Browsing by Author "Norton, Larry"

Now showing 1 - 4 of 4
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    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, Katherine
    Women 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.
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    Multiomics in primary and metastatic breast tumors from the AURORA US network finds microenvironment and epigenetic drivers of metastasis
    (Springer Nature, 2023) Garcia-Recio, Susana; Hinoue, Toshinori; Wheeler, Gregory L.; Kelly, Benjamin J.; Garrido-Castro, Ana C.; Pascual, Tomas; De Cubas, Aguirre A.; Xia, Youli; Felsheim, Brooke M.; McClure, Marni B.; Rajkovic, Andrei; Karaesmen, Ezgi; Smith, Markia A.; Fan, Cheng; Gonzalez Ericsson, Paula I.; Sanders, Melinda E.; Creighton, Chad J.; Bowen, Jay; Leraas, Kristen; Burns, Robyn T.; Coppens, Sara; Wheless, Amy; Rezk, Salma; Garrett, Amy L.; Parker, Joel S.; Foy, Kelly K.; Shen, Hui; Park, Ben H.; Krop, Ian; Anders, Carey; Gastier-Foster, Julie; Rimawi, Mothaffar F.; Nanda, Rita; Lin, Nancy U.; Isaacs, Claudine; Marcom, P. Kelly; Storniolo, Anna Maria; Couch, Fergus J.; Chandran, Uma; Davis, Michael; Silverstein, Jonathan; Ropelewski, Alexander; Liu, Minetta C.; Hilsenbeck, Susan G.; Norton, Larry; Richardson, Andrea L.; Symmans, W. Fraser; Wolff, Antonio C.; Davidson, Nancy E.; Carey, Lisa A.; Lee, Adrian V.; Balko, Justin M.; Hoadley, Katherine A.; Laird, Peter W.; Mardis, Elaine R.; King, Tari A.; AURORA US Network; Perou, Charles M.; Medicine, School of Medicine
    The AURORA US Metastasis Project was established with the goal to identify molecular features associated with metastasis. We assayed 55 females with metastatic breast cancer (51 primary cancers and 102 metastases) by RNA sequencing, tumor/germline DNA exome and low-pass whole-genome sequencing and global DNA methylation microarrays. Expression subtype changes were observed in ~30% of samples and were coincident with DNA clonality shifts, especially involving HER2. Downregulation of estrogen receptor (ER)-mediated cell-cell adhesion genes through DNA methylation mechanisms was observed in metastases. Microenvironment differences varied according to tumor subtype; the ER+/luminal subtype had lower fibroblast and endothelial content, while triple-negative breast cancer/basal metastases showed a decrease in B and T cells. In 17% of metastases, DNA hypermethylation and/or focal deletions were identified near HLA-A and were associated with reduced expression and lower immune cell infiltrates, especially in brain and liver metastases. These findings could have implications for treating individuals with metastatic breast cancer with immune- and HER2-targeting therapies.
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    MYBL1 rearrangements and MYB amplification in breast adenoid cystic carcinomas lacking the MYB–NFIB fusion gene
    (Wiley, 2017) Kim, Jisun; Geyer, Felipe C.; Martelotto, Luciano G.; Ng, Charlotte K. Y.; Lim, Raymond S.; Selenica, Pier; Li, Anqi; Pareja, Fresia; Fusco, Nicola; Edelweiss, Marcia; Kumar, Rahul; Gularte-Merida, Rodrigo; Forbes, Andre N.; Khurana, Ekta; Mariani, Odette; Badve, Sunil; Vincent-Salomon, Anne; Norton, Larry; Reis-Filho, Jorge S.; Weigelt, Britta; Pathology and Laboratory Medicine, School of Medicine
    Breast adenoid cystic carcinoma (AdCC), a rare type of triple-negative breast cancer, has been shown to be driven by MYB pathway activation, most often underpinned by the MYB–NFIB fusion gene. Alternative genetic mechanisms, such as MYBL1 rearrangements, have been reported in MYB–NFIB-negative salivary gland AdCCs. Here we report on the molecular characterization by massively parallel sequencing of four breast AdCCs lacking the MYB–NFIB fusion gene. In two cases, we identified MYBL1 rearrangements (MYBL1–ACTN1 and MYBL1–NFIB), which were associated with MYBL1 overexpression. A third AdCC harboured a high-level MYB amplification, which resulted in MYB overexpression at the mRNA and protein levels. RNA-sequencing and whole-genome sequencing revealed no definite alternative driver in the fourth AdCC studied, despite high levels of MYB expression and the activation of pathways similar to those activated in MYB–NFIB-positive AdCCs. In this case, a deletion encompassing the last intron and part of exon 15 of MYB, including the binding site of ERG-1, a transcription factor that may downregulate MYB, and the exon 15 splice site, was detected. In conclusion, we demonstrate that MYBL1 rearrangements and MYB amplification probably constitute alternative genetic drivers of breast AdCCs, functioning through MYBL1 or MYB overexpression. These observations emphasize that breast AdCCs probably constitute a convergent phenotype, whereby activation of MYB and MYBL1 and their downstream targets can be driven by the MYB–NFIB fusion gene, MYBL1 rearrangements, MYB amplification, or other yet to be identified mechanisms. Copyright © 2017 Pathological Society of Great Britain and Ireland.
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    Randomised trial of expressive writing for distressed metastatic breast cancer patients
    (Elsevier, 2012-01-01) Mosher, Catherine E.; DuHamel, Katherine N.; Lam, Joanne; Dickler, Maura; Li, Yuelin; Massie, Mary Jane; Norton, Larry
    Women with metastatic breast cancer and significant psychological distress (N = 87) were assigned randomly to engage in four home-based sessions of expressive writing or neutral writing. Women in the expressive writing group wrote about their deepest thoughts and feelings regarding their cancer, whereas women in the neutral writing group wrote about their daily activities in a factual manner. No statistically significant group differences in existential and psychological well-being, fatigue and sleep quality were found at 8-weeks post-writing. However, the expressive writing group reported significantly greater use of mental health services during the study than the neutral writing group (55% vs. 26%, respectively; p < 0.05). Findings suggest that expressive writing may improve the uptake of mental health services among distressed cancer patients, but is not broadly effective as a psychotherapeutic intervention.