Molecular Biology of Lung Cancer among Puerto Ricans - Doug Cress, PhD (Moffitt) and Pedro Santiago, PhD (PHSU)
Uncovering Breast Cancer Predisposition Factors in Puerto Rico - Alvaro Monteiro, PhD (Moffitt) and Julie Dutil, PhD (PHSU)
Infiltrating Immune Cells in Breast Cancer Subtypes - Shari Pilon-Thomas, PhD (Moffitt) and Jaime Matta, PhD (PHSU)
While lung cancer is a leading killer among all ethnic groups, emerging data suggest that the genetic mutations that drive lung cancer differ in frequency and nature among different ethnic groups. As one example, recent work demonstrates that when compared to Whites, Latino and Asian populations have a much higher rate of mutations in the gene coding for the Epidermal Growth Factor Receptor involved in the response to proliferation-inducing signals. At this point it is not clear why different ethnic groups differ in the genetic mutations that drive their lung cancers. However, understanding these mutations is of paramount importance as their nature determines treatment choices and could predict therapeutic outcomes. This is particularly important as novel anti-cancer drugs emerge that specifically target the protein products of these mutant genes. Therefore it will become increasingly important to understand the specific nature of mutations that drive lung cancer among various ethnic groups in order to make treatment as ethnic-specific, and therefore as effective, as possible. Currently, there are no significant databases addressing the mutations that drive lung cancer among Puerto Ricans, even though lung cancer is the leading cancer killer among Puerto Rican men and second killer among Puerto Rican women. This project will fill this knowledge gap by utilizing tumor tissue samples from Puerto Rican lung cancer patient to characterize and catalog mutations and epigenetic changes in candidate genes known to play an important role in lung cancer formation such as TP53, EGFR, CDKN2A and KRAS. This will produce valuable data on the genetics and the molecular biology of lung cancer in Puerto Ricans, which will in turn affect genetic testing and treatment recommendations for Puerto Ricans patients if the alterations characterized in this project can be clinically targeted and their molecular consequences characterized.
In women, breast cancer is the most common invasive cancer worldwide with over 1 million new cases annually. Significant progress has been made in the identification of genetic factors that influence the risk of breast cancer. These include the two major predisposition genes BRCA1 and BRCA2, the tumor suppressor TP53, as well as many other genes. Intriguingly, most of these genes play important roles in the system that protects cells from damage to DNA. Damage to DNA can happen due to external environmental factors (e.g. radiation, cigarette smoking, and sun exposure). Individuals carrying defects in these genes are then less well equipped to fix breaks to their DNA and more prone to cancer.
Importantly, defects in the system that guards cells against damage to DNA and facilitate the development of tumors can be also exploited for treatment. For example, drugs that inhibit PARP1 (also participates in repairing damage to DNA) are highly effective for BRCA-linked tumors. Treatment with PARP inhibitors leads to the inactivation of an alternative way for DNA repair, leaving the tumor cells with a diminished ability to resist DNA damage induced by chemotherapy. Because the BRCA-mediated DNA repair is still intact in normal non-tumor cells, side effects are minimal. This strategy can be extended, provided that we know which genes that participate in DNA damage repair are defective in individual tumors.
Unfortunately, there is a dearth of information regarding which genes are preferentially inactivated in breast cancer in Puerto Rico (PR). Thus, our long term goal is to identify these genes and develop methods to accurately identify women at increased risk of developing breast cancer in PR. Our objectives are a) to identify the inherited changes that play a role in the DNA damage repair and are frequently inactivated in breast cancer in PR; and b) to identify the additional somatic (not inherited) changes prevalent in tumors arising in Puerto Rico that could inform therapeutic decisions.
Several professional organizations have established criteria to identify BC survivors at increased risk for hereditary breast and ovarian cancer (HBOC) due to germline mutations in known cancer susceptibility genes such as BRCA 1 and BRCA 2 (BRCA). Previous studies have documented the presence of BRCA mutations in U.S. Hispanic women and proven risk management strategies for BRCA carriers. However, high-risk BC survivors Hispanics participate in genetic counseling (GC) and testing (GT) at strikingly lower rates than non-Hispanic Whites. Our team has documented that lower uptake of GC and/or testing among Hispanic BC patients may be due to less patient and provider awareness/referral of and access to genetics services, insurance, language, and cultural barriers. In order to address this issue, alternatives to current models that fail to promote uptake and participation of Hispanic women in genetic counseling should be provided. Alternative approaches should include identification, referral, and delivery of GC for high–risk BC survivors that address geographical, linguistic (1% of U.S. genetic counselors are Hispanic/Latino), and logistic access barriers. A recent study demonstrated that telephone GC could provide an opportunity to remove geographical, linguistic (e.g., readily available bilingual professional), and logistic access barriers (e.g., appointment availability) aside from being a cost-effective strategy to increase access to GC. In addition, data from our pilot study (U54CA163068) highlights that brief mailed educational communications are an effective strategy to reaching Hispanics with health information. Our goal with this pilot project is to test an educational approach to increase uptake of telephone GC among high-risk Hispanic BC survivors in Tampa, FL and Ponce, Puerto Rico.
The majority of studies on breast cancer subtyping and the prognostic value of immune infiltrates have included Caucasian women with little information generated in Hispanic breast cancer patients. The current project seeks to understand molecular differences among breast cancers of Hispanic and Caucasian women, specifically focusing on: 1) prevalence of intrinsic molecular subtypes and risk factors and 2) distribution and type of infiltrating immune cells by subtype. Our hypothesis is that Hispanic breast cancer patients will have distinct (1) incidences of breast cancer subtypes and (2) distributions of immune infiltrates in each one of these subtypes. This research project brings together our expertise in tumor micro-environments, breast cancer genomics and immune cell biology. We have access to currently banked samples as well future accrual of bio-specimens from the Puerto Rico Bio-bank and the Moffitt Cancer Center Tissue Core that provide a unique resource for studying breast cancer in Hispanic patients. Our long-term goals are to develop bio-markers for breast cancer disease progression and to determine which Hispanic breast cancer patients would benefit from personalized immunotherapy.
Breast cancer survivors’ knowledge, attitudes, and information needs about fertility and pregnancy - Gwendolyn Quinn, PhD (MCC) and Eida M. Castro, PsyD, MSc (PHSU)
Breast cancer is the most common malignancy among women in developed countries. Improvements in screening programs and new treatment advances have contributed increased survival. Since breast cancer is also the most common cancer among reproductive aged women, an increasing number of survivors have not yet started or completed their families when diagnosed. Therefore, identifying concerns regarding future reproductive health, fertility and consequences of adjutant therapies are paramount to quality of life.
Understanding survivor’s knowledge, attitudes and informational needs towards this topic is essential to aid health care professionals in devising better educational tools, improving patient-provider communication and supplying needed information for improved decision making. Such tools will aid patients and survivors in making educated decisions about reproductive health issues such as fertility and childbirth which ultimately will improve quality of life. There is a need to overcome the methodological limitations of previous research on this topic. These include use of small sample sizes, reliance on qualitative interviews describing women’s attitudes about fertility-related issues, without determining the degree of endorsement of such attitudes. Finally, there is need to examine culturally and linguistically diverse samples.
The primary aim of this study is to examine young breast cancer survivors’ knowledge, attitudes, informational needs and decisions about fertility and pregnancy among breast cancer survivors using self-report questionnaires. In addition, we aim to identify if clinical, demographic factors, or quality of life ratings, influence the reproductive decisions and attitudes of survivors. This study has begun and is on-going under the direction of Dr. Vania Goncalves in Portugal (University of Coimbra). Dr. Gwendolyn Quinn and Dr. Eida Castro will replicate this study at Moffitt Cancer Center and Puerto Rico and compare results between these diverse populations.
Identifying Cancer Health Communication Channels for Hispanic Audiences - Gwendolyn Quinn, PhD (MCC) and Julio Jiménez, MD (PHSU)
Results from our previous U56 outreach projects and other public health research indicate that reaching Puerto Rican audiences requires more culturally appropriate, direct interpersonal communication methods than traditional US mainland-based cancer communication channels (e.g., distribution of educational materials). To this end, we will focus our examination on effective and efficient health communication methods.
HPV vaccination rates offer a cost effective strategy for drastically reducing HPV disease burden; including the prevention of HPV-caused cervical, vulvar, vaginal, and anal cancers; precancerous cervical, vulvar, vaginal, and anal lesions; and genital warts. While rates of vaccine series initiation are higher in Hispanics both in the United States (U.S.) and Puerto Rico (PR), series completion remains an ongoing issue. Healthy People 2020 goals of 80% of 13-15 year old adolescents receiving all three doses of the HPV vaccine series are unlikely to be attained without additional intervention. A recent study conducted in safety- net clinics in Texas found that educational materials describing the HPV vaccine were effective for Hispanic populations in promoting HPV vaccine uptake. While this intervention holds promise for increasing HPV vaccine initiation rates in the Hispanic population, future refinement of the content (e.g., greater emphasis on series completion and male vaccination) and approach (i.e., a set of booklets/videos timed to coincide with series doses at 1 month and 6 months) may also facilitate series completion rates. In addition, our previous research demonstrates the importance of adapting Spanish educational materials within Hispanic sub-ethnic populations. Our goal with this pilot project is to adapt educational materials focusing on HPV- vaccine series completion and male vaccination tailored for the Hispanic population in Tampa, FL and Ponce, PR.