Iman K. Martin

African Ancestry and Higher Prevalence of Triple-Negative Breast Cancer: Findings From an International Study

The study of breast cancer in women with African ancestry offers the promise of identifying markers for risk assessment and treatment of triple‐negative disease.

Vitamin D deficiency predicts prostate biopsy outcomes

Purpose: The association between vitamin D and prostate biopsy outcomes has not been evaluated. We examine serum vitamin D levels with prostate biopsy results in men with an abnormal prostate-specific antigen and/or digital rectal examination. Experimental Design: Serum 25-hydroxyvitamin D (25-OH D) was obtained from 667 men, ages 40 to 79 years, prospectively enrolled from Chicago urology clinics undergoing first prostate biopsy. Logistic regression was used to evaluate the associations between 25-OH D status and incident prostate cancer, Gleason score, and tumor stage. Results: Among European American (EA) men, there was an association of 25-OH D <12 ng/mL with higher Gleason score ≥ 4+4 [OR, 3.66; 95% confidence interval (CI), 1.41–9.50; P = 0.008] and tumor stage [stage ≥ cT2b vs. ≤ cT2a, OR, 2.42 (1.14–5.10); P = 0.008]. In African American (AA) men, we find increased odds of prostate cancer diagnosis on biopsy with 25-OH D < 20 ng/mL [OR, 2.43 (1.20–4.94); P = 0.01]. AA men demonstrated an association between 25-OH D < 12 ng/mL and Gleason ≥ 4+4 [OR, 4.89 (1.59–15.07); P = 0.006]. There was an association with tumor stage ≥ cT2b vs. ≤ cT2a [OR, 4.22 (1.52–11.74); P = 0.003]. Conclusions: In AA men, vitamin D deficiency was associated with increased odds of prostate cancer diagnosis on biopsy. In both EA and AA men, severe deficiency was positively associated with higher Gleason grade and tumor stage. Clin Cancer Res; 20(9); 2289–99. ©2014 AACR.

Expression of aldehyde dehydrogenase 1 as a marker of mammary stem cells in benign and malignant breast lesions of Ghanaian women

Breast cancers that are negative for the estrogen receptor (ER), the progesterone receptor (PR), and the HER2 (human epidermal growth factor receptor 2) marker are more prevalent among African women, and the biologically aggressive nature of these triple‐negative breast cancers (TNBCs) may be attributed to their mammary stem cell features. Little is known about expression of the mammary stem cell marker aldehyde dehydrogenase 1 (ALDH1) in African women. Novel data are reported regarding ALDH1 expression in benign and cancerous breast tissue of Ghanaian women.

Predictors of Serum Vitamin D Levels in African American and European American Men in Chicago

Vitamin D deficiency is epidemiologically linked to prostate, breast, and colon cancer. When compared with European American (EA) men, African American (AA) men have increased risk of prostate cancer, but few studies evaluate vitamin D status in AA men. The authors evaluate the biological and environmental predictors of vitamin D deficiency in AA and EA men in Chicago, Illinois, a low ultraviolet radiation environment. Blood samples were collected from 492 men, aged between 40 and 79 years, from urology clinics at three hospitals in Chicago, along with demographic and medical information, body mass index, and skin melanin content using a portable narrow-band reflectometer. Vitamin D intake and ultraviolet radiation exposure were assessed using validated questionnaires. The results demonstrated that Black race, cold season of blood draw, elevated body mass index, and lack of vitamin D supplementation increase the risk of vitamin D deficiency. Supplementation is a high-impact, modifiable risk factor. Race and sunlight exposure should be taken into account for recommended daily allowances for vitamin D intake.

Smoking and Prostate Cancer in a Multi-Ethnic Cohort

Prostate cancer (PCa) and smoking‐related morbidity disproportionately burdens African American (AA) men. Smoking is associated with high‐grade PCa and incidence, but few studies have focused on AA men. This study aims to determine the effect of tobacco‐use on odds of PCa and of high‐grade PCa in a population of predominantly AA men.

Are HIV-Infected Men Vulnerable to Prostate Cancer Treatment Disparities?

Background: HIV-infected (HIV+) men face cancer treatment disparities that impact outcome. Prostate cancer treatment and treatment appropriateness in HIV+ men are unknown. Methods: We used electronic chart review to conduct a retrospective cohort study of 43 HIV+ cases with prostate cancer and 86 age- and race-matched HIV-uninfected (HIV−) controls with prostate cancer, ages 40 to 79 years, from 2001 to 2012. We defined treatment appropriateness using National Comprehensive Cancer Network guidelines and the Charlson comorbidity index (CCI) to estimate life expectancy. Results: Median age was 59.5 years at prostate cancer diagnosis. Median CD4+ T-cell count was 459.5 cells/mm3, 95.3% received antiretroviral therapy, and 87.1% were virally suppressed. Radical prostatectomy was the primary treatment for 39.5% of HIV+ and 71.0% of HIV− men (P = 0.004). Only 16.3% of HIV+ versus 57.0% of HIV− men received open radical prostatectomy (P < 0.001). HIV+ men received more radiotherapy (25.6% vs. 16.3%, P = 0.13). HIV was negatively associated with open radical prostatectomy (OR = 0.03, P = 0.007), adjusting for insurance and CCI. No men were undertreated. Fewer HIV+ men received appropriate treatment (89.2% vs. 100%, P = 0.003), due to four overtreated HIV+ men. Excluding AIDS from the CCI still resulted in fewer HIV+ men receiving appropriate treatment (94.6% vs. 100%, P = 0.03). Conclusion: Prostate cancer in HIV+ men is largely appropriately treated. Under- or overtreatment may occur from difficulties in life expectancy estimation. HIV+ men may receive more radiotherapy and fewer radical prostatectomies, specifically open radical prostatectomies. Impact: Research on HIV/AIDS survival indices and etiologies and outcomes of this prostate cancer treatment disparity in HIV+ men are needed. Cancer Epidemiol Biomarkers Prev; 23(10); 2009–18. ©2014 AACR.

Guide for investigators conducting international cancer research involving developing nations

International medical collaborations, previously known as ‘‘medical missionary work,’’ have existed for centuries. As aptly described by Panosian and Coates, historical motivations for this type of outreach included the desire to spread ‘‘religion as well as compassionate care.’’ The term ‘‘medical missionary’’ has endured over the years because of this history, and is therefore used in this commentary, but it is not intended to carry any paternalistic implications. Today, we see many programs (although one easily could argue that the supply is nowhere near close to meeting the demand), coordinated by individuals as well as by entire healthcare institutions and schools, that feature students, trainees, nurses, and physicians from developed areas of the world donating their time, expertise, and resources to medically underserved communities. These programs are mutually beneficial and enlightening. Medical missionary-based efforts have witnessed a recent increase in activity related to oncology. Global partnerships in cancer prevention, detection, treatment, and research are expanding in both scope and volume. This growth has been fueled by strengthened recognition of the following issues:

Self-reported Black race predicts significant prostate cancer independent of clinical setting and clinical and socioeconomic risk factors

INTRODUCTION AND OBJECTIVE Studies have linked Black race to prostate cancer (CaP) risk but most fail to account for established risk factors such as 5-ARI use, prostate volume, socioeconomic status, and hospital setting. We assess whether Black race remains associated with CaP and Gleason ≥3 + 4 CaP, after adjusting for clinical setting and socioeconomic and clinical factors at prostate biopsy, with a focus on men aged 40-54 years, who may be excluded from current screening guidelines. METHODS We recruited 564 men age 40-79 undergoing initial prostate biopsy for abnormal PSA or digital rectal examination (DRE) from three publicly funded and two private hospitals from 2009-2014. Univariate and multivariate analyses examined the associations between hospital type, race, West African Ancestry (WAA), clinical, and sociodemographic risk factors with CaP diagnosis and Gleason ≥3 + 4 CaP. Given changes in CaP screening recommendations, we also assess the multivariate analyses for men aged 40-54. RESULTS Black and White men had similar age, BMI, and prostate volume. Black men had higher PSA (8.10 ng/mL vs. 5.63 ng/mL) and PSA density (0.22 ng/mL/cm3 vs. 0.15 ng/mL/cm3, all p < 0.001). Blacks had higher frequency of CaP (63.1% vs. 41.5%, p<0.001) and Gleason ≥3+4 CaP relative to Whites in both public (27.7% vs 11.6%, p<0.001) and private (48.4% vs 21.6%, p = 0.002) settings. In models adjusted for age, first degree family history, prostate volume, 5-ARI use, hospital type, income, marital and educational status, Black race was independently associated with overall CaP diagnosis (OR = 2.13, p = 0.002). There was a significant multiplicative interaction with Black race and abnormal DRE for Gleason ≥3 + 4 CaP (OR = 2.93, p = 0.01). WAA was not predictive of overall or significant CaP among Black men. Black race (OR = 5.66, p = 0.02) and family history (OR = 4.98, p = 0.01) were independently positively associated with overall CaP diagnosis for men aged 40 to 54. CONCLUSIONS Black race is independently associated with CaP and Gleason ≥3+4 CaP after accounting for clinical and socioeconomic risk factors including clinical setting and WAA, and has a higher odds ratio of CaP diagnosis in younger men. Further investigation into optimizing screening in Black men aged 40 to 54 is warranted.

Abstract B034: Time to treatment and overall survival among men with localized prostate cancer

Background: Prostate cancer is the second most common cancer diagnosed among men in the United States. Delays from the time of confirmed diagnosis to primary treatment are more common for prostate compared to other malignancies. The objective of this study was to investigate factors associated with time to treatment and the effect of time to treatment on overall survival among men with early-stage prostate cancer. Methods: From the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, men diagnosed with localized prostate cancer who received treatment within a year of diagnosis were selected for analysis (N=6,349). Selected men had date of diagnosis, treatment date, and mortality status as of 2012. We investigated sociodemographic and clinical factors associated with time to treatment using Cox regression. We also used Cox regression to examine the effect of time to treatment on overall survival. Covariates included Gleason score, PSA level, age at diagnosis, employment status, education level, race, marital status, and comorbidity burden. Results: The median time to treatment was 73 (IQR: 44-120) days. Demographic factors associated with longer time to treatment included being Black (adjusted hazard ratio (aHR)= 0.85, 95%CI: 0.76-0.95), having some college education (aHR= 0.91, 95%CI: 0.85-0.97), and having a baccalaureate degree or a post-baccalaureate degree (aHR= 0.89, 95% CI: 0.84-0.95). Clinical factors associated with longer time to treatment were being diagnosed at an older age (aHR= 0.86, 95%CI:0.80-0.93 for age of 70-74 years and aHR= 0.80, 95%CI: 0.74-0.87 for 75 year and older) and having an elevated PSA level (HR=0.89, 95%CI: 0.81-0.94 for third PSA quartile (6.11-9.0) and HR=0.87, 95%CI: 0.81-0.94 for fourth PSA quartile (9.0 and above). Gleason score and comorbidity burden were not associated with time to treatment. Being married (aHR=1.11, 95%CI: 1.03-1.19) and being retired (aHR=1.09, 95%CI:1.034-1.16) were associated with shorter time to treatment. After adjusting for sociodemographic and clinical characteristics, time to treatment did not have a significant effect on overall survival. Conclusions: College education, being Black, older age at diagnosis, and higher PSA levels were associated with longer time to treatment. Being married and being retired were associated with shorter time to treatment. Longer time to treatment was not associated with overall mortality among PLCO men with localized prostate cancer. Citation Format: Dudith Pierre-Victor, Paul Pinsky, Iman K. Martin, Worta McCaskill-Stevens. Time to treatment and overall survival among men with localized prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr B034.

Abstract B41: Hyperlipidemia and prostate cancer in African American men

Background: African American men suffer disproportionately from prostate cancer. Evidence suggests that hyperlipidemia may increase prostate cancer risk; however, studies examining the disease processes within African American men are limited. We evaluated hyperlipidemia in African American men with and without prostate cancer (PCa) to investigate new and existing associations of serum lipid levels and prostate cancer risk. Methods: From 2000 to 2004, 250 African American men, aged 40-97 years were recruited from an urban academic urology clinic. Cases had histologically confirmed prostate cancer. Controls were men without clinical cancer who were seen at the same clinic. Hyperlipidemia was defined as patient having one or more of the following: high triglycerides (>200mg/dL), high LDL (>160mg/dL), and/or high total cholesterol(>240mg/dL) serum levels. Binary logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) between lipid exposures and PCa. The adjusted model included age,family history of prostate cancer, obesity, alcohol use, annual income, and Gleason index. Results: From the patient population, we obtained 141 incident PCa cases and 109 healthy controls. We observed a significant association between hyperlipidemia (OR= 1.7 [1.0-3.1]; unadjusted) and PCa, as well as hypertriglyceridemia (OR= 2.1[1.0-4.5]; adjusted) and PCa. Hypertriglyceridemia showed significant associations with aggressive disease (Gleason≥7) in both unadjusted (OR = 2.8[1.1–7.4]) and adjusted models (OR = 3.5 [1.1–10.7]). Both income (OR=2.2[1.1-4.0]) and alcohol (OR=0.5[0.3-0.9]) were significantly associated with PCa. Furthermore, we observed significant interaction between hyperlipidemia and obesity (OR=4.7[1.0-21.8]; adjusted). There were no associations found between hypercholesterolemia or elevated LDL serum and PCa. Conclusions: This study adds to recent evidence that hyperlipidemia has a positive relationship with PCa in African American men. Citation Format: Sparkle Springfield, Adam Murphy, Beverly Ifeanyi Chukwudozie, Iman Martin, Chiledum Ahaghotu, Rick Kittles. Hyperlipidemia and prostate cancer in African American men. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr B41.