Browsing by Author "Miller, Kathy"
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Item 244 Couples' Daily Health in Breast Cancer Survivorship: Dyadic Associations in Psychological, Physical, and Relational Health(Cambridge University Press, 2024-04-03) Shrout, Rosie; Friedman, Elliot; Miller, Kathy; Tisdale, James; Medicine, School of MedicineOBJECTIVES/GOALS: Breast cancer survivors who experience psychological and physical symptoms after treatment ends have an increased risk for comorbid disease development, reduced quality of life, and premature mortality. However, survivors in satisfying marriages report lower stress and better health than those in dissatisfying marriages. METHODS/STUDY POPULATION: Research is needed to identify how survivors’ marriages provide these health benefits across the cancer continuum. Including both survivors and their partners’ perspectives can identify key pathways connecting relationships to better health. This study examined survivors’ and their partners’ psychological, physical, and relational health. Breast cancer survivors (stage 0-III) and their partners (n=34 individuals, 17 couples) completed a baseline online survey followed by a 7-day diary study with three ecological momentary assessments across the day. Questionnaires assessed their cancer-related communication, relationship distress, and psychological and physical symptoms. RESULTS/ANTICIPATED RESULTS: Survivors reported poorer sleep quality and greater fatigue than their partners. Survivors also reported disclosing more thoughts, feelings, and information about cancer compared to their partners. For both survivors and partners, feeling more satisfied with each other’s cancer-related discussions and reporting lower relational distress correlated with fewer physical symptoms, sleep problems, fatigue, and psychological distress. DISCUSSION/SIGNIFICANCE: For both survivors and their partners, feeling more satisfied with how often they talked about survivorship and the cancer experience was associated with better psychological and physical health. This research demonstrates the health benefits and importance of open communication for both survivors and their partners across the cancer continuum.Item 64Cu-MM-302 Positron Emission Tomography Quantifies Variability of Enhanced Permeability and Retention of Nanoparticles in Relation to Treatment Response in Patients with Metastatic Breast Cancer(AACR, 2017-08) Lee, Helen; Shields, Anthony F.; Siegal, Barry A.; Miller, Kathy; Krop, Ian; Ma, Cynthia; LoRusso, Patricia M.; Munster, Pamela; Campbell, Karen; Gaddy, Daniel F.; Leonard, Shannon C.; Geretti, Elena; Blocker, Stephanie; Kirpotin, Dmitri; Moyo, Victor; Wickham, Thomas; Hendriks, Bart S.; Medicine, School of MedicinePurpose: Therapeutic nanoparticles are designed to deliver their drug payloads through enhanced permeability and retention (EPR) in solid tumors. The extent of EPR and its variability in human tumors is highly debated and has been proposed as an explanation for variable responses to therapeutic nanoparticles in clinical studies. Experimental Design: We assessed the EPR effect in patients using a 64Cu-labeled nanoparticle, 64Cu-MM-302 (64Cu-labeled HER2-targeted PEGylated liposomal doxorubicin), and imaging by PET/CT. Nineteen patients with HER2-positive metastatic breast cancer underwent 2 to 3 PET/CT scans postadministration of 64Cu-MM-302 as part of a clinical trial of MM-302 plus trastuzumab with and without cyclophosphamide (NCT01304797). Results: Significant background uptake of 64Cu-MM-302 was observed in liver and spleen. Tumor accumulation of 64Cu-MM-302 at 24 to 48 hours varied 35-fold (0.52–18.5 %ID/kg), including deposition in bone and brain lesions, and was independent of systemic plasma exposure. Computational analysis quantified rates of deposition and washout, indicating peak liposome deposition at 24 to 48 hours. Patients were classified on the basis of 64Cu-MM-302 lesion deposition using a cut-off point that is comparable with a response threshold in preclinical studies. In a retrospective exploratory analysis of patient outcomes relating to drug levels in tumor lesions, high 64Cu-MM-302 deposition was associated with more favorable treatment outcomes (HR = 0.42). Conclusions: These findings provide important evidence and quantification of the EPR effect in human metastatic tumors and support imaging nanoparticle deposition in tumors as a potential means to identify patients well suited for treatment with therapeutic nanoparticles.Item Allogeneic Mesenchymal Cell Therapy in Anthracycline-Induced Cardiomyopathy Heart Failure Patients(Elsevier, 2020-11) Bolli, Roberto; Perin, Emerson C.; Willerson, James T.; Yang, Phillip C.; Traverse, Jay H.; Henry, Timothy D.; Pepine, Carl J.; Mitrani, Raul D.; Hare, Joshua M.; Murphy, Michael P.; March, Keith L.; Ikram, Sohail; Lee, David P.; O’Brien, Connor; Durand, Jean-Bernard; Miller, Kathy; Lima, Joao A.; Ostovaneh, Mohammad R.; Ambale-Venkatesh, Bharath; Gee, Adrian P.; Richman, Sara; Taylor, Doris A.; Sayre, Shelly L.; Bettencourt, Judy; Vojvodic, Rachel W.; Cohen, Michelle L.; Simpson, Lara M.; Lai, Dejian; Aguilar, David; Loghin, Catalin; Moyé, Lem; Ebert, Ray F.; Davis, Barry R.; Simari, Robert D.; Surgery, School of MedicineBackground: Anthracycline-induced cardiomyopathy (AIC) may be irreversible with a poor prognosis, disproportionately affecting women and young adults. Administration of allogeneic bone marrow-derived mesenchymal stromal cells (allo-MSCs) is a promising approach to heart failure (HF) treatment. Objectives: SENECA (Stem Cell Injection in Cancer Survivors) was a phase 1 study of allo-MSCs in AIC. Methods: Cancer survivors with chronic AIC (mean age 56.6 years; 68% women; NT-proBNP 1,426 pg/ml; 6 enrolled in an open-label, lead-in phase and 31 subjects randomized 1:1) received 1 × 108 allo-MSCs or vehicle transendocardially. Primary objectives were safety and feasibility. Secondary efficacy measures included cardiac function and structure measured by cardiac magnetic resonance imaging (CMR), functional capacity, quality of life (Minnesota Living with Heart Failure Questionnaire), and biomarkers. Results: A total of 97% of subjects underwent successful study product injections; all allo-MSC-assigned subjects received the target dose of cells. Follow-up visits were well-attended (92%) with successful collection of endpoints in 94% at the 1-year visit. Although 58% of subjects had non-CMR compatible devices, CMR endpoints were successfully collected in 84% of subjects imaged at 1 year. No new tumors were reported. There were no significant differences between allo-MSC and vehicle groups with regard to clinical outcomes. Secondary measures included 6-min walk test (p = 0.056) and Minnesota Living with Heart Failure Questionnaire score (p = 0.048), which tended to favor the allo-MSC group. Conclusions: In this first-in-human study of cell therapy in patients with AIC, transendocardial administration of allo-MSCs appears safe and feasible, and CMR was successfully performed in the majority of the HF patients with devices. This study lays the groundwork for phase 2 trials aimed at assessing efficacy of cell therapy in patients with AIC.Item Cardiac Outcomes of Patients Receiving Adjuvant Weekly Paclitaxel and Trastuzumab for Node-Negative, ERBB2-Positive Breast Cancer(American Medical Association, 2016-01) Dang, Chau; Guo, Hao; Najita, Julie; Yardley, Denise; Marcom, Kelly; Albain, Kathy; Rugo, Hope; Miller, Kathy; Ellis, Matthew; Shapira, Iuliana; Wolff, Antonio C.; Carey, Lisa A.; Moy, Beverly; Groarke, John; Moslehi, Javid; Krop, Ian; Burstein, Harold J.; Hudis, Clifford; Winer, Eric P.; Tolaney, Sara M.; Department of Medicine, IU School of MedicineIMPORTANCE: Trastuzumab is a life-saving therapy but is associated with symptomatic and asymptomatic left ventricular ejection fraction (LVEF) decline. We report the cardiac toxic effects of a nonanthracycline and trastuzumab-based treatment for patients with early-stage human epidermal growth factor receptor 2 (ERBB2, formerly HER2 or HER2/neu)-positive breast cancer. OBJECTIVE: To determine the cardiac safety of paclitaxel with trastuzumab and the utility of LVEF monitoring in patients with node-negative, ERBB2-positive breast cancer. DESIGN, SETTING, AND PARTICIPANTS: In this secondary analysis of an uncontrolled, single group study across 14 medical centers, enrollment of 406 patients with node-negative, ERBB2-positive breast cancer 3 cm, or smaller, and baseline LVEF of greater than or equal to 50% occurred from October 9, 2007, to September 3, 2010. Patients with a micrometastasis in a lymph node were later allowed with a study amendment. Median patient age was 55 years, 118 (29%) had hypertension, and 30 (7%) had diabetes. Patients received adjuvant paclitaxel for 12 weeks with trastuzumab, and trastuzumab was continued for 1 year. Median follow-up was 4 years. INTERVENTIONS: Treatment consisted of weekly 80-mg/m2 doses of paclitaxel administered concurrently with trastuzumab intravenously for 12 weeks, followed by trastuzumab monotherapy for 39 weeks. During the monotherapy phase, trastuzumab could be administered weekly 2-mg/kg or every 3 weeks as 6-mg/kg. Radiation and hormone therapy were administered per standard guidelines after completion of the 12 weeks of chemotherapy. Patient LVEF was assessed at baseline, 12 weeks, 6 months, and 1 year. MAIN OUTCOMES AND MEASURES: Cardiac safety data, including grade 3 to 4 left ventricular systolic dysfunction (LVSD) and significant asymptomatic LVEF decline, as defined by our study, were reported. RESULTS: Overall, 2 patients (0.5%) (95% CI, 0.1%-1.8%) developed grade 3 LVSD and came off study, and 13 (3.2%) (95% CI, 1.9%-5.4%) had significant asymptomatic LVEF decline, 11 of whom completed study treatment. Median LVEF at baseline was 65%; 12 weeks, 64%; 6 months, 64%; and 1 year, 64%. CONCLUSIONS AND RELEVANCE: Cardiac toxic effects from paclitaxel with trastuzumab, manifesting as grade 3 or 4 LVSD or asymptomatic LVEF decline, were low. Patient LVEF was assessed at baseline, 12 weeks, 6 months, and 1 year, and our findings suggest that LVEF monitoring during trastuzumab therapy without anthracyclines could be simplified for many individuals.Item Comparison of younger and older breast cancer survivors and age-matched controls on specific and overall quality of life domains(Wiley, 2014-08) Champion, Victoria L.; Wagner, Lynne I.; Monahan, Patrick O.; Daggy, Joanne; Smith, Lisa; Cohee, Andrea A.; Ziner, Kim W.; Haase, Joan E.; Miller, Kathy; Pradhan, Kamnesh; Unverzagt, Frederick W.; Cella, David; Ansari, Bilal; Sledge, George W. Jr.; Nursing, School ofBACKGROUND: Younger survivors (YS) of breast cancer often report more survivorship symptoms such as fatigue, depression, sexual difficulty, and cognitive problems than older survivors (OS). This study sought to determine the effect of breast cancer and age at diagnosis on quality of life (QoL) by comparing 3 groups: 1) YS diagnosed at age 45 years or before, 2) OS diagnosed between 55 and 70, and 3) for the YSs, age-matched controls (AC) of women not diagnosed with breast cancer. METHODS: Using a large Eastern Cooperative Oncology Group (ECOG) database, 505 YS were recruited who were aged 45 years or younger when diagnosed and 622 OS diagnosed at 55 to 70 years of age. YS, OS, and AC were compared on physical, psychological, social, spiritual, and overall QoL variables. RESULTS: Compared to both AC and to OS, YS reported more depressive symptoms (P = .005) and fatigue (P < .001), poorer self-reported attention function (P < .001), and poorer sexual function (P < .001) than either comparison group. However, YS also reported a greater sense of personal growth (P < .001) and perceived less social constraint (P < .001) from their partner than AC. CONCLUSIONS: YS reported worse functioning than AC relative to depression, fatigue, attention, sexual function, and spirituality. Perhaps even more important, YS fared worse than both AC and OS on body image, anxiety, sleep, marital satisfaction, and fear of recurrence, indicating that YS are at greater risk for long-term QoL problems than survivors diagnosed at a later age.Item Factors underlying metastatic breast cancer patients' perceptions of symptom importance: a qualitative analysis(Wiley, 2018-01) Mosher, Catherine E.; Daily, Susan; Tometich, Danielle; Matthias, Marianne S.; Outcalt, Samantha D.; Hirsh, Adam; Johns, Shelley A.; Rand, Kevin; Schneider, Bryan; Mina, Lida; Storniolo, Anna Maria; Newton, Erin; Miller, Kathy; Psychology, School of ScienceThe symptom literature in cancer has primarily examined symptom severity, frequency and distress. Assessing cancer patients' perceptions of symptom importance-how important it is for them to see improvement in a symptom following an intervention-and factors influencing these judgments would also inform patient-centred care, but this analysis has not been undertaken. This qualitative study aimed to identify factors underlying perceptions of symptom importance among 25 symptomatic metastatic breast cancer (MBC) patients. Participants were recruited from a cancer centre in the Midwestern USA. Semi-structured interviews focused on patients' rationale for considering common symptoms (i.e., anxiety, sadness, sleep problems, pain or fatigue) to be important. Thematic analyses revealed five interrelated factors underlying MBC patients' perceptions of symptom importance: activity restriction, concentration difficulties, exacerbation of other physical symptoms, symptom-related long-term health concerns and negative impact on their relationships with others. Patients most frequently stated that a physical or psychological symptom was important because of the resulting activity restriction. Additionally, some patients considered pain to be important because it signalled potential long-term health concerns, such as worsening metastatic disease. Findings suggest that clinicians should take into account MBC patients' perceptions of symptom importance and factors underlying these judgments when making shared treatment decisions.Item Indiana Center for Breast Cancer Research(Office of the Vice Chancellor for Research, 2014-04-11) Nakshatri, Harikrishna; Gilley, David P.; Wells, Clark D.; Nephew, Kenneth; Radovich, Milan; Guise, Theresa; Bales, Casey; Perkins, Susan; Badve, Sunil; Vladislav, Ioan Tudor; Miller, KathyThe mission of IUPUI breast cancer signature center is to address prevention, early detection, and treatment of breast cancer through translational projects, supportive cores, and synergistic programs. This poster details our efforts improve resources for breast cancer research and efforts to develop multi-PI investigator proposals. The Signature Center has developed two web resources: the Breast Cancer Prognostics Database (PROGgene) to study prognostic implications of genes of interest in publically available breast cancer databases and PROGmiR, a microRNA database. The PROGgene can be used to study overall, recurrence free and metastasis free survival in large patient series. PROGmiR allows investigators to study the prognostic importance of microRNAs. Both PROGgene and PROGmiR have recently been published and accessed by investigators from >10 countries. The signature center has also devoted considerable efforts in developing tumor tissue resource. Tissue Bank includes a total sample of N = 600 cases with 30% non-Caucasian cases. Currently 460 cases have been assembled into a Tissue Microarray with clinical and follow up data. Expression pattern of AP2γ, a potential marker of breast cancer progression, has been analyzed in a TMA with ~170 cases. The breast cancer signature center has funded four pilot projects and projects for the fourth round of funding are currently under review. Drs. Clark Wells received funding for the project “Histologic Analysis of the Protein Levels of Amot130, AmotL1 and YAP in Normal, Hyperplastic and Invasive Breast Cancer Tissues”, which resulted in a publication in PNAS. Dr. David Gilley and his group received funding for the project: “Luminal mammary progenitors are a unique site of telomere dysfunction”, which was published in Stem Cell Reports. In the third project, Dr. Theresa Guise is investigating the mechanisms of cancer-associated muscular dysfunction with a future plan for a clinical trial. Drs. Ken Nephew and Milan Radovich received funding to obtain preliminary results for a multi-PI R01 or P01, which will explore genomics and epigenomics of breast cancer using clinical trial materials. Progress made by the signature center was integral in our request to Vera Bradley Foundation for Breast Cancer. This foundation has recently committed $15 million for the breast cancer program, which will be used to develop three themes of research with a focus on personalized therapies to improve outcome in breast cancer patients.Item Rationale and Design of the SENECA (StEm cell iNjECtion in cAncer survivors) Trial(Elsevier, 2018) Bolli, Roberto; Hare, Joshua M.; Henry, Timothy D.; Lenneman, Carrie G.; March, Keith; Miller, Kathy; Pepine, Carl J.; Perin, Emerson C.; Traverse, Jay H.; Willerson, James T.; Yang, Phillip C.; Gee, Adrian P.; Lima, João A.; Moyé, Lem; Vojvodic, Rachel W.; Sayre, Shelly L.; Bettencourt, Judy; Cohen, Michelle; Ebert, Ray F.; Simari, Robert; Medicine, School of MedicineObjectives SENECA (StEm cell iNjECtion in cAncer survivors) is a phase I, randomized, double-blind, placebo-controlled study to evaluate the safety and feasibility of delivering allogeneic mesenchymal stromal cells (allo-MSCs) transendocardially in subjects with anthracycline-induced cardiomyopathy (AIC). Background AIC is an incurable and often fatal syndrome, with a prognosis worse than that of ischemic or nonischemic cardiomyopathy. Recently, cell therapy with MSCs has emerged as a promising new approach to repair damaged myocardium. Methods The study population is 36 cancer survivors with a diagnosis of AIC, left ventricular (LV) ejection fraction ≤40%, and symptoms of heart failure (NYHA class II-III) on optimally-tolerated medical therapy. Subjects must be clinically free of cancer for at least two years with a ≤ 30% estimated five-year risk of recurrence. The first six subjects participated in an open-label, lead-in phase and received 100 million allo-MSCs; the remaining 30 will be randomized 1:1 to receive allo-MSCs or vehicle via 20 transendocardial injections. Efficacy measures (obtained at baseline, 6 months, and 12 months) include MRI evaluation of LV function, LV volumes, fibrosis, and scar burden; assessment of exercise tolerance (six-minute walk test) and quality of life (Minnesota Living with Heart Failure Questionnaire); clinical outcomes (MACE and cumulative days alive and out of hospital); and biomarkers of heart failure (NT-proBNP). Conclusions This is the first clinical trial using direct cardiac injection of cells for the treatment of AIC. If administration of allo-MSCs is found feasible and safe, SENECA will pave the way for larger phase II/III studies with therapeutic efficacy as the primary outcome.Item Symptom experiences in metastatic breast cancer patients: relationships to activity engagement, value-based living, and psychological inflexibility(Wiley, 2017-11) Mosher, Catherine E.; Tometich, Danielle B.; Hirsh, Adam; Rand, Kevin L.; Johns, Shelley A.; Matthias, Marianne S.; Outcalt, Samantha D.; Bricker, Jonathan; Schneider, Bryan; Mina, Lida; Storniolo, Anna Maria; Newton, Erin; Miller, Kathy; Psychology, School of ScienceOBJECTIVE: This study examined symptom-based subgroups of metastatic breast cancer (MBC) patients and the extent to which they differed across key constructs of acceptance and commitment therapy (ACT). METHODS: Eighty women with MBC completed self-report surveys assessing 10 common symptoms and several ACT variables (ie, activity engagement, psychological inflexibility, value obstruction, and value progress) during a single time point. RESULTS: A cluster analysis yielded 3 patient subgroups: low symptoms, low-moderate symptoms, and moderate-high symptoms. Relative to the subgroup with low symptoms, the other subgroups reported less activity engagement. In addition, compared with patients with low symptoms, the subgroup with moderate-high symptoms reported greater psychological inflexibility (ie, avoidance of unwanted internal experiences) and greater difficulty living consistently with their values. CONCLUSIONS: Women with MBC show heterogeneity in their symptom profiles, and those with higher symptom burden are more likely to disengage from valued activities and avoid unwanted experiences (eg, thoughts, feelings, and bodily sensations). Findings are largely consistent with the ACT model and provide strong justification for testing ACT to address symptom interference in MBC patients.Item The efficacy and safety of enzalutamide with trastuzumab in patients with HER2+ and androgen receptor-positive metastatic or locally advanced breast cancer(Springer, 2021) Wardley, Andrew; Cortes, Javier; Provencher, Louise; Miller, Kathy; Chien, A. Jo; Rugo, Hope S.; Steinberg, Joyce; Sugg, Jennifer; Tudor, Iulia C.; Huizing, Manon; Young, Robyn; Abramson, Vandana; Bose, Ron; Hart, Lowell; Chan, Stephen; Cameron, David; Wright, Gail S.; Graas, Marie‑Pascale; Neven, Patrick; Rocca, Andrea; Russo, Stefania; Krop, Ian E.; Medicine, School of MedicinePurpose: Androgen receptor (AR) expression occurs in up to 86% of human epidermal growth factor receptor 2-positive (HER2+) breast cancers. In vitro, AR inhibitors enhance antitumor activity of trastuzumab, an anti-HER2 antibody, in trastuzumab-resistant HER2+ cell lines. This open-label, single-arm, phase II study evaluated the efficacy and safety of enzalutamide, an AR-signaling inhibitor, in patients with advanced HER2+ AR+ breast cancer previously treated with trastuzumab. Methods: Eligible patients had measurable or non-measurable evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Eastern Cooperative Oncology Group status ≤ 1, no history of brain metastases, and previously received ≥ 1 anti-HER2 regimen for advanced disease. Patients received 160 mg oral enzalutamide daily and 6 mg/kg intravenous trastuzumab every 21 days until disease progression or unacceptable toxicity. Primary end point was clinical benefit rate at 24 weeks (CBR24); secondary end points included progression-free survival (PFS) and safety. Results: Overall, 103 women were enrolled [median age 60 years (range 34-83)]; 62% had received ≥ 3 lines of prior anti-HER2 therapy. CBR24, comprising patients with confirmed partial responses (5%) and durable stable disease at 24 weeks (19%), was 24% in the efficacy evaluable set (n = 89). CBR24 did not seem related to AR-expression levels or hormone receptor status. Median PFS was 3.4 months (95% confidence interval 2.0-3.8). Overall, 97 (94%) patients experienced treatment-emergent adverse events (TEAEs), with fatigue most common (34%). Dyspnea (4%) and malignant neoplasm progression (3%) were the only TEAEs grade ≥ 3 reported in ≥ 3 patients. 22 patients (21%) reported serious TEAEs. Four patients (4%) experienced fatal, non-drug-related TEAEs. Conclusions: Enzalutamide plus trastuzumab was well tolerated, and a subset of patients in this heavily pretreated population had durable disease control. Determination of biomarkers is needed to identify patients most likely to benefit from this combination.