Tumor Characteristics in Blacks and Whites with Endometrial Cancer - PowerPoint PPT Presentation

Tumor Characteristics in Blacks and Whites with Endometrial Cancer with Endometrial Cancer Larry Maxwell, M.D. Chairman, Dept of OB-GYN at Inova Fairfax Hospital Co-Director, GYN Cancer Center of Excellence Professor, Virginia Commonwealth University 17 March 2014

Mortality Associated with Endometrial Cancer Mortality Associated with Endometrial Cancer • According to SEER, the mortality associated with y uterine cancer has almost doubled over the past 20 years and has been associated with and has been associated with a steady increase in the incidence of disease

Racial Disparity in Cancer Mortality Racial Disparity in Cancer Mortality African American Caucasian 8 6 4 2 0 0

Relation Between Ethnicity and Race y Race Hispanic or Latino % of U.S. Non H/L % of U.S. Any Races 35,305,818 12.5 246,116,088 87.5 White 16,907,852 6.0 194,552,774 69.1 Black/AA 710,353 0.3 33,947,837 12.1 Asian 119,829 <0.1 10,123,169 3.6 Hawaiian/PI 45,326 <0.1 353,509 0.1 Amer Indian/Alaska 407,073 0.1 2,068,883 0.7 **2000 C **2000 Census of Population, Public Law 94-171 f P l ti P bli L 94 171

Diversity Diversity Race R Hi Hispanic or Latino i L ti % of U.S. % f U S N Non H/L H/L % f U S % of U.S. One race 33,081,736 11.8 241,513,942 85.8 2+ races 2,224,082 0.8 2,602,146 1.6

Access to Care and Equivalency of Treatment q y • Conflicting reports regarding inequalities in frequency of hysterectomy • No apparent racial disparities in referral to gynecologic oncologist for management • Adjuvant radiation and chemotherapy found to be similar in population studies Liu et al: Obstet Gynecol 1995;86:486-90 Sherman et al: Cancer 2003;98:176-86 Trimble et al: Gynecol Oncol 2004;93:125-30 Randall et al: J Clin Oncol 2003;21:4200-6 Hicks et al: Cancer 1998;83:2629-37 Madison et al: Am J Public Health 2004;94:2104-11

Endometrial Cancer Outcome According to Race g Prevalence Mortality Blacks (denoted by red line) with endometrial cancer have a lower Blacks (denoted by red line) with endometrial cancer have a lower incidence but higher mortality compared to other racial groups Long et al: Gynecol Oncol 2013;130:562-659

Racial Disparities in T Tumor Stage and Histology S d Hi l • • Blacks are less likely to present with endometrioid histology and more likely Blacks are less likely to present with endometrioid histology and more likely to present with less favorable histologic subtypes (i.e. serous, clear cell, etc) • Blacks present more often with regional or systemic metastasis than Whites • U diff Undifferentiated histology more often found in Blacks compared to Whites ti t d hi t l ft f d i Bl k d t Whit Setiwan et al: Am J Epidemiol 2007;165:262-70 Wright et al: Cancer 2009;115:1276-85 Jemal et al: Cancer 2008;58:71-96

Overall Survival in African Americans and Caucasians with Advanced/Recurrent Endometrial Carcinoma with Advanced/Recurrent Endometrial Carcinoma 1.0 Log Log-rank test: p=0.005 g rank test: p=0.005 p 0.9 ving ving 0.8 on surviv on surviv 0 7 0.7 0.6 White White 0.5 Proportio Proportio 0 4 0.4 Black Black 0.3 0.2 P 0.1 0.0 0 12 24 36 48 60 Months on Study Months on Study Maxwell et al: Cancer 2006;107:2197-205

Tumor Response to Treatment by Race White Black Protocol Patients (No.) Response (%) Protocol (No.) Response (%) GOG 107 A 127 35 17 11.8 P 110 42.7 17 41.2 GOG 139 GOG 139 A+P 271 47.6 53 43.4 GOG 163 A+P A+P 128 128 40 6 40.6 21 21 28 6 28.6 A+T 130 43.9 24 33.3 GOG 177 A+P A+P 111 111 37 8 37.8 12 12 8 3 8.3 A/P/T 105 59.1 25 48.0 Total 982 43.2 169 34.9 Maxwell et al: Cancer 2006;107:2197-205

Treatment Related Adverse Events by Race in Advanced Stage Endometrial Cancer Advanced Stage Endometrial Cancer White Black p p- Adverse Effect (n=982) (n=169) value % % Selected Grade 3 or 4 Leukopenia 61.6 55.6 0.14 Thrombocytopenia 10.3 9.5 0.75 Neutropenia p 67.9 63.9 0.30 Anemia 14.2 20.1 0.05 Gastrointestinal 16.7 10.1 0.03 Genitourinary Genitourinary 1 4 1.4 4.7 4 7 0 009 0.009 Neurologic 3.0 3.6 0.68 Cardiovascular 5.3 4.1 0.53 A Any Grade 3 or 4 G d 3 4 82 1 82.1 82 3 82.3 0 96 0.96 Farley et al: Cancer 2010;116:355-61

Recurrence Free Survival in African A Americans with Stage I Endometrial Cancer i ith St I E d t i l C Estrogen Replacement Therapy Placebo 1.0 1.0 0.9 0.9 0.8 0.8 Log-rank test: p=0.247 0.7 0.7 Log-rank test: p=0.0002 0.6 0.6 RFS RFS 0.5 0.5 0.4 0.4 0.3 0.3 0.2 0.2 0.1 0.1 White White Black Black 0.0 0.0 0 12 24 36 48 60 0 12 24 36 48 60 Time from Entry onto Study (Months) Time from Entry onto Study (Months) Maxwell et al: Cancer 2008;113:1431-7

Obesity in Minorities • 77% of Black women are overweight • 77% of Black women are overweight • 50% are obese

Molecular Features of Endometrial Cancer TYPE I TYPE II Ploidy diploid aneuploid K-ras yes yes HER-2/ neu no yes p53 p53 no no yes yes MSI yes no yes no PTEN CTNNB1 yes no

Mean Racial Genetic Admixture Scores S lf Self-Designated African American i d Af i A i Admixture Mean Min Max African 65% 4% 86% Amerindian 15% 4% 50% European 20% 5% 83% Rocconi et al: SGO book of abstracts, 2013

Analysis of PFS by Quintile of R Racial Genetic Admixture i l G i Ad i African Admixture (%) N HR (95% CI) † 0 – 2% 49 Reference Category 3 – 5% 44 1.18 (0.42, 3.31) 6 – 10% 37 3.01 (0.95, 9.55) 11 – 71% 45 2.95 (0.81, 10.80) 72 – 86% 42 7.75 (3.22, 18.65) The risk of “genetic definition of race” exists irrespective of self-designated race g Rocconi et al: SGO book of abstracts, 2013

Racial Disparity in Gene Mutations Among African American Patients with Advanced Endometrial Cancer American Patients with Advanced Endometrial Cancer PTEN Mutation P53 Mutation 25 60 50 50 20 40 % 15 % % 30 10 20 5 10 0 0 African-American Kohler et al: Am J Obstet Gynecol. 1996;175:1246-52 Caucasian Clin Cancer Res. 2000;6:2999-3005

aGCH Analysis of Endometrioid Cancer and Comparison of Blacks vs Whites Comparison of Blacks vs Whites • aCGH performed on 80 endometrioid endometrial cancers d t i id d t i l from GOG-210 (40 Blacks and 40 Whites matched from stage, histology and grade • A 1.6-Mbp region of gain at 1q23 was identified by aCGH in all Black patients and high grade Whit White patients, but not White low ti t b t t Whit l grade patients. • The number of Blacks in the validation set was too small to validation set was too small to confirm the CGH association with racial disparity Morrison et al: Genes, Chromosomes and Cancer 2010;49:791-802

Her-2 Neu Expression in Blacks and Whites with Endometrial Cancer Race HER-2 Positive IHC HER-2Positive FISH No. % No. % No. % White: 446 (91) 58 (13) 26 (6) Black: 33 (8) 11 (33) 6 (18) p=0 004 p=0.004 p=0 017 p=0.017 Santin et al: 2005;192:813-8 Morrison et al: JCO 2006;24:2376-85

Phosphoserine Phosphatase Like (PSPHL) • PSPH identified on Affy could not be internally validated be internally validated • We acknowledged that PSPHL shares homology with PSPH and is the differentially expressed transcript by race • PSPHL increased in ovarian cancer from Blacks compared to Whites Whites • PSPHL increased in normal endometrium and normal ovary from Blacks compared to Whites from Blacks compared to Whites Ferguson et al: Gynecol Oncol 2006;101:209-13 Risinger et al: Front Oncol 2012;2:1-15

Global Transcript Expression in Endometrial Cancers: Preliminary Analysis of Race Cancers: Preliminary Analysis of Race All Cases • Transcript expression compared between 18 Blacks and 27 Whites with endometrial cancers • Differences noted in early stage cancers but not advanced stage cancers with internal validation and consistency with published data consistency with published data • Concerns over imbalanced groups and lack of external validation prompted further investigation Early Stage Cases Early Stage Cases African American Caucasian

Global Transcript Expression in Endometrial Cancers: Associations with Stage Histology and Race A i ti ith St Hi t l d R Stage I/II • 25 Black and 25 White women with 25 Black and 25 White women with -0.2 0 0 0 2 0.2 Stage III/IV Stage III/IV -0.15 endometrial cancers matched by stage, -0.1 Z grade and histology 0.05 • Global differences in gene expression noted 0 Y in early versus advanced stage as well as endometrioid vs non-endometrioid d t i id d t i id comparisons 0.15 • No racial differences in tumor transcript expression observed X Endometrioid Black Z 0.05 Z 0.05 Serous White -0.15 -0.15 0.1 0.1 Y Y 0 0 -0.1 -0.1 -0.2 0 2 0 0 0.2 0.2 -0.2 0 X X Maxwell et al: Gynecol Oncol 2013;130:169-73

Global Transcript Expression in Endometrial Cancers: A Associations with Race and Technique or Preparation i ti ith R d T h i P ti LCM prepared, Black LCM prepared, White LCM d Whi Whole tumor, Black Whole tumor, White -150 0 150 0 150 -0.1 0.15 0.1 4%) PC #2 (14 0 -0.15 -150 PC #3 (6%) PC #1 (23%) Multidimensional Scaling Multidimensional Scaling Principal Component Analysis Principal Component Analysis Maxwell et al: Gynecol Oncol 2013;130:169-73