Abstract
Background: Little is known regarding the effect of somatic tumor genomic testing on patient perceptions and psychological well-being. We previously demonstrated that patient perceptions of ...care can be negatively affected if their next cancer treatment is not supported by the genomic test. To further understand this, we investigated psychological effects of genomic testing, as well as sociodemographic and genomic comprehension factors that may attenuate these effects. Methods: In a prospective, single institution, single-arm trial, patients with metastatic breast cancer underwent next-generation sequencing (NGS) using Foundation Medicine at study entry, with sequencing results released to providers at time of next disease progression. We evaluated patient survey data before and after NGS, including questions about psychosocial characteristics, genetic comprehension, and perceived risks and expectations of the genomic testing. We evaluated psychosocial characteristics using 4 validated psychology measures: the Center for Epidemiologic Studies Depression Scale (CES-D), the Beck Anxiety Inventory (BAI), the Trust in Physician Scale (TPS), and the Communication and Attitudinal Self-Efficacy scale for Cancer (CASE-cancer). CASE-cancer measures self-efficacy, how confident patients are in their ability to navigate their cancer care. Genetic comprehension was assessed with a 7-question objective measure and a 6-question subjective measure. No formal genetic education was provided, but the informed consent process included an introduction to NGS. We included exploratory questions on perceived risks and expectations of NGS. Results: Among the 58 patients who completed the pre-NGS survey, we found high rates of depression (38%) and anxiety (47%) using validated metrics. Depression and anxiety were positively correlated (Pearson’s r=0.61; p<0.0001) but both were negatively correlated with self-efficacy (Pearson’s r=-0.43 and -0.42 for depression and anxiety, respectively; p=0.001 for both). Baseline genetic knowledge was significantly lower for non-white and lower income status patients (p=0.04 and 0.001, respectively). Genetic knowledge was not associated with any of the 4 validated psychological measures. The validated psychological measures were not associated with demographic characteristics, treatment decisions, or number of treatment options offered by the NGS test. The average time between pre-test and post-test surveys was 7.6 months. Additionally, the validated psychology measures did not significantly change from pre- to post-study (n=40 patients). However, there was a strong trend of self-efficacy decreasing from pre- to post-NGS testing (p=0.05). Subjectively, patients gained confidence in their ability to teach others about genetics from the start (33% “confident”) to the end of study (46%). Yet, objective comprehension of genetics remained modest throughout the study, with an average score of 72% in both the pre- and post-NGS surveys. The exploratory patient perception questions revealed that 33% of patients felt learning their cancer had a high chance of progressing would be too much to cope with emotionally. Conclusions: This is the first study, to our knowledge, to longitudinally evaluate multiple validated psychological metrics in MBC. NGS did not have a significant effect on depression, anxiety, or trust, but there was a trend towards decreased self-efficacy. This may be influenced by the already high rates of depression, anxiety, and trust in this population. In this study, patient genetic knowledge was limited and associated with race and income. These findings raise important questions about how to support MBC patient emotional well-being and how to improve comprehension of somatic genomic testing in future studies.
Citation Format: Elizabeth J Adams, Sarah Asad, Mahmoud Abdel-Rasoul, Raquel E Reinbolt, Robert Wesolowski, Kaitlyn Tolliver, Susan Gillespie, Katherine A Collier, Anne Noonan, Sargar Sardesai, Jeffrey VanDeusen, Nicole Williams, Charles L Shapiro, Erin R Macre, Bhuvaneswari Ramaswamy, Clara N Lee, Maryam B Lustberg, Daniel G Stover. Perceptions of somatic genomic testing in patients with metastatic breast cancer: Psychosocial factors, emotional well-being, and genetic comprehension abstract. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-10-03.
Abstract
Background: Many individuals diagnosed with MBC and their loved ones struggle to find tailored disease specific resources and support (Mayer 2010). Due to a variety of constraints, ...oncologists are often challenged to adequately address MBC patients’ needs and concerns within the space of a standard medical visit. Managing expectations and emotions, as well as providing education on the complexities of the MBC journey, is daunting. Moreover, survivorship care to date has not addressed the unique needs of the rapidly growing population of individuals living with MBC. The Living Well with Advanced Breast Cancer Clinic (LWABC) was created to address these gaps in care and to offer comprehensive and personalized consultations for MBC patients.
Methods: MBC-specific support services are provided in one multidisciplinary setting, providing a comprehensive experience that incorporates expert medical oncology and symptom education, integrative medicine, palliative medicine, dietetics, and a personalized check out experience with LWABC nurses. MBC patients are referred by their primary medical oncologists for a one-time visit to this clinic. Second opinions are not provided in LWABC; the visit is strictly focused on education for the patient and their caregivers. Each patient receives multidisciplinary one-on-one education from a medical oncologist using audio-visual aides, mind-body interaction by an integrative medicine physician, personalized dietary recommendations by an experienced dietician, and an introduction to the role of palliative care in improving quality of life while living with cancer. Services also include personalized care planning for supportive care, future trials, and referrals for other resources during their 2.5 hour visit.
Results: Between October 2017-February 2019, 73 patients were scheduled twice a month in the half day LWABC clinic; 44 completed consultations. All patients had MBC with all subtypes represented: ER+PR+HER2- (28, 38%), HER2+ (6, 8%) and ER-PR-HER2- (6, 8%). Median age was 60 years (range 36-75). Median time from time of MBC diagnosis to clinic visit was 2 years (range 1-7 years). Referrals placed at the completion of the visit included: social work (5, 11%), psychosocial oncology (9, 20%), physical therapy (12, 27%), occupational therapy (4, 9%), and palliative medicine (3, 6%). Of the 28 patients (63%) who completed satisfaction surveys regarding their experience at the LWABC, 14 (63%) reported a 5/5 experience in every section reviewed. On average, overall experience was evaluated as a 4.82/5 SD 0.42. Comments from participants included: “I feel less fearful and more empowered. Knowledge is power. I am now armed with accurate and useful information and am less uncertain”; “I appreciated the relaxed setting that encouraged conversation. I may have received brochures in the past regarding different options but this setting changes how receptive I am to different treatments.” Many patients reported wanting additional follow up visits in the future. Barriers included provider availability, financial reimbursement, and time for patient travel/additional medical appointments.
Conclusion: The LWABC consultative model is an innovative adjunct to the traditional medical oncology visit and provides critically needed education and exposure of MBC patients to supportive care services within a relaxed and intimate setting while screening for unmet needs. Feasibility and satisfaction with this model of care was high; patients felt empowered by the knowledge delivered during the sessions. Additional expansion opportunities, including an introduction to physical therapy and psychosocial oncology, are planned. To our knowledge, this is a unique and first-of a kind resource offered to patients with MBC.
Citation Format: Bhuvaneswari Ramaswamy, Raquel R Reinbolt, Heidi Basinger, Lindsey Radcliff, Brittany Unthank, Kathy Hauck, Kelly Hoffman, Neil A. Borja, Sandra Pedraza, Erin E. Holley, Lanny O. Ntukidem, Mathew Cherian, Anne Noonan, Sagar Sardesai, Daniel G Stover, Jeffrey VanDeusen, Nicole Williams, Robert Wesolowski, Maryam B. Lustberg. Living well with advanced breast cancer: A unique multidisciplinary clinic designed to empower and educate patients with metastatic breast cancer (MBC) abstract. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-13-06.
Abstract
Background: Many breast cancer (BC) patients, particularly those who receive chemotherapy (chemo), experience affective symptoms and cognitive changes that can negatively impact their ...quality of life. Causal links between inflammatory mediators and the development of depressive-like behavior and cognitive defects, have been established in mouse models, including studies by our group showing increased microglial activation following chemo (A.C DeVries et al). Microglia are resident immune cells of the brain, which release proinflammatory cytokines when activated. Doxorubicin (DOX) induces microglial activation in the brain. Minocycline, a second generation tetracycline, has been shown to suppress inflammation by inhibiting microglial activation in CNS disease models. We hypothesize that (1) chemo activates microglia in the brains of women being treated for BC, which can precipitate or exacerbate depression, anxiety and cognitive deficits and (2) Minocycline administration during neoadjuvant or adjuvant chemo will prevent chemo-induced microglial activation and will reduce affective and cognitive symptom burden. Trial Design: This is a single center, Phase II, double blinded randomized study of minocycline (100 mg twice a day) vs placebo twice a day in women with BC receiving DOX-based or other chemo for BC. Pts will be randomized to either oral minocycline or placebo for up to a 1 week loading period plus chemo treatment period and an optional subsequent 2 week period. Eligibility Criteria: Women diagnosed with BC stages I-III initiating first line adjuvant or neoadjuvant chemo. Aims: (1) to evaluate symptoms related to anxiety and depression and cognitive changes during and after chemo completion (2) to evaluate markers of neuro inflammation as assessed by blood based inflammatory cytokines and central markers of inflammation and microglia activation using 1 F-Fludeoxyglucose and 11C-PK11195 positron emission tomography. Primary endpoints are changes in Center for Epidemiological Studies Depression Scale (CES-D) and State Trait Anxiety Index (STAI) from baseline to end of study after minocycline vs placebo intervention. Secondary endpoints are changes in cognitive function during chemo using validated cognitive testing including N-Back Test, Behavioural Rating Inventory of Executive Function (BRIEF) and the Multifactorial Memory Questionnaire Ability Scale (MMQ). Statistical Methods: Primary analysis for efficacy will be intention-to-treat. The main objective is to preliminarily evaluate the effect of minocycline on chemo-induced depressive symptoms in terms of changes in CES-D and STAI scores. Mixed models will be used to evaluate cognitive function changes. A sample size of 23 per group, will give 80% power to detect an effect size of 0.74 standard deviation (SD) difference between the 2 groups at significance level of 0.10 based on a 2 sided two-sample t-test. From our experience, attrition of less than 20% is expected for studies in this patient population in our center, and to account for this, we plan to recruit up to 60 patients. 16 of 46 evaluable pts have been accrued to date. Accrual started in January 2016. Funded by Pelotonia grant from The OSUCCC. Contact: Study PI: Maryam.lustberg@osumc.edu
Citation Format: Boutrid H, Reinbolt R, Knopp M, Williams N, VanDeusen J, Sardesai S, Noonan A, Flora L, Gleich E, Pan X, Berger M, Vargo C, Wesolowski R, Ramaswamy B, DeVries AC, Lustberg M. Does minocycline mitigate chemotherapy induced neuroinflammation? A phase II randomized placebo controlled study abstract. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT2-05-03.
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TPS1127
Background: Heat shock protein 90 (HSP90) is a molecular chaperone which is necessary for proper folding and stabilization of proteins. Client proteins of HSP90 include many ...oncogenic proteins known to be over-activated in triple negative breast cancer such as AKT, EGFR, members of RAS/MAPK signaling pathway and androgen receptor. High expression of HSP90 in breast cancer has been associated with poor outcome. In addition, over-expression of HSP90 client proteins such as AKT and c-RAF has been implicated in paclitaxel resistance. Onalespib (AT13387) is a synthetic non-ansamycin small molecule that acts as an inhibitor of HSP90 by binding to the amino terminal of the protein and has dissociation constant (Kd) of 0.71 nM. Methods: Patients with inoperable or metastatic, triple negative or < 10% hormone receptor positive breast cancer are treated with onalespib and paclitaxel on days 1, 8, 15 every 28 days. Paclitaxel is given at a standard dose of 80 mg/m2 while the dose of onalespib is gradually increased using standard 3+3 design (see table). In order to assess the effect of each drug on pharmacokinetics of the other drug, onalespib is given on day -7 prior to cycle 1 and skipped on day 1 of cycle 1 during which paclitaxel is administered alone. The primary objective of the study is to determine recommended phase II dose and assess the toxicity profile of the combination. The secondary objectives include pharmacokinetic of each agent. Overall response rate, response duration and progression-free survival will also be assessed. The study is currently enrolling patients to dose level 2. Clinical trial information: NCT02474173. Table: see text
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