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PURPOSE: Arthralgias occur in up to 50% of women with breast cancer treated with adjuvant aromatase inhibitors (AIs), and are one of the most common reasons for poor adherence to therapy. We examined whether a year-long exercise program improves arthralgias in breast cancer survivors taking AIs. METHODS: Postmenopausal women diagnosed with hormone receptor-positive breast cancer were identified via the Connecticut Tumor Registry. Women who were taking an AI for at least 6-months and reported ≥ 3 out of 10 on the worst joint pain item of the Brief Pain Inventory-Short Form (BPI) were eligible and randomized to either exercise (150 min/wk of moderate-intensity aerobic exercise and twice-weekly supervised resistance exercise sessions) or usual care. The BPI questionnaire was completed at baseline, 6- and 12-months. VO2 max testing and Dual Energy X-ray Absorptiometry (DEXA) scans were also collected at baseline, 6- and 12-months. The primary outcome was change in BPI worst joint pain score between 0 and 12 months. We performed intent-to-treat statistical analyses including analysis of covariance, where each participant's change in outcome was modeled as a function of randomization group RESULTS: Out of 728 women screened that were taking an AI, we randomized 121 women, with 61 women randomized to exercise and 60 women randomized to usual care. Baseline characteristics were comparable between the two groups. Over 12 months, women randomized to exercise attended, on average, 80% ± 14% of the twice-weekly supervised resistance training exercise sessions and participated in an average 146 ± 75 min/wk of at least moderate-intensity aerobic exercise. Worst joint pain scores decreased by 20% at 12 months among women randomized to exercise vs. a 3% decrease among women randomized to usual care (p = .017). Joint pain severity also decreased significantly in exercise vs. usual care groups (p = 0.025), as well as joint pain-related interference (p = 0.005). The exercise intervention also favorably impacted body weight (p = 0.0057) and cardiorespiratory fitness (p = 0.024). Baseline to 12 month changes in BPI joint pain scores (mean (SD)) Baseline Values  Change from baseline to 12 months  BPI ItemExercisersUsual Carep-valueExercisersUsual Carep-valueWorst Pain5.5 (1.9)5.9 (1.9)0.29-1.1 (2.5)-0.2 (1.6)0.017Pain Severity3.9 (1.6)4.3 (1.8)0.27-0.8 (2.1)0.0 (1.5)0.025Pain Interference2.8 (2.1)2.9 (2.3)0.81-0.8 (2.0)0.2 (1.9)0.005Body weight (kg)80.9 (16.8)74.6 (14.5)0.11-3.5 (6.0)0.1 (3.7)0.0057VO2max (ml/kg/min)23.5 (4.8)23.1 (4.3)0.751.9 (1.9)0.4 (2.7)0.024 CONCLUSION: We found that participating in an exercise intervention led to clinically meaningful improvements in AI-induced arthralgias in breast cancer survivors experiencing moderate joint pain. The intervention also induced favorable changes in body weight and cardiorespiratory fitness, factors that may be linked to incidence and severity of AI-induced arthralgias. Further work is needed to determine whether exercise leads to increased AI adherence and possibly better outcomes in women with breast cancer. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr S3-03.

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Background: Older pts with BC receiving adjuvant tx are at increased risk of chemo tox; however, no BC-specific tool exists to quantify this risk. The Cancer and Aging Research Group (CARG) developed/validated a chemo tox score for older pts with all stages of solid tumor. The goals of this study were to: 1) build upon the CARG score by developing/validating CARG-BC (a BC specific adjuvant chemo tox score for older pts) and 2) evaluate its association with dose modifications, reduced relative dose intensity (RDI) and hospitalizations. Methods: 501 pts age ≥65 with stage I-III BC from 16 sites were accrued (300 development; 201 validation cohort). A pre-chemo assessment captured: CARG chemo tox score, BC tumor/tx variables, and additional geriatric assessment (GA) items. Grade 3-5 chemo tox by NCI CTCAE v 4.0 was captured. Univariate analysis identified chemo tox risk factors (p<0.10) in addition to the CARG score which were used to develop a predictive model by best subset method; each risk factor was assigned a score, and summed to yield a total score (CARG-BC). Model performance was assessed by area under the ROC curves (AUC) of the development cohort, 10-fold internal validation, external validation, and goodness of fit. Results: Among 501 pts, 28 received non-standard regimens and were excluded, leaving 473 evaluable pts: 283 development and 190 validation cohort. The development cohort (median age 70; range 65-85) had Stage I (39%), II (41%), & III (20%) BC with 65% hormone positive, 24% triple negative, 27% Her2 positive; and 37% received an anthracycline. Grade 3-5 tox occurred in 46% (36% grade 3, 10% grade 4, 0.4% grade 5). The CARG score was significantly associated with grade 3-5 tox (p<0.001; AUC 0.64). The addition of BC tumor/tx & GA variables (CARG-BC: see table) improved the AUC to 0.76 (95% CI, 0.70-0.82; goodness of fit p=0.28). The score ranged from 0-19, (low risk 0-5, mid risk 6-9, high risk 10+) and was significantly associated with grade 3-5 tox (p<0.001) while KPS was not (p=0.20). The 10-fold internal validation AUC was 0.78. The external validation AUC (0.69) was not statistically different (p=0.15) from the development AUC. A higher CARG-BC score was associated with dose delay/reduction, chemo discontinuation, hospitalization, and RDI<85% (all p-value <0.001). Conclusions: We developed and validated a risk score (CARG-BC) which identifies an older pt's risk for adjuvant BC chemo tox and is associated with dose reduction, delay, reduced RDI, and hospitalization. This tool could be considered as a part of adjuvant tx decision-making. Chemo Tox Risk Score for BC (CARG-BC) Grade 3-5 Tox (%)ScoreCARG-Score: age, # of chemo drugs, dose, hemoglobin, creatinine clearance, hearing, falls, ability to walk 1 block and take meds, decreased social activitiesLow360Middle573High613StageI330II/III552Planned Tx Duration≤ 3 mo.330> 3 mo.584AnthracyclineNo380Yes591Liver FunctionNormal450Abnormal623Ability to Walk a MileNot limited370Limited613Someone to Provide AdviceMost of Time440None to Some of Time613 CARG-BC Risk ScoreLow210-5Middle456-9High7910+ Citation Format: Hurria A, Magnuson A, Gross CP, Tew WP, Klepin HD, Wildes TM, Muss HB, Dotan E, Freedman R, O'Connor T, Dale W, Cohen HJ, Katheria V, Arsenyan A, Levi A, Kim H, Sun C-L. Development and validation of a chemotherapy toxicity (Chemo Tox) risk score for older patients (Pts) with breast cancer (BC) receiving adjuvant/neoadjuvant treatment (Adjuvant Tx): A R01 and BCRF funded prospective multicenter study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS6-04.