Abstract Background: Neoadjuvant chemotherapy is available to women with locally advanced breast cancer where chemotherapy is given prior to surgery. By examining resected tissue following neoadjuvant chemotherapy pathological complete response (pCR) can be determined. pCR is a favorable prognostic factor associated with longer survival compared to residual disease after neoadjuvant chemotherapy. Physical activity and diet may improve some side effects during treatment, but less is known about their effect on chemotherapy completion and more specifically on pCR in the neoadjuvant setting. Utilizing data from a randomized trial of diet and physical activity with a primary endpoint of chemotherapy completion in women with newly diagnosed breast cancer initiating chemotherapy, we evaluated the effect of a lifestyle intervention on pCR among the subset of women in the trial who received neoadjuvant chemotherapy. Methods: The Lifestyle, Exercise and Nutrition Early after Diagnosis (LEANer) Study enrolled 173 women with Stage I-III breast cancer who were randomized to usual care (n = 86) or a yearlong, 16-session, in-person or telephone-administered diet and physical activity intervention (n = 87) delivered by registered dietitians. Among study participants, 73 women received neoadjuvant chemotherapy and of these, 72 (98.6%) had complete follow-up pCR data (intervention = 40; usual care = 32). pCR, dates, doses and reason for dose-adjustments/delays of chemotherapy were abstracted from electronic medical records and confirmed with treating oncologists. A Chi-square test was used to examine the effect of the intervention versus usual care on pCR. Results: The 72 women receiving neoadjuvant chemotherapy with complete follow-up pCR data in LEANer were 49.4±11.6 years old, had a body mass index of 30.0+6.7 kg/m2, and 37.0% and 49.3% had stage I or II breast cancer, respectively. Just over half (52.1%) of women had ER/PR positive cancers and 32.9% of tumors were HER2 positive, with no statistically significant differences in tumor type by study arm. 92.7% of the women randomized to intervention adhered to all of the counseling sessions during their neoadjuvant chemotherapy and had statistically significant improvements in mean physical activity (161 minute increase versus 40 minute increase, p-value = < 0.001) and fiber intake (0.21 gram/day increase versus -5.17 g/day decrease, p-value = 0.020), as well as median fruit and vegetable intake (0.6 serving/day increase versus -0.5 serving/day decrease, p-value = 0.041) compared to usual care. There was a benefit of the intervention on pCR compared to usual care (52.5% with pCR in the intervention arm versus 28.1% with pCR in the usual care arm, p-value = 0.037). The intervention effect on pCR did not appear to be impacted by chemotherapy completion (relative dose intensity of 92% in intervention versus 90% in usual care) or chemotherapy dose delays as these were similar in the two study arms. In mediation analyses, results suggested that the changes in physical activity mediated, at least partially, the intervention effect on pCR. Conclusions: A primarily telephone-based diet and physical activity intervention led to improved pCR compared to usual care among the subset of women with breast cancer in the LEANer Study who received neoadjuvant chemotherapy. As pCR is an important prognostic factor for breast cancer, additional lifestyle interventions focusing on the neoadjuvant treatment setting with pCR as the primary outcome are necessary to confirm the potential benefits of lifestyle changes on pCR. Citation Format: Leah Ferrucci, Tara B. Sanft, Maura Harrigan, Brenda Cartmel, Fangyong Li, Michelle Zupa, Courtney McGowan, Leah Puklin, Thai Hien Nguyen, Anna M. Tanasijevic, Marian L. Neuhouser, Dawn Hershman, Karen Basen-Engquist, Beth Jones, Tish Knobf, Anees B. Chagpar, Andrea L.M. Silber, Jennifer A. Ligibel, Melinda L. Irwin. PD12-08 Randomized trial of exercise and nutrition on pathological complete response among women with breast cancer receiving neoadjuvant chemotherapy: the Lifestyle, Exercise and Nutrition Early after Diagnosis (LEANer) Study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD12-08.
Importance Chemotherapy-induced peripheral neuropathy (CIPN), one of the most common and severe adverse effects of chemotherapy, is associated with worse quality of life among survivors of ovarian cancer. Currently, there is no effective treatment for CIPN. Objective To evaluate the effect of a 6-month aerobic exercise intervention vs attention-control on CIPN among women treated for ovarian cancer in the Women’s Activity and Lifestyle Study in Connecticut (WALC) to provide evidence to inform the guidelines and recommendations for prevention or treatment of CIPN. Design, Setting, and Participants This prespecified secondary analysis evaluated the Women’s Activity and Lifestyle Study in Connecticut (WALC), a multicentered, open-label, population-based, phase 3 randomized clinical trial of an aerobic exercise intervention vs attention control for CIPN in patients who were diagnosed with ovarian cancer. Only WALC participants who received chemotherapy were included in this analysis. Participants were randomized 1:1 to either a 6-month aerobic exercise intervention or to attention control. All analyses were conducted between September 2022 and January 2023. Interventions The exercise intervention consisted of home-based moderate-intensity aerobic exercise facilitated by weekly telephone counseling from an American College of Sports Medicine/American Cancer Society–certified cancer exercise trainer. Attention control involved weekly health education telephone calls from a WALC staff member. Main Outcomes and Measure Change in CIPN was the primary outcome in this secondary analysis. This outcome was represented by CIPN severity, which was self-measured by participants at baseline and 6 months using the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group–Neurotoxicity scale, with a score range of 0 to 44. A mixed-effects model was used to assess the 6-month change in CIPN between the exercise intervention and attention control arms. Results Of the 134 participants (all females; mean [SD] age, 57.5 [8.3] years) included in the analysis, 69 were in the exercise intervention arm and 65 were in the attention control arm. The mean (SD) time since diagnosis was 1.7 (1.0) years. The mean (SD) baseline CIPN scores were 8.1 (5.6) in the exercise intervention arm and 8.8 (7.9) in the attention control arm ( P = .56). At 6 months, the self-reported CIPN score was reduced by 1.3 (95% CI, −2.3 to −0.2) points in the exercise intervention arm compared with an increase of 0.4 (95% CI, −0.8 to 1.5) points in the attention control arm. The between-group difference was −1.6 (95% CI, −3.1 to −0.2) points. The point estimate was larger among the 127 patients with CIPN symptoms at enrollment (−2.0; 95% CI, −3.6 to −0.5 points). Conclusions and Relevance Findings of this secondary analysis of the WALC trial indicate that a 6-month aerobic exercise intervention vs attention control significantly improved self-reported CIPN among patients who were treated for ovarian cancer. While replication of the findings in other studies is warranted, incorporating referrals to exercise programs into standard oncology care could reduce CIPN symptoms and increase quality of life in patients with ovarian cancer. Trial Registration ClinicalTrials.gov Identifier: NCT02107066
174 Background: Because obesity portends a higher risk of breast cancer mortality, achieving a healthy weight is recommended for breast cancer survivors. The impact of weight history on the ability to lose weight is unclear. We previously reported a 6.2 + 0.7% vs. 2.1 + 0.9% weight loss (p = .0003) in 100 breast cancer survivors randomized to a 6-month weight loss intervention vs. usual care. We examined whether weight history modified the effect of the intervention on body weight changes. Methods: Breast cancer survivors with a BMI > 25 kg/m 2 were randomized to usual care or 6-month, 11-session diet and exercise-counseling intervention. Baseline and 6 month weight and height were measured; weight at ages 18 and 35, 5 years and 1 year before and at diagnosis were self-reported. We defined weight history as: 1) change in weight between each time point and baseline; and 2) duration of obesity (i.e., number of years of having a BMI > 30 between age 18 and baseline). Generalized linear models were used to evaluate mean changes at 6 months between the intervention and usual care groups, adjusted and stratified by weight history variables. Results: Mean age and time since diagnosis were 59 + 7 years and 2.9 + 2.1 years, respectively. BMI increased over time (age 18 BMI = 21.8 + 2.9; baseline BMI = 32.4 + 6.5). Number of years being obese was 5.3 + 8.2 years (range 0-40 years). BMI at baseline, change in BMI from various time points to baseline, and years of obesity did not modify weight loss results. After adjusting for weight history, women randomized to intervention vs. usual care lost 6.1 + 0.7% vs. 2.0 + 0.9%, p = .0006, respectively. Conclusions: Participants reported a history of steady weight gain over time. The duration of obesity did not modify weight loss results. Weight history did not hinder survivors’ ability to lose clinically meaningful weight via a structured intervention.
5561 Background: Physical activity (PA) has been associated with a lower risk of developing or dying of many cancers, including ovarian cancer (OC). Inflammatory and metabolic pathways may underlie these associations. We examined the effect of exercise (EX) vs. attention control (AC) on insulin, insulin-like growth factor (IGF)-I, leptin, adiponectin, C-reactive protein (CRP), TNF-α, and IL-6 in women with OC. Methods: We randomized 144 inactive, post-chemotherapy OC survivors into a 6-month (6M) RCT of EX vs. AC; blood samples were available on a subgroup EX (n=53) vs. AC (n=51). All women received weekly phone calls; those in the EX arm were counseled on increasing their PA to 150 min/wk of aerobic exercise and those in the AC arm given information on health topics. Fasting blood samples were drawn at baseline (BL) and 6M. Biomarkers were assayed by ELISA, auto analyzer or RIA. Mixed model repeated analysis was used to compare BL to 6M changes in biomarkers, and included adjustment for BL biomarker levels, study sites, prior recurrence and treatment. Results: At BL women were 1.6 ± 1.0 (mean + SE) yrs post-diagnosis, 52% stage III-IV, 57 ± 9 years old, and exercised 31 ± 46 mins/wk. At 6M women in the EX arm did 176± 64 min/wk of exercise, predominately walking. Significant between-group differences were observed for BL to 6M changes in leptin and IGF-1 (Table). Conclusions: 6M of PA led to a 27% and 15% decrease in leptin and IGF-1 respectively. The impact of exercise and these biomarkers on OC prognosis remains to be determined. Clinical trial information: NCT02107066.Effect of EX vs. AC on BL to 6M changes in biomarkers (mean (SE)). BL Change (6M-BL) EX AC p-value EX AC p-value IGF-1 (ng/ml) 90.9 (5.5) 77.7 (4.8) 0.07 -10.1 (4.30) 3.58 (4.59) 0.02 Leptin (ng/ml) 30.9 (4.4) 36.0 (2.9) 0.34 -4.47 (2.74) 4.56 (2.90) 0.02 Adiponectin (µg/ml) 17.4 (1.3) 16.9 (1.4) 0.80 -0.82 (1.03) -0.64 (1.09) 0.90 CRP (mg/L) 4.37 (0.8) 5.96 (1.4) 0.32 -0.31 (1.12) -0.49 (1.17) 0.90 IL-6 (pg/ml) 2.06 (0.2) 2.21 (0.2) 0.64 0.18 (0.36) 0.11 (0.38) 0.89 Insulin (µU/ml) 13.2 (1.2) 16.4 (1.6) 0.11 1.43 (1.54) 3.42 (1.65) 0.39 TNFα (pg/ml) 1.06 (0.04) 1.24 (0.1) 0.03 0.04 (0.05) 0.01 (0.05) 0.56
10103 Background: Obesity and physical inactivity are associated with breast cancer recurrence and mortality. The mechanisms explaining these associations are not fully understood. Vascular Endothelial Growth Factor (VEGF) is an essential component in angiogenesis, common to both tumor vascularization and adipose tissue expansion. VEGF levels have been found to be elevated in the serum of women with breast cancer and associated with a poorer prognosis. This study looked at VEGF changes in breast cancer survivors participating in either a weight loss study or an exercise study. We hypothesized that weight loss would be correlated with decreased VEGF levels compared to exercise alone. Methods: We examined changes in serum VEGF in two randomized trials in overweight breast cancer survivors: a diet-induced weight loss trial of 100 women randomized to a weight loss and exercise counseling intervention with either telephone or in-person counseling (n = 67) or usual care (n = 33), and a supervised exercise trial in which 121 women were randomized to aerobic exercise (n = 61) or usual care (n = 60). Body composition (height, weight, and DEXA scans), physical activity and diet were measured at baseline and 6-months. Fasting blood samples were collected at baseline and 6 months. We compared mean baseline to 6-month between groups using a general linear regression model. Results: In the weight-loss trial, the weight loss group had a 6% weight loss and a 5.0% decrease in VEGF (mean ± 95% CI -16.4 pg/ml ± 9.2) while the usual care group had a 2% weight loss and a 4.8% increase in VEGF (12.5 pg/ml ± 11.7), p = 0.05 between groups. In the exercise trial, no significant weight loss was observed in either group. The change in VEGF from baseline to 6 months did not differ by randomization group. The 6 month change in the exercise group was 1.4 ± 6.8 (0.5% increase) and usual care group was 12.6 ± 7.3 (4.6% increase), p = 0.27 between groups. Conclusions: VEGF decreased in breast cancer survivors randomized to a weight loss intervention but did not change in those participating in an exercise only trial. Weight loss may play a larger role in mediating changes in VEGF compared to exercise alone.
Abstract Our pilot study aimed to evaluate the needs of community oncology providers with regard to cancer survivorship education, develop a survivorship curriculum based on the needs assessment, and evaluate the acceptability of the Project ECHO® (Extension for Community Healthcare Outcomes) model for delivery of the survivorship curriculum. A needs assessment was delivered to participants in suburban community cancer practices, and a curriculum was developed based on the results. Participants were enrolled in an ECHO curriculum consisting of 6 sessions from October to December 2019. Participants included registered nurses (RN), registered dietitians (RD), clinical social workers (LCSW), advanced practice providers (APP), radiation oncologists, and medical oncologists (MD). Participants were invited to participate in exit interviews designed to better evaluate the participant experience. Ninety percent of needs assessment participants ( n = 37) expressed an interest in cancer survivorship education. Eight participants from 3 community practices in suburban Connecticut enrolled in the ECHO curriculum. Four participants (50%) agreed to participate in exit interviews. Five themes emerged from the exit interviews: interest in survivorship, time, positive experience, empowerment, and community. Our Survivorship ECHO pilot demonstrated the acceptability of the Project ECHO® model for delivering cancer survivorship education to oncology providers. Further research confirming the feasibility of this model in additional oncology provider settings is needed.
The use of dietary supplements is common in the general population and even more prevalent among cancer survivors. The World Cancer Research Fund/American Institute for Cancer Research specifies that dietary supplements should not be used for cancer prevention. Several dietary supplements have potential pharmacokinetic and pharmacodynamic interactions that may change their clinical efficacy or potentiate adverse effects of the adjuvant endocrine therapy prescribed for breast cancer treatment. This analysis examined the prevalence of self-reported dietary supplement use and the potential interactions with tamoxifen and aromatase inhibitors (AIs) among breast cancer survivors enrolled in three randomized controlled trials of lifestyle interventions conducted between 2010 and 2017. The potential interactions with tamoxifen and AIs were identified using the Natural Medicine Database. Among 475 breast cancer survivors (2.9 (mean) or 2.5 (standard deviation) years from diagnosis), 393 (83%) reported using dietary supplements. A total of 108 different types of dietary supplements were reported and 36 potential adverse interactions with tamoxifen or AIs were identified. Among the 353 women taking tamoxifen or AIs, 38% were taking dietary supplements with a potential risk of interactions. We observed a high prevalence of dietary supplement use among breast cancer survivors and the potential for adverse interactions between the prescribed endocrine therapy and dietary supplements was common.
