In patients with breast cancer who received induction chemotherapy for 18 weeks, subsequent continuous chemotherapy was associated with a significant prolongation of the time before progression as compared with those receiving no further therapy; overall survival, however, was not significantly different in the two groups.

We have compared the oxidative metabolism of human eosinophils (80%-90% purity) to that of neutrophils. Hexose monophosphate (HMP) shunt activity of eosinophils was higher than that of neutrophils under either resting or phagocytizing conditions. Eosinophil HMP shunt activity also was stimulated by phorbol myristate acetate, a membrane- active agent. Eosinophils showed a marked incorporation of 125I into trichloroacetic acid-insoluble material under resting conditions, which increased markedly during phagocytosis. Eosinophils likewise showed a greater reduction of nitroblue tetrazolium dye during phagocytosis than did neutrophils. Measurement of other parameters of oxidative metabolism indicated that eosinophils generated superoxide anion following phagocytosis and also elicited a burst of chemiluminescence similar to that observed during phagocytosis by neutrophils. Measurement of NADPH oxidase activity demonstrated that this enzyme was 3–6 times more active in fractions isolated from eosinophils than in corresponding fractions isolated from neutrophils; this was observed over a range of substrate concentrations. The eosinophil enzyme sedimented differently than the neutrophil enzyme with differential centrifugation; neither showed sedimentation characteristics of peroxidase. These data indicate that eosinophils possess a similar, although in some ways more potent, oxidative burst than neutrophils and are consistent with a role for NADPH oxidase in the initiation of that burst.

Eosinophils from a patient with hypereosinophilia were observed to phagocytize radiolabeled E. coli or S. aureus as effectively as neutrophils from a normal control. This was observed at a number of bacteria/cell ratios and a various time intervals following initial challenge and was confirmed by direct microscopic examination. In spite of comparables rates of phagocytosis, the eosinophils were consistently less capable of killing the bacteria. This correlates with an inability of eosinophil peroxidase to catalyze the peroxidase-H2O2-CI--mediated decarboxylation of amino acids; in contrast, both eosinophil and neutrophil peroxidases showed similar capabilities to iodinate protein in vitro. These data are compatible with the importance of the chloride- mediated mechanism in the bactericidal activity of intact phagocytes.

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.