Background:The mechanisms by which stress hormones impact triple-negative breast cancer (TNBC) etiology and treatment are unclear. We have previously shown that stress hormones, cortisol, and catecholamines induce rapid DNA damage and impact DNA repair in NIH 3T3 fibroblasts. This study investigates whether stress hormones increase DNA damage in breast cancer cells and if this impacts drug efficacy.Methods:We first screened a panel of 39 breast cancer cell lines for expression of adrenergic and glucocorticoid receptors and examined if stress hormones induce DNA damage and alter cell cycle regulation in vitro. A TNBC xenograft model was used to assess the impact of restraint stress on tumour growth and chemosensitivity to paclitaxel.Results:We found that stress hormones induced DNA damage, phosphorylation of ATR, which was accompanied by an up-regulation of the G1 cell kinase inhibitor p21 and a cell cycle halt of TNBCs in the G1 phase. p21 knockdown abrogated G1 arrest by stress hormones. We also demonstrated that stress significantly decreased efficacy of paclitaxel.Conclusion:We describe a novel mechanism through which stress hormones can induce drug resistance to paclitaxel, which may have profound implications for treating drug resistance in patients with TNBC.

BACKGROUND Minority patients with breast cancer are at risk for undertreatment of cancer-related pain. We evaluated the feasibility and efficacy of an automated pain intervention for improving pain and symptom management of underserved African American and Latina women with breast cancer. METHODS Sixty low-income African American and Latina women with breast cancer and cancer-related pain were enrolled in a pilot study of an automated, telephone-based interactive voice response (IVR) intervention. The intervention group patients were called twice per week by the IVR system and asked to rate the intensity of their pain and other symptoms. The patients’ oncologists received e-mail alerts if reported symptoms were moderate to severe. The patients also reported barriers to pain management and received education regarding any reported obstacles. RESULTS The proportion of women in both groups reporting moderate to severe pain decreased during the study, but the decrease was significantly greater for the intervention group. The IVR intervention was also associated with improvements in other cancer-related symptoms, including sleep disturbance and drowsiness. Although patient adherence to the IVR call schedule was good, the oncologists treating the patients rated the intervention as only somewhat useful for improving symptom management. CONCLUSIONS The IVR intervention reduced pain and symptom severity for underserved minority women with breast cancer. Additional research on technological approaches to symptom management is needed.

The ability of stress to induce immune suppression is widely recognized, but the mechanisms underlying the effects of stress on the adaptive immune system during tumor progression are not completely understood. To study the effect of stress on the immune system in vivo, we used a preclinical immunocompetent mouse model bearing 4T1 mammary adenocarcinoma cells. Mice were randomized into 4 groups, including social isolation (SI), acute restraint stress (aRRS), chronic restraint stress (cRRS), or no stress (NS). We found that SI significantly decreased the number of tumor-bearing mice still alive at the end of protocol (28 days), compared to NS mice. Although we did not detect significant changes in primary tumor volume, we observed a significant increase in the endothelial marker CD31 in primary tumors of SI mice and in lung metastases in SI and RRS mice. Survival decline in SI mice was associated with significant decreases in splenic CD8 cells and in activated T cells. From a mechanistic standpoint, RRS increased expression of FOXP3, CXCL-10, and granzyme B in mouse tumors, and the effects were reversed by propranolol. Our data demonstrate that various forms of stress differentially impact adaptive immunity and tumor angiogenesis, and negatively impact survival.

PURPOSE: Long wait times at chemotherapy infusion centers adversely affect patients’ perception of quality of care and result in patient dissatisfaction. We conducted a quality improvement initiative at a busy community hospital to improve infusion center efficiency and reduce patient wait time, while maintaining patient safety and avoiding chemotherapy waste. METHODS: We used a coordinated and collaborative effort between providers, infusion center nurses, and pharmacists to ensure completion of orders, review of laboratory data, and prepreparation of chemotherapy 1 day ahead of each patient’s scheduled infusion center appointment. Monthly Plan-Do-Study-Act cycles were conducted for 6 months beyond the pilot month to refine and sustain the intervention. RESULTS: The average patient cycle time, measured as time from patient check-in to check-out from the infusion chair, decreased from 252 minutes to 173 minutes in the last 4 months evaluated (30% decrease) after the intervention. Similarly, the average chemotherapy turnaround time, measured as time from chemotherapy request by nursing to pharmacy delivery, improved from 90 minutes to 27 minutes after the intervention (70% decrease). Infusion center capacity was unaffected by the intervention. The cost of wasted chemotherapy was minimal after the first postintervention month. Surveys revealed extremely high patient and employee satisfaction with the new system. CONCLUSION: A strategy involving prepreparation of chemotherapy on the day before the scheduled infusion is feasible to implement at a busy community hospital infusion center and is associated with significant improvement in infusion center efficiency as well as patient and employee satisfaction.

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