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Browsing by Author "Storniolo, Anna Maria"
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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 Acquisition, processing, and single-cell analysis of normal human breast tissues from a biobank(Cell Press, 2021-12-16) Bhat-Nakshatri, Poornima; Marino, Natascia; Gao, Hongyu; Liu, Yunlong; Storniolo, Anna Maria; Nakshatri, Harikrishna; Surgery, School of MedicineThe Komen Tissue Bank is the only biorepository in the world for normal breast tissues from women. Below we report the acquisition and processing of breast tissue from volunteer donors and describe an experimental and analysis pipeline to generate a single-cell atlas. This atlas is based on single-cell RNA-seq and is useful to derive breast epithelial cell subcluster-specific gene expression signatures, which can be applied to breast cancer gene expression data to identify putative cell-of-origin. For complete details on the use and execution of this protocol, please refer to Bhat-Nakshatri et al. (2021).Item Association between CYP2D6 genotype and tamoxifen-induced hot flashes in a prospective cohort(Springer, 2009-10) Henry, N. Lynn; Rae, James M.; Li, Lang; Azzouz, Faouzi; Skaar, Todd C.; Desta, Zereunesay; Sikora, Matthew J.; Philips, Santosh; Nguyen, Anne T.; Storniolo, Anna Maria; Hayes, Daniel F.; Flockhart, David A.; Stearns, VeredWomen with reduced CYP2D6 activity have low endoxifen concentrations and likely worse long term benefits from tamoxifen. We investigated the association between CYP2D6 genotype and tamoxifen-induced hot flashes in a prospective cohort. We collected hot flash frequency and severity data over 12 months from 297 women initiating tamoxifen. We performed CYP2D6 genotyping using the AmpliChip CYP450 test and correlated inherited genetic polymorphisms in CYP2D6 and tamoxifen-induced hot flashes. Intermediate metabolizers had greater mean hot flash scores after 4 months of tamoxifen therapy (44.3) compared to poor metabolizers (20.6, P = 0.038) or extensive metabolizers (26.9, P = 0.011). At 4 months, we observed a trend toward fewer severe hot flashes in poor metabolizers compared to intermediate plus extensive metabolizers (P = 0.062). CYP2D6 activity may be a modest predictive factor for tamoxifen-induced hot flashes. The presence or absence of hot flashes should not be used to determine tamoxifen's efficacy.Item Automated lesion detection of breast cancer in [18F] FDG PET/CT using a novel AI-Based workflow(Frontiers, 2022-11-14) Leal, Jeffrey P.; Rowe, Steven P.; Stearns, Vered; Connolly, Roisin M.; Vaklavas, Christos; Liu, Minetta C.; Storniolo, Anna Maria; Wahl, Richard L.; Pomper, Martin G.; Solnes, Lilja B.; Medicine, School of MedicineApplications based on artificial intelligence (AI) and deep learning (DL) are rapidly being developed to assist in the detection and characterization of lesions on medical images. In this study, we developed and examined an image-processing workflow that incorporates both traditional image processing with AI technology and utilizes a standards-based approach for disease identification and quantitation to segment and classify tissue within a whole-body [18F]FDG PET/CT study. Methods One hundred thirty baseline PET/CT studies from two multi-institutional preoperative clinical trials in early-stage breast cancer were semi-automatically segmented using techniques based on PERCIST v1.0 thresholds and the individual segmentations classified as to tissue type by an experienced nuclear medicine physician. These classifications were then used to train a convolutional neural network (CNN) to automatically accomplish the same tasks. Results Our CNN-based workflow demonstrated Sensitivity at detecting disease (either primary lesion or lymphadenopathy) of 0.96 (95% CI [0.9, 1.0], 99% CI [0.87,1.00]), Specificity of 1.00 (95% CI [1.0,1.0], 99% CI [1.0,1.0]), DICE score of 0.94 (95% CI [0.89, 0.99], 99% CI [0.86, 1.00]), and Jaccard score of 0.89 (95% CI [0.80, 0.98], 99% CI [0.74, 1.00]). Conclusion This pilot work has demonstrated the ability of AI-based workflow using DL-CNNs to specifically identify breast cancer tissue as determined by [18F]FDG avidity in a PET/CT study. The high sensitivity and specificity of the network supports the idea that AI can be trained to recognize specific tissue signatures, both normal and disease, in molecular imaging studies using radiopharmaceuticals. Future work will explore the applicability of these techniques to other disease types and alternative radiotracers, as well as explore the accuracy of fully automated and quantitative detection and response assessment.Item Characterizing Burden, Role Strains and Psychological Distress of Husbands of Breast Cancer Patients During Treatment and Beyond(Wolters Kluwer, 2011) Wagner, Christina D.; Das, Lala Tanmoy; Bigatti, Silvia M.; Storniolo, Anna MariaBackground: Husbands, as the primary providers of support for women with breast cancer, can experience significant burden and role strain, but also perceive positive aspects to the caregiving. Little is known about the specific caregiving tasks husbands perform, for how long, or how burden and positive aspects relate to later psychological distress. Objective: Our primary aim was to better characterize the caregiving responsibilities and role strains of husbands during active cancer treatment and 1 year later. We also evaluated positive aspects during active treatment. Our second aim was to determine which of these predicted psychological distress 1 year later. Methods: Husbands of women undergoing chemotherapy for breast cancer completed a battery of surveys during the time of wives' treatment and again 1 year later. Results: Husbands performed a variety of caregiving tasks for wives during and after breast cancer treatment and also reported benefits associated with caregiving. Breast cancer-related worries were high at both time points. At 1 year after treatment, role strains improved in the social domain but worsened in the domestic domain. Domestic strains during active treatment were the strongest predictor of 1-year distress. Conclusions: Husbands who report persistent domestic role strain are at high risk for continued psychological distress following their wives' breast cancer treatment. Implications for practice: Health care providers should monitor husbands' caregiver burden regularly. Providing couples with resources to reduce domestic role strain (such as social support and communication training) may prevent or alleviate psychological distress in these husbands.Item Depressive rumination and cognitive processes associated with depression in breast cancer patients and their spouses(Families, Systems, & Health Journal, 2014) Steiner, Jennifer L.; Wagner, Christina D.; Bigatti, Silvia M.; Storniolo, Anna MariaDepression is common among patients with breast cancer (BC) and their spouses. The diagnosis of BC often results in negative cognitive processes, such as appraisals of harm/loss, intrusive thoughts, and depressive rumination, all of which contribute to the occurrence of depression in both the patient and spouse. The present research is a cross-sectional exploration of the mediating role of depressive rumination in the relationships of intrusive thoughts and appraisal of harm/loss with depression, in a sample of 56 BC patients and their partners. We hypothesized that depressive rumination would mediate the relationships between cognitive processes and depression in both BC patient and their partners. Participants completed self-report measures of depressive symptoms, depressive rumination, cognitive appraisals, and intrusive thoughts. Path analyses using hierarchical linear regression were conducted to assess the relationships among variables. Results indicated that for BC patients, harm/loss appraisals and intrusive thoughts had direct effects on depression; only harm/loss appraisals had indirect effects through depressive rumination. For partners, both harm/loss appraisal and intrusive thoughts had direct effects on depression, and both had indirect effects through depressive rumination. Dyadic analysis showed no relation of partner cognitive variables with patient depression or patient cognitive variables with partner depression. Findings show that the perseverative practice of dwelling on these negative thoughts of loss and harm relates to depressive symptoms. Rumination may act as 1 possible mechanism by which intrusive thoughts and harm/loss appraisals lead to depressive symptoms.Item DNA methylation age is elevated in breast tissue of healthy women(Springer, 2017-07) Sehl, Mary E.; Henry, Jill E.; Storniolo, Anna Maria; Ganz, Patricia A.; Horvath, Steve; Medicine, School of MedicineBACKGROUND: Limited evidence suggests that female breast tissue ages faster than other parts of the body according to an epigenetic biomarker of aging known as the "epigenetic clock." However, it is unknown whether breast tissue samples from healthy women show a similar accelerated aging effect relative to other tissues, and what could drive this acceleration. The goal of this study is to validate our initial finding of advanced DNA methylation (DNAm) age in breast tissue, by directly comparing it to that of peripheral blood tissue from the same individuals, and to do a preliminary assessment of hormonal factors that could explain the difference. METHODS: We utilized n = 80 breast and 80 matching blood tissue samples collected from 40 healthy female participants of the Susan G. Komen Tissue Bank at the Indiana University Simon Cancer Center who donated these samples at two time points spaced at least a year apart. DNA methylation levels (Illumina 450K platform) were used to estimate the DNAm age. RESULTS: DNAm age was highly correlated with chronological age in both peripheral blood (r = 0.94, p < 0.0001) and breast tissues (r = 0.86, p < 0.0001). A measure of epigenetic age acceleration (age-adjusted DNAm Age) was substantially increased in breast relative to peripheral blood tissue (p = 1.6 × 10-11). The difference between DNAm age of breast and blood decreased with advancing chronologic age (r = -0.53, p = 4.4 × 10-4). CONCLUSIONS: Our data clearly demonstrate that female breast tissue has a higher epigenetic age than blood collected from the same subject. We also observe that the degree of elevation in breast diminishes with advancing age. Future larger studies will be needed to examine associations between epigenetic age acceleration and cumulative hormone exposure.Item Dual TGFβ/BMP Pathway Inhibition Enables Expansion and Characterization of Multiple Epithelial Cell Types of the Normal and Cancerous Breast(American Association for Cancer Research, 2019-07-01) Prasad, Mayuri; Kumar, Brijesh; Bhat-Nakshatri, Poornima; Anjanappa, Manjushree; Sandusky, George; Miller, Kathy D.; Storniolo, Anna Maria; Nakshatri, Harikrishna; Surgery, School of MedicineFunctional modeling of normal breast epithelial hierarchy and stromal-epithelial cell interactions have been difficult due to inability to obtain sufficient stem-progenitor-mature epithelial and stromal cells. Recently reported epithelial reprogramming assay has partially overcome this limitation, but cross contamination of cells from the feeder layer is a concern. The purpose of this study was to develop a feeder-layer independent inexpensive method to propagate multiple cell types from limited tissue resources. Cells obtained after enzymatic digestion of tissues collected at surgery or by core-needle biopsies were plated on tissue culture dishes pre-coated with laminin-5-rich conditioned media from the rat bladder tumor cell line 804G and a defined growth media with inhibitors of ROCK, TGFβ, and BMP signaling. Cells were characterized by flow cytometry, mammosphere assay, 3D cultures, and xenograft studies. Cells from the healthy breasts included CD10+/EpCAM- basal/myoepithelial, CD49f+/EpCAM+ luminal progenitor, CD49f-/EpCAM+ mature luminal, CD73+/EpCAM+/CD90- rare endogenous pluripotent somatic stem, CD73+/CD90+/EpCAM-, Estrogen Receptor alpha (ERα)-expressing ALCAM (CD166)+/EpCAM+, and ALDFLUOR+ stem/luminal progenitor subpopulations. Epithelial cells were luminal (KRT19+), basal (KRT14+) or dual positive luminal/basal hybrid cells. While breast cells derived from BRCA1, BRCA2, and PALB2 mutation carriers did not display unique characteristics, cells from women with breast cancer protective alleles showed enhanced differentiation. Cells could also be propagated from primary tumors and metastasis of breast, ovarian, and pancreatic cancer-neuroendocrine subtype. Xenograft studies confirmed tumorigenic properties of tumor-derived cells.Item Effects of SLCO1B1 polymorphisms on plasma estrogen concentrations in women with breast cancer receiving aromatase inhibitors exemestane and letrozole(Future Medicine, 2019-06-13) Dempsey, Jacqueline M.; Kidwell, Kelley M.; Gersch, Christina L; Pesch, Andrea M; Desta, Zeruesenay; Storniolo, Anna Maria; Stearns, Vered; Skaar, Todd C.; Hayes, Daniel F; Henry, N Lynn; Rae, James M; Hertz, Daniel L; Medicine, School of MedicineAim: This study tested for associations between SLCO1B1 polymorphisms and circulating estrogen levels in women with breast cancer treated with letrozole or exemestane. Patients & methods: Postmenopausal women with hormone-receptor positive breast cancer were genotyped for SLCO1B1*5 (rs4149056) and rs10841753. Pretreatment and on-treatment plasma estrogens and aromatase inhibitor (AI) concentrations were measured. Regression analyses were performed to test for pharmacogenetic associations with estrogens and drug concentrations. Results: SLCO1B1*5 was associated with elevated pretreatment estrone sulfate and an increased risk of detectable estrone concentrations after 3 months of AI treatment. Conclusion: These findings suggest SLCO1B1 polymorphisms may have an effect on estrogenic response to AI treatment, and therefore may adversely impact the anticancer effectiveness of these agents.Item Estrogen receptor genotypes influence hot flash prevalence and composite score before and after tamoxifen therapy.(ASCO, 2008-12-20) Jin, Yan; Hayes, Daniel F.; Li, Lang; Robarge, Jason D.; Skaar, Todd C.; Philips, Santosh; Nguyen, Anne; Schott, Anne; Hayden, Jill; Lemler, Suzanne; Storniolo, Anna Maria; Flockhart, David A.; Stearns, VeredPURPOSE: Hot flashes are common and frequently lead to drug discontinuation among women prescribed tamoxifen. We determined whether genetic polymorphisms in estrogen receptors (ESRs) alpha and beta (ESR1 and ESR2, respectively) are associated with tamoxifen-induced hot flashes. PATIENTS AND METHODS: We determined ESR1 PvuII and XbaI and ESR2-02 genotypes in 297 women who were initiating tamoxifen. One-week hot flash diaries were collected to calculate a hot flash score (frequency x severity) before and 1, 4, 8, and 12 months after starting tamoxifen. RESULTS: Approximately 80% of 297 participants reported hot flashes before or during the first year of tamoxifen. After 4 months of tamoxifen, premenopausal women who did not receive adjuvant chemotherapy had a four-fold increase in hot flash score (from 5.9 to 23.6; P = .003) compared with a 1.17-fold increase (from 19.6 to 23; P = .34) in those who received chemotherapy. In premenopausal women, increased number of ESR1 PvuII and XbaI CG alleles was associated with higher baseline hot flash scores compared with those who had other haplotypes (P = .0026). At 4 months, postmenopausal women with ESR1 PvuII CC and ESR2-02 GG genotypes had 4.6 times increases in hot flash scores than other postmenopausal women (56 v 12; P = .0007). Women who had the ESR2-02 AA genotype were significantly less likely to experience tamoxifen-induced hot flashes than women who carried at least one ESR-02 G allele (hazard ratio, 0.26; 95% CI, 0.10 to 0.63; P = .001). CONCLUSION: Knowledge of menopausal status, prior chemotherapy, and ESR genotype may help predict which women are most likely to suffer hot flashes during tamoxifen treatment.