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BackgroundImpaired DNA damage response (DDR) can affect immune checkpoint inhibitors (ICI) efficacy and lead to heightened immune activation. We assessed the impact of pathogenic or likely pathogenic (P/LP) germline DDR mutations on ICI response and toxicity.Materials and methodsA retrospective analysis of 131 cancer patients with germline DNA testing and ICI treatment was performed.ResultsNinety-two patients were DDR-negative (DDR-), and 39 had ≥1 DDR mutation (DDR+). DDR+ patients showed higher objective response rates (ORRs) compared to DDR- in univariate and multivariable analyses, adjusting for age and metastatic disease (62% vs. 23%, unadjusted OR = 5.41; 95% CI, 2.41-12.14; adjusted OR 5.94; 95% CI, 2.35-15.06). Similar results were seen in mismatch repair (MMR), DDR pathways with intact MMR (DDR+MMRi), and homologous recombination (HR) subgroups versus DDR- (adjusted OR MMR = 24.52; 95% CI 2.72-221.38, DDR+MMRi = 4.26; 95% CI, 1.57-11.59, HR = 4.74; 95% CI, 1.49-15.11). DDR+ patients also had higher ORRs with concurrent chemotherapy (82% vs. 39% DDR-, p=0.03) or concurrent tyrosine kinase inhibitors (50% vs. 5% DDR-, p=0.03). No significant differences in immune-related adverse events were observed between DDR+ and DDR- cohorts.ConclusionP/LP germline DDR mutations may enhance ICI response without significant additional toxicity.

PurposeGastrointestinal stromal tumor (GIST) is associated with increased risk of additional cancers. In this study, synchronous GIST, and peritoneal mesothelioma (PM) were characterized to evaluate the relationship between these two cancers.MethodsA retrospective chart review was conducted for patients diagnosed with both GIST and PM between July 2010 and June 2021. Patient demographics, past tumor history, intraoperative reports, cross-sectional imaging, peritoneal cancer index (PCI) scoring, somatic next-generation sequencing (NGS) analysis, and histology were reviewed.ResultsOf 137 patients who underwent primary GIST resection from July 2010 to June 2021, 8 (5.8%) were found to have synchronous PM, and 4 patients (50%) had additional cancers and/or benign tumors. Five (62.5%) were male, and the median age at GIST diagnosis was 57 years (range: 45-76). Seventy-five percent of GISTs originated from the stomach. Of the eight patients, one patient had synchronous malignant mesothelioma (MM), and the remaining had well-differentiated papillary mesothelioma (WDPM), which were primarily located in the region of the primary GIST (89%). The median PCI score was 2 in the WDPM patients. NGS of GIST revealed oncogenic KIT exon 11 (62.5%), PDGFRA D842V (25%), or SDH (12.5%) mutations, while NGS of the MM revealed BAP1 and PBRM1 alterations.ConclusionsOne in 17 GIST patients undergoing resection in this series have PM, which is significantly higher than expected if these two diseases were considered as independent events. Our results indicate that synchronous co-occurrence of GIST and PM is an underrecognized finding, suggesting a possible relationship that deserves further investigation.

Germline testing is becoming increasingly relevant in prostate cancer (PCa) screening, prognosis, and management. A subset of patients with PCa harbor pathogenic/likely pathogenic variants (P/LPVs) in genes mediating DNA-repair processes, and these P/LPVs have implications for cancer screening, treatment, and cascade testing. As a result, it is recommended that all men with high-risk localized and metastatic PCa undergo routine germline testing. As more PCa patients undergo germline testing, it is important that clinicians and genetics experts recognize current disparities in germline testing rates among racial/ethnic minorities in the United States. The reasons for these disparities are multiple and require similarly manifold consideration to close the germline testing gap and reduce inequities in PCa screening, management, and treatment.

IntroductionPhysical exercise and cognitive training have the potential to enhance cognitive function and mobility in older adults at risk of Alzheimer's disease and related dementia (ADRD), but little is known about the feasibility of delivering multidomain interventions in home settings of older adults at risk of ADRD. This study aims to assess the feasibility of home-based delivery of exercise and cognitive interventions, and to evaluate the relationship between participants' intervention preferences and their subsequent adherence. Secondary objectives include the effect of the interventions on ADRD risk factors, including frailty, mobility, sleep, diet and psychological health.Methods and analysisThe SYNchronising Exercises, Remedies in GaIt and Cognition at Home (SYNERGIC@Home) feasibility trial is a randomised control trial that follows a 2×2 factorial design, with a 16-week home-based intervention programme (3 sessions per week) of physical exercises and cognitive training. Participants will be randomised in blocks of four to one of the following four arms: (1) combined exercise (aerobic and resistance)+cognitive training (NEUROPEAK); (2) combined exercise+control cognitive training (web searching); (3) control exercise (balance and toning)+cognitive training; and (4) control exercise+control cognitive training. SYNERGIC@Home will be implemented through video conferencing. Baseline and post-intervention assessments at 4-month and 10-month follow-up will include measures of cognition, frailty, mobility, sleep, diet and psychological health. Primary feasibility outcome is adherence to the interventions. Primary analytic outcome is the relationship between pre-allocation preference for a given intervention and subsequent adherence to the allocated intervention. A series of secondary analytic outcomes examining the potential effect of the individual and combined interventions on cognitive, mobility and general well-being will be measured at baseline and follow-up.Ethics and disseminationEthics approval was granted by the relevant research ethics boards. Findings of the study will be presented to stakeholders and published in peer-reviewed journals and at provincial, national and international conferences.Trial registration numberNCT04997681, Pre-results.

Up to 10% of patients with pancreatic ductal adenocarcinoma (PDAC) carry underlying germline pathogenic variants in cancer susceptibility genes. The GENetic Education Risk Assessment and TEsting (GENERATE) study aimed to evaluate novel methods of genetic education and testing in relatives of patients with PDAC. Eligible individuals had a family history of PDAC and a relative with a germline pathogenic variant in APC, ATM, BRCA1, BRCA2, CDKN2A, EPCAM, MLH1, MSH2, MSH6, PALB2, PMS2, STK11, or TP53 genes. Participants were recruited at six academic cancer centers and through social media campaigns and patient advocacy efforts. Enrollment occurred via the study website (https://GENERATEstudy.org) and all participation, including collecting a saliva sample for genetic testing, could be done from home. Participants were randomized to one of two remote methods that delivered genetic education about the risks of inherited PDAC and strategies for surveillance. The primary outcome of the study was uptake of genetic testing. From 5/8/2019 to 5/6/2020, 49 participants were randomized to each of the intervention arms. Overall, 90 of 98 (92%) of randomized participants completed genetic testing. The most frequently detected pathogenic variants included those in BRCA2 (N = 15, 17%), ATM (N = 11, 12%), and CDKN2A (N = 4, 4%). Participation in the study remained steady throughout the onset of the Coronavirus disease (COVID-19) pandemic. Preliminary data from the GENERATE study indicate success of remote alternatives to traditional cascade testing, with genetic testing rates over 90% and a high rate of identification of germline pathogenic variant carriers who would be ideal candidates for PDAC interception approaches. PREVENTION RELEVANCE: Preliminary data from the GENERATE study indicate success of remote alternatives for pancreatic cancer genetic testing and education, with genetic testing uptake rates over 90% and a high rate of identification of germline pathogenic variant carriers who would be ideal candidates for pancreatic cancer interception.

Risk-reducing endocrine therapy use, though the benefit is validated, is extremely low. The FDA has approved tamoxifen and raloxifene for a 5-year Breast Cancer Risk Assessment Tool (BCRAT) risk ≥ 1.67%. We examined the threshold at which high-risk women are likely to be using endocrine risk-reducing therapies among Athena Breast Health Network participants from 2011-2018. We identified high-risk women by a 5-year BCRAT risk ≥ 1.67% and those in the top 10% and 2.5% risk thresholds by age. We estimated the odds ratio (OR) of current medication use based on these thresholds using logistic regression. One thousand two hundred and one (1.2%) of 104,223 total participants used medication. Of the 33,082 participants with 5-year BCRAT risk ≥ 1.67%, 772 (2.3%) used medication. Of 2445 in the top 2.5% threshold, 209 (8.6%) used medication. Participants whose 5-year risk exceeded 1.67% were more likely to use medication than those whose risk was below this threshold, OR 3.94 (95% CI = 3.50-4.43). The top 2.5% was most strongly associated with medication usage, OR 9.50 (8.13-11.09) compared to the bottom 97.5%. Women exceeding a 5-year BCRAT ≥ 1.67% had modest medication use. We demonstrate that women in the top 2.5% have higher odds of medication use than those in the bottom 97.5% and compared to a risk of 1.67%. The top 2.5% threshold would more effectively target medication use and is being tested prospectively in a randomized control clinical trial.

Along with early-onset cancers, multiple primary cancers (MPCs) are likely resulting from increased genetic susceptibility; however, the associated predisposition genes or prevalence of the pathogenic variants genes in MPC patients are often unknown. We screened 71 patients with MPC of the stomach, colorectal, and endometrium, sequencing 65 cancer predisposition genes. A subset of 19 patients with early-onset MPC of stomach and colorectum were further evaluated for variants in cancer related genes using both normal and tumor whole exome sequencing. Among 71 patients with MPCs, variants classified to be pathogenic were observed in 15 (21.1%) patients and affected Lynch Syndrome (LS) genes: MLH1 (n = 10), MSH6 (n = 2), PMS2 (n = 2), and MSH2 (n = 1). All carriers had tumors with high microsatellite instability and 13 of them (86.7%) were early-onset, consistent with LS. In 19 patients with early-onset MPCs, loss of function (LoF) variants in RECQL5 were more prevalent in non-LS MPC than in matched sporadic cancer patients (OR = 31.6, 2.73-1700.6, p = 0.001). Additionally, there were high-confidence LoF variants at FANCG and CASP8 in two patients accompanied by somatic loss of heterozygosity in tumor, respectively. The results suggest that genetic screening should be considered for synchronous cancers and metachronous MPCs of the LS tumor spectrum, particularly in early-onset. Susceptibility variants in non-LS genes for MPC patients may exist, but evidence for their role is more elusive than for LS patients.

Abstract: Background: WISDOM is a 100,000 healthy women preference-tolerant, pragmatic study comparing traditional annual screening to personalized risk-based breast screening. The novelty of WISDOM personalized screening is the integration of previously validated genetic and clinical risk factors (age, family history, breast biopsy results, ethnicity, mammographic density) into a single risk assessment model that directs the starting age, timing, and frequency of screening. The goal of WISDOM is to determine if personalized screening, compared to annual screening, is as safe, less morbid, enables prevention, and is more accepted by women. The study is registered on ClinicalTrials.gov, NCT02620852. Methods: Women aged 40-74 years with no history of breast cancer or DCIS, and no previous double mastectomy can join the study online at wisdomstudy.org. Participants can either elect randomization or self-select a study arm. Then, they can provide electronic consent and sign the Release for Medical Information via DocuSign. For all participants, 5-year risk of developing breast cancer is calculated according to the Breast Cancer Screening Consortium (BCSC) model. Participants in the personalized arm undergo panel-based mutation testing (BRCA1, BRCA2, TP53, PTEN, STK11, CDH1, ATM, PALB2, and CHEK2), and their 5-year risk is calculated using the BCSC score combined with a Polygenic Risk Score (BCSC-PRS) that includes 75 single nucleotide polymorphisms (SNPs) known to increase breast cancer risk (will increase to 229). The SNPs and mutations are assessed by saliva-based testing through Color Genomics. 5-year risk level thresholds are used to stratify for low-, moderate- and high risk. Risk stratification determines age to start, stop, and frequency of screening. Accrual: As of July 2019, the WISDOM study is open to all eligible women in California, North Dakota, South Dakota, Minnesota, Iowa, Illinois, and New Jersey. To date, 30,392 eligible women have registered, and 21,392 women have consented to participate in the trial. The median age was 56 years. 85% of participants were Caucasian, 2% African-American, and 5% Asian. 6% self-reported Hispanic ethnicity. WISDOM is actively partnering with Blue Cross Blue Shield Association for national coverage, self-insured companies (Salesforce, Genentech, Qualcomm, CalPERS) and Medi-Cal (Inland Empire Health Plan) using a coverage with evidence progression approach. Accrual expansion and diversity: To strengthen generalizability, the WISDOM Study is enhancing the diversity of our potential participant population by expanding to other states (Alabama, Louisiana), and partnering with other health insurers and self-insured companies. Future expansion regions include Texas, Florida, South Carolina, Oklahoma, Montana, and New Mexico. Additionally, we have translated the whole study experience to Spanish to further reach Spanish-speaking communities. With the engagement of patient advocates and community partnerships, expanding diversity recruitment will strengthen our scientific knowledge of breast cancer risk and increase access to personalized breast cancer screening recommendations for all women. WISDOM enrollment will continue through 2020. Conclusions: Results at 5 years will enable us to demonstrate that personalized screening improves healthcare value by reducing screen volumes and costs without jeopardizing outcomes. Citation Format: Mandy Che, Allison Stover Fiscallini, Irene Acerbi, Yiweh Shieh, Lisa Madlensky, Jeffrey Tice, Elad Ziv, Martin Eklund, Amie Blanco, Barry Tong, Deborah Goodman, Lamees Nassereddine, Nancy Anderson, Heather Harvey, Steele Fors, Hannah L Park, Antonia Petruse, Skye Stewart, Janet Wernisch, Larissa Risty, Ian Hurley, Barbara Koenig, Celia Kaplan, Robert Hiatt, Neil Wenger, Vivian Lee, Diane Heditsian, Susie Brain, Leah Sabacan, Barbara Parker, Alexander Borowsky, Hoda Anton-Culver, Hoda Anton-Culver, Arash Naeim, Andrea Kaster, Melinda Talley, Laura van't Veer, Andrea LaCroix, Olufunmilayo I Olopade, Deepa Sheth, WISDOM Study and Athena Breast Health Network Investigators and Advocate Partners and Laura Esserman. Personalized breast cancer screening in a population-based study: Women informed to screen depending on measures of risk (WISDOM) [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 OT3-03-02.

ObjectiveElevated anxiety and breast cancer worry can impede mammographic screening and early breast cancer detection. Genetic advances and risk models make personalized breast cancer risk assessment and communication feasible, but it is unknown whether such communication of risk affects anxiety and disease-specific worry. We studied the effect of a personalized breast cancer screening intervention on risk perception, anxiety, and breast cancer worry.MethodsWomen with a normal mammogram but elevated risk for breast cancer (N = 122) enrolled in the Athena Breast Health risk communication program were surveyed before and after receiving a letter conveying their breast cancer risk and a breast health genetic counselor consultation. We compared breast cancer risk estimation, anxiety, and breast cancer worry before and after risk communication and evaluated the relationship of anxiety and breast cancer worry to risk estimation accuracy.ResultsWomen substantially overestimated their lifetime breast cancer risk, and risk communication somewhat mitigated this overestimation (49% pre-intervention, 42% post-intervention, 13% Gail model risk estimate, P < .001). Both general anxiety and breast cancer worry declined significantly after risk communication in women with high baseline anxiety. Baseline anxiety and breast cancer worry were essentially unrelated to risk estimation accuracy, but risk communication increased alignment of worry with accuracy of risk assessment.ConclusionsPersonalized communication about breast cancer risk was associated with modestly improved risk estimation accuracy in women with relatively low anxiety and less anxiety and breast cancer worry in women with higher anxiety. We detected no negative consequences of informing women about elevated breast cancer risk.

PurposeGI stromal tumors (GISTs) are commonly associated with somatic mutations in KIT and PDGFRA. However, a subset arises from mutations in NF1, most commonly associated with neurofibromatosis type 1. We define the anatomic distribution of NF1 alterations in GIST.MethodsWe describe the demographic/clinicopathologic features of 177 patients from two institutions whose GISTs underwent next-generation sequencing of ≥315 cancer-related genes.ResultsWe initially identified six (9.7%) of 62 GISTs with NF1 genomic alterations from the first cohort. Of these six patients, five (83.3%) had unifocal tumors at the duodenal-jejunal flexure (DJF). Two additional patients with DJF GISTs had non-NF1 (KIT and BRAF) genomic alterations. After excluding one DJF GIST with an NF1 single nucleotide polymorphism, four (57.1%) of seven sequenced DJF tumors demonstrated deleterious NF1 alterations, whereas only one (1.8%) of 55 sequenced non-DJF GISTs had a deleterious NF1 somatic mutation (P < .001). One patient with DJF GIST had a germline NF1 variant that was associated with incomplete penetrance of clinical neurofibromatosis type 1 features along with a somatic NF1 mutation. Of the five DJF GISTs with any NF1 alteration, three (60%) had KIT mutations, and three (60%) had Notch pathway mutations (NOTCH2, MAML2, CDC73). We validated these findings in a second cohort of 115 GISTs, where two (40%) of five unifocal NF1-mutated GISTs arose at the DJF, and one of these also had a Notch pathway mutation (EP300).ConclusionBroad genomic profiling of adult GISTs has revealed that NF1 alterations are enriched in DJF GISTs. These tumors also may harbor concurrent activating KIT and/or inactivating Notch pathway mutations. In some cases, germline NF1 genetic testing may be appropriate for patients with DJF GISTs.

Oncology guidelines clearly outline evidence-based recommendations for patients with newly diagnosed cancer to help oncologists determine which patients are appropriate for a genetic assessment. Ideally, patients with newly diagnosed cancer, who have personal or family histories suggestive of hereditary cancer predisposition, are referred for genetics work up in the nonurgent setting. However, in some cases, a genetics work up is delayed until the end of life. This is a time of heightened stress and additional obstacles, including discordance between family members regarding the obtainment of genetic information, paying for testing, selecting a surrogate to receive and disperse information in the case of a patient's death, and the use of DNA banking for future evaluation. To meaningfully participate and support patients, family members, and our colleagues facing requests at the end of life for genetic testing, we provide a practical approach and highlight resources to effectively engage in this rising challenge.

BackgroundAbout 10-15% of adult, and most pediatric, gastrointestinal stromal tumors (GIST) lack mutations in KIT, PDGFRA, SDHx, or RAS pathway components (KRAS, BRAF, NF1). The identification of additional mutated genes in this rare subset of tumors can have important clinical benefit to identify altered biological pathways and select targeted therapies.MethodsWe performed comprehensive genomic profiling (CGP) for coding regions in more than 300 cancer-related genes of 186 GISTs to assess for their somatic alterations.ResultsWe identified 24 GIST lacking alterations in the canonical KIT/PDGFRA/RAS pathways, including 12 without SDHx alterations. These 24 patients were mostly adults (96%). The tumors had a 46% rate of nodal metastases. These 24 GIST were more commonly mutated at 7 genes: ARID1B, ATR, FGFR1, LTK, SUFU, PARK2 and ZNF217. Two tumors harbored FGFR1 gene fusions (FGFR1-HOOK3, FGFR1-TACC1) and one harbored an ETV6-NTRK3 fusion that responded to TRK inhibition. In an independent sample set, we identified 5 GIST cases lacking alterations in the KIT/PDGFRA/SDHx/RAS pathways, including two additional cases with FGFR1-TACC1 and ETV6-NTRK3 fusions.ConclusionsUsing patient demographics, tumor characteristics, and CGP, we show that GIST lacking alterations in canonical genes occur in younger patients, frequently metastasize to lymph nodes, and most contain deleterious genomic alterations, including gene fusions involving FGFR1 and NTRK3. If confirmed in larger series, routine testing for these translocations may be indicated for this subset of GIST. Moreover, these findings can be used to guide personalized treatments for patients with GIST. Trial registration NCT 02576431. Registered October 12, 2015.

Some communities and populations lack access to genetic cancer risk assessment (GCRA) and testing. This is particularly evident in safety-net institutions, which serve a large segment of low-income, uninsured individuals. We describe the experience of a safety-net clinic with limited resources in providing GCRA and BRCA1/2 testing. We compared the proportion and characteristics of high-risk women who were offered and underwent GCRA and genetic testing. We also provide a description of the mutation profile for affected women. All 125 patients who were offered GCRA accepted to undergo GCRA. Of these, 72 % had a breast cancer diagnosis, 70 % were Hispanic, 52.8 % were non-English speakers, and 66 % did not have health insurance. Eighty four (67 %) were offered genetic testing and 81 (96 %) agreed. Hispanic women, those with no medical insurance, and those with a family history of breast cancer were significantly more likely to undergo testing (p > 0.01). Twelve of 81 (15 %) patients were found to have deleterious mutations, seven BRCA1, and five BRCA2. Our experience shows that it is possible to offer GCRA and genetic testing even in the setting of limited resources for these services. This is important given that a large majority of the low-income women in our study agreed to undergo counseling and testing. Our experience could serve as a model for similar low-resource safety-net health settings.

BackgroundMost gastrointestinal stromal tumors (GISTs) are considered nonhereditary or sporadic. However, single-institution studies suggest that GIST patients develop additional malignancies at increased frequencies. It was hypothesized that greater insight could be gained into possible associations between GISTs and other malignancies with a national cancer database inquiry.MethodsPatients diagnosed with GISTs (2001-2011) in the Surveillance, Epidemiology, and End Results database were included. Standardized prevalence ratios (SPRs) and standardized incidence ratios (SIRs) were used to quantify cancer risks incurred by GIST patients before and after GIST diagnoses, respectively, in comparison with the general US population.ResultsThere were 6112 GIST patients, and 1047 (17.1%) had additional cancers. There were significant increases in overall cancer rates: 44% (SPR, 1.44) before the GIST diagnosis and 66% (SIR, 1.66) after the GIST diagnosis. Malignancies with significantly increased occurrence both before and after diagnoses included other sarcomas (SPR, 5.24; SIR, 4.02), neuroendocrine-carcinoid tumors (SPR, 3.56; SIR, 4.79), non-Hodgkin lymphoma (SPR, 1.69; SIR, 1.76), and colorectal adenocarcinoma (SPR, 1.51; SIR, 2.16). Esophageal adenocarcinoma (SPR, 12.0), bladder adenocarcinoma (SPR, 7.51), melanoma (SPR, 1.46), and prostate adenocarcinoma (SPR, 1.20) were significantly more common only before the GIST diagnosis. Ovarian carcinoma (SIR, 8.72), small intestine adenocarcinoma (SIR, 5.89), papillary thyroid cancer (SIR, 5.16), renal cell carcinoma (SIR, 4.46), hepatobiliary adenocarcinoma (SIR, 3.10), gastric adenocarcinoma (SIR, 2.70), pancreatic adenocarcinoma (SIR, 2.03), uterine adenocarcinoma (SIR, 1.96), non-small cell lung cancer (SIR, 1.74), and transitional cell carcinoma of the bladder (SIR, 1.65) were significantly more common only after the GIST diagnosis.ConclusionsThis is the first population-based study to characterize the associations and temporal relations between GISTs and other cancers by both site and histological type. These associations may carry important clinical implications for future cancer screening and treatment strategies.

Familial breast and ovarian cancer prevalence was assessed among 1150 women of Mexican descent enrolled in a case-only, binational breast cancer study. Logistic regression was conducted to compare odds of triple negative breast cancer (TNBC) to non-TNBC according to family history of breast and breast or ovarian cancer among 914 of these women. Prevalence of breast cancer family history in a first- and first- or second-degree relative was 13.1% and 24.1%, respectively; that for breast or ovarian cancer in a first-degree relative was 14.9%. After adjustment for age and country of residence, women with a first-degree relative with breast cancer were more likely to be diagnosed with TNBC than non-TNBC (OR=1.98; 95% CI, 1.26-3.11). The odds of TNBC compared to non-TNBC were 1.93 (95% CI, 1.26-2.97) for women with a first-degree relative with breast or ovarian cancer. There were non-significant stronger associations between family history and TNBC among women diagnosed at age

ObjectiveLymphedema is a distressing and chronic condition affecting up to 30% of breast cancer survivors. Using a cross-sectional study design, we examined the impact of self-reported lymphedema-related distress on psychosocial functioning among breast cancer survivors in the Women's Healthy Eating and Living Study. The Women's Healthy Eating and Living Study has a dataset that includes self-report data on lymphedema status, symptoms, and distress.MethodsChi-square tests and binary logistic regression models were used to examine how specific participant characteristics, including lymphedema-related distress, were associated with physical health and mental health as measured by the SF-36-Item Health Survey and depressive symptoms assessed by the Center for Epidemiologic Studies Depression Scale screening form.ResultsOf the 2431 participants included in the current study population, 692 (28.5%) self-reported ever having lymphedema. A total of 335 (48.9%) women reported moderate to extreme distress as a result of their lymphedema and were classified as having lymphedema-related distress. The logistic regression models showed that women with lymphedema-related distress had 50% higher odds of reporting poor physical health (p = 0.01) and 73% higher odds of having poor mental health (p

PurposeLimited information exists on breast cancer patients' compliance to attend outpatient appointments with an occupational therapy (OT) lymphedema specialist. The objectives of this study were (1) to examine patient compliance with a health care provider referral for an OT lymphedema consult and (2) to identify potential barriers to compliance.MethodsA retrospective chart review of female breast cancer patients at the UC San Diego Health System was conducted. Electronic medical records were queried for breast cancer patients, who received a health care provider referral for an OT lymphedema consult between June 1, 2010 and December 31, 2011. Descriptive statistics and Fisher's exact chi-square tests were used to examine how specific participant characteristics were associated with attending an OT appointment.ResultsA total of 210 female patients received an OT referral from a health care provider related to their breast cancer diagnosis. Forty-three (20.5%) patients did not attend an OT appointment. Non-attenders were more likely to have had fewer lymph nodes removed (P

Abstract Introduction The increasing number of targeted therapies, together with a deeper understanding of cancer genetics and drug response, have prompted major healthcare centers to implement personalized treatment approaches relying on high-throughput tumor DNA sequencing. However, the optimal way to implement this transformative methodology is not yet clear. Current assays may miss important clinical information such as the mutation allelic fraction, the presence of sub-clones or chromosomal rearrangements, or the distinction between inherited variants and somatic mutations. Here, we present the evaluation of ultra-deep targeted sequencing (UDT-Seq) to generate and interpret the molecular profile of 38 breast cancer patients from two academic medical centers. Methods We sequenced 47 genes in matched germline and tumor DNA samples from 38 breast cancer patients. The selected genes, or the pathways they belong to, can be targeted by drugs or are important in familial cancer risk or drug metabolism. Results Relying on the added value of sequencing matched tumor and germline DNA and using a dedicated analysis, UDT-Seq has a high sensitivity to identify mutations in tumors with low malignant cell content. Applying UDT-Seq to matched tumor and germline specimens from the 38 patients resulted in a proposal for at least one targeted therapy for 22 patients, the identification of tumor sub-clones in 3 patients, the suggestion of potential adverse drug effects in 3 patients and a recommendation for genetic counseling for 2 patients. Conclusion Overall our study highlights the additional benefits of a sequencing strategy, which includes germline DNA and is optimized for heterogeneous tumor tissues.

This is an exploratory, qualitative investigation of breast cancer survivors’ experiences with breastfeeding. Previous studies have focused on the physiology of lactation after surgery and treatment, but have not explored factors influencing breastfeeding decisions and behavior.We used purposeful sampling to identify 11 breast cancer survivors who had a child after their diagnosis and treatment. Participants were recruited from among those in the Women’s Healthy Eating and Living (WHEL) study and a Young Survival Coalition (YSC) affiliate. We conducted semi-structured, open-ended telephone interviews lasting 45–75 min. We used social cognitive theory (SCT) to structure questions regarding influences on breastfeeding behavior. We transcribed interviews and used cross-case, inductive analysis to identify themes.Ten of 11 participants initiated breastfeeding. The following main themes emerged: 1) Cautiously hopeful, 2) Exhausting to rely on one breast, 3) Motivated despite challenges, 4) Support and lack of support, and 5) Encouraging to others.Study participants were highly motivated to breastfeed but faced considerable challenges. Participants described problems that are not unique to women with breast cancer, but experienced these to a much greater degree because they relied mostly or entirely on one lactating breast. This study revealed a need for improved access to information and support and greater sensitivity to the obstacles faced by breast cancer survivors.Results of this qualitative analysis indicate that interventions to support the efforts of breast cancer survivors who are interested in breastfeeding are warranted. Additional research would aid in the development of such interventions.

We examined the effect of dietary energy density change on body weight in participants of a randomized trial. Intervention participants markedly increased fruit and vegetable intake while reducing energy intake from fat. Participants were 2,718 breast cancer survivors, aged 26-74 yr, with baseline mean body mass index of 27.3 kg/m(2) (SD = 6.3). We assessed dietary intake by sets of four 24-h dietary recalls and validated with plasma carotenoid concentrations. Weight and height were measured at baseline, 1 yr, and 4 yr. Dietary energy density was calculated using food but excluding beverages. Intervention participants significantly reduced dietary energy density compared to controls and maintained it over 4 yr-both in cross-sectional (P < 0.0001) and longitudinal (Group x Time interaction, P < 0.0001) analyses. Total energy intake or physical activity did not vary between groups. The intervention group had a small but significant weight loss at 1 yr (Group x Time interaction, P < 0.0001), but no between-group weight difference was observed at 4 yr. Our study showed that reducing dietary energy density did not result in a reduction in total energy intake and suggests that this strategy alone is not sufficient. to promote long-term weight loss in a free-living population.

Background: Impaired DNA damage response (DDR) can affect immune checkpoint inhibitors (ICI) efficacy and lead to heightened immune activation. We assessed the impact of pathogenic or likely pathogenic (P/LP) germline DDR mutations on ICI response and toxicity. Materials and methods: A retrospective analysis of 131 cancer patients with germline DNA testing and ICI treatment was performed. Results: Ninety-two patients were DDR-negative (DDR-), and 39 had =1 DDR mutation (DDR+). DDR+ patients showed higher objective response rates (ORRs) compared to DDR- in univariate and multivariable analyses, adjusting for age and metastatic disease (62% vs. 23%, unadjusted OR = 5.41; 95% CI, 2.41-12.14; adjusted OR 5.94; 95% CI, 2.35-15.06). Similar results were seen in mismatch repair (MMR), DDR pathways with intact MMR (DDR+MMRi), and homologous recombination (HR) subgroups versus DDR- (adjusted OR MMR = 24.52; 95% CI 2.72-221.38, DDR+MMRi = 4.26; 95% CI, 1.57-11.59, HR = 4.74; 95% CI, 1.49- 15.11). DDR+ patients also had higher ORRs with concurrent chemotherapy (82% vs. 39% DDR-, p=0.03) or concurrent tyrosine kinase inhibitors (50% vs. 5% DDR-, p=0.03). No significant differences in immune-related adverse events were observed between DDR+ and DDR- cohorts. Conclusion: P/LP germline DDR mutations may enhance ICI response without significant additional toxicity. [ABSTRACT FROM AUTHOR]

This case study focuses on a video telehealth consult to discuss genetic testing results. Participants include a Genetic Counselor (GC) and a Patient (P) previously diagnosed with ovarian cancer who is currently undergoing chemotherapy treatments. Utilizing conversation analysis (CA), attention is first given to a series of interactional dilemmas as GC delivers and P responds to negative, uncertain, and complex test results. Specific findings address practices employed by GC to structure the encounter and establish authority, impacts on P's participation and understandings, recurring and at times problematic orientations to "negative" findings, and inherent ambiguities faced by GC and P when attempting to discern good and bad news. Close examination of these moments provides a unique opportunity to identify, describe, and explain genetic counseling as a co-produced, interactional achievement. These findings are then integrated with patient's post-counseling survey (susceptibility, anxiety, uncertainty, fear, and hope), including reported experiences which broaden understandings of the interactional environment. Specific recommendations are raised for improving counseling skills, enhancing patients' understandings, and building therapeutic alliances addressing both patients' emotional circumstances and the complexities of genetic test results. [ABSTRACT FROM AUTHOR]

Byline: Gordon A. Saxe, MD, PhD (Department of Family and Preventive Medicine, University of California San Diego, La Jolla, Moores UCSD Cancer Center, Cancer Prevention and Control, University of California [...]