Browsing by Subject "Metastatic breast cancer"
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Item Acceptance and commitment therapy for symptom interference in metastatic breast cancer patients: a pilot randomized trial(Springer Nature, 2018-06) Mosher, Catherine E.; Secinti, Ekin; Li, Ruohong; Hirsh, Adam T.; Bricker, Jonathan; Miller, Kathy D.; Schneider, Bryan; Storniolo, Anna Maria; Mina, Lida; Newton, Erin V.; Champion, Victoria L.; Johns, Shelley A.; Psychology, School of SciencePURPOSE: Breast cancer is the leading cause of cancer mortality in women worldwide. With medical advances, metastatic breast cancer (MBC) patients often live for years with many symptoms that interfere with activities. However, there is a paucity of efficacious interventions to address symptom-related suffering and functional interference. Thus, this study examined the feasibility and preliminary efficacy of telephone-based acceptance and commitment therapy (ACT) for symptom interference with functioning in MBC patients. METHODS: Symptomatic MBC patients (N = 47) were randomly assigned to six telephone sessions of ACT or six telephone sessions of education/support. Patients completed measures of symptom interference and measures assessing the severity of pain, fatigue, sleep disturbance, depressive symptoms, and anxiety. RESULTS: The eligibility screening rate (64%) and high retention (83% at 8 weeks post-baseline) demonstrated feasibility. When examining within-group change, ACT participants showed decreases in symptom interference (i.e., fatigue interference and sleep-related impairment; Cohen's d range = - 0.23 to - 0.31) at 8 and 12 weeks post-baseline, whereas education/support participants showed minimal change in these outcomes (d range = - 0.03 to 0.07). Additionally, at 12 weeks post-baseline, ACT participants showed moderate decreases in fatigue and sleep disturbance (both ds = - 0.43), whereas education/support participants showed small decreases in these outcomes (ds = - 0.24 and - 0.18 for fatigue and sleep disturbance, respectively). Both the ACT and education/support groups showed reductions in depressive symptoms (ds = - 0.27 and - 0.28) at 12 weeks post-baseline. Group differences in all outcomes were not statistically significant. CONCLUSIONS: ACT shows feasibility and promise in improving fatigue and sleep-related outcomes in MBC patients and warrants further investigation.Item Circulating tumour DNA characterisation of invasive lobular carcinoma in patients with metastatic breast cancer(Elsevier, 2022) Davis, Andrew A.; Gerratana, Lorenzo; Clifton, Katherine; Medford, Arielle J.; Velimirovic, Marko; Hensing, Whitney L.; Bucheit, Leslie; Shah, Ami N.; D’Amico, Paolo; Reduzzi, Carolina; Zhang, Qiang; Dai, Charles S.; Denault, Elyssa N.; Bagegni, Nusayba A.; Opyrchal, Mateusz; Ademuyiwa, Foluso O.; Bose, Ron; Gradishar, William J.; Behdad, Amir; Ma, Cynthia X.; Bardia, Aditya; Cristofanilli, Massimo; Medicine, School of MedicineBackground: Limited data exist to characterise molecular differences in circulating tumour DNA (ctDNA) for patients with invasive lobular carcinoma (ILC). We analysed metastatic breast cancer patients with ctDNA testing to assess genomic differences among patients with ILC, invasive ductal carcinoma (IDC), and mixed histology. Methods: We retrospectively analysed 980 clinically annotated patients (121 ILC, 792 IDC, and 67 mixed histology) from three academic centers with ctDNA evaluation by Guardant360™. Single nucleotide variations (SNVs), copy number variations (CNVs), and oncogenic pathways were compared across histologies. Findings: ILC was significantly associated with HR+ HER2 negative and HER2 low. SNVs were higher in patients with ILC compared to IDC or mixed histology (Mann Whitney U test, P < 0.05). In multivariable analysis, HR+ HER2 negative ILC was significantly associated with mutations in CDH1 (odds ratio (OR) 9.4, [95% CI 3.3-27.2]), ERBB2 (OR 3.6, [95% confidence interval (CI) 1.6-8.2]), and PTEN (OR 2.5, [95% CI 1.05-5.8]) genes. CDH1 mutations were not present in the mixed histology cohort. Mutations in the PI3K pathway genes (OR 1.76 95% CI [1.18-2.64]) were more common in patients with ILC. In an independent cohort of nearly 7000 metastatic breast cancer patients, CDH1 was significantly co-mutated with targetable alterations (PIK3CA, ERBB2) and mutations associated with endocrine resistance (ARID1A, NF1, RB1, ESR1, FGFR2) (Benjamini-Hochberg Procedure, all q < 0.05). Interpretation: Evaluation of ctDNA revealed differences in pathogenic alterations and oncogenic pathways across breast cancer histologies with implications for histologic classification and precision medicine treatment.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 Landmark trials in the medical oncology management of metastatic breast cancer(Elsevier, 2021) Lu, Pei; Santa-Maria, Cesar A.; Ballinger, Tarah J.; Sheng, Jennifer Y.; Medicine, School of MedicineSignificant advances in the management of metastatic breast cancer (MBC) have guided more personalized treatment according to disease biology and led to improved survival outcomes and quality of life for patients. In this review, we discuss landmark clinical trials in medical oncology that have shaped the current standard of care for MBC. Combinations of endocrine therapy with cyclin-dependent kinase 4/6 inhibitors have led to substantial improvements in overall survival, thus becoming standard first-line treatment for patients with HR-positive MBC. Inhibition of the PI3K and mTOR pathway is another promising strategy to overcome resistance to endocrine therapy. HER2-targeted therapies have also evolved with the addition of pertuzumab to trastuzumab plus a taxane demonstrating remarkable overall survival advantage in patient with HER2-positive MBC. In second or later line therapies, novel anti-HER2 antibody-drug conjugates and TKIs have durable antitumor activity, survival benefit, and encouraging efficacy in the subgroup of patients with brain metastases. Triple negative breast cancer remains the most challenging subtype due to lack of druggable targets. Immunotherapy for patients with PDL-1 expression on tumor infiltrating immune cells and poly (ADP-ribose) polymerase inhibitors for those with germline BRCA1/2 mutations are the latest approved targeted strategies in this population. Numerous obstacles still exist in treating MBC, especially for patients whose disease develops resistance to available agents. Future research is eagerly awaited to address the optimal sequence or combination of therapies and to identify better biomarkers to guide precision medicine.Item Living with Metastatic Breast Cancer: A Qualitative Analysis of Physical, Psychological, and Social Sequelae(Wiley, 2013) Mosher, Catherine E.; Johnson, Courtney; Dickler, Maura; Norton, Larry; Massie, Mary Jane; DuHamel, KatherineWomen with metastatic breast cancer face a wide range of medical, practical, and emotional challenges that impact their quality of life. Research to date, however, has not focused on the quality-of-life concerns of metastatic breast cancer patients with significant distress. The present study examined a range of concerns among distressed metastatic breast cancer patients, including physical and emotional distress, social functioning, and existential issues. Forty-four distressed women with metastatic breast cancer wrote their deepest thoughts and feelings regarding their illness. These essays were thematically analyzed for effects of the illness on quality of life. Three themes were identified in patients’ essays. First, metastatic breast cancer and its treatment may result in a number of quality-of-life concerns, including physical symptom burden, emotional distress, body image disturbance, and disrupted daily activities. Second, social constraints on disclosure of cancer-related concerns may exacerbate patients’ distress. Third, many women experience a heightened awareness of life’s brevity and search for meaning in their cancer experience. Results highlight a range of quality-of-life concerns following a metastatic breast cancer diagnosis and suggest that addressing social constraints on cancer-related disclosure and the search for meaning may improve patients’ psychological adjustment.Item Low neighborhood socioeconomic status is associated with higher mortality and increased surgery utilization among metastatic breast cancer patients(Elsevier, 2021) Bhattacharyya, Oindrila; Li, Yaming; Fisher, James L.; Tsung, Allan; Eskander, Mariam F.; Hamad, Ahmad; Obeng-Gyasi, Samilia; Economics, School of Liberal ArtsPurpose: Low socioeconomic status (SES) is associated with advanced stage, lower-quality care, and higher mortality among breast cancer patients. The purpose of this study is to examine the association between neighborhood SES (nSES), surgical management, and disease-specific mortality in de novo metastatic breast cancer (MBC) patients in the Surveillance, Epidemiology, and End Results (SEER) Program. Methods: MBC patients ages 18 to 85+ years diagnosed from 2010 through 2016 were identified in SEER. The cohort was divided into low, middle, and high nSES based on the NCI census tract-level index. Univariable and multivariable analyses were used to examine the relationship between nSES, surgery, and disease specific mortality in MBC patients. Results: There were 24,532 de novo MBC patients who met study criteria, with 28.7 % undergoing surgery. Over the study period, surgery utilization decreased across all nSES groups. However, lower nSES was associated with a higher odds of undergoing surgery (low OR 1.25 [1.15-1.36] p < 0.001; middle OR 1.09 [1.01-1.18] p = 0.022; ref high). Living in an area with lower SES was associated with a worse disease specific mortality (low HR 1.24 [1.25, 1.44; ], middle 1.20 [1.1-1.29]: ref high). Specifically, there was a 9.26 month mean survival differences between the lowest (41.02 ± 0.47 months) and highest (50.28 ± 0.47 months) nSES groups. Conclusion: These results suggest area of residence may contribute to differences in surgical management and clinical outcomes among de novo MBC patients. Future studies should examine the contributions of patient characteristics and preferences within the context of surgeon recommendations.Item LyP-1-Modified Oncolytic Adenoviruses Targeting Transforming Growth Factor β Inhibit Tumor Growth and Metastases and Augment Immune Checkpoint Inhibitor Therapy in Breast Cancer Mouse Models(Mary Ann Liebert, Inc., 2020-08) Xu, Weidong; Yang, Yuefeng; Hu, Zebin; Head, Maria; Mangold, Kathy A.; Sullivan, Megan; Wang, Edward; Saha, Poornima; Gulukota, Kamalakar; Helseth, Donald L., Jr.; Guise, Theresa; Prabhkar, Bellur S.; Kaul, Karen; Schreiber, Hans; Seth, Prem; Medicine, School of MedicineWe report here the development of oncolytic adenoviruses (Ads) that have reduced toxicity, enhanced tumor tropism, produce strong antitumor response, and can overcome resistance to immune checkpoint inhibitor therapy in breast cancer. We have shown that LyP-1 receptor (p32) is highly expressed on the surface of breast cancer cells and tumors from cancer patients, and that increased stromal expression of transforming growth factor β-1 (TGFβ-1) is associated with triple-negative breast cancer. Therefore, we constructed oncolytic Ads, AdLyp.sT and mHAdLyp.sT, in which the p32-binding LyP-1 peptide was genetically inserted into the adenoviral fiber protein. Both AdLyp.sT and mHAdLyp.sT express sTGFβRIIFc, a TGFβ decoy that can inhibit TGFβ pathways. mHAdLyp.sT is an Ad5/48 chimeric hexon virus in which hypervariable regions (HVRs 1–7) of Ad5 are replaced with the corresponding Ad48 HVRs. AdLyp.sT and mHAdLyp.sT exhibited better binding, replication, and produced higher sTGFβRIIFc protein levels in breast cancer cell lines compared with Ad.sT or mHAd.sT control viruses without LyP-1 peptide modification. Systemic delivery of mHAdLyp.sT in mice resulted in reduced hepatic/systemic toxicity compared with Ad.sT and AdLyp.sT. Intravenous delivery of AdLyp.sT and mHAdLyp.sT elicited a strong antitumor response in a human MDA-MB-231 bone metastasis model in mice, as indicated by bioluminescence imaging, radiographic tumor burden, serum TRACP 5b and calcium, and body weight analyses. Furthermore, intratumoral delivery of AdLyp.sT in 4T1 model in immunocompetent mice inhibited tumor growth and metastases, and augmented anti-PD-1 and anti-CTLA-4 therapy. Based on these studies, we believe that AdLyp.sT and mHAdLyp.sT can be developed as potential targeted immunotherapy agents for the treatment of breast cancer.Item Pain and Nausea Intensity, Social Function, and Psychological Well-Being among Women with Metastatic Breast Cancer(Sage, 2022-11-01) Senkpeil, Ryan R.; Olson, Julie S.; Fortune, Erica E.; Zaleta, Alexandra K.; Engineering Technology, Purdue School of Engineering and TechnologyAdvances in diagnostics and therapeutics have improved prognosis for metastatic breast cancer (MBC). Yet, treatment and disease burden-including experiences of pain and nausea-present practical and emotional challenges. To better support patients and enhance quality of life, deeper understanding of the pathways linking physical and psychological health is needed. To this end, we examined associations of pain and nausea with depression and anxiety among women with MBC. In doing so, we highlighted social function as a potentially important mechanism in this relationship. This observational, cross-sectional study included 148 predominantly non-Hispanic White, highly educated women living with MBC. Multivariate regression models demonstrated that more intense pain and nausea were significantly associated with higher levels of depression and anxiety (p < .001). Causal mediation analyses confirmed significant indirect effects whereby decreases in social function associated with pain and nausea contributed to depression and anxiety. Thus, our findings illustrate decreased social function as one pathway through which pain and nausea contribute to escalation of depression and anxiety. Our results, therefore, underscore the importance of supporting social function among women with MBC to potentially reduce psychological sequelae of pain and nausea.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.