Browsing by Author "Benfante, Nicole"

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    Genetic Factors Associated with Prostate Cancer Conversion from Active Surveillance to Treatment
    (Elsevier, 2022) Jiang, Yu; Meyers, Travis J.; Emeka, Adaeze A.; Folgosa Cooley, Lauren; Cooper, Phillip R.; Lancki, Nicola; Helenowski, Irene; Kachuri, Linda; Lin, Daniel W.; Stanford, Janet L.; Newcomb, Lisa F.; Kolb, Suzanne; Finelli, Antonio; Fleshner, Neil E.; Komisarenko, Maria; Eastham, James A.; Ehdaie, Behfar; Benfante, Nicole; Logothetis, Christopher J.; Gregg, Justin R.; Perez, Cherie A.; Garza, Sergio; Kim, Jeri; Marks, Leonard S.; Delfin, Merdie; Barsa, Danielle; Vesprini, Danny; Klotz, Laurence H.; Loblaw, Andrew; Mamedov, Alexandre; Goldenberg, S. Larry; Higano, Celestia S.; Spillane, Maria; Wu, Eugenia; Carter, H. Ballentine; Pavlovich, Christian P.; Mamawala, Mufaddal; Landis, Tricia; Carroll, Peter R.; Chan, June M.; Cooperberg, Matthew R.; Cowan, Janet E.; Morgan, Todd M.; Siddiqui, Javed; Martin, Rabia; Klein, Eric A.; Brittain, Karen; Gotwald, Paige; Barocas, Daniel A.; Dallmer, Jeremiah R.; Gordetsky, Jennifer B.; Steele, Pam; Kundu, Shilajit D.; Stockdale, Jazmine; Roobol, Monique J.; Venderbos, Lionne D.F.; Sanda, Martin G.; Arnold, Rebecca; Patil, Dattatraya; Evans, Christopher P.; Dall’Era, Marc A.; Vij, Anjali; Costello, Anthony J.; Chow, Ken; Corcoran, Niall M.; Rais-Bahrami, Soroush; Phares, Courtney; Scherr, Douglas S.; Flynn, Thomas; Karnes, R. Jeffrey; Koch, Michael; Dhondt, Courtney Rose; Nelson, Joel B.; McBride, Dawn; Cookson, Michael S.; Stratton, Kelly L.; Farriester, Stephen; Hemken, Erin; Stadler, Walter M.; Pera, Tuula; Banionyte, Deimante; Bianco, Fernando J., Jr.; Lopez, Isabel H.; Loeb, Stacy; Taneja, Samir S.; Byrne, Nataliya; Amling, Christopher L.; Martinez, Ann; Boileau, Luc; Gaylis, Franklin D.; Petkewicz, Jacqueline; Kirwen, Nicholas; Helfand, Brian T.; Xu, Jianfeng; Scholtens, Denise M.; Catalona, William J.; Witte, John S.; Urology, School of Medicine
    Men diagnosed with low-risk prostate cancer (PC) are increasingly electing active surveillance (AS) as their initial management strategy. While this may reduce the side effects of treatment for PC, many men on AS eventually convert to active treatment. PC is one of the most heritable cancers, and genetic factors that predispose to aggressive tumors may help distinguish men who are more likely to discontinue AS. To investigate this, we undertook a multi-institutional genome-wide association study (GWAS) of 5,222 PC patients and 1,139 other patients from replication cohorts, all of whom initially elected AS and were followed over time for the potential outcome of conversion from AS to active treatment. In the GWAS we detected 18 variants associated with conversion, 15 of which were not previously associated with PC risk. With a transcriptome-wide association study (TWAS), we found two genes associated with conversion (MAST3, p = 6.9 × 10−7 and GAB2, p = 2.0 × 10−6). Moreover, increasing values of a previously validated 269-variant genetic risk score (GRS) for PC was positively associated with conversion (e.g., comparing the highest to the two middle deciles gave a hazard ratio [HR] = 1.13; 95% confidence interval [CI] = 0.94–1.36); whereas decreasing values of a 36-variant GRS for prostate-specific antigen (PSA) levels were positively associated with conversion (e.g., comparing the lowest to the two middle deciles gave a HR = 1.25; 95% CI, 1.04–1.50). These results suggest that germline genetics may help inform and individualize the decision of AS—or the intensity of monitoring on AS—versus treatment for the initial management of patients with low-risk PC.
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    The Relationship Between PSA and Total Testosterone Levels in Men With Prostate Cancer
    (Oxford University Press, 2022) Flores, Jose M.; Bernie, Helen L.; Miranda, Eduardo; Nascimento, Bruno; Schofield, Elizabeth; Benfante, Nicole; Carlsson, Sigrid; Mulhall, John P.; Urology, School of Medicine
    Background: Prostate-specific antigen (PSA) secretion is a testosterone (T) dependent process. Published data suggest that a low T level is an independent predictor of higher-grade prostate cancer (PC). Aim: To evaluate the relationship between T and PSA in patients with PC. Methods: All men diagnosed with PC with a recorded pre-treatment total T level measurement were included in this analysis. We analyzed demographic, clinical, and pathological data. Patients were stratified according to pretreatment PSA levels: <2 ng/mL, 2-4 ng/mL, >4 ng/mL. Low T was defined as total T < 10.4 nmol/L (300 ng/dL), very low T < 6.9 nmol/L (200 ng/dL). Outcomes: T levels by PSA groups according to the PC pathology. Results: In this retrospective study, mean patient age was 61 years among 646 men. The distribution by PSA group was: 8% (<2), 17% (2-4), and 76% (>4). The mean T level across the entire cohort was 13 nmol/L (374 ng/dL). Overall, 30% had a T level < 10.4 nmol/L (300 ng/dL). The mean total T level by PSA group was: <2 ng/mL, 7 nmol/L (206 ng/dL); 2-4 ng/mL, 13 nmol/L (362 ng/dL); >4 ng/mL, 14 nmol/L (393 ng/dL), P < .001. PSA <4 ng/mL was a significant predictor of low T in men with PC GS ≥8. PSA <2 ng/mL was a significant predictor of very low T independent of the PC pathology. Clinical implications: These findings suggest that clinicians should consider measuring T levels when a patient diagnosed with PC GS ≥8 and PSA level <4 ng/mL, and for each patient with PSA level <2 ng/mL independent of the PC pathology. Strengths & limitations: Our study has several strengths including (i) inclusion of a large population of men, (ii) use of a database which is audited and reviewed for accuracy annually, and (iii) use of an accurate T assay (LCMS). Nonetheless, there are limitations: (i) the subjects of the study are from a single institution, and (ii) we did not measure free T levels. Conclusion: In men with PC with GS ≥8, PSA level <4 ng/mL predicts low T. PSA <2 ng/mL predicts very low T independent of the PC pathology.
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    The Utilization and Impact of Aromatase Inhibitor Therapy in Men With Elevated Estradiol Levels on Testosterone Therapy
    (Oxford University Press, 2021) Punjani, Nahid; Bernie, Helen; Salter, Carolyn; Flores, Jose; Benfante, Nicole; Mulhall, John P.; Urology, School of Medicine
    Introduction: Testosterone therapy (TTH) for testosterone deficiency (TD) may lead to elevated estradiol (E2) levels requiring management to avoid unnecessary adverse effects. Aim: To examine the impact of aromatase inhibitors, specifically anastrozole (AZ), in men with elevated E2 on TTH. Methods: All patients on TTH at a high volume sexual medicine practice between 2005 and 2019 were reviewed. Men with E2 levels >60 pg/mL regardless of symptoms or 40–60 pg/mL with subjective symptoms were started on AZ 0.5 mg 3x/week. Routine hormone profile and symptom assessment were completed to ensure symptom resolution, reduction of E2 levels and maintenance of testosterone levels. Multivariable logistic regression was completed to determine predictors of men more likely to respond to therapy. Main Outcome Measure: Demographic and hormonal profiles of men on AZ and predictors of response to therapy. Results: 1708 men with TD were placed on TTH. Of these, 51 (3%) were treated with AZ (AZ+). After exclusions, 44 (2.6%) had elevated estradiol levels >60 pg/mL or >40 pg/mL with symptoms. Demographics were similar between groups. TTH distribution between groups was different with greater rates of topical TTH in the AZ- groups (AZ+:34.1% vs AZ-:53.5%) and greater rates of intramuscular TTH in the AZ+ group (AZ+:38.6% vs AZ-:18.5%) (P = .017 overall). Of the 44 men treated with AZ, 68.0% had pre-AZ E2 levels ≥60 pg/mL and 32.0% had levels between 40 and 60 pg/mL. Median pre-AZ E2 levels were 65 (interquartile range [IQR], 55–94) pg/mL in comparison to 22 (IQR 15–38) pg/mL post-AZ E2 levels (P < .001). Total testosterone levels were similar before and after AZ use (616 (IQR 548–846) ng/dL and 596 (IQR 419–798) ng/dL, respectively, P = .926). No statistically significant predictive factors of E2 reduction using AZ were found. Conclusion: While no statistically significant predictors for E2 recovery in men on AZ were found, AZ remains a reasonable option for E2 reduction in men with elevated levels on TTH.