Early-stage Breast Cancer Survivors Research Articles

Prediction models of persistent taxane-induced peripheral neuropathy among breast cancer survivors using whole-exome sequencing

Persistent taxane-induced peripheral neuropathy (TIPN) is highly prevalent among early-stage breast cancer survivors (ESBCS) and has detrimental effect on quality of life. We leveraged logistic regression models to develop and validate polygenic prediction models to estimate the risk of persistent PN symptoms in a training cohort and validation cohort taking clinical risk factors into account. Based on 337 whole-exome sequenced ESBCS two of five prediction models for individual PN symptoms obtained AUC results above 60% when validated. Using the model for numbness in feet (35 SNVs) in the test cohort, 73% survivors were correctly predicted. For tingling in feet (55 SNVs) 70% were correctly predicted. Both models included SNVs from the ADAMTS20, APT6V0A2, CCDC88C, CYP2C8, EPHA5, NR1H3, PSKH2/APTV0D2, and SCN10A genes. For cramps in feet, difficulty climbing stairs and difficulty opening a jar the validation was unsuccessful. Polygenic prediction models including clinical risk factors can estimate the risk of persistent taxane-induced numbness in feet and tingling in feet in ESBCS.

Abstract PO4-14-05: Germline and acquired genetic variants and long-term cancer-related fatigue among survivors of early-stage breast cancer (BC)

Abstract BACKGROUND: Previous studies suggested that bio-behavioral models explain part of the variability of cancer-related fatigue, and pro-inflammatory and age-related processes emerged as contributors to persistent fatigue. However, the biological underpinnings of this complex symptom, including its relevant genomic correlates, are still poorly understood. We aimed to comprehensively explore the association of genetic variants with long-term cancer-related fatigue. METHODS: We used the prospective, multicenter, longitudinal CANcer TOxicity cohort, enrolling patients at diagnosis of stage I-III BC (NCT01993498). Outcomes included severe (≥40/100) global (EORTC QLQ-C30) as well as physical, emotional, and cognitive (FA12) fatigue at year (Y)1, Y2, and Y4 after BC diagnosis. Applying a hypothesis-driven approach, we investigated (i) germline genetic variants in a pre-specified Genetic Risk Index (GRI) assaying expression-regulating single nucleotide polymorphisms (SNPs) in the promoter regions of 3 pro-inflammatory cytokine genes (IL1B [rs16944], IL6 [rs1800795], and TNF [rs1800629]; Bower J, JCO 2013; N=9035), and (ii) age-related expansions of hematopoietic clones carrying recurrent acquired mutations, commonly defined as clonal hematopoiesis of indeterminate potential (CHIP; NGS with unique molecular identifiers for 17 genes [including DNMT3A, TET2, ASXL1, PPM1D, ATM, JAK2, and TP53]; N=1219). The contribution of GRI and CHIP to fatigue was assessed by multivariable logistic regression models. Taking an agnostic approach, we then performed a genome-wide association study (GWAS) of fatigue and 1,894,511 germline SNPs (Illumina InfiniumExome24/Illumina GSA24; N=9056). All genetic variants were assessed at BC diagnosis. Tested associations were adjusted by validated clinical predictors (Di Meglio A, JCO 2022). RESULTS: In the overall cohort (N=9056) mean age was 56.5 years (SD 11.2), 51.0% had stage II or III BC, 52.6% received chemotherapy, and 82.1% endocrine therapy. The prevalence of severe fatigue was 26.1% at diagnosis and increased to 36.5%, 34.3%, and 32.6% at Y1, Y2, and Y4 after diagnosis, respectively. Most patients (77.4%) had 3-6 high-frequency alleles across the 3 SNPs in the pro-inflammatory GRI. Among patients with available CHIP data, 15.2% and 3.7% had a Variant Allele Frequency (VAF) >2% and >10%, respectively. The pro-inflammatory GRI was not associated with fatigue outcomes. We found significant associations between CHIP and severe long-term global fatigue at Y4 (adjusted OR [95%CI]: VAF ≥2% vs < 2%, 1.64 [1.08-2.51], p=0.021; VAF ≥10% vs < 10%, 2.22 [1.00-4.94], p=0.050). The GWAS identified several regions (each including ≥2 SNPs) as associated with severe fatigue outcomes (suggestive p-value cut-off < 5 × 10−5; see Table for number of identified regions by outcome and respective nearby genes). Overlap in biological pathways was observed in some of the gene regions associated with global and physical fatigue, but not for emotional or cognitive fatigue. Common biological processes that were associated (FDR < 0.05) with such genes included synaptic transmission, hemoglobin-oxygen binding, and response to stress. CONCLUSIONS: This study provides suggestive association data between gene variants and long-term cancer-related fatigue. While previously reported associations with pro-inflammatory GRI were not confirmed, some biological processes that may inform the mechanistic understanding of this symptom emerged, including associations with aging and response to stress that warrant further exploration. ///: marks different regions. All association analyses were adjusted by age, body mass index, smoke behavior, pre-treatment fatigue, pain, insomnia, and anxiety, and by the first ten axes of principal component analysis of the genetic data to control for population stratification. There was no overlap in biological pathways for the gene regions associated with emotional or cognitive fatigue (gene regions not shown). Table. Genes in proximity of regions associated with severe fatigue outcomes Citation Format: Antonio Di Meglio, Emilie Thomas, Youenn Drouet, Jean-Baptiste Micol, Davide Soldato, Maria Alice Franzoi, Martina Pagliuca, Julie Havas, Anne-Laure Martin, Sibille Everhard, Celine Besse, Anne Boland, Christophe Marzac, Nathalie Droin, Sandrine Boyault, Marina Rousseau, Olivier Trédan, Paul Cottu, Christelle Jouannaud, Marion Fournier, Laurence Vanlemmens, Charles Coutant, Asma Dhaini Merimeche, Baptiste Sauterey, Florence Joly, Mario Campone, Florence Lerebours, Marie-Ange Mouret-Reynier, Olivier Rigal, Thierry Petit, Sophie Guillermet, Antoine Arnaud, Mahmoud Ibrahim, Sylvie Giacchetti, Florence Dalenc, Johanna Wassermann, Olivier Arsène, Ariane Darut-Jouve, Aurélie Bertaut, Fabrice André, Jean-Francois Deleuze, Alain Viari, Ines Vaz Luis. Germline and acquired genetic variants and long-term cancer-related fatigue among survivors of early-stage breast cancer (BC) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-14-05.

Abstract PO2-11-01: Prevalence of Nonadherence to Endocrine Therapy and Cardiovascular Medications Among Breast Cancer Survivors

Abstract Background: Cardiovascular disease (CVD) and cancer are the two leading causes of death in the U.S, and breast cancer (BC) is the most common cancer among women. Most survivors of early-stage BC are prescribed adjuvant endocrine therapy (ET) to decrease their BC recurrence risk; many of them are also on statins and/or antihypertensives to manage concurrent CVD risk factors. Nonadherence to ET or CVD medications is associated with decreased survival and other poor outcomes, yet little is known about how best to identify nonadherence to multiple classes of medications in BC survivors. Methods: We reviewed pharmacy fill data from our electronic health record (EHR) for a diverse cohort of patients seen in our breast oncology clinic with prescriptions for ET and CVD medications (statin and/or antihypertensive(s)). Patients were excluded if their pharmacy data did not show both an active ET order and an active CVD order or fill. Nonadherence to any medication was defined as proportion of days covered (PDC) < 80% over the previous 180 days. A subset of patients also responded to a patient-reported nonadherence screener administered through our EHR at appointment registration starting in 2/2022. Descriptive statistics were used to determine the prevalence of nonadherence to all medications (defined as PDC< 80% for either ET and/or CVD medications) and for each class of medication separately. We also compared the PDC-based combined nonadherence to the self-reported nonadherence. Results: We identified a total of 1,015 BC survivors on ET and CVD medications last seen in clinic between 2/1/2020 and 6/6/2023 (mean age 69 yo; 23.6% non-Hispanic White, 11.3% non-Hispanic Black, and 38.9% Hispanic). Of these, 567 (55.9%) were prescribed ET and statins, and 745 (73.4%) were prescribed ET and antihypertensives. With nonadherence defined as PDC< 80% for any medication (ET and/or CVD medications), the nonadherence prevalence was 38.4%. The nonadherence prevalence by medication class was slightly lower for ET (20.7%) than for statins (25.9%) and antihypertensives (25.0%). Among patients on ET and statins, 10.1% were nonadherent to both medications and 24.3% were nonadherent to only 1 class of medications; the proportion of patients nonadherent to ET only was almost half that of patients nonadherent to statins only (8.5% vs 15.9%). A similar trend was observed among patients on ET and antihypertensives: 10.3% were nonadherent to both classes of medications and 26.2% were nonadherent to only 1 class of medications, with 11.5% of patients nonadherent to ET only and 14.6% nonadherent to antihypertensives only. Of the 1,015 patients, 390 (38.4%) responded to the nonadherence screener between 2/16/2022 and 6/6/2023, of which 93 (23.8%) reported any level of medication nonadherence. Among these, 57 (61.3%) had PDC≥ 80% and thus were categorized as adherent under our PDC-based adherence determination. Of the 297 patients who self-reported adherence to all medications on the screener, 32.3% had PDC< 80% for any medication. When combining nonadherence by PDC and self-report, the overall nonadherence rate for the 390 patients who responded to the screener was considerably higher at 48.5% (vs 33.8% by PDC only and 23.8% by self-report only). Conclusions: EHR-based screening can identify patients with or at risk for medication nonadherence for targeted interventions. Using a combined approach of pharmacy fill data and patient reports, close to 50% of patients were identified as having nonadherence to at least 1 medication. Nonadherence to statins and antihypertensives was more common than nonadherence to ET, which is concerning as early-stage BC survivors are more likely to die from CVD than BC. Interventions to improve adherence to multiple classes of medications are warranted in this population. Citation Format: Claire Sathe, David DeStephano, Shing Lee, Melissa Beauchemin, Nadia Liyanage-Don, Melissa Accordino, Katherine Crew, Ian Kronish, Dawn Hershman. Prevalence of Nonadherence to Endocrine Therapy and Cardiovascular Medications Among Breast Cancer Survivors [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-11-01.

Dietary Composition, Meal Timing, and Cancer-Related Fatigue: Insights From the Women's Healthy Eating and Living Study.

Cancer-related fatigue is difficult to treat, and dietary interventions are promising yet underused. We explored associations between dietary patterns and fatigue, and the effect of a dietary intervention versus control on fatigue using Women's Healthy Eating and Living study data, plus mediators and moderators of the intervention effect. The Women's Healthy Eating and Living study was a randomized controlled trial among early-stage breast cancer survivors. The 4-year intervention encouraged fruits, vegetables, fiber, and 15% to 20% calories from fat. Fatigue outcomes included a 9-item energy scale and a single-item tiredness question. Dietary quality was estimated using a modified Healthy Eating Index (24-hour dietary recall) and serum carotenoid concentrations. Nutrient timing was obtained from 4-day food logs. Among 2914 total participants, lower body mass index was associated with less tiredness and more energy at baseline (P < .001 for both). Earlier start and end times for daily eating windows were associated with less tiredness (P = .014 and P = .027, respectively) and greater energy (P = .006 and P = .102, respectively). The intervention did not lead to improvements in fatigue on average (P > .125). However, the intervention was more effective for participants who were younger, had fewer comorbidities, and did not have radiation treatment. Mediators included increases in serum carotenoids, increases in the modified Healthy Eating Index, and weight loss/maintenance. Diet quality and earlier eating windows were associated with less fatigue. Programs that encourage high diet quality and a morning meal and discourage nighttime eating should be tested for efficacy in reducing cancer-related fatigue in survivorship.

Health-related quality of life in long-term early-stage breast cancer survivors compared to general population in Korea.

This study assessed health-related quality of life (HRQoL) of long-term breast cancer (BC) survivors diagnosed at early stages and compare with cancer-free, age-matched women. The study population included BC survivors diagnosed with ductal carcinoma in situ (DCIS) or breast cancer stages I-II, who had undergone lumpectomy/mastectomy, with time since diagnosis ranging from 9 to 16years. Survey was conducted at two tertiary hospitals in 2020. Data for cancer-free female controls was randomly drawn from a population-based survey and age-, education-matched with 1 case: 3 controls ratio. Self-reported HRQoL was assessed using EQ-5D with five dimentions. EQ-5D utility index score was calculated. Difference in EQ-5D score was evaluated using the Tobit regression model with adjustment for other covariates. Of 273 survivors. 88% and 12% underwent mastectomy and lumpectomy, respectively. The mean (standard deviation, SD) age at survey was 57.3 (8.5) years old. BC survivors reported significantly more problems performing daily activities (11% vs. 5%, p < 0.001), pain/discomfort (46% vs. 23%, p < 0.001), and anxious/depressed feelings (44% vs. 8%, p < 0.001) relative to the controls. Difference in EQ-5D score between BC survivors and the general population was higher in older age groups. The overall EQ-5D score of BC survivors was statistically lower than that of the control subjects (adjusted [Formula: see text]=0.117, p < 0.001). Long-term BC survivors who survived beyond ten years post-diagnosis experience more pain, anxiety, and distress, leading to an overall poorer HRQoL. This study suggest the importance of follow-up care, particularly focusing on pain, anxiety, and distress management to enhance the HRQoL of long-term BC survivors.

Experiences of everyday discrimination and use of online resources in a population-based sample of breast cancer survivors.

318 Background: For many cancer survivors, clinical spaces may not feel safe for support and information seeking. Individuals experiencing more discrimination in their daily lives may be more likely to seek resources online. Given the varying quality of online resources, understanding this relationship is important as it may exacerbate existing breast cancer survivorship disparities. Methods: The iCanCare study is a longitudinal study of women diagnosed with breast cancer in 2014-15 identified in the Los Angeles and Georgia Surveillance, Epidemiology and End Results registries. Women were surveyed during initial treatment and again 6 years later in survivorship (2021-22) (Expected final N=1430, 60% current response rate). Respondents were asked about the frequency of 5 types of perceived discrimination in the past 12 months using the short Everyday Discrimination scale. Responses were averaged to generate a mean discrimination frequency (range: 0 (never) - 5 (almost every day)). Respondents were also asked, in the past 12 months 1) how often they had looked online for medical information related to their breast cancer follow-up care and 2) how often they had used social medial to offer or receive support for breast cancer related issues. Responses were categorized into never vs. any. The associations between everyday discrimination and dependent variables 1) online information seeking and 2) online support seeking were evaluated using multivariable-adjusted logistic regression models adjusted for demographics and socioeconomic status. Results: In this sample of 1,058 women with complete responses, 42.2% reported seeking medical information related to survivorship care online and 22.0% reported seeking online support related to their breast cancer. Being treated with less respect than other people (24.3%) and people acting as if they think you are not smart (20.2%) were the most experienced types of discrimination, but “never” was the most common frequency for each type of discrimination. The mean discrimination frequency across the sample was 0.25 (range: 0 (never)-4.2 (once a week)). Mean discrimination frequency was highest in black women (mean=0.35), Latina women (mean=0.31), and people with no insurance (mean=0.49) (P&lt;0.01). In the adjusted model, a one-unit increase in average discrimination frequency was associated with 50% higher odds of online information seeking (OR 1.52 CI 1.16, 1.99) and twice the odds of using social media for breast cancer support (OR 2.15 CI 1.31, 3.52). Conclusions: In this sample of early-stage breast cancer survivors, more frequent experiences of discrimination were associated with higher likelihood of online information and support seeking for breast cancer. Future work delineating the validity of information sources for patients is needed to prevent worsening disparities.

The association of cancer-related fatigue on the social, vocational and healthcare-related dimensions of cancer survivorship.

Cancer-related fatigue (CRF) is well documented in cancer survivors, but little is known about the personal and societal impact of CRF. This study aimed to examine the impact of CRF in relation to social and vocational functioning and health care utilization in a large sample of post-treatment cancer survivors. We conducted a cross-sectional descriptive study of early stage breast and colorectal cancer survivors (n = 454) who were within 5 years from treatment completion. Social difficulties (SDI-21), work status, absenteeism and presenteeism (WHO-HPQ) and healthcare utilization (HSUQ) were compared in those with (CFR +) and without (CRF -) clinically significant fatigue (FACT-F ≤ 34). A total of 32% met the cut-off criteria for CRF (≤ 34). Participants with CRF + had significantly higher scores on the SDI-21 across all domains and 55% of CRF + vs. 11% in CRF - was above the SDI cut-off (> 10) for significant social difficulties. Participants with CRF + were 2.74 times more likely to be unemployed or on leave (95% CI 1.62, 4.61, p < 0.001). In the subgroup of participants who were currently working (n = 249), those with CRF + reported working on average 27.4 fewer hours in the previous 4 weeks compared to CRF - (p = 0.05), and absolute presenteeism was on average 13% lower in the CRF + group (95% CI 8.0, 18.2, p < 0.001). Finally, individuals with CRF + reported significantly more physician (p < 0.001), other health care professional (p = 0.03) and psychosocial visits (p = 0.002) in the past month. CRF is associated with substantial disruption in social and work role functioning in the early transitional phase of cancer survivorship. Better management of persistent CRF and funding for the implementation of existing guidelines and recommended evidence-based interventions are urgently needed.

Primary care provider attitudes about and tendency to use non-recommended surveillance tests after curative breast cancer treatment.

Little is known about the factors contributing to the receipt of non-recommended surveillance testing among early-stage breast cancer survivors. We assessed primary care providers (PCP) attitudes about and tendency to order non-recommended surveillance testing for asymptomatic early-stage breast cancer survivors post-adjuvant chemotherapy. A stratified random sample of PCPs identified by early-stage breast cancer survivors were surveyed (N = 518, 61% response rate). PCPs were asked how likely they would be to order bone scans, imaging and/or tumor marker testing using a clinical vignette of an early-stage asymptomatic patient where these tests are non-recommended. A composite tendency to order score was created and categorized by tertiles (low, moderate, high). PCP-reported factors associated with high and moderate tendency to order non-recommended testing (vs. low) were estimated using multivariable, multinomial logistic regression. In this sample, 26% reported a high tendency to order non-recommended surveillance tests during survivorship for early-stage breast cancer survivors. PCPs who identified as family practice physicians and PCPs reporting more confidence in ordering surveillance testing were more likely to report a high tendency to order non-recommended testing (vs. low) ((aOR family practice 2.09, CI 1.2, 3.8; aOR more confidence 1.9, CI 1.1, 3.3). In this population-based sample of PCPs caring for breast cancer survivors, over a quarter of PCPs reported they would order non-recommended surveillance testing for asymptomatic early-stage breast cancer survivors. Efforts to better support PCPs and disseminate information about appropriate surveillance for cancer survivors are warranted.

Fear of cancer recurrence eight years after early-stage breast cancer – results from a national survey

Background Fear of cancer recurrence (FCR) in breast cancer survivors (BCSs) is common, associated with reduced quality of life and effective interventions exist. There are knowledge gaps concerning FCR among long-term, early-stage BCSs and its associations with other late effects. Within a national cohort, we explored these knowledge gaps, with the ultimate aim of improved care for BCSs experiencing long-term FCR. Methods In this cross-sectional study, all BCSs aged 20–65 years with early-stage breast cancer in 2011–2012 (n = 2803), were identified by the Cancer Registry of Norway in 2019 and mailed a survey including the Assessment of Survivor Concerns used to measure FCR. Factors associated with moderate/high FCR (defined as a sum score of ≥ 6 of a possible range 3–12, or a single score on one of the items of ≥ 3) were explored using a three-block regression analyses including relevant sociodemographic-, health- and cancer-related variables. Results In total, 1311 BCSs were included (47%). Median age at survey was 60 years. Fifty-six % reported moderate-to-high FCR, associated with younger age (OR 0.96, 95% CI 0.95–0.97) and receiving chemo- and endocrine therapy (OR 1.59, 95% CI 1.15–2.20). After adding late effects into the model, FCR remained significantly associated with these variables, in addition to sleep disturbances (OR 1.58, 95% CI 1.18–2.10). In the final block, adding mental distress, FCR remained significantly associated with younger age (OR 0.97, 95% CI 0.96–0.99), receiving chemo- and endocrine therapy (OR 1.14, 95% CI 1.00–1.97), sleep disturbances (OR 1.44, 95% CI 1.08–1.94) and anxiety (OR 2.67, 95% CI 1.38–5.19). Conclusions FCR was prevalent eight years after early-stage breast cancer. Being younger, receiving intensive treatment, experiencing sleep disturbances and/or anxiety were associated with moderate/high FCR. Addressing FCR should be part of standard follow-up care of long-term BCSs.

Associations between body mass index with cancer recurrence and all-cause mortality among survivors of breast cancer.

12074 Background: It is widely recognized that obesity is associated with increased breast cancer incidence. While body mass index (BMI) does not capture measures of body composition, it is routinely collected during clinical care. However, we do not know whether BMI at breast cancer diagnosis affects cancer recurrence or all-cause mortality. This study aims to investigate the associations between clinical categories of BMI, cancer recurrence, and all-cause mortality in this population. Methods: All breast cancer survivors treated at Northwestern Medicine on or after 1/1/2005 were included. We applied the WHO classification of BMI (kg/m2): underweight ( &lt; 18.5), normal (18.5-24.9), overweight (25-29.9), class I obesity (30-34.9), class II obesity (35-39.9), and class III obesity (≥ 40). Cox proportional hazards models were used to determine the associations between BMI category at baseline and cancer recurrence plus all-cause mortality for breast cancer survivors. Models were adjusted for potential confounders including age, gender, race, ethnicity, histological grade, clinical stage, chemotherapy use, smoking, alcohol use, history of coronary artery disease, and history of Diabetes Mellitus. Results: Among all the 20,322 breast cancer survivors, 1,371 all-cause deaths and 1,183 cancer recurrences were observed. For patients aged 55 and above at diagnosis, there were 964 deaths and 632 cancer among 11,818 cases. When compared with a normal BMI (18.5-24.9), a BMI of 40 and above is associated with a higher risk of all-cause mortality among stage 1 breast cancer survivors (HR 1.90, 95 % CI 1.17-3.09), whereas a BMI of lower than 18.5 is associated with a higher risk of all-cause mortality among stage 4 breast cancer patients (HR 3.21, 95 % CI 1.24-8.30). For cancer recurrence, when compared with a normal BMI (18.5-24.9), a BMI of 40 and above is associated with a higher risk of cancer recurrence among stage 0 breast cancer survivors (HR 3.78, 95 % CI 1.21-11.81) and a BMI of 35 to 39.9 is associated with a higher risk of cancer recurrence among stage 3 breast cancer patients (HR 1.91, 95 % CI 1.01-3.61). We did not observe effect modification for either association by age at diagnosis using a cut-point of 55 years, which is considered as reaching postmenopausal status. Conclusions: Higher levels of obesity are associated with a higher mortality risk among early-stage breast cancer survivors whereas underweight is associated with a higher mortality risk for terminal-stage breast cancer. The associations between high-class obesity and increased risk of cancer recurrence were observed among stage 0 and stage 3 breast cancer survivors. These findings emphasize the importance of BMI as a tool for monitoring the health of breast cancer survivors. However, further study is needed to better understand the impact of BMI, and more importantly body composition, on the health and longevity of breast cancer survivors.

Investigation of Factors Affecting Adherence to Adjuvant Hormone Therapy in Early-Stage Breast Cancer Patients: A Comprehensive Systematic Review.

Adherence and persistence to adjuvant hormone therapy (AHT) are seldom maintained among early-stage hormone receptor-positive breast cancer (BC) survivors, despite the significant clinical benefits of long-term AHT. As the factors influencing adherence to AHT remain unclear, this study aimed to comprehensively identify such factors and classify them into specific dimensions. PubMed, Cochrane Library, Embase, PsycINFO, and CINAHL were searched for qualified articles. The search mainly focused on three components: early-stage (0-III) BC, oral AHT administration, and adherence to AHT, with keywords derived from MeSH and entry terms. The factors identified were then classified into six categories based on a modified WHO multidimensional model. Overall, 146 studies were included; the median sample size was 651 (range, 31-40,009), and the mean age of the population was 61.5 years (standard deviation, 8.3 years). Patient- and therapy-related factors were the most frequently investigated factors. Necessity/concern beliefs and self-efficacy among patient-related factors were consistently related to better adherence than depression. Although drug side effects and medication use cannot be modified easily, a refined prescription strategy for the initiation and switching of AHT is likely to increase adherence levels. An effective psychological program that encourages positive views and beliefs about medication and management strategies for each therapy may be necessary to improve adherence to AHT. Social support and a sense of belonging can be enhanced through community participation and social media for better adherence to AHT. Patient-centered communication and appropriate recommendations by physicians may be attributable to better adherence outcomes. Findings from systematically organized factors that influence adherence to AHT may contribute to the establishment of intervention strategies to benefit patients with early-stage BC to achieve optimal health.

Multiscale modeling intervention development and perspectives from early-stage breast cancer survivors on technology to improve long-term adherence to endocrine therapy.

442 Background: Despite the important role of endocrine therapy (ET) in preventing cancer recurrence, rates of long-term adherence are poor among certain breast cancer survivors (BCS). Traditional medication adherence (MA) interventions that have primarily incorporated medication-taking reminders mainly focused on a “one size fits all” approach, which may explain why many interventions have proven unsuccessful. However, when combined with other context, sensors (i.e., wearable sensors, smartphone sensors) can facilitate a better understanding of medication-taking behaviors leading to individualized interventions that are time and context appropriate. The project team is developing a multiscale modeling and intervention (MMI) system designed to improve adherence to ET among BCS. This study describes MMI development. Methods: MMI development has included: 1) usability testing; 2) review of research literature regarding factors associated with ET MA; and 3) a neural network analysis of previously collected ET MA data. In usability testing, 20 BCS were recruited via social media posts to participate in semi-structured usability interviews. Interviews were conducted via videoconferencing and assessed perceptions of and willingness to use an ecological momentary assessment (EMA) smartphone app, smartwatch, smart pill bottle, and smart pill box. The literature review examined multiple systematic reviews to identify constructs associated with ET MA. Randomized neural network analysis with 32 early stage BCS taking ET was used to determine important features of ET MA 4 weeks following completion of a 346-item survey. Four-week medication adherence was measured daily with a medication event monitoring system (MEMS). Results: Usability testing participants were accepting of each technology and willing to use each technology at various frequencies. Forty-two surveys were reviewed as predictors of MA in systematic reviews. Randomized neural network analysis found 104 survey items had absolute weights at the 70th percentile, indicating a strong influence on week 4 ET MA, and 11 surveys were determined theoretically relevant. Conclusions: BCS are willing to use 4 components of the MMI system. The MMI system will soon be deployed for 6 months of data collection. If shown to be effective, the MMI framework can be used by oncologists and researchers to develop personalized interventions focused on understanding and increasing ET MA.

172P Prediction of persistent taxane-induced peripheral neuropathy among early-stage breast cancer survivors using whole-exome sequencing

Persistent taxane-induced peripheral neuropathy (TIPN) among early-stage breast cancer survivors (ESBCS) is common and impacts quality of life. We aimed to explore genetic variants as risk factors. A population-based cohort of 884 residual-free ESBCS in Sweden were sent the EORTC chemotherapy-induced PN (CIPN20), 342 agreed to additional whole-exome sequencing for prediction modelling. Analysis focused on the symptoms tingling and numbness in feet, cramps in feet, difficulty opening a jar and difficulty climbing stairs since these showed highest relative risks compared to controls in our previous studies1 and are of clinical importance (under review). The raw sequencing data was aligned to the human reference genome (GRCh38), quality controls according to standard guidelines using the Genome Analysis Toolkit. The final filtered set included 55150 common genetic variants (MAF ≥ 1%). We adjusted for age, taxane, cumulative dose, time since treatment, BMI, and diabetes mellitus. Prediction models (logistic regression) were based on the single-nucleotide variants (SNVs) and insertions/deletions (INDELs) associated with TIPN in a training set of 70% of the ESBCS (N=237) with planned subsequent validation of the remaining 30%. P-value thresholds for permutations with 50-80% false discovery rates (FDR) was ≤ 0.000875, ≤ 0.001125, ≤ 0.001125, ≤ 0.0005, and ≤ 0.0005 for numbness feet, tingling feet, cramps feet, difficulty opening a jar, and difficulty climbing stairs. Using these thresholds 71, 79, 69, 33, and 46 genetic variants were identified representing in total 282 unique variants. Prediction models developed, reaches a max accuracy of 70-90% (Table).Table: 172PAccuracySensitivitySpecificityNumbness feet79,15%52,46%88,51%Tingling feet80,85%41,27%95,35%Cramps feet75,32%31,94%94,48%Diff opening jar77,64%13,79%98,32%Diff climbing stairs90,72%32,14%98,56% Open table in a new tab Genetic prediction models of persistent TIPN may indicate a genetic risk, which could contribute to more individualised adjuvant treatment decisions. Further analysis is needed and ongoing. 1Engvall BJC 2021.

Impact of persistent peripheral neuropathy on health-related quality of life among early-stage breast cancer survivors: a population-based cross-sectional study

BackgroundWe explored the impact of persistent sensory and motor taxane-induced peripheral neuropathy (TIPN) symptoms on health-related quality of life (HRQL) among early-stage breast cancer survivors (ESBCS).MethodsA population-based cohort of 884 residual-free ESBCS received a postal questionnaire, including the EORTC chemotherapy-induced PN (CIPN20) and the EORTC QLQ-C30 instruments. Mean scores of QLQ-C30 scales among ESBCS with and without TIPN were calculated and adjusted for confounding factors (age, lifestyle factors, co-morbidities; linear regression analyses). Interpretation of QLQ-C30 results were based on guidelines.ResultsResponse rate was 79%, and 646 survivors were included in the analysis. In median, 3.6 (1.5–7.3) years had elapsed post-taxane treatment. All TIPN symptoms had a significant impact on global QoL, which worsened with increased severity of TIPN. Between 29.5% and 93.3% of ESBCS with moderate-severe TIPN reported a clinical important impairment of functioning and personal finances, 64.3–85.7% reporting “difficulty walking because of foot drop,” and 53.1–81.3% reporting “problems standing/walking because of difficulty feeling ground under feet” had impaired functioning/finances. The difference in mean scores between affected and non-affected survivors was highest for “numbness in toes/feet” and “difficulty walking because of foot drop.” Moderate-severe “difficulty climbing stairs or getting out of chair because of weakness of legs” and “problems standing/walking because of difficulty feeling ground under feet” were associated with the largest clinically important differences on all scales.ConclusionPersistent sensory and motor TIPN is associated with clinically relevant impairment of global QoL, functioning, and personal finances among ESBCS, which increased with level of TIPN severity.

Kindness interventions for early-stage breast cancer survivors: An online, pilot randomized controlled trial

ABSTRACT Online interventions that elicit kindness may enhance well-being. We tested the efficacy of three kindness interventions among breast cancer survivors. Participants (N = 137, M age = 62.65 years) were randomized to perform acts of kindness for others, acts of kindness for self, self-kindness meditation, or a daily-activities-writing control and completed three activities each week for 4 weeks. Primary (well-being, depressive symptoms) and secondary outcomes (social support, self-kindness) were assessed pre- and post-intervention. No differences emerged in the primary outcomes. However, relative to controls, participants in the acts of kindness to others condition reported greater increases in social support, and participants in the self-kindness meditation condition reported greater decreases in self-kindness. Among breast cancer survivors, performing prosocial acts may enhance feelings of social support. The two self-kindness conditions yielded either null or detrimental effects, suggesting that further research is needed on best practices for conducting self-focused kindness interventions.

209P Clinically relevant impact of persistent peripheral neuropathy on health-related quality of life among early-stage breast cancer survivors: A population-based study

We explored the impact, and estimated the clinical importance, of sensory and motor Taxane-Induced Peripheral Neuropathy (TIPN) symptoms on Health-Related Quality of Life (HRQOL) among Early-Stage Breast Cancer Survivors (ESBCS).

Pilot study to assess prolonged overnight fasting in breast cancer survivors (longfast)

Retrospective analysis of nightly fasting among women with breast cancer suggests that fasting < 13h may be associated with a higher risk of breast cancer recurrence. We sought to evaluate prolonged overnight fasting (POF), an accessible nonpharmacological intervention, in a prospective feasibility study. We designed a single-arm, pilot study to evaluate the feasibility of fasting for 13h overnight for 12weeks among women with a history of early-stage breast cancer survivors. Baseline and end of study assessments included measurements of body mass index (BMI), blood biomarkers, quality of life (QOL), mood, fatigue, and physical activity. Patient-reported outcome questionnaires were also administered at 6weeks. Feasibility was defined as ≥ 60% of participants documenting fasting for 13h on at least 70% of nights during the study period. Forty women with a history of breast cancer were enrolled with a median age of 60 (range 35-76) and median time since diagnosis of 4.5years (range 0.8-20.7). At baseline, BMI was ≥ 25 in 37.5%. Ninety-five percent of participants fasted ≥ 13h for at least 70% of study days (95% CI 83-99%). There was a statistically significant improvement in anxiety (p = 0.0007) at 6weeks and BMI (p = 0.0072), anxiety (p = 0.0141), depression (p = 0.0048), and fatigue (p = 0.0105) at 12weeks. There was no significant change in overall QOL, physical activity levels, or blood biomarkers at 12weeks. POF is feasible among patients with a history of breast cancer and may potentially improve BMI, mood, and fatigue without detrimental effects on overall QOL.

Cost-Savings Analysis of an Individualized Exercise Oncology Program in Early-Stage Breast Cancer Survivors: A Randomized Clinical Control Trial.

PURPOSE:In an attempt to promote the integration of exercise oncology as a standard part of clinical practice, economic evaluations are warranted. Thus, the purpose of this study was to prospectively analyze cost savings of an individualized exercise oncology program when patients were randomly assigned.METHODS:For this open-label, randomized, prospective, comparative clinical trial, patients with early-stage breast cancer (stage I-II) were randomly assigned into two groups: the control group (CG, n = 120) and the exercise training group (EX, n = 123). Patients in the exercise intervention group completed 12 weeks of prescribed, individualized exercise that aligned with ACSM exercise guidelines for cancer survivors. The CG received the current standard of care, which includes a resource guide with various options available to the cancer survivor.RESULTS:In the EX group, all physical fitness measures significantly improved compared with baseline (P < .001), while remaining unchanged for the CG (P > .05). Patients in the CG had the highest total mean health care utilization across all measures (CG: $8,598 US dollars, compared with EX: $6,356 US dollars) for emergency visits, outpatient visits, and office-base visits that were not a part of their treatment plan. At baseline, the mean Eastern Cooperative Oncology Group (ECOG) scores did not significantly differ (P > .05); however, at follow-up, a larger proportion of the EX group had ECOG scores of 0 or 1, compared with the CG (P < .05). Finally, patient-reported outcomes were significantly higher in the exercise group, compared with the CG at the 12-week follow-up (P < .001).CONCLUSION:A supervised, individualized 12-week exercise intervention led to significant improvements in fitness parameters and ECOG scores, as well as a decrease in unplanned health care utilization among early-stage breast cancer survivors.

Documenting patients\u2019 and providers\u2019 preferences when proposing a randomized controlled trial: a qualitative exploration

BackgroundWith advances in cancer diagnosis and treatment, women with early-stage breast cancer (ESBC) are living longer, increasing the number of patients receiving post-treatment follow-up care. Best-practice survivorship models recommend transitioning ESBC patients from oncology-provider (OP) care to community-based care. While developing materials for a future randomized controlled trial (RCT) to test the feasibility of a nurse-led Telephone Survivorship Clinic (TSC) for a smooth transition of ESBC survivors to follow-up care, we explored patients’ and OPs’ reactions to several of our proposed methods.MethodsWe used a qualitative study design with thematic analysis and a two-pronged approach. We interviewed OPs, seeking feedback on ways to recruit their ESBC patients for the trial, and ESBC patients, seeking input on a questionnaire package assessing outcomes and processes in the trial.ResultsOPs identified facilitators and barriers and offered suggestions for study design and recruitment process improvement. Facilitators included the novelty and utility of the study and simplicity of methods; barriers included lack of coordination between treating and discharging clinicians, time constraints, language barriers, motivation, and using a paper-based referral letter. OPs suggested using a combination of electronic and paper referral letters and supporting clinicians to help with recruitment. Patient advisors reported satisfaction with the content and length of the assessment package. However, they questioned the relevance of some questions (childhood trauma) while adding questions about trust in physicians and proximity to primary-care providers.ConclusionsOPs and patient advisors rated our methods for the proposed trial highly for their simplicity and relevance then suggested changes. These findings document processes that could be effective for cancer-patient recruitment in survivorship clinical trials.

Abstract P4-11-11: Effect of home-based smartphone-supported high-intensity interval training on cardiorespiratory fitness in breast cancer survivors: A randomized controlled trial of the habit-B program

Abstract Background: A strategy for maintaining and/or improving cardiorespiratory fitness (CRF) in the growing population of cancer survivors is of major clinical importance in the COVID-19 era. With the aim of increasing CRF, recent studies have focused on the use of high-intensity interval training (HIIT) in supervised experimental settings, which appeared to be more beneficial than usual care in cancer survivors at all stages of treatment and aftercare. However, the effect of unsupervised HIIT on increasing CRF in breast cancer survivors is not known. Purpose: To determine whether the newly developed habit-B program, which involves home-based smartphone-supported HIIT using body-weight exercises, improves CRF in early-stage breast cancer survivors. We hypothesized that the habit-B program would improve VO2peak compared with a control group. Methods: This single-center, 12-week, parallel-group, single-blind, randomized controlled trial involved 50 women with stage I-IIa breast cancer, aged 20 to 59 years, who had completed initial treatment except for hormone therapy. Participants wore a smartwatch and were randomized to either the exercise or control group from May 27, 2019 through November 30, 2020. The planned sample size was 60 patients to detect the increase of 2.0 ml/kg/min change in VO2peak with a standard deviation of 2.6 ml/kg/min, one-sided significance level of 2.5% and 80% power. The exercise group underwent home-based HIIT using a smartphone and a Fitbit Versa thrice weekly for 12 weeks (three times per week). The primary outcome was the 12-week change in peak oxygen uptake (VO2peak; mL/kg/min) between the groups. Other outcomes included muscle strength, 6-min walk test, resting heart rate, physical activity, fatigue, safety, and quality of life. Results: Of the 50 participants, 44 (exercise group, n=23; control group, n=21) completed the CRF assessment and 6 did not because of issues related to the COVID-19 pandemic. The change in VO2peak increased significantly in the exercise group (0.9 [95%CI, 0.1 to 1.7]) compared with the control group (-0.8 [95%CI, -1.5 to -0.1]) (mean difference, 1.7 [95% CI, 0.7 to 2.7], p &amp;lt; .01). Leg strength also increased significantly in the exercise group compared with the control group (mean difference, 13.5 [95% CI, 2.9 to 24.1], p &amp;lt; .01). Changes in other outcomes were not significantly different between the groups. Conclusion: A home-based HIIT intervention can lead to improved cardiorespiratory fitness and muscle strength in early-stage breast cancer survivors; however, a multicenter pragmatic clinical trial is required to confirm the benefits of the habit-B program. Table 1.Demographic and medical characteristicsCharacteristicshabit-B (n = 25)Control (n = 25)Age, mean (SD), y48 (6)49 (5)Body mass index, mean (SD), kg/m221.0 (2.2)20.9 (2.0)Diastolic blood pressure, mean (SD), mmHg78 (8)81 (10)Systolic blood pressure, mean (SD), mmHg119 (13)129 (11)Alcohol consumption, n (%)≤weekly8 (32)5 (20)1–6 drinks per week15 (60)19 (76)Daily2 (8)1 (4)Highest Education, n (%)Junior high school0 (0)1 (4)High school3 (12)0 (0)College or more22 (88)24 (96)Employment status, n (%)Full- or part-time worker21 (84)21 (84)On leave1 (4)0 (0)Housewife3 (12)4 (16)Time the patient can use for herself, n (%)&amp;lt;14 hours/week10 (40)5 (20)14–25 hours/week8 (32)11 (44)&amp;gt;25 hours/week7 (28)9 (36)Past history of medical illness, n (%)6 (24)6 (24)Breast cancer stageI18 (72)18 (72)IIA7 (28)7 (28)TumorEstrogen receptor positive24 (96)25 (100)Progesterone receptor positive24 (96)24 (96)HER2 positive1 (4)0 (0)Receiving hormone therapy, n (%)24 (96)23 (92)Tamoxifen, n (%)18 (72)18 (72)Anastrozole, n (%)1 (4)4 (16)Other, n (%)5 (20)1 (4)Receiving radiotherapy, n (%)11 (44)12 (48)Time since surgery, mean (SD) months5 (4)6 (4) Table 2.Changes in cardiorespiratory fitness and muscle strength from baseline to week 12habit-B (n = 21)Control (n = 23)Between-group differenceMean (SD)Mean (SD)Mean (95% CI)ESpPrimary endpointVO2peak (ml/kg/min)Baseline25.0 (3.0)24.9 (4.6)Week 1225.9 (2.8)24.1 (4.0)Within-group difference0.9 (1.7)-0.8 (1.6)1.7 (0.7 to 2.7)1.06&amp;lt;0.01Secondary endpointCardiorespiratory fitness6-min walk test (m)Baseline586 (43)603 (59)Week 12615 (42)631 (68)Within-group difference30 (30)29 (40)1 (-21 to 23)0.260.93VO2peak (L/min)Baseline1.33 (0.18)1.32 (0.29)Week 121.39 (0.23)1.29 (0.26)Within-group difference0.06 (0.11)-0.03 (0.09)0.10 (0.03 to 0.16)0.95&amp;lt;0.01Muscle strengthGrip strength (kgw)Baseline22.4 (3.8)23.3 (4.2)Week 1223.2 (4.2)23.7 (3.4)Within-group difference0.8 (2.0)0.4 (2.1)0.4 (-0.9 to 1.6)0.260.53Leg press one-repetition maximum (kg)Baseline93.6 (24.3)98.7 (40.6)Week 12106.6 (26.7)98.2 (30.9)Within-group difference13.0 (15.9)-0.5 (18.1)13.5 (2.9 to 24.1)0.790.01Chair stand test (s)Baseline14.4 (3.2)13.7 (2.5)Week 1213.5 (2.9)13.3 (2.5)Within-group difference-0.9 (2.7)-0.4 (1.8)-0.5 (-1.9 to 0.9)-0.210.50 Citation Format: Eisuke Ochi, Katsunori Tsuji, Tomomi Narisawa, Yoichi Shimizu, Aya Kuchiba, Akihiko Suto, Kenjiro Jimbo, Shin Takayama, Taro Ueno, Naomi Sakurai, Yutaka J Matsuoka. Effect of home-based smartphone-supported high-intensity interval training on cardiorespiratory fitness in breast cancer survivors: A randomized controlled trial of the habit-B program [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-11-11.