Advancing the Science of Cancer in Latinos, 1st ed. 2020

This open access book gives an overview of the sessions, panel discussions, and outcomes of the Advancing the Science of Cancer in Latinos conference, held in February 2018 in San Antonio, Texas, USA, and hosted by the Mays Cancer Center and the Institute for Health Promotion Research at UT Health San Antonio.

Latinos ? the largest, youngest, and fastest-growing minority group in the United States ? are expected to face a 142% rise in cancer cases in coming years. Although there has been substantial advancement in cancer prevention, screening, diagnosis, and treatment over the past few decades, addressing Latino cancer health disparities has not nearly kept pace with progress.

The diverse and dynamic group of speakers and panelists brought together at the Advancing the Science of Cancer in Latinos conference provided in-depth insights as well as progress and actionable goals for Latino-focused basic science research, clinical best practices, community interventions, and what can be done by way of prevention, screening, diagnosis, and treatment of cancer in Latinos. These insights have been translated into the chapters included in this compendium; the chapters summarize the presentations and include current knowledge in the specific topic areas, identified gaps, and top priority areas for future cancer research in Latinos.

Topics included among the chapters:

• Colorectal cancer disparities in Latinos: Genes vs. Environment
• Breast cancer risk and mortality in women of Latin American origin
• Differential cancer risk in Latinos: The role of diet
• Overcoming barriers for Latinos on cancer clinical trials
• Es tiempo: Engaging Latinas in cervical cancer research
• Emerging policies in U.S. health care

Advancing the Science of Cancer in Latinos proves to be an indispensable resource offering key insights into actionable targets for basic science research, suggestions for clinical best practices and community interventions, and novel strategies and advocacy opportunities to reduce health disparities in Latino communities. It will find an engaged audience among researchers, academics, physicians and other healthcare professionals, patient advocates, students, and others with an interest in the broad field of Latino cancer.

Preface

Amelie G. Ramirez, DrPH, UT Health San Antonio

Edward J. Trapido, ScD, FACE, LSU Health Science Center

Part 1: Introduction

Ch 1: What Is the Science of Cancer in Latinos?

Eliseo J. Perez-Stable, MD, National Institute on Minority Health & Health Disparities

Part 2: Genetics, Environment, Lifestyle, and Cancer

Ch 2: 21st-Century Cancer Patterns Among Latinos─Why Disaggregation Matters

Paulo S. Pinheiro, MD, PhD, University of Nevada Las Vegas

The cancer burden of Latinos in the U.S. has doubled in 15 years, with 124,000 deaths in 2014. As the relatively young Latino population ages, their cancer burden will inevitably increase. Accurate characterization of the Latino cancer experience is critical. Latinos are heterogeneous, with varying socioeconomic circumstances, nativity and/or immigration experiences, and cultural values and practices, which all impact cancer risk factors and outcomes. While disaggregated incidence and survival profiles for subgroups─Puerto Ricans, Mexicans, Cubans, Central Americans, South Americans, Dominicans─are problematic under the existing cancer surveillance systems, cancer mortality data can be an important source of more accurate granular evidence.

Our research shows that cancer patterns by subgroup can be quite distinct, particularly among first-generation immigrants, according to country of origin. However, patterns tend to become more homogenous for second-generation Latinos and beyond, with an increased burden, for certain cancers across subgroup affiliation, such as U.S.-born Mexicans in California and Puerto Ricans born in New York. Birthplace (U.S. vs. foreign-born), used as a proxy measure of acculturation, is a strong confounder in epidemiological analyses, dramatically influencing cancer patterns. In this context, the examples of colorectal and liver cancers are intriguing. Studying these patterns, often parallel to those of other U.S. minority groups disproportionately impacted by low socioeconomic status such as Native Americans and non-Hispanic blacks, sheds light on the impact of negative acculturation. Here we summarize the findings from several studies on Latino subgroups, addressing the so-called “Hispanic Paradox” and the “Healthy Immigrant Effect”; suggest future research directions; and highlight how these analyses should frame efforts to formulate cancer prevention and control strategies in the burgeoning U.S. Latino population.

Marcia R. Cruz-Correa, MD, PhD, University of Puerto Rico

Part 3: Cancer Risk, Prevention, and Screening

Ch 4: Breast Cancer Risk in Hispanics/Latinas: A Panoramic View

Laura Fejerman, PhD, University of California San Francisco

U.S. Hispanic/Latina women (Latinas) and Latin American women have a lower incidence of breast cancer than Non-Hispanic White (NHW) and African American women, but higher incidence of hormone receptor negative tumors and lower breast cancer survival than NHW women. This general statement breaks down when Latina women are stratified into subgroups based on birthplace, country of origin, and region within countries or genetic ancestry. For example, the incidence of breast cancer in Puerto Ricans and Cubans in the U.S. is higher than that of African Americans, which is not the case for Mexican-American women who have a relatively low incidence. Among Latinas in California, those of Caribbean origin have lower breast cancer survival than those from Central or South America. Studies in Colombia and Peru have shown that the prevalence of triple negative breast cancer varies between regions within those countries. In general, higher European genetic ancestry is associated with higher breast cancer risk, and higher African ancestry is associated with higher risk of hormone receptor negative tumors. These, and other differences, are possibly due to a complex interplay between socioeconomic, sociocultural, and biological factors, which need to be understood and addressed in cancer prevention and treatment of Latino individuals. A key challenge to accomplish this is that adequate data to further explore and understand group differences in breast cancer incidence and survival among Latinas is scarce. Until we develop the necessary resources to investigate breast cancer in diverse Latino cohorts we will not be able to understand, and if necessary eliminate, observed differences and disparities in breast and other cancers.

Ch 5: Prostate Cancer in Latinos: What Have We Learned and Where Should We Focus Our Attention

Ch 6: Differential Cancer Risk Among Latinos ─ The Role of Diet

Katherine L. Tucker, PhD, University of Massachusetts Lowell

Part 4: The Biology of Cancer Health Disparities

Ch 7: Biomarkers of Gastric Premalignant Lesions

Jovanny Zabaleta, PhD, Louisiana State University

Gastric cancer is one of the most common and deadliest cancers worldwide. There is a significant diversity risk and aggressiveness associated with the disease in terms of ethnicity, age, diet, among other things. However, one thing that is common is the fact that infection with Helicobacter pylori (H. pylori) is commonly associated with the development of gastric adenocarcinoma. Infection with H. pylori induces a series of events that lead to non-atrophic gastritis (NAG), multi-focal atrophic gastritis (MAG), intestinal metaplasia (IM), dysplasia and cancer. All the pre-malignant, pro-inflammatory stages are treatable, but it has been shown that the rate of progression to more advanced lesions is higher than the rate of regression. Most of the effort has been focused on the on the understanding of the cancer stage, but there is still a big gap in the knowledge of the biomarkers of the inflammatory stages and those of the progression/regression. Using samples from African American and Caucasian individuals with gastritis we have been able to identify specific sets of single nucleotide polymorphisms (SNPs) and haplotypes in cytokine genes associated with ethnicity. Interestingly, those same SNPs were also associated with advanced gastric lesions. On the other hand, using a cohort of Hispanic/Latino individuals with gastritis we identified CD44 as a marker of disease progression and DMBT1 as a marker of disease aggressiveness. Both markers were validated in in vitro and in vivo systems.

Ch 8: Molecular Sub-types, Driver Gene Mutations, and Intratumor Heterogeneity in Latinos with Gastric Cancer: Implications for Etiological and Translational Research

Gastric cancer (GC) is a worldwide leading cause of cancer morbidity and mortality and a common malignancy that disproportionally affect individuals of Hispanic/Latino American (HLA) ancestry. Relative to non-Hispanic Whites (NHW), HLAs are >2 times more likely to be diagnosed with and to die of GC. Despite such blatant cancer health disparities, the genetics and genomics of GC in this minority remains understudied in HLA. Lack of genetic and genomic data represents a major limitation of the development and application of precision prevention and treatment of GC in HLAs. In this talk, I will present data from our ongoing studies of germline and somatic GC genetics in populations of HLA ancestry. I will discuss our recent discovery of a new familial form of GC in the region, which involves germline mutations in homologous recombination genes, a finding that has dual implications for the prevention and treatment of GC in HLAs and other populations. I will also present unpublished data from our ongoing microsatellite instability (MSI) and exome and targeted sequencing studies in tumor samples indicating that HLAs, when compared to NHWs, are less likely to have MSI positive tumors but more likely to have tumors driven by Epstein-Barr virus infection. Tumors from HLA patients also have unique profiles in terms of frequency of mutations in known driver genes when compared to NHW data. Finally, I will present data from our multi-regional sequencing study where we analyzed cancer gene panel data in 122 geographically separated biopsies from 33 GC patients and where we uncovered extensive intra-tumor heterogeneity. I will discuss the implications from the latter study for molecular testing as well as for future GC drug efficacy studies and clinical trials in this under-studied and under-served minority population. 

Ch 9: The Biology of Breast Cancer Disparities in Hispanics: Current Knowledge, Gaps, and Research Opportunities

Gerardo Colon-Otero, MD, Mayo Clinic

Epidemiologic data shows that U.S. Hispanics have a lower incidence and mortality from breast cancer compared to Whites. Despite this, Hispanics who develop breast cancer are more likely to present at an earlier age, are more likely to have the aggressive triple negative subtypes and are more likely to present with more advanced stage disease, clinical features associated with worse outcomes. Socio-economic determinants and the main contributor to these clinical findings, but genetic factors and their interaction with the environment are also significant. In this presentation we will review the data supporting these findings, emerging data on the potential role of estrogen metabolites in the role of obesity in breast cancer and review gaps in knowledge.

Ch 10: Molecular Profiles of Breast Cancer in Hispanic-Latinas

Jovanny Zabaleta, PhD, Louisiana State University

Breast cancer (BC) is the most common malignancy in women worldwide. Different risk factors have been associated with the disease, which is classified into several intrinsic subtypes according to the expression of hormone receptors (estrogen and progesterone) and the human epidermal growth factor receptor 2 (HER2). The advent of high throughput techniques has allowed the molecular classification of BC and the development of diagnostic/prognostic tools to predict outcome and progression of the disease. However, most of the molecular classifications and diagnostic/prognostic tools are developed using samples from European/Caucasian women. Hispanic/Latino describes an admixed group of individuals with different fractions of European, African and Indigenous American ancestries. We determined the frequency of the different intrinsic subtypes of BC in Colombia and their association with genetic ancestry and found that Luminal B subtype was the most prevalent in Colombian women with BC. We found that African ancestry was associated with more aggressive forms of BC. We then used next generation sequencing techniques to determine the underlying markers of Luminal B subtype of BC in Colombia. We found 67 genes differentially expressed between Luminal A and Luminal B subtypes and of those 6 were common between patients with high European/low Indigenous American ancestries. Interestingly, 3 genes (ERBB2, MIEN1 and GRB7) form a genomic “block” in Ch. 17 from which ERBB2 and GRB7 are co-expressed. The expression of ERBB2 was independent of HER-2 labeling. Our results suggest a major role of ethnicity in the modulation of these genes in BC in Hispanic/Latina and may serve as the basis for future larger studies to investigate the role of ethnicity in BC susceptibility in minority groups.

Part 5: Advances in Cancer Therapy and Clinical Trials

Edith A. Perez, MD, Genentech

Ch 12: Overcoming Barriers to Latino Enrollment in Cancer Clinical Trials

Ruben A. Mesa, MD, Mays Cancer Center at UT Health San Antonio

The process for cancer patients to enter into clinical trials continues to become more complex. In 2018 this complexity for clinical trial enrollment includes, for all patients, narrowed eligibility criteria frequently by the presence or absence of molecular mutation, the ease of access to information regarding trials and concerns about randomization amongst enrolling patients, more non-experimental treatment options, and expense. Indeed specific of expense include many aspects including direct standard of care expenses which frequently can be worn by the patient through co-pays, financial burdens of the patient on a trial including travel and lodging, even third-party payor exclusions. Latino patients enrolling on cancer clinical trials have been found to have additional barriers including preconceived biases against their participation in clinical trials by the providers’ inadequate understanding as to the role and safety of cancer clinical trials, as well as language barriers both in the trial process (i.e., consent and management). We will discuss a variety of strategies that have employed to try to facilitate improved enrollment in general and those interventions that may be beneficial for Latino patients. Efforts at Mays Cancer Center as well as other centers have included dedicated resource specialists, improved insurance coordination, communication training, education and clinical trial awareness building, decision making tools, and better engagement of caregivers into the consenting process. We will discuss the current literature regarding the efficacy of these interventions as well as future steps.

Part 6: Cancer in the Era of Precision Medicine

Ch 13: Breast Cancer Precision Medicine in Latina Patients

Lucio Miele, MD, PhD, Louisiana State University

Hispanic/Latino (H/L) populations are a genetically admixed and heterogeneous group, with variable fractions of European, Indigenous American and African ancestries. Although breast cancer incidence tends to be highest among Non-Hispanic Whites (NHW) and African Americans, some studies suggest that breast cancer-specific 5-year survival rate in U.S. H/L is lower than in NHW after adjustment for socioeconomic status and education. This may be due to numerous factors, including access to optimal care and the effect of co-morbidities such as obesity and diabetes. Additionally, there remain significant knowledge gaps on the biology of breast cancer in minorities including H/L. The molecular profiles of breast cancer have been extensively examined in NHWs but equivalent knowledge is lacking in Hispanic/Latinas. Importantly, we know little about the validity of gene expression-based molecular tests used to classify breast cancers and predict outcomes in genetically admixed H/L patients. We have previously reported that the most prevalent breast cancer intrinsic subtype in Colombian H/L women was Luminal B as defined by surrogate St. Gallen criteria. Luminal B tumors tend to have poorer prognosis and develop endocrine resistance more frequently than their Luminal A counterparts. More recently, we explored ancestry-associated differences in molecular profiles of Luminal B tumors among highly admixed Colombian H/L women. Using whole transcriptome analysis and a set of ancestry-informative markers selected to be most informative in H/L patients, we identified genes potentially modulated by genetic ancestry: ERBB2, GRB7, GSDMB, MIEN1 and ONECUT2. ERBB2, GRB7 and MIEN1 are contiguously located in a region of chromosome 17q that is frequently amplified in HER2-enriched breast cancers. Expression of ERBB2 (Her2/Neu) is associated with endocrine resistance in Luminal cancers. We also observed statistically a significant association of ERBB2 expression with Indigenous American ancestry (p^ in Luminal breast cancers. These results suggests that ERBB2, a gene responsible for endocrine resistance in a significant fraction of luminal breast cancers, may be more likely to be highly expressed in women with higher Indigenous American ancestry. As ERBB2 is a therapeutically important gene, which encodes the target of trastuzumab and other Her2-targeted agents, these findings may have important therapeutic implications in Hispanic patients with Luminal breast cancers. Additionally, we observed considerable discordance between immunohistochemistry and PAM50-assigned intrinsic subtypes in our patient population. Only 50% of the patients identified as Luminal B by immunohistochemistry were accurately classified as Luminal B by PAM50. Yet, their clinico-pathological features and outcomes were consistent with Luminal B classification in other ethnic groups. Thus, our data suggest that commonly used breast cancer molecular tests should be validated in diverse populations including sufficient numbers of Hispanic/Latina patients. Given the considerable genetic heterogeneity of Hispanic/Latinos, more studies are necessary to confirm these findings in patients from the U.S. and other Central and Southern American countries.

Ch 14: Is Precision Medicine Widening Cancer Care Disparities in Latino Populations?

Lorna Rodriguez, MD, PhD, Rutgers University

Precision medicine in oncology aims to treat a patient based on the molecular makeup of the individual’s tumor. Guidelines have already been adopted in certain tumor types for the use of targeted therapies as standard-of-care, including lung, colon and rectum, thyroid, kidney, and breast cancers; melanoma; and gastrointestinal stromal tumors. Of these tumor types, Latinos have a higher incidence of colorectal cancer and a higher mortality rate from thyroid cancer than non-Latino whites. While the potential benefit of precision medicine is substantial, research has shown that its implementation in the Latino population is limited. For example, Latino representation in The Cancer Genome Atlas was ^udy showed that while 20% of participants of a 2016 analysis of genome-wide association studies were of non-European descent, less than 1% were Latino. Research has shown that physicians have been less likely to offer genomic testing (including germline BRCA1/2 testing for breast cancer) to Latino versus white non-Latino women, meanwhile data on positive attitudes and the willingness of Latino patients to participate in testing has been documented.  

Ch 15: What Doctors, Patients, and the Latino Community Need to Do to Prepare for Precision Medicine

Part 7: Cancer Outcomes and Survivorship in Latinos

Ch 16: Nuevo Amanecer: Stress Management Training for Latina Cancer Survivors

Summarizes outcomes of the first-ever international conference on Advancing the Science of Cancer in Latinos held in February 2018 in San Antonio, Texas

Features the latest in cutting-edge Latino cancer research and policy

Highlights research from leading experts in the field

Identifies priority areas for future research in the field of Latino cancer health disparities

Serves as a resource for physicians and other healthcare professionals, researchers, scientists, academics, patient advocates, public health professionals, and students at all levels to inform about Latino cancer health disparity issues and solutions

Is available with Open Access