study was to determine whether Kyn activated the AHR in mice to induce obesity. Methods Mice were fed a low-fat diet and the same diet supplemented with Kyn. Body mass, liver status, and the expression of identified relevant genes were determined. Results Kyn caused mice to gain significant body mass, develop fatty liver and hyperglycemia, and increase expression levels of cytochrome P450 1B1 and stearoyl-CoA desaturase 1. The hyperglycemia was accompanied with decreased insulin levels, which may have been due to the repression of genes involved in insulin secretion. Kyn plasma concentrations and BMI were measured in female patients, and a significant association was observed between Kyn and age in patients with obesity but not in patients who were lean. Conclusions Results show that (1) Kyn or a metabolite thereof is a ligand responsible for inducing AHR-based obesity, fatty liver, and hyperglycemia in mice; (2) plasma Kyn levels increase with age in women with obesity but not in lean women; and (3) an activated AHR is necessary but not sufficient to attain obesity, a status that also requires fat in the diet.

PURPOSE: Circulating tumor DNA in plasma may present a minimally invasive opportunity to identify tumor-derived mutations to inform selection of targeted therapies for individual patients, particularly in cases of oligometastatic disease where biopsy of multiple tumors is impractical. To assess the utility of plasma DNA as a “liquid biopsy” for precision oncology, we tested whether sequencing of plasma DNA is a reliable surrogate for sequencing of tumor DNA to identify targetable genetic alterations. METHODS: Blood and biopsies of 1–3 tumors were obtained from 4 evaluable patients with advanced breast cancer. One patient provided samples from an additional 7 tumors post-mortem. DNA extracted from plasma, tumor tissues, and buffy coat of blood were used for probe-directed capture of all exons in 149 cancer-related genes and massively parallel sequencing. Somatic mutations in DNA from plasma and tumors were identified by comparison to buffy coat DNA. RESULTS: Sequencing of plasma DNA identified 27.94 +/− 11.81% (mean +/− SD) of mutations detected in a tumor(s) from the same patient; such mutations tended to be present at high allelic frequency. The majority of mutations found in plasma DNA were not found in tumor samples. Mutations were also found in plasma that matched clinically undetectable tumors found post-mortem. CONCLUSIONS: The incomplete overlap of genetic alteration profiles of plasma and tumors warrants caution in the sole reliance of plasma DNA to identify therapeutically targetable alterations in patients, and indicates that analysis of plasma DNA complements, but does not replace, tumor DNA profiling. TRIAL REGISTRATION: Subjects were prospectively enrolled in trial NCT01836640 (registered April 22, 2013).

Effective communication between providers and patients with serious illness is critical to ensure that treatment is aligned with patient goals. We developed and tested an implementation strategy for incorporating the previously developed Serious Illness Conversation Guide (SICG), a clinician script, into hematology-oncology fellowship training at a single US academic medical center. Between December 2017 and April 2018, we trained 8 oncology fellows to use and document the SICG. The training included associated communication skills—such as handling emotion and headlining—over 7 didactic sessions. Implementation strategies included training 4 oncology faculty as coaches to re-enforce fellows’ skills and an electronic medical record template to document the SICG. We assessed effectiveness using 4 approaches: (1) SICG template use among fellows in the 12 months following training, (2) fellow confidence pre- and post-intervention via survey, (3) performance in 2 simulated patient encounters, and (4) semi-structured interviews after 12 months. Fellows successfully implemented the SICG in simulated patient encounters, though only 2 of 6 fellows documented any SICG in the clinical practice. Most fellows reported greater confidence in their communication after training. Thematic analysis of interviews revealed the following: (1) positive training experience, (2) improved patient preference elicitation, (3) selected SICG components used in a single encounter, (4) prioritize other clinical duties, (5) importance of emotion handling skills, (6) no faculty coaching receive outside training. Despite acquisition of communication skills, promoting new clinical behaviors remains challenging. More work is needed to identify which implementation strategies are required in this learner population.

Breast imaging capacity in Tanzania is currently very limited. In a country of almost 60 million people, mammographic units are exceedingly rare. The few existing units are compromised by lack of maintenance and quality control and extremely limited technologist training. Breast cancer incidence continues to increase in East Africa, while the ability to accurately diagnose and differentiate benign and malignant breast disease remains a challenge. However, as ultrasound technology improves and becomes more affordable, there is increased access to devices including hand-held point of care ultrasound. Additionally, there has been a recent expansion in the training of academic radiologists in Tanzania, creating an opportunity for possible sustainable improvement of breast imaging and intervention. Our initial efforts at the Muhimbili Academic Medical Center (MAMC) included social media advertising for symptomatic and asymptomatic women, followed by screening (clinical breast exam) and subsequent ultrasound imaging of symptomatic women. We then initiated a workflow for ultrasound-guided breast intervention, performed biopsies, reviewed results by local pathologists, and brought the postbiopsy patients back for radiologic–pathologic correlation, wound assessment, and coordination of follow-up and treatment.

Purpose: Metaplastic breast cancer (MpBC) is a rare aggressive subtype that responds poorly to cytotoxics. Median survival is approximately 8 months for metastatic disease. We report results for advanced MpBC treated with ipilimumab + nivolumab, a cohort of S1609 for rare cancers (DART: NCT02834013). Patients and Methods: Prospective, open-label, multicenter phase II (two-stage) trial of ipilimumab (1 mg/kg i.v. every 6 weeks) plus nivolumab (240 mg i.v. every 2 weeks) for advanced MpBC. Primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity. Results: Overall, 17 evaluable patients enrolled. Median age was 60 years (26–85); median number of prior therapy lines was 2 (0–5). ORR was 18%; 3 of 17 patients achieved objective responses (1 complete, 2 partial responses; 2 spindle cell, 1 chondromyxoid histology), which are ongoing at 28+, 33+, and 34+ months, respectively. Median PFS and OS were 2 and 12 months, respectively. Altogether, 11 patients (65%) experienced adverse events (AE), including one grade 5 AE. Eight patients (47%) developed an immune-related AE (irAE), with adrenal insufficiency observed in all 3 responders. Responses occurred in tumors with low tumor mutational burden, low PD-L1, and absent tumor-infiltrating lymphocytes. Conclusions: The ipilimumab and nivolumab combination showed no new safety signals and met its primary endpoint with 18% ORR in advanced, chemotherapy-refractory MpBC. All responses are ongoing at >2 to almost 3 years later. The effect of ipilimumab and nivolumab was associated with exceptional responses in a subset of patients versus no activity. This combination warrants further investigation in MpBC, with special attention to understanding mechanism of action, and carefully designed to weigh against the significant risks of irAEs.

Background: The global burden of cancer is rising exponentially in countries with the least resources to manage it. Breast cancer mortality is higher in African women than European women, but neither race nor access to care completely account for this discrepancy. Molecular profiling and methylation analysis could be informative but is expensive and the feasibility of using archived samples from low-resource settings is not known. We present a retrospective tissue collection study of breast cancer patients diagnosed at the University of Rwanda to investigate the quality of DNA from FFPE. Methods IRB approval and Material Transfer Agreement were obtained. Fifty tumor blocks and eight sets of FFPE slides from 2014-2018 were transported from Rwanda to USA in 2 batches. Pathology was reviewed for concordance. DNA was extracted using the QIAamp DNA FFPE Tissue kit (Qiagen). Batch 1: DNA quality and quantity was assessed using the Qubit 3.0 fluorometer (Life Technologies). Batch 2: DNA quality was assessed using Kapa hgDNA pPCR QC Assay. Bisulfite conversion and array hybridization protocols for the Illumina EPIC methylation platform to detect 2.5% methylated DNA target were used. DNA methylation data generated using the Infinum MethylationEPIC BeadChip (Illumina, Inc.) were pre-processed using minfi (v1.30.0), prior to quality control using Enmix (v1.20.2). A detection P-value threshold of 1E-06 was used to identify poorly detected probes, and a maximum threshold of 5% low quality data was used to identify poorly performing samples and CpG loci. Outliers based on beta-value distributions were also flagged as poor-quality samples. Mean bisulfite intensity values were calculated using Infinium type I and II control probes. DNA methylation beta-values were calculated to assess the proportion of methylated alleles at each individual CpG locus. Results: Histology was 82% concordant. All samples in Batch 1 had >5% low quality CpG’s. FFPE processing was reviewed and buffered formalin was not used. For Batch 2 10% neutral buffered formalin was transported and delivered to Central University Hospital of Kigali in March 2019. Eight additional patient samples were obtained and 6 out of 8 had Conclusion: Complex molecular studies are feasible with international collaboration. Optimal reagents and processing are crucial for successful analysis. Quality checkpoints must be done early in the process to maximize the potential for interpretable results. Capacity-building to improve DNA quality is the first step toward optimizing cancer treatment and minimizing disparities as molecular profiling increasingly directs cost-effective treatment.These results confirm methods appropriate for future molecular research on breast cancer in low resource settings. Citation Format: Mary Dickinson Chamberlin, Victoria Forbes, Germaine Dushimimana, Arminja Kettenbach, Kristen Muller, Emile Musoni, Eric Rutaganda, Owen M. Wilkins, Fred W. Kolling, Brock Christensen. Capacity-building for molecular analyses of formalin-fixed paraffin-embedded breast cancer samples from Rwanda [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-11-20.

PURPOSE: This study evaluated epidemiologic and immune factors associated with pathologic complete response (pCR), breast cancer-specific survival (BCSS) and disease-free survival (DFS) outcomes in inflammatory (IBC) and locally advanced breast cancer (LABC) patients. METHODS: Tumor-infiltrating lymphocytes (TILs) and CD20(+) B-cell frequencies (CD20(+)), and PD-L1 expression on tumor (PD-L1(+)carcinoma cells) and immune (PD-L1(+)TILs) cells were analyzed by immunohistochemistry along with clinicopathologic factors as modifiers of pCR and outcomes in 221 IBC and 162 LABC patients. Analysis included Kaplan–Meier curves and Cox proportional hazard models. RESULTS: IBC and LABC display similar levels of TILs, CD20(+), and combined CD20(+) and PD-L1(+)TILs (CD20(+)PD-L1(+)TILs), while LABC contained more PD-L1(+)TILs and PD-L1(+) carcinoma cells. Absence of lymphovascular involvement, high TILs, PD-L1(+) carcinoma cells, and combined CD20(+) and PD-L1(+) carcinoma cells correlated with pCR in IBC and LABC patients. High PD-L1(+)TILs correlated with pCR only in LABC; less lymph node involvement at diagnosis, CD20(+) and CD20(+)PD-L1(+)TILs correlated with pCR only in IBC (P < 0.04, all comparisons). Achievement of pCR in IBC and LABC patients correlated with BCSS and DFS (P < 0.02). In multivariate analyses, pCR remained an independent prognostic factor of improved DFS in IBC and LABC patients, but of BCSS in only LABC. CD20(+)PD-L1(+)TILs remained an independent prognostic factor of improved DFS and BCSS only in IBC. CONCLUSION: CD20(+)PD-L1(+)TILs are an independent prognostic biomarker of improved outcomes in IBC, but not LABC. Selecting IBC patients by CD20 and PD-L1 status could stratify patients and potentially identify those in whom activating CD20 agents and anti-PD-1/PD-L1 therapy could be explored.

Effective communication between providers and patients with serious illness is critical to ensure that treatment is aligned with patient goals. We developed and tested an implementation strategy for incorporating the previously developed Serious Illness Conversation Guide (SICG), a clinician script, into hematology-oncology fellowship training at a single US academic medical center. Between December 2017 and April 2018, we trained 8 oncology fellows to use and document the SICG. The training included associated communication skills-such as handling emotion and headlining-over 7 didactic sessions. Implementation strategies included training 4 oncology faculty as coaches to re-enforce fellows' skills and an electronic medical record template to document the SICG. We assessed effectiveness using 4 approaches: (1) SICG template use among fellows in the 12 months following training, (2) fellow confidence pre- and post-intervention via survey, (3) performance in 2 simulated patient encounters, and (4) semi-structured interviews after 12 months. Fellows successfully implemented the SICG in simulated patient encounters, though only 2 of 6 fellows documented any SICG in the clinical practice. Most fellows reported greater confidence in their communication after training. Thematic analysis of interviews revealed the following: (1) positive training experience, (2) improved patient preference elicitation, (3) selected SICG components used in a single encounter, (4) prioritize other clinical duties, (5) importance of emotion handling skills, (6) no faculty coaching receive outside training. Despite acquisition of communication skills, promoting new clinical behaviors remains challenging. More work is needed to identify which implementation strategies are required in this learner population.

11006 Background: Comprehensive patient care requires an understanding of medical guidelines and the intersectional context of the patient’s identity and experiences. Hematology/Oncology programs must explicitly teach topics addressing various disparities of care to prepare trainees for informed care. We have developed a Global Oncology and Disparities of Cancer Program to address this gap. Methods: The telementoring program was piloted in 2019 at Dartmouth and has evolved to include didactics, discussion, and evaluations. Participants from across the globe include medical students, residents, Hematology/Oncology Fellows, Faculty, Global Health Scholars, and cancer clinicians. US Hematology/Oncology trainees from Dartmouth and the University of Connecticut consistently participate in the international program. Monthly sessions from September 2021-June 2022 include: Esophageal and GI Cancers in Rwanda, HCC and Cholangiocarcinomas, Gastric Cancer, ASCO International, Global Med ED in Haiti, Breast Cancer in Kosovo, Breast Cancer Risk Factor Prediction Tools Research, Shared Decision Making in Breast Cancer, Hemoglobinopathies, and Health Disparities and Capacity-Building in Rwanda. A pre-course survey was sent to identify participant’s demographics, barriers, and expectations. We will administer a post-course survey. Results: We have preliminary data for our ongoing project. However, we anticipate complete data collection and analysis before the ASCO Meeting. 24 participants were enrolled. 12 (52%) of the participants were located outside of the US in locations such as Haiti, Kosovo, and France. Using a 5-point Likert scale, 11 (46%) participants were “not at all” or only “slightly” aware of obstacles faced by Oncology patients and caregivers in seeking access to healthcare in the US. 7 (29%) participants answered similarly regarding those in low- and middle-income countries. Meanwhile, participants rated ‘’gaining different perspectives’’ as their most important reason for attending with 19 (79%) rating this as “very important” or above. For anticipated improvement from the course, understanding risk factors and cancer biology internationally and recognizing disparities in healthcare between domestic and international settings were the highest rated with 18 (75%) expecting an improvement to a “large degree” or higher. Conclusions: We developed a virtual educational experience to enhance participants’ ability to address disparities of care through challenging Global Oncology topics. Our course is ongoing however initial surveys show a need and desire for this content from participants. We intend to analyze the course surveys to shape future courses. This program can serve as a model for Hematology-Oncology programs to address unmet needs in the curriculum and prepare trainees to provide more complete care to improve cancer outcomes.

TPS12153 Background: Physical inactivity is a modifiable risk factor for breast cancer recurrence, but estimates suggest at least 50% of breast cancer survivors are insufficiently active. Guidelines specify all cancer survivors should avoid inactivity, and 90-minutes of moderate-vigorous physical activity (MVPA) per week is associated with clinically meaningful benefits (e.g., reduced cancer-related fatigue). Among the general population, how people feel during exercise (i.e., “affective response to exercise”) predicts future exercise engagement. Past work shows prescribing affect-regulated exercise can increase MVPA among inactive adults; however, this strategy has yet to be tested with cancer survivors. The overarching goal of this trial-in-progress is to test the hypothesis that an affect-regulated exercise prescription (Affect-Rx) can promote clinically meaningful increases in MVPA among inactive breast cancer survivors. Methods: Design: The Obesity-Related Behavioral Intervention Trials (ORBIT) model was used to inform all choices about design and key research milestones for two sequential studies. Study 1 (Phase Ib) is a stakeholder-centered, single-arm pilot trial (NCT04903249). Study 2 (Phase IIa) is a randomized (2:1) proof-of-concept trial. In both studies, MVPA will be measured using waist-worn ActiGraph wGT3X-BT accelerometers for 10 days at baseline, 2-, 6- and 12-weeks follow-up. Participants also complete brief ecological momentary assessments (EMAs) of their feeling states (e.g., pain, fatigue) three times per day for the same 10-day data collection periods. Participants: >18 years or older, physically inactive, stage 0-III breast cancer survivors, with primary cancer-treatment completed within the last 5-years. Intervention: Both studies deliver the Affect-Rx prescription: Exercise at the highest pace that still feels good. The Control condition in Study 2 is a heart-rate regulated exercise prescription. Endpoints and Planned Analyses: The goal of Study 1 is to refine the study protocol for acceptability via participant interviews and objective indicators of acceptability (e.g., accelerometer wear-time). The primary milestone for Study 1 is a fixed protocol ready for testing in Study 2. The goal of Study 2 is to quantify the effect of Affect-Rx on MVPA at 12-weeks relative to Control. The primary milestone for Study 2 is clinically meaningful impact on MVPA operationalized as >50% participants completing 90-minutes of MVPA at the end of 12 weeks. The associations between daily variability in feeling states and MVPA will be analyzed using a mixed-effects, hierarchical regression modeling approach. Current Enrollment: Data collection for Study 1 are ongoing. To date, N = 37 women have enrolled in Study 1 and data collection is complete for N = 13 at week-12. We aim to collect complete data from at least N = 20 women in Study 1 and N = 60 women in Study 2. Clinical trial information: NCT04903249.

PURPOSETo provide expert guidance to clinicians and policymakers in resource-constrained settings on the management of patients with late-stage colorectal cancer.METHODSASCO convened a multidisciplinary, multinational Expert Panel that reviewed existing guidelines, conducted a modified ADAPTE process, and used a formal consensus process with additional experts for two rounds of formal ratings.RESULTSExisting sets of guidelines from four guideline developers were identified and reviewed; adapted recommendations from five guidelines form the evidence base and provided evidence to inform the formal consensus process, which resulted in agreement of ≥ 75% on all recommendations.RECOMMENDATIONSCommon elements of symptom management include addressing clinically acute situations. Diagnosis should involve the primary tumor and, in some cases, endoscopy, and staging should involve digital rectal exam and/or imaging, depending on resources available. Most patients receive treatment with chemotherapy, where chemotherapy is available. If, after a period of chemotherapy, patients become candidates for surgical resection with curative intent of both primary tumor and liver or lung metastatic lesions on the basis of evaluation in multidisciplinary tumor boards, the guidelines recommend patients undergo surgery in centers of expertise if possible. On-treatment surveillance includes a combination of taking medical history, performing physical examinations, blood work, and imaging; specifics, including frequency, depend on resource-based setting. Additional information is available at www.asco.org/resource-stratified-guidelines .

PURPOSE To evaluate the feasibility of brigade-style, multiphasic cancer screening in Honduras, exploring data from 3 screening events that each tested for multiple cancers on single occasions. METHODS This series of 3 studies each used a single-arm, post-test–only design to explore the feasibility of implementing multiphasic, community-based cancer screening at the same rural location in 2013, 2016, and 2017. The 2013 event for women screened for 2 cancers (breast and cervix), and the 2016 event for women screened for 3 cancers (breast, cervix, and thyroid). The 2017 event for men screened for 5 cancers (skin, prostate, colorectal, oropharynx, and testes). RESULTS Totals of 473 and 401 women participated in the 2013 and 2016 events, respectively, and 301 men participated in the 2017 event. Staffing for each event varied from 33 to 44 people and relied primarily on in-country medical students and local community members. High rates (mean, 88%) of compliance with referral for follow-up testing at clinics and primary care facilities were observed after the screening events. CONCLUSION The multiphasic, community-based approach proved feasible for both women and men and resulted in high rates of compliance with follow-up testing. This approach appears highly replicable: it was conducted multiple times across the years with different screening targets, which could be further scaled elsewhere using the same technique.

Matching of actionable tumor mutations with targeted therapy increases response rates and prolongs survival in lung cancer patients. Drug development and trials targeting genetic alterations are expanding rapidly. We describe the role of a Molecular Tumor Board (MTB) in the design of molecularly informed treatment strategies in our lung cancer patient population. Tumor DNA was sequenced using a 50-gene targeted next-generation sequencing panel. Cases were evaluated by a multidisciplinary MTB who suggested a course of treatment based on each patient’s molecular findings. During a three-year period, 21 lung cancer patients were presented at the MTB. All patients lacked common activating EGFR mutations and ALK rearrangements. One patient had Stage IIIb disease; all others were Stage IV; 18 patients had received ≥1 prior line of therapy (range 0–5). Suggestions for treatment with a targeted therapy were made for 19/21 (90.5%) patients, and four patients (21%) underwent treatment with a targeted agent, two as part of a clinical trial. Identified barriers to treatment with targeted therapy included: ineligibility for clinical trials (n ​= ​2), lack of interest in study/distance to travel (n ​= ​2), lack of disease progression (n ​= ​2), poor performance status (n ​= ​5), decision to treat next with immunotherapy (n ​= ​3), and unknown (n ​= ​1). For the majority of lung cancer patients, the MTB provided recommendations based on tumor genetic profiles. Identified barriers to treatment suggest that presentation to the MTB at earlier stages of disease may increase the number of patients eligible for treatment with a genetically informed targeted agent.

Purpose: Gastrointestinal (GI) endoscopy is a growing field in Rwanda, a country of 12.6 million with significant GI morbidity and mortality. Endoscopy alongside Helicobacter pylori identification and eradication aids in GI cancer prevention and diagnosis in this population. Our collaborative training-focused endoscopy conference provides preliminary data to focus future training and capacity building programs in Rwanda to improve oncologic outcomes. Methods: Since 2017, ‘Rwanda Endoscopy Week' (REW) is held annually at multiple hospitals throughout Rwanda. It consists of several days of didactic training in endoscopy, oncology and research, followed by a week of endoscopy procedures performed jointly by visiting and hosting endoscopists, and ending with a summary of results of didactic and endoscopic activity. Results: Four (4) hospitals performed 244 training endoscopies in 2017 and 448 cases in 2018. In 2019 this expanded to 668 endoscopies performed at 7 hospitals, including academic, district, and private hospitals. The case distribution remained similar over 3 years at 86.0% (1170/1360) upper endoscopies, 13.2% (180/1360) colonoscopies, and 0.7% (10/1360) endoscopic retrograde cholangiopancreatographies. Thirty-nine (5.8%, 39/668) patients had a tumor finding suspicious for gastric (4.0%, 27/668), colorectal (1.5%,10/668), ampullary (0.1%, 1/668), or gallbladder (0.1%, 1/668) malignancy. 54% of patients receiving endoscopy were tested for H. Pylori (367/669); 38% of those tested had inconclusive results (141/367) and 20% were positive (74). There were 2 non-serious bleeding events. Conclusions: Participation by Rwandan urban, district, public and private hospitals in a cooperative international GI training conference has experienced a nearly three-fold increase in patients and identified malignant pathology while maintaining safe endoscopic care over a three-year period. H. pylori, ubiquitous in this population, is an important risk factor for gastric cancer and gastric diseases. Necessary next steps include increased training and capacity-building interventions to improve the quality of the testing and surveillance of those treated. Citation Format: Nikitha Gangasani, Eric Rutaganda, Felcien Shikama, Steve Bensen, Vincent Dusabejambo, Mary Chamberlin. International Collaborative Rwanda Endoscopy Week Conferences Demonstrate Feasibility and identify H. pylori Testing as an Important Target for Capacity-Building Interventions [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 41.

Despite the clinical efficacy of anthracycline agents such as doxorubicin, dose-limiting cardiac toxicities significantly limit their long-term use. Here, we present the case of a 33-year-old female patient with extensive metastatic ER+/PR+/HER2– mucinous adenocarcinoma of the breast, who was started on doxorubicin/cyclophosphamide therapy after progressing on paclitaxel and ovarian suppressor goserelin with aromatase inhibitor exemestane. The patient was comanaged by cardiology, who carefully monitored measures of cardiac function, including EKGs, serial echocardiograms, and profiling of lipids, troponin, and pro-BNP every 2 months. The patient was treated with the cardioprotective agent dexrazoxane, and changes in cardiac markers [e.g. decreases in ejection fraction (EF)] were immediately addressed by therapeutic intervention with the ACE inhibitor lisinopril and beta-blocker metoprolol. The patient had a complete response to doxorubicin therapy, with a cumulative dose of 1,350 mg/m2, which is significantly above the recommended limits, and to our knowledge, the highest dose reported in literature. Two and a half years after the last doxorubicin cycle, the patient is asymptomatic with no cardiotoxicity and an excellent quality of life. This case highlights the importance of careful monitoring and management of doxorubicin-mediated cardiotoxicity, and that higher cumulative doses of anthracyclines can be considered in patients with ongoing clinical benefit.

Purpose In Honduras, the breast cancer burden is high, and access to women’s health services is low. This project tested the connection of community-based breast cancer detection with clinical diagnosis and treatment in a tightly linked and quickly facilitated format. Methods The Norris Cotton Cancer Center at Dartmouth College partnered with the Honduran cancer hospital La Liga Contra el Cancer to expand a cervical cancer screening program, which included self-breast exam (SBE) education and clinical breast exams (CBEs), to assess patient attitudes about and uptake of breast cancer education and screening services. The cervical cancer screening event was held in Honduras in 2013; 476 women from 31 villages attended. Results Half of the women attending elected to receive a CBE; most had concerns about lactation. Clinicians referred 12 women with abnormal CBEs to La Liga Contra el Cancer for additional evaluation at no cost. All referred patients were compliant with the recommendation and received follow-up care. One abnormal follow-up mammogram/ultrasound result was negative on biopsy. One woman with an aggressive phyllodes tumor had a mastectomy within 60 days. Multimodal education about breast cancer screening maximized delivery of women’s health services in a low-tech rural setting. Conclusion The addition of opportunistic breast cancer education and screening to a cervical cancer screening event resulted in high uptake of services at low additional cost to program sponsors. Such novel strategies to maximize delivery of women’s health services in low-resource settings, where there is no access to mammography, may result in earlier detection of breast cancer. Close follow-up of positive results with referral to appropriate treatment is essential.

The majority of advanced breast cancers have genetic alterations that are potentially targetable with drugs. Through initiatives such as The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC), data can be mined to provide context for next-generation sequencing (NGS) results in the landscape of advanced breast cancer. Therapies for targets other than estrogen receptor alpha (ER) and HER2, such as cyclin-dependent kinases CDK4 and CDK6, were recently approved based on efficacy in patient subpopulations, but no predictive biomarkers have been found, leaving clinicians to continue a trial-and-error approach with each patient. Next-generation sequencing identifies potentially actionable alterations in genes thought to be drivers in the cancerous process including phosphatidylinositol 3-kinase (PI3K), AKT, fibroblast growth factor receptors (FGFRs), and mutant HER2. Epigenetically directed and immunologic therapies have also shown promise for the treatment of breast cancer via histone deacetylases (HDAC) 1 and 3, programmed T cell death 1 (PD-1), and programmed T cell death ligand 1 (PD-L1). Identifying biomarkers to predict primary resistance in breast cancer will ultimately affect clinical decisions regarding adjuvant therapy in the first-line setting. However, the bulk of medical decision-making is currently made in the secondary resistance setting. Herein, we review the clinical potential of PI3K, AKT, FGFRs, mutant HER2, HDAC1/3, PD-1, and PD-L1 as therapeutic targets in breast cancer, focusing on the rationale for therapeutic development and the status of clinical testing. J. Cell. Biochem. 117: 2454-2463, 2016. © 2016 Wiley Periodicals, Inc.

e16081 Background: There are few studies on CRC in sub-Saharan Africa. BCCOE in Rwanda provides patients with CRC access to chemotherapy, surgery and radiotherapy referrals. Here, we describe patient characteristics, treatments delivered and outcomes. Methods: This retrospective observational study included 136 patients with CRC who presented between July 2012 and June 2018. We abstracted patient characteristics, diagnostic and treatment data, and outcomes from electronic and paper records. We compared baseline and treatment characteristics for colon cancer (CC) versus (vs.) rectal cancer (RC) patients. For patients treated with curative intent, we plotted Kaplan Meier estimation of disease free survival (DFS), defined as time from presentation to cancer recurrence, progression or death. Log-rank test was used to examine subgroup differences. Results: The mean age was 52.5, and 71 (52.2%) were female. 101 (74.2%) patients had RC. Compared to CC, patients with RC were older 54.5 vs. 46.9 (p = 0.0084), and more likely female 59.4 vs. 31.4 (p = 0.0043). All provinces in Rwanda were represented including 14 (10.3%) from outside Rwanda; 79 (58.1%) patients lived in rural areas. Median duration of symptoms prior to presentation was 12 months, and 57 (41.9%) had used traditional medicine prior to presentation. 72 (52.9%) patients were non-metastatic, 46 (33.8%) de novo metastatic, 4 (2.9%) recurrent, and 14 (10.2%) had indeterminate stage. Of the patients treated with curative intent, 54 (65.1%) had neoadjuvant and/or adjuvant chemotherapy, while only 34 (41.0%) had curative surgery. 40 (48.2%) patients received a permanent colostomy. 18 (27.7%) patients with RC received concurrent chemoradiation. Over the follow up period, 49 (36%) patients died or were referred for end of life care, 13 (9.3%) remain in surveillance, while 65 (47.8%) were lost to follow up. Median DFS for patients with non-metastatic disease was 22.2 months. On exploratory analyses, there were no statistically significant differences in DFS by cancer type, gender, or performance status, though these analyses were underpowered and follow-up short. Conclusions: CRC treatment requires multidisciplinary care, which is a challenge in low-resource settings. Our results highlight gaps in CRC care delivery and suboptimal patient outcomes; most striking gaps were the low rates of surgery and radiation, and high loss to follow up rates. Rigorous research is needed to understand the underlying causes, and to develop interventions to address these gaps.

More than half of cancer patients worldwide reside in low-resource countries, and a greater proportion of these patients die compared to those in developed countries. Vulnerability is the result of limited access to resources relative to health status. In addition to an increased risk of cancer and poorer survival among economically vulnerable populations, many environmental toxicants also disproportionately affect these communities (e.g., air pollution, lead, pesticides). In this chapter we will highlight the impact of pollution on the economically vulnerable as a potentially preventable cause of cancer and present two focus studies on populations in Ecuador and Rwanda.

Background. Although genetic profiling of tumors is a potentially powerful tool to predict drug sensitivity and resistance, its routine use has been limited because clinicians are often unfamiliar with interpretation and incorporation of the information into practice. We established a Molecular Tumor Board (MTB) to interpret individual patients’ tumor genetic profiles and provide treatment recommendations. Patients and Methods. DNA from tumor specimens was sequenced in a Clinical Laboratory Improvement Amendments-certified laboratory to identify coding mutations in a 50-gene panel (n = 34) or a 255-gene panel (n = 1). Cases were evaluated by a multidisciplinary MTB that included pathologists, oncologists, hematologists, basic scientists, and genetic counselors. Results. During the first year, 35 cases were evaluated by the MTB, with 32 presented for recommendations on targeted therapies, and 3 referred for potential germline mutations. In 56.3% of cases, MTB recommended treatment with a targeted agent based on evaluation of tumor genetic profile and treatment history. Four patients (12.5%) were subsequently treated with a MTB-recommended targeted therapy; 3 of the 4 patients remain on therapy, 2 of whom experienced clinical benefit lasting >10 months. Conclusion. For the majority of cases evaluated, the MTB was able to provide treatment recommendations based on targetable genetic alterations. The most common reasons that MTB-recommended therapy was not administered stemmed from patient preferences and genetic profiling at either very early or very late stages of disease; lack of drug access was rarely encountered. Increasing awareness of molecular profiling and targeted therapies by both clinicians and patients will improve acceptance and adherence to treatments that could significantly improve outcomes. Implications for Practice: Case evaluation by a multidisciplinary Molecular Tumor Board (MTB) is critical to benefit from individualized genetic data and maximize clinical impact. MTB recommendations shaped treatment options for the majority of cases evaluated. In the few patients treated with MTB-recommended therapy, disease outcomes were positive and support genetically informed treatment.

OBJECTIVE. The objective of this study was to assess the feasibility of conducting a future full-scale trial to test the efficacy of an in-home occupational therapy intervention designed to reduce disability in older adult cancer survivors. METHOD. Participants reporting activity limitations during or after cancer treatment were enrolled in a Phase 1 pilot randomized controlled trial comparing the 6-wk intervention (n = 30) to usual care (n = 29). Descriptive data on retention rates were collected to assess feasibility of intervention and study procedures. Potential efficacy was explored through participants’ self-reported disability, quality of life, activity level, and behavioral activation at 0, 8, and 16 wk after enrollment. RESULTS. Retention rates were high regarding completion of the intervention (90%) and outcome assessments (90% of usual-care participants and 80% of intervention participants). Outcomes consistently favored the intervention group, although group differences were small. CONCLUSION. The procedures were feasible to implement and acceptable to participants.

The majority of advanced breast cancers have genetic alterations that are potentially targetable with drugs. Through initiatives such as The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC), data can be mined to provide context for next-generation sequencing (NGS) results in the landscape of advanced breast cancer. Therapies for targets other than estrogen receptor alpha (ER) and HER2, such as cyclin-dependent kinases CDK4 and CDK6, were recently approved based on efficacy in patient subpopulations, but no predictive biomarkers have been found, leaving clinicians to continue a trial-and-error approach with each patient. Next-generation sequencing identifies potentially actionable alterations in genes thought to be drivers in the cancerous process including phosphatidylinositol 3-kinase (PI3K), AKT, fibroblast growth factor receptors (FGFRs), and mutant HER2. Epigenetically directed and immunologic therapies have also shown promise for the treatment of breast cancer via histone deacetylases (HDAC) 1 and 3, programmed T cell death 1 (PD-1), and programmed T cell death ligand 1 (PD-L1). Identifying biomarkers to predict primary resistance in breast cancer will ultimately affect clinical decisions regarding adjuvant therapy in the first-line setting. However, the bulk of medical decision-making is currently made in the secondary resistance setting. Herein, we review the clinical potential of PI3K, AKT, FGFRs, mutant HER2, HDAC1/3, PD-1, and PD-L1 as therapeutic targets in breast cancer, focusing on the rationale for therapeutic development and the status of clinical testing. J. Cell. Biochem. 117: 2454-2463, 2016. © 2016 Wiley Periodicals, Inc.

Background Metastatic breast cancer is a genetically heterogeneous disease and effective therapies for advanced stage disease are limited. Methods In this study, distant metastases of 22 formalin-fixed, paraffin-embedded (FFPE) breast cancer samples were sequenced using the Ion Torrent PGM and the 50 gene AmpliSeq Cancer Hotspot Panel v2 from 10 ng of extracted DNA using 318 chips. Data analysis was performed with the Ion Torrent Variant Caller Plugin (hg19) and Golden Helix's SVS software for annotation and prediction of the significance of the variants. Results All patients were female with a median age of 61 years (range 37–85 years). Metastatic sites included liver (n = 6, 27%), skin (n = 5, 23%), brain (n = 4, 18%), lymph node (n = 3, 14%), lung (n = 2, 9%), retroperitoneum (n = 1, 4.5%), and colon (n = 1, 4.5%). Overall, 28 variants in 11 genes were observed. Five (23%) samples showed no alterations and 17 (77%) showed at least one potentially biologically significant variant (BSV) defined as having FDA-approved drugs or clinical trials evaluating their significance. BSVs included mutations in the following genes: TP53 (n = 8), APC (n = 4), PIK3CA (n = 5), MET (n = 2), ERBB2 (n = 2), AKT1 (n = 1), CDKN2A (n = 1), KRAS (n = 1), and FGFR3 (n = 1). Conclusions Potentially actionable mutations were identified in the majority of breast cancer metastases. Evaluating metastatic breast tumors using a NGS approach provides a better understanding of the mechanisms behind tumor progression and evolution and also identifies additional potentially beneficial therapeutic targets for patient management or eligibility for clinical trials.

Introduction: Poverty, poor health infrastructure, and rurality contribute to lack of cancer screening for most residents of Honduras (HN). We hypothesized that if community-identified barriers were mitigated, rural Hondurans would participate in cancer screening; initial low-tech screening methods would be useful in identifying high-risk individuals in a large group; and that we could operationalize an acceptable and effective multiorgan screening program. Our objective was to test multiorgan cancer-screening strategies for challenging rural environments such as our site in rural El Rosario, Honduras and develop a strategy that would be generalizable to rural sites in other low-income countries. Methods: We conducted three cancer-screening projects (2013/n=449 women, 2016/n=389 women, 2017/n=299 men) by developing relationships with rural community leaders and Honduran oncologists. Together, we launched multiorgan screening events via a brigade-style medical outreach model designed to mitigate barriers to early detection of cancers. Key strategies: 1) a screening cascade system and low-tech methods to identify high-risk individuals for further screening; 2) triage for findings requiring additional workup, rather than focusing on making a definitive cancer diagnosis; 3) inserting cancer education into the participants' experience; and 4) multiorgan screening to maximize cancer prevention with little additional use of resources. Community-identified barriers were transportation, cost, fear, and inconvenience; we negotiated an array of minimalist and highly effective community-based strategies to mitigate the barriers. In 2013 and 2016 we screened women for cancers including cervix, breast, oropharynx, and thyroid, and in 2017 screened men for testicular, oropharynx, skin, prostate, and colon cancers. Post-study, participants with suspicious findings were connected with follow-up care at a cancer center in HN. On-site screening methods ranged from no-tech, including surveys, clinical breast exams, throat palpation for thyroid, digital rectal exam for prostate, physical exam of testes, and visual skin inspection for skin cancer; to mid-tech, including telepathology for oral cancer, fecal occult blood test for colon cancer, and PSA for prostate; and high-tech PCR screening for high-risk HPV (hrHPV). Well-trained HN medical students staffed the screening areas; their participation is intended to increase long-term screening capacity in HN. Community leaders were responsible for promoting the screening clinic by training teens who traveled to villages to introduce the opportunity. Results: Participants came via a free bus, horse, motorbike, and on foot from 31 (2013), 40 (2016), and 38 (2017) different communities. Median age and years of education were 38/5 (2013), 40/6 (2016), and 47/4 (2017). Almost every participant completed all screenings. We found 11 types of hrHPV; in 2013/8.4% and 2016/12.5% were positive for 1 or more types. Referrals for breast follow-up were 2013/2.7% and 2016/4.4%. In 2017 (men), 26 referrals were: skin screening/2; testicular exams/2; colon/2; oropharynx/0; and 20 men for clinical prostate follow-up by a screening cascade of survey, digital rectal exam, and PSA. 249 men self-identified based on ASCO colon standards and brought stool samples for FOBT/4 tested positive. We used oral consent and focus groups for post-event evaluation. Comments reflected satisfaction with the medical students, convenience of a free bus, and protection of participants' privacy. Conclusion: With community engagement and attention to planning for organized and rapid throughput, large-scale multiorgan cancer screening is feasible in low-income rural communities. Despite low expectation of male participation because it is “common knowledge” that Honduran males avoid clinics, our experience demonstrates that with mitigation of barriers, men will participate. Citation Format: Linda Skewes Kennedy, Kayla A. Marra, Ethan Phillip Marshall LaRochelle, Mary D. Chamberlin, Kathleen D. Lyons, Suyapa A. Bejarano, Gregory J. Tsongalis. Cancer screening in rural Honduras: Maximizing impact with a multiorgan screening approach [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr B20.

e12655Background: NIRST provides biophysical data including oxy- and deoxy-hemoglobin, water, lipid, and scatter components, useful in distinguishing cancer from normal breast tissue. Unlike anatom...

11009Background: To meet the rising demand for cancer care in low-middle-income countries (LMIC’s), an accredited Global Health track in Hematology-Oncology Fellowship programs (HOFP) is needed. To...

Abstract 36 Background: Women in rural Honduras have limited access to cancer education, screening, and care. With village leaders, we piloted breast and cervical cancer screening in El Rosario, Honduras. Our objectives were to improve awareness and access, mitigate barriers, connect community and Honduran providers, and link patients with abnormal findings to cancer treatment. In 2013, health professionals and staff from Norris Cotton Cancer Center at Dartmouth- Hitchcock joined Honduran clinicians and medical students from La Liga Contra el Cáncer for two days of rural cancer screening. Peer educators taught 475 participants from 31 rural communities how to conduct self-breast exams. Of these participants, 238 chose clinical breast exams; 5% were clinically abnormal and 2.9% were referred for services at La Liga with 100% compliance. 34% reported barriers to cervical cancer screening due to distance and lack of transportation. 14.5% tested positive for HPV and 8% were positive for high risk HPV genotypes including 11 of 13 known high risk types. This group has been retested periodically by Pap. The collaborators will return in April 2016 to repeat the study, adding oral and thyroid screening. Genotyping for hrHPV will be onsite with a novel assay for PCR developed at Dartmouth-Hitchcock. Reflex testing with Pap will follow as needed. Follow up will be at La Liga where care is offered for free or at a reduced cost. A similar project for 400 urban factory-workers will also take place in April 2016. Methods: 2-day, multi-modal education and screening outreach run brigade-style combining low-tech primary screening with onsite molecular pathology. Conclusions: Partnerships between local leaders and clinicians are predicted to be essential to project implementation. Targeting populations with education and screening plus building connections to follow up care will provide earlier detection of breast and cervical cancer. We predict that community leadership will be critical to preventing loss to follow-up. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST: Derek S. Stenquist No relationship to disclose Suyapa Bejarano No relationship to disclose Linda S. Kennedy No relationship to disclose Silvia Portillo No relationship to disclose Ana Barrientos No relationship to disclose Suzanne P. Burgos No relationship to disclose Roberto Armando Elvir Zelaya No relationship to disclose Christine Averill No relationship to disclose Emmeline Liu No relationship to disclose Francine de Abreau No relationship to disclose Paul Burchard No relationship to disclose Torrey Gallagher No relationship to disclose Martha Goodrich No relationship to disclose Scottie Eliassen No relationship to disclose Julie Weiss No relationship to disclose Camilo Mandujano No relationship to disclose Jennifer Alford-Teaster No relationship to disclose Gregory J. Tsongalis Research Funding: Illumina, Qiagen, Thermofisher Tracy Onega No relationship to disclose Mary D. Chamberlin No relationship to disclose

OBJECTIVE. In this pilot study of a home-based occupational therapy intervention intended to reduce disability and improve quality of life, our objective was to identify rates of goal attainment and patterns of goal adjustment of participants. METHOD. Thirty older adults with cancer were randomized to the intervention arm, and 24 participants identified goals and completed the six-session intervention. An exploratory content analysis of qualitative and quantitative session data was performed. RESULTS. Participants set 63 6-wk goals and attained 62% of them. Most of the goals addressed walking (28%), sedentary leisure (24%), exercising (16%), or instrumental activities of daily living (14%). When 6-wk goals were not attained (n = 24), there were 10 instances of goal disengagement and 14 instances of goal reengagement. CONCLUSION. Although most participants were able to meet their goals, many also changed their goals and priorities after reflection and attempts to resume or initiate meaningful activities.

Background: Gastric cancer is associated with high morbidity and mortality around the world. In developing countries, patients often present with advanced disease creating a challenge for effective treatment. Next generation sequencing is identifying mutations in more than 50% of gastric cancers in developed countries. Chronic infections and other geographic differences may lead to variations in somatic mutations that could lead to different approaches to treatment. In this pilot study we sought to determine if an overseas collaboration between the University of Rwanda College of Medicine and Health Sciences and the Geisel School of Medicine at Dartmouth was feasible and effective at determining molecular profiles of gastric cancer. Methods: Patients referred for endoscopy at University Teaching Hospital of Kigali, Rwanda were consented to participate prior to the procedure. Biopsy tissues were processed for routine pathologic assessment and those confirmed as gastric adenocarcinoma were included. Formalin-fixed paraffin embedded tissues, H&E stained slides and tissue blocks were transported from Rwanda to New Hampshire, USA by visiting professors participating in the Human Resources for Health Program between May 2015 and July 2016. DNA and RNA from 39 samples were extracted using at least 7 FFPE unstained slides according to AllPrep RNA/DNA FFPE Kit Protocol. Library preparation was performed using 5 ng gDNA using the Pillar NGS SLIMampTM Lung and Colon Hot Spot Panel. Library quanitification was performed using Qubit, and samples with at least 4 nM were normalized, pooled and sequenced on the v3 cartridge on the Illumina's MiSeq system. For data analysis, FASTq files were uploaded to Pillar Biosciences, where sequence alignment, annotation, and variant classification were performed. Results: Eighteen samples had insufficient tissue for nucleic acid extraction. Of the 39 samples processed for sequencing, 17 had low library quantification due to low DNA concentration or poor quality. Mutations were detected in 9/22 samples (41%). One sample contained 3 mutations while the majority of mutated cases had 1-2 mutations identified. A total of 12 mutations were identified: TP53 (4), SMAD4 (2), ERBB4 (2) (S341L and D228N), PTEN (2)(K267RfsTer9 and C136Y), FBXW7 (1) and KRAS (1). Conclusions: Overseas collaboration for next generation sequencing of gastric cancer samples is feasible. Quality control is a common challenge and may improve with larger sized biopsies or tissue blocks. Frequency of mutations is lower than expected. ERBB4 mutations identified are not known to be pathogenic. The PTEN mutations observed are considered pathogenic and this may be a feasible target for therapy. A fusion panel and amplification profiling may be more effective in identifying potential targets for therapeutic trials. Limitations: Small sample size. Panel limited to mutations. Citation Format: Mary D. Chamberlin, Francine B. De Abreu, Torrey L. Gallagher. Next-generation sequencing of gastric cancer samples from Rwanda: a feasibility study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4376. doi:10.1158/1538-7445.AM2017-4376

e18057 Background: Gastric cancer is the third leading cause of cancer death worldwide. In Rwanda and East Africs in general, gastric cancer is common in young men and women to the point where the region is known as the "stomach cancer region." Previously reported molecular profiling of Rwandan gastric cancer specimens indicate a lower mutation burden than expected based on historic western-based data; the corresponding database of endoscopy results suggests lsrge differences in access to care. This study compares a US endoscopy database to one from the University of Rwanda, to highlight the disparities of care in low and middle income countries (LMIC’s) compared to higher income countries. Methods: Retrospective pathology, demographic and radiographic data was collected from 164 Rwandan patients who presented for endoscopy at the Kigali University Teaching Hospital and compared with a matching cohort of patients at Dartmouth-Hitchcock Medical Center , Lebanon, NH (DHMC). Results: Approximately 85% of the Rwandan endoscopy cohort presented with gastric cancer, whereas none was seen in the DHMC cohort; the latter group was older than the Rwandan cohort (62.3 vs. 58.6 years). The most common indication for endoscopy among the DHMC cohort was gastroesophageal reflux disease (GERD) or anemia (72%) while the Rwandan cohort most commonly presented with pain or vomiting (68%). A matched US gastric cancer cohort revealed that 63% of US cases of gastric cancer receive treatment with curative intent compared to 7.4% of Rwandan cases. Conclusions: The Rwandan cohort presented with more severe symptoms and was more likely to be diagnosed with gastric cancer than the DHMC patients yet less likely to receive treatment with curative intent. These results highlight the disparities of care in LMIC’s and the need for improving access to early detection and curative treatments.

e20585 Background: Matching of actionable tumor mutations with targeted therapy has been shown to increase response rates and prolong survival in lung cancer patients. Drug development and trials targeting genetic alterations are expanding rapidly. We describe the role of a Molecular Tumor Board (MTB) in the design of molecularly informed treatment strategies in our lung cancer patient population. Methods: DNA from tumor specimens was sequenced to identify coding mutations using a 50-gene targeted next-generation sequencing panel (Ampliseq v2). Cases were evaluated by a multidisciplinary MTB that included medical oncologists, hematologists, molecular and anatomic pathologists, genetic counselors, and basic science researchers who suggested a course of treatment based on the patient’s molecular findings. Results: During a three-year period, 88 patients were presented to the MTB. Of these, 21 patients had lung cancer (23.9%). All patients lacked common (indicated for FDA approved drug) activating EGFR and ALK mutations. One patient was stage IIIb, all others were stage IV; 18 had previously received at least one prior line of therapy (range 0-5). Suggestions for treatment with a targeted therapy were made for 19 of 21 (90.5%) and four patients underwent treatment with a MTB-suggested targeted agent (21.1%); two as part of a clinical trial. One patient received targeted therapy for 27 months before his disease eventually progressed. Barriers to treatment with targeted therapy included: ineligibility for study (n = 2), lack of interest in study/distance to travel (n = 2), lack of disease progression (n = 2), death/hospice enrollment (n = 5), decision to treat with immunotherapy (n = 3), and unknown (n = 1). Conclusions: For the majority of lung cancer patients, the MTB was able to provide suggestions based on targetable genetic alterations. The largest barriers to treatment were death and hospice enrollment indicating that molecular testing and presentation to the MTB at earlier stages of disease may increase the number of patients who ultimately are eligible for treatment with a targeted agent.

e18086 Background: Despite the rising burden of cancer, opportunities for global health education (GHE) at the fellowship level are lacking in hematology and oncology (HO). The Geisel School of Medicine at Dartmouth (GSMD) is pioneering a supervised one-month elective in Rwanda for HO fellows enrolled in U.S. programs. The goals are to expose fellows to a wider spectrum of disease states, improve clinical acumen, cultural sensitivity, and learn about health delivery in low-resource countries, while providing educational support for the local staff in a multidirectional learning paradigm. Methods: In partnership with the Rwandan Ministry of Health (MOH) and Partners in Health (PIH), GSMD created a one month elective rotation at the Butaro Cancer Center of Excellence (BCCOE) in Rwanda. HO Fellows with an interest in GHE apply to work in the outpatient clinic and inpatient wards in at BCCOE under direct supervision by GSMD faculty to provide input on cancer management including diagnosis, treatment, and chemotherapy administration. Fellows and attendings give lectures to hospital faculty and staff on topics requested by the leadership of BCCOE and participate in weekly telemedicine tumor boards. Fellows are evaluated using ACGME clinical competencies. Feedback from the Rwandan staff is obtained through customized evaluations. Results: The HO fellow gained exposure to advanced cancers including HIV-related malignancies, rare sarcomas and gestational trophoblastic disease, adhered to locally developed staging and treatment pathways, and gained confidence in guiding medical decisions. Fellows and faculty gave didactic presentations and provided bedside teaching. The local MOH and PIH staff gained new insight about approaches to management of complex disease states. This program promoted a multidirectional exchange of ideas related to patient care, disease states, and collaborative research projects. Conclusions: The institution of a global health fellowship elective in oncology has measurable benefits to HO fellows, cancer care providers in Rwanda and American faculty sub-specialists. This novel educational program will help to bridge the gap in global health disparities in a multifaceted approach.