The androgen aromatization hypothesis was examined in the male lizard, Anolis carolinensis. After castration, sc silastic implants of testosterone (T) restored both challenge and courtship behavior, while dihydrotestosterone (DHT) or 17beta-estradiol (E) had no effect on male behaviors. Both T and DHT, but not E, stimulated hypertrophy and colloid production by the renal sex segment, a secondary sexual characteristic of male lizards. In two separate studies, castrates received DHT in combination with E. In each replicate, half of the castrates responded with increases in courtship behavior after hormone treatment. Epithelial cell height of the sex segment of all DHT and E-treated castrates was comparable to T- or DHT-treated castrates, but colloid production was not stimulated. These experiments indicate that in this species, treatment with T stimulates both sexual behavior and secondary sex character development, whereas treatment with E alone is without effect centrally or peripherally.

Background: Genetic resources are underutilized when it comes to being incorporated into a breast cancer patient’s treatment, but that isn’t the only piece being overlooked. The Ki-67 proliferation index expressed (Ki-67%) is an established marker of tumor proliferation and aggressive behavior. We hypothesized that Ki-67% could have increased clinical utility when correlated with genomic testing results. Methods: Data was obtained from the Informed Genetics Annotated Patient Registry (iGAP), an IRB-approved, multi-center longitudinal registry designed to capture biomarker test results and their impact on treatment practices and outcomes. Tumor grades and Ki-67% were taken from patient pathology reports. The average Ki-67% was then calculated and compared for each tumor grade, MammaPrint genomic recurrence risk category (ultra low risk, low risk, and high risk), and Blueprint molecular subtype (Luminal type A, Luminal type B, Basal, and HER 2 type). ANOVA statistical analysis was performed for significance values. Results: Of 3102 patients enrolled in the iGAP Registry, 733 were diagnosed with breast cancer and had available tumor grade and Ki-67% data. Among these patients, 357 had genomic recurrence risk (MammaPrint) and 220 genomic molecular subtyping (BluePrint) reports. As expected, tumor grades were significantly positively correlated with Ki-67% (p< 0.0001 between all 3 tumor grade groups). Average Ki-67% in each genomic recurrence risk revealed a significant difference between Low Risk (14%, range 1-70%) and High Risk (36%, range 1-95%, p< 0.0001). Among the genomic molecular subtypes, there were significant differences in Ki-67% between Basal (avg 69%, 17-95%) and Luminal type A (avg 13%, 1-70%, p< 0.0001)) and all other subtypes, while Luminal type B (avg 24%, 1-80%) and HER 2 (avg 38%, 29-45%) were not significantly different from each other (p=0.2817), but still significantly different to all other subtypes. Conclusion: From these results, we can deduce that molecular subtype correlates with, but is clinically distinct from, Ki-67 proliferation index. These results also indicate that molecular subtype correlates with higher tumor grades, possibly due to increased cell proliferation. Achieving truly personalized clinical decision making requires utilizing multiple modalities and biomarkers, integrating the results into management. Citation Format: Chloe Wernecke, Krista Ortega, Kelly Bontempo, Brenna Bentley, Christina Hoyer-Kimura, Peter Beitsch, Rakesh Patel, Barry Rosen, Gia Compagnoni, Ian Grady, Eric Brown, Lindsay Gold, Pat Whitworth, Linda Ann Smith, Richard Reitherman, Mariusz Wirga, Steven Cai, Toan Nguyen, Valerie Traina, Dennis Holmes, Paul Baron, Brittany Krautheim, Anne Peled, Walt Taylor. Genomic testing and Ki-67 Percentage: Two puzzle pieces being undervalued in breast cancer treatment [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-44.

Background: With the rise of genomic testing, more clinicians are using panels to understand the genetic profile of breast cancer to help aid in clinical management. However, little is known about the relationship between the results of genomic tests and the likelihood of identifying an underlying germline variant, and how this should integrate into clinical decision making. Methods: Data was obtained from the Informed Genetics Annotated Patient Registry (iGAP), an IRB-approved, multi-centered longitudinal registry designed to capture biomarker test results and their impact on treatment practices and outcomes. Two genomic tumor profiling tests were studied - MammaPrint recurrence risk and Blueprint molecular subtypes, including Luminal type A, Luminal type B, Basal, and HER 2 type. Of the 3400 patients currently enrolled in the registry, 528 have been diagnosed with breast cancer and underwent tumor profiling by both MammaPrint and BluePrint as well as germline genetic testing, including analyses of 24 cancer susceptibility genes (ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, NBN, PALB2, PTEN, STK11, TP53, APC, BMPR1A, CDK4, EPCAM, MLH1, MSH2, MSH6, MUTYH, PMS2, RAD51C, RAD51D, SMAD4). Differences in positive germline variant rates were tested for with two-sided, Chi-Square tests using the prop.test function in R. Results: 231 (44.17%) were classified as High-Risk for recurrence on MammaPrint, with a 0.13 PVs detected per patient tested (positive germline variant (PV) Rate), 269 (51.34%) were identified as having a Low-Risk, with a 0.0849 PV rate, and 23 (4.4%) Ultra-Low-Risk, with a 0.0455 PV rate. There is not a significant difference between the High-Risk and Low-Risk for recurrence (p=0.09). 45 (8.54%) Basal molecular subtype identified by BluePrint panel, with a 0.1778 PV rate, 292 (55.41%) classified as Luminal A type, with a 0.0819 PV rate, 171 (32.45%) Luminal B with 0.1078 PV rate, and 13 (2.47%) HER2 Type with 0.07 PV rate. There was a significant difference between Basal and Luminal A PV rates (p=0.042), but no other statistically significant differences were found. Conclusions: Patients with a Basal molecular subtype have a significantly higher likelihood of having a germline pathogenic variant compared to Luminal A subtype. There was a trend that did not reach statistical significance for MammaPrint High Risk to have a higher likelihood of germline pathogenic result compared to MammaPrint Low Risk. This data adds another parameter for germline testing in those breast cancer patients who fall outside of current NCCN testing criteria. Citation Format: Peter Beitsch, Chloe Wernecke, Rakesh Patel, Barry Rosen, Eric Brown, Gia Compagnoni, Ian Grady, Lindsay Gold, Pat Whitworth, Linda Ann Smith, Mariusz Wirga, Richard Reitherman, Steven Cai, Toan Nguyen, Valerie Traina, Dennis Holmes, Paul Baron, Brittany Krautheim, Anne Peled, Walt Taylor, Kelly Bontempo, Brenna Bentley, Krista Ortega, Pouyan Ahmadi. Germline Testing Results in Patients with Genomic Tumor Profiling [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-43.

Background: Racial/ethnic disparities have been well-documented in access to cancer screening and treatment, as well as treatment outcomes. Less is known regarding the yield of genetic pathogenic variants (PVs) in non-white populations. Methods: Patient data was obtained from the Informed Genetics Annotated Patient Registry (iGAP), an IRB-approved multi-center longitudinal, observational study, in which 2148 patients self-declared race/ethnicity and underwent germline genetic testing at any lab. Analyses were limited to 24 cancer susceptibility genes (ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, NBN, PALB2, PTEN, STK11, TP53, APC, BMPR1A, CDK4, EPCAM, MLH1, MSH2, MSH6, MUTYH, PMS2, RAD51C, RAD51D, SMAD4), 21 of which have clinical management guidelines from the NCCN (excluding NBN, BARD1, CDK4).1 Descriptive statistics were used to assess and compare data from these populations and germline genetic testing results. Results: The Registry included 2148 patients, 1662 (77.37%) with a personal history and 1536 (71.51%) with a family history of cancer. The patients were 74.39% White, 6.33% Hispanic, 5.59% African/Black, 5.03% Asian, 1.63% Other, 1.35% Ashkenazi, and 5.68% Unknown. The overall germline PV rate in the cohort was 0.1089 PVs/patient tested, with 234 PVs detected in 227 patients. The PV rate among racial/ethnic groups were as follows: White 170/1598 (0.1064), Asian 8/108 (0.0741), Hispanic 27/136 (0.1985), African/Black 11/120 (0.0917), Ashkenazi 6/29 (0.2069). In patients self-reporting as Hispanic, the PV rate was similar to PV rate in those self-reporting as Ashkenazi, and significantly higher (p=0.00027) than PV rate in those of other self-reported race/ethnicity. Gene level PV rates are shown in Table 1. Conclusions: Those who reported being Hispanic had an increased overall PV rate. This could be due to the greater representation of Hispanics from New Mexico who may have Ashkenazi ethnicity. Further studies are needed to understand whether these differences are a result of disparate access to testing, true population differences, lack of data in non-White populations skewing variant classification or other factors. Table 1. Gene PV Rates by Racial/Ethnic Category. Citation Format: Peter Beitsch, Chloe Wernecke, Rakesh Patel, Barry Rosen, Gia Compagnoni, Ian Grady, Eric Brown, Lindsay Gold, Pat Whitworth, Linda Ann Smith, Mariusz Wirga, Richard Reitherman, Steven Cai, Toan Nguyen, Valerie Traina, Dennis Holmes, Paul Baron, Brittany Krautheim, Anne Peled, Walt Taylor, Kelly Bontempo, Brenna Bentley, Krista Ortega, Pouyan Ahmadi. Racial/Ethnic Groups Have Different Rates of Pathogenic Variants in Common Cancer Genes [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-02-09.