Browsing by Author "Bales, Casey L."

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    Association of Circulating Tumor DNA and Circulating Tumor Cells After Neoadjuvant Chemotherapy With Disease Recurrence in Patients With Triple-Negative Breast Cancer: Preplanned Secondary Analysis of the BRE12-158 Randomized Clinical Trial
    (American Medical Association, 2020-09) Radovich, Milan; Jiang, Guanglong; Hancock, Bradley A.; Chitambar, Christopher; Nanda, Rita; Falkson, Carla; Lynce, Filipa C.; Gallagher, Christopher; Isaacs, Claudine; Blaya, Marcelo; Paplomata, Elisavet; Walling, Radhika; Daily, Karen; Mahtani, Reshma; Thompson, Michael A.; Graham, Robert; Cooper, Maureen E.; Pavlick, Dean C.; Albacker, Lee A.; Gregg, Jeffrey; Solzak, Jeffrey P.; Chen, Yu-Hsiang; Bales, Casey L.; Cantor, Erica; Shen, Fei; Storniolo, Anna Maria V.; Badve, Sunil; Ballinger, Tarah J.; Chang, Chun-Li; Zhong, Yuan; Savran, Cagri; Miller, Kathy D.; Schneider, Bryan P.; Medical and Molecular Genetics, School of Medicine
    Importance: A significant proportion of patients with early-stage triple-negative breast cancer (TNBC) are treated with neoadjuvant chemotherapy. Sequencing of circulating tumor DNA (ctDNA) after surgery, along with enumeration of circulating tumor cells (CTCs), may be used to detect minimal residual disease and assess which patients may experience disease recurrence. Objective: To determine whether the presence of ctDNA and CTCs after neoadjuvant chemotherapy in patients with early-stage TNBC is independently associated with recurrence and clinical outcomes. Design, setting, and participants: A preplanned secondary analysis was conducted from March 26, 2014, to December 18, 2018, using data from 196 female patients in BRE12-158, a phase 2 multicenter randomized clinical trial that randomized patients with early-stage TNBC who had residual disease after neoadjuvant chemotherapy to receive postneoadjuvant genomically directed therapy vs treatment of physician choice. Patients had blood samples collected for ctDNA and CTCs at time of treatment assignment; ctDNA analysis with survival was performed for 142 patients, and CTC analysis with survival was performed for 123 patients. Median clinical follow-up was 17.2 months (range, 0.3-58.3 months). Interventions: Circulating tumor DNA was sequenced using the FoundationACT or FoundationOneLiquid Assay, and CTCs were enumerated using an epithelial cell adhesion molecule-based, positive-selection microfluidic device. Main outcomes and measures: Primary outcomes were distant disease-free survival (DDFS), disease-free survival (DFS), and overall survival (OS). Results: Among 196 female patients (mean [SD] age, 49.6 [11.1] years), detection of ctDNA was significantly associated with inferior DDFS (median DDFS, 32.5 months vs not reached; hazard ratio [HR], 2.99; 95% CI, 1.38-6.48; P = .006). At 24 months, DDFS probability was 56% for ctDNA-positive patients compared with 81% for ctDNA-negative patients. Detection of ctDNA was similarly associated with inferior DFS (HR, 2.67; 95% CI, 1.28-5.57; P = .009) and inferior OS (HR, 4.16; 95% CI,1.66-10.42; P = .002). The combination of ctDNA and CTCs provided additional information for increased sensitivity and discriminatory capacity. Patients who were ctDNA positive and CTC positive had significantly inferior DDFS compared with those who were ctDNA negative and CTC negative (median DDFS, 32.5 months vs not reached; HR, 5.29; 95% CI, 1.50-18.62; P = .009). At 24 months, DDFS probability was 52% for patients who were ctDNA positive and CTC positive compared with 89% for those who were ctDNA negative and CTC negative. Similar trends were observed for DFS (HR, 3.15; 95% CI, 1.07-9.27; P = .04) and OS (HR, 8.60; 95% CI, 1.78-41.47; P = .007). Conclusions and relevance: In this preplanned secondary analysis of a randomized clinical trial, detection of ctDNA and CTCs in patients with early-stage TNBC after neoadjuvant chemotherapy was independently associated with disease recurrence, which represents an important stratification factor for future postneoadjuvant trials.
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    “How is it going to help?”: Exploring Black breast cancer patients’ questions about biomarker testing to predict chemotherapy-induced peripheral neuropathy
    (Elsevier, 2022-12-13) Head, Katharine J.; Hayes, Lisa R.; Miller, Nadia E.; Shakil, Safia; Bales, Casey L.; Schneider, Bryan P.; Communication Studies, School of Liberal Arts
    Objective: Many Black breast cancer patients experience chemotherapy-induced peripheral neuropathy (CIPN). Our study assessed Black breast cancer patients' questions about a biomarker test that can predict likelihood of CIPN. Methods: Nineteen Black women who were previous/current breast cancer patients participated in focus groups. Researchers briefly explained CIPN and the biomarker test, and then participants were asked what questions they would have about the test and its use in treatment decisions. These participant-voiced questions composed the data for this study and were analyzed using thematic analysis. Results: Participants' questions centered on six themes: reasons for the test, effect on timeline of breast cancer treatment, testing procedure, limits of test (including accuracy), research done to develop this test (including research participants), and concerns about personal information connected to the test (including DNA). Conclusion: This study provides an exploratory look at questions that Black breast cancer patients may have about toxicity biomarker testing use in breast cancer treatment decisions. Innovation: These findings provide a starting point for developing patient-centered approaches for integrating this precision medicine tool into clinical care. The methodological choice to generate participants' questions (rather than answers to a question) led to robust, actionable data.
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    The impact of SBF2 on taxane-induced peripheral neuropathy
    (PLOS, 2022-01-05) Cunningham, Geneva M.; Shen, Fei; Wu, Xi; Cantor, Erica L.; Gardner, Laura; Philips, Santosh; Jiang, Guanglong; Bales, Casey L.; Tan, Zhiyong; Liu, Yunlong; Wan, Jun; Fehrenbacher, Jill C.; Schneider, Bryan P.; Medical and Molecular Genetics, School of Medicine
    Taxane-induced peripheral neuropathy (TIPN) is a devastating survivorship issue for many cancer patients. In addition to its impact on quality of life, this toxicity may lead to dose reductions or treatment discontinuation, adversely impacting survival outcomes and leading to health disparities in African Americans (AA). Our lab has previously identified deleterious mutations in SET-Binding Factor 2 (SBF2) that significantly associated with severe TIPN in AA patients. Here, we demonstrate the impact of SBF2 on taxane-induced neuronal damage using an ex vivo model of SBF2 knockdown of induced pluripotent stem cell-derived sensory neurons. Knockdown of SBF2 exacerbated paclitaxel changes to cell viability and neurite outgrowth while attenuating paclitaxel-induced sodium current inhibition. Our studies identified paclitaxel-induced expression changes specific to mature sensory neurons and revealed candidate genes involved in the exacerbation of paclitaxel-induced phenotypes accompanying SBF2 knockdown. Overall, these findings provide ex vivo support for the impact of SBF2 on the development of TIPN and shed light on the potential pathways involved.
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    Leveraging a relationship-based sexual health framework for sexual risk prevention in adolescent men in the United States
    (CSIRO, 2017) Hensel, Devon J.; Bales, Casey L.; Taylor, Julia F.; Fortenberry, J. Dennis; Medicine, School of Medicine
    Background: Studies link sexual health to lower sexual risk in adolescent women, yet no empirical literature evaluates these associations in adolescent men. Methods: Data were drawn from a longitudinal cohort study of sexual relationships and sexual behaviour among adolescent men (n = 72; 14–16 years) in the US. Participants contributed quarterly partner-specific interviews, from which sexual health information and partnered sexual behaviours were drawn. A multidimensional measure of sexual health was constructed and linked to partnered outcomes, including oral–genital, vaginal and anal sex, condom use, partner concurrency and intimate partner violence. Random intercept, mixed-effects linear, ordinal logistic or binary logistic regression were for analyses. Models controlled for participant age, race/ethnicity and relationship length. Results: Adolescent men contributed 651 unique partner-specific interviews. A higher sexual health score with partners was significantly associated with more frequent oral–genital and vaginal sex, as well as higher condom use, lower partner concurrency and lower received and perpetuated intimate partner violence. Conclusion: Positive sexually related experiences in adolescent men contribute to a core of sexual wellbeing, which in turn is linked to lower levels of sexual risk with partners. The present study data support both developmental and public health applications of sexual health, with attention on promoting healthy sexuality as well as risk reduction. Higher sexual health among adolescent men from the US is associated with more frequent condom use, lower partner concurrency and less frequent intimate partner violence. Young men’s exercising the skills associated with healthy sexuality may also reinforce the skills needed to both enjoy sexuality with partners and to avoid adverse sexual outcomes.