Renal cell carcinoma (RCC) is amongst the ten most prevalent malignancies in the United States, with 76,000 new cases each year and almost 14,000 deaths. Over the past half-century, RCC has more than doubled in incidence. RCC seems to have a greater incidence among Hispanics with a nearly three-fold increase. The epidemiology of RCC has been studied. However, there is a gap in knowledge on disparities in RCC within minority populations. We aimed to analyze epidemiologic patterns of RCC within our community, where Hispanics alone make up 70% of the population. We conducted a retrospective study to describe characteristics and calculate rates of recurrence of RCC among patients treated at Sylvester Comprehensive Cancer Center in Miami, FL, from June 2010 to April 2020. The patients were aged 18 and older and had a pathologic diagnosis of RCC. We identified ethnicity as Hispanic/Latino (HL) or non-Hispanic/Latino (NHL). Clinical presentation was classified based on information from the last encounter as either local RCC without recurrence, metastatic RCC after nephrectomy, or metastatic RCC at diagnosis/de novo. We analyzed a total of 1168 patients, from which 661 patients (55.7%) were identified as NHL and 507 (42.7%) as HL. A subtotal of 333 patients (28.5%) had metastatic RCC at diagnosis/de novo, from which 199 (59.7%) were NHL, and 134 (40.2%) were HL. A subtotal of 835 patients (71.5%) were diagnosed with local RCC and underwent nephrectomy, from which 462 (55.3%) were identified as NHL and 373 (44.7%) as HL. From the NHL group that underwent nephrectomy, 189 patients (40.9%) had recurrent disease and 273 (59%) did not. From the HL group, 121 patients (32.4%) had recurrent disease and 252 (67.5%) did not. Overall, 310 patients had metastasis after nephrectomy, from which 121 (39%) were HL and 189 (60.9%) were NHL. In this cohort of patients with RCC, four out of every ten patients with metastasis at diagnosis were HL. NHL appeared to have more recurrence of disease after nephrectomy compared to Hispanics. Further histopathologic, clinical, and genomic characteristics will be presented, along with treatment outcomes and clinical trial participation in the NHL and HL cohorts. Citation Format: Abner Antonio Murray Melo, Jesus Antonio Ocejo Gallegos, Jaime Rafael Merchan. Epidemiological characteristics and patterns of recurrence of renal cell carcinoma in Hispanics: A single US center cohort study [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C121.
e16554 Background: Annually, there are over 400,000 new renal cell carcinoma (RCC) cases and more than 170,000 deaths worldwide. RCC is one of the top ten more prevalent malignancies in the United States, with 76,000 new cases each year and almost 14,000 deaths. Over the past half-century, RCC has more than doubled in incidence. Studies demonstrate histologic differences and outcome disparities among Hispanic and Latino patients diagnosed with RCC. Research to date describes earlier and more advanced diseases at diagnosis, higher rates of obesity at presentation, and higher mortality among these cohorts. However, there is limited data on clinical, pathological, molecular, and treatment outcomes in this patient population. This study aims to characterize clinical features and treatment outcomes in this patient population in South Florida. Methods: We conducted a retrospective cohort study to describe the characteristics and rates of recurrence of RCC among patients treated at Sylvester Comprehensive Cancer Center in Miami (which serves four counties in South Florida) between June 2010 to June 2022. An IRB-approved advanced RCC database was developed on RedCap, where clinical, laboratory, pathological, treatment, and response information were captured. Ethnicity was determined as Hispanic/Latino (HL) or non-Hispanic/Latino (NHL). Clinical groups were classified based on the last encounter as local RCC after nephrectomy, recurrent metastatic RCC after nephrectomy, and metastatic RCC at diagnosis/de novo. Results: We analyzed a total of 2048 patients aged 18 and older diagnosed with RCC, from which 1008 patients (47.70%) were identified as NHL and 963 (47.92%) as HL. RCC was in over a 2:1 ratio of men to women in both HLs and NHLs. A subtotal of 435 patients (22.87%) had metastatic RCC at diagnosis/de novo, from which 245 (55.59%) were NHL, and 175 (40.32%) were HL. A subtotal of 1613 patients (78.76%) were diagnosed with local RCC and underwent nephrectomy, from which 763 (45.46%) were identified as NHL and 788 (50.15%) as HL. From the NHL group that underwent nephrectomy, 222 patients (28.21%) had recurrent disease, and 541 patients (71.79%) did not. From the HL group, 175 patients (21.69%) had recurrent disease, and 613 (78.31%) did not. Overall, 408 patients had metastasis after nephrectomy, of which 175 (44.31%) were HL, and 203 (52.24%) were NHL. Conclusions: In this cohort of patients with RCC, over 40% of patients diagnosed with metastasis were HL. NHL appeared to have more disease recurrence after nephrectomy and higher rates of metastatic disease at diagnosis compared to Hispanics. Further histopathological differences, clinical outcomes, genomic characterization, and rates of clinical trial participation between the NHL and HL cohorts will be presented at the meeting, along with comparisons between US and foreign-born HLs.
561 Background: The RAS pathway regulates tumorigenesis and cell proliferation. HRAS is a RAS family member that activates via farnesylation. Indirectly targeting mutant HRAS with tipifarnib, a farnesyltransferase inhibitor (FTI), recently demonstrated efficacy in head and neck tumors. We aimed to investigate the molecular characteristics and clinical outcomes of HRAS mutations (HRASmut) for any potential role as a prognostic and therapeutic biomarker in breast cancer (BC). Methods: A total of 14,013 BC tissue samples had molecular profiling, including next generation DNA (592 Gene Panel, NextSeq, or WES, NovaSeq) or RNA sequencing (NovaSeq, WTS), and immunohistochemistry analyses, at Caris Life Sciences. MAP kinase (MAPK) activation and likelihood of a tumor’s response to anti-PD1 therapy were evaluated via MAPK Pathway Activity Score (MAPS) and interferon (IFN) score, respectively. Wilcoxon, Fisher’s exact, or Dunnett’s tests were used to determine statistical significance. Overall survival (OS) was calculated from date of tissue collection to insurance claims last contact using the Kaplan-Meier method. HRAS mutations (HRASmut) were compared to the general BC cohort (GC). Results: HRASmut were significantly enriched in older patients (median 69 vs 60 yrs; q<.0001), and in primary compared to metastatic BC tumor samples (55.9% vs 41.9%, p<.05). There were 70 total HRASmut (0.5%): Q61 was the most frequent (41.4%), followed by G12 (28.6%) and G13 (24.3%). Patients with Q61 HRASmut had significantly worse OS compared to GC (HR 1.86, 95% CI [1.10-3.13]; p<0.05). HRASmut had significantly higher MPAS compared to GC (1.26, all; 1.31, Q61; 1.7, G12; -.39, GC, q<.01). HRASmut were found in HR+/HER2- (22.6%) and TNBC (77.4%) tumors, but no HR-/HER2+ BC. TNBC samples with HRASmut displayed more PIK3CA (62.5% VS. 18.9%, q<.05) but less TP53 mutations (50% vs 84.9%, q<.05), higher expression of PD-L1 (41.2% vs 10.8%, p<.05) and androgen receptor (AR, 45.8% vs 24.4%, p<.05), and more frequent ARv7 fusions (20.7% vs 4.3%, p<.05) compared to HR+/HER2- (Table 1). Q61 HRASmut had the highest MPAS (2.39 vs -0.28, p<.01) in TNBC, whereas G12 HRASmut displayed the highest MPAS (2.01 VS -0.47, p<.05) in HR+/HER2- BC. Conversely, Q61 had the lowest IFN score (-0.45 vs -0.3) in HR+/HER2- but the highest (-0.18 vs -0.3) in TNBC. Conclusions: HRASmut were mutually exclusive with HER2+ BC. The association of Q61 HRASmut with worse survival highlights the oncogenic role of these mutations and supports therapeutic investigation using FTI. PIK3CA was significantly co-mutated in HRASmut, highlighting a potential benefit of combining PIK3CA inhibitors with tipifarnib. Overall, HRASmut displayed a subtype-specific distinct genomic landscape and may represent a key therapeutic target in BC. [Table: see text]
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