Dr. Jean Latimer

Nova Southeastern University

“Impact of S. Florida environmental chemicals on breast cells derived from women of different ancestries” 

There is an ongoing disparity in breast cancer (BC) outcomes for the African American community. In Broward County, Florida there are 7 zip codes that show higher frequencies of advanced stage BC (55%) than in the rest of the US (35%). There are a greater percentage of men and women of African ancestry (AA) in these zip codes compared with other ancestries. Many potential explanations have been proposed to explain the higher disparity in AA populations for negative health outcomes in BC, but one that has not been explored as much is the role of the environment. We are in a unique position to study environmental impact that leads to genetic changes consistent with BC, because we have developed a unique tissue engineering system for non-diseased human breast that allows us to establish cultures with high success rates. As primary cultures, these cells develop into ductal structures resembling the breast plumbing system over a period of 2-4 weeks. From these primary cultures we have established 48 extended explants or cell lines (> 13 passages). 12 are from AA women, while 36 are from European White derived ancestry (EW) in America. We hypothesize that these 2 groups will show differences in their response to environmental carcinogens. A previous study in our lab showed that there was a significantly higher percentage of breast stem cells in the AA cultures compared with the EW cultures. Now we would like to expose these cell lines and isolated stem cells derived from them to chemicals that are proven to be or likely to be carcinogenic, and present in S. Florida water (arsenic), agriculture or lawns (glyphosate). After exposure, RNA sequencing will be performed to look for changes in gene expression that are consistent with early stages of malignancy, compared with untreated controls. This work will fill an unmet void involving the unique vulnerabilities of people of different ancestries to environmental chemicals and their subsequent risk for developing BC.


Dr. Jennifer Hu

University of Miami Miller School of Medicine

“Impact of Precision Intervention on Reducing Breast Cancer Disparities” 

Breast cancer is a serious public health challenge. The proposed research will address 2 FBCF 2022 Special Emphasis Areas: (1) Minority populations/disparities and (2) Co-morbidities/adverse side effects. To date, there are more than 3.8 million breast cancer survivors in the US and many of them receive adjuvant radiotherapy (RT) that significantly improve survival. However, more than 42% of our breast cancer patients (87% minorities and many with multiple co-morbidities) suffered RT-induced skin toxicities and pain. Therefore, we design this cost-effective innovative research to minimize RT-induced skin toxicities and pain that negatively impact breast cancer prognosis. To achieve our long-term goals of improving breast cancer survival, this Phase II placebo-control trial will further test the hypothesis supported by pre-clinical and Phase I clinical trial data, that Ching Wan Hung (CWH), a plant-based over-the-counter burn ointment with anti-inflammatory properties will prevent RT-induced skin toxicities/pain using clinician- and patient-reported outcomes. If validated, CHW can serve as a low-cost product (30 g for < $15) to benefit all breast cancer patients, particularly underserved minorities with worse survival and many financial challenges.


The PI is a molecular epidemiologist with expertise in breast cancer research. She has assembled a multi-disciplinary research team with complementary expertise. We will address highly important issues of breast cancer treatment and survival disparities that are under-explored and poorly understood. Capitalizing on a large minority breast cancer population, strong pilot data, and an outstanding research team, we are in an exceptional position to transform breast cancer survivorship with a radical, revolutionary impact on precision intervention and clinical outcomes that are important for breast cancer patients. The findings from the proposed research will lead to improvements in the prevention and treatment of breast cancer.


Dr. Kamran Ahmed

H. Lee Moffitt Cancer Center & Research Institute, Inc.

“Predicting Brain Metastasis Progression in Stage IV Breast Cancer”

The three most common cancers to develop brain metastases are melanoma, non-small cell lung cancer (NSCLC), and breast cancer. Compared with other sites of metastatic spread, the development of brain metastases portends a poorer prognosis. Screening brain MRIs are currently recommended for non-metastatic patients with NSCLC and melanoma due to the prevalence of brain metastasis in these populations. However, brain MRIs are only recommended in metastatic or recurrent breast cancer patients when neurologic symptoms are present per National Comprehensive Cancer Network (NCCN) Guidelines. We have opened a phase II trial to conduct screening brain MRIs in stage IV breast cancer. We are collecting blood and tissue from patients in the trial to identify factors that may predict for brain metastasis progression. The objective of this grant will be to conduct assessments of circulating tumor DNA to determine if higher levels correlate to an increased risk for brain metastasis and if characterization of T cells and density correlate to intracranial progression. Together, completion of the clinical trial and grant aims may help identify which breast cancer patients are at sufficiently high risk to warrant brain MRI screening.


Dr. Brian Law

University of Florida

“Novel Breast Cancer Therapeutics Targeting a Unique Subset of Disulfide Isomerases”

Breast cancer is highly treatable if detected early. However, the disease remains a major cause of death among women, because current therapeutic strategies are ineffective after breast malignancies have acquired the ability to metastasize and resist available drugs. These capabilities of advanced cancers stem in part from cancer-specific defects in the cell death machinery that are difficult to correct. A family of growth factor receptors including the Epidermal Growth Factor Receptor (EGFR/HER1), Human Epidermal growth factor Receptor-2 (HER2), and HER3 proteins play central roles in driving breast cancer formation, metastasis, and drug resistance. Since these receptors (HER1-3) can substitute for each other in some situations, overcoming drug resistance may require inactivation of all three proteins. Our collaborative team has discovered and investigated a new class of drugs termed Disulfide bond Disrupting Agents (DDAs). DDAs decrease the levels of EGFR, HER2, and HER3 in parallel and are effective against cancers that have become resistant to the clinically used inhibitor of EGFR and HER2, Lapatinib. Unlike previous approaches that have used antibodies that bind to HER1- 3 or inhibitors of EGFR and HER2 enzymatic activities, DDAs interfere with the production of HER1-3 proteins to selectively kill the breast cancer cells that rely on these receptors for their survival and proliferation. Animal studies demonstrate massive tumor cell death in DDA treated animals without effects on adjacent normal tissues. DDAs do not cause adverse effects on the animals even with long term administration of high doses. The goals of the work proposed here are to 1) select the best candidate DDA from a group of optimized compounds for pursuing future clinical trials, 2) determine precisely how DDAs decrease HER1-3 protein levels in cancer cells, and 3) investigate if DDAs synergize with existing therapeutics that interfere with HER1-3 production in ways distinct from the DDAs.


Dr. Yi Guo and Dr. Dejana Braithwaite

University of Florida

“Risk of adverse cardiovascular events in breast cancer patients receiving systemic adjuvant therapy: impact of comorbidity burden” 

Breast cancer is an age-related disease, with average age of diagnosis at 62 years in the United States. Research data suggest that about 80% of breast cancer cases are diagnosed at an age of 50 years or older. Although survival of breast cancer patients has been substantially improved over the past decades, old breast cancer patients receiving cancer treatments are at elevated risk for adverse health events, especially cardiotoxicity. The underlying reason can be related to age-associated body changes and cancer treatment toxicity. About 5-20% of breast cancer patients can have cardiotoxicity within 5 years after treatment. Moreover, as patients become older, the burden of co-existing illnesses increases, which is associated with poorer cancer outcomes. In clinical practice, breast cancer patients with a high burden of comorbidities usually receive different treatment compared to healthier patients due to the worry that cancer treatment may induce more harms than benefits to them, especially fatal side effects like cardiotoxicity. However, the relationship between comorbidity burden and cardiotoxicity in breast cancer patients is not well studied, and this may mislead clinical practice for breast cancer treatment. In addition, there are no population-based studies on racial-ethnic disparity in risk pattern of cardiotoxicity in older breast cancer patients, although race/ethnicity minority groups have a higher cardiac risk. To address the abovementioned issues, we propose to assess how risk of cardiotoxicity and cardiovascular disease (CVD)-specific death in older breast cancer patients in Florida vary by burden of comorbidities. We will also investigate if impact of comorbidity burden is stronger for Black versus White patients. We hypothesize that patients with a higher burden of comorbidities have a higher risk of cardiotoxicity and CVD-specific death, and impact of comorbidity burden on cardiotoxicity outcomes is greater in Black than White patients.


Dr. Didem Ilter

H. Lee Moffitt Cancer Center & Research Institute, Inc.

“Epigenetic mechanisms of breast cancer dormancy”

Breast cancer is the most common malignant disease that affects Western women, and the most commonly diagnosed cancer in women in the State of Florida. While the primary tumors often can be cured by surgery and adjuvant therapy, recurrent metastases that arise from these primary tumors are highly resistant to therapies and are the most common reason for breast cancer mortality. Thus, the ability to effectively treat breast cancer is largely dependent on the capacity to treat recurrent metastases. This is particularly important for triple negative breast cancers (TNBCs), which are a heterogeneous group of breast tumors that are often associated with adverse pathological characteristics, poorer clinical outcomes and a lack of targeted therapeutic options. The metastatic cascade comprises a series of steps that cancer cells undergo in order to thrive as metastasis. Thus, in order for metastasis to arise cancer cells must be able to adapt to the everchanging conditions throughout the metastatic cascade. Even though epigenetic alterations are central to enable cell fate decisions, our understanding of the epigenetic mechanisms that regulate each step of the metastatic cascade are largely unknown. We have identified a specific epigenetic regulator as a major regulator of TNBC dormancy – a key step in the metastatic cascade that enables recurrent metastatic disease. Here, we propose on one hand to establish the role of this epigenetic regulator in the establishment of dormancy using mouse models, and on the other hand to define the mechanisms by which said epigenetic regulator enables the survival of breast cancer cells in the dormant state. Together, this work has the potential to unveil new therapeutic targets for dormant cells and thereby lead to the development of targeted therapies that can effectively eradicate recurrent metastatic disease in TNBC patients.


Dr. Michael Antoni and Dr. Bonnie Blomberg

University of Miami

“Changes in cellular and molecular mechanisms for aging, immunity, metabolism and health after stress management intervention in older overweight/obese breast cancer survivors” 

The majority of breast cancer (BCa) survivors are distressed, overweight or obese (OW/OB) and reveal elevated inflammation, which promotes immune senescence, and may accelerate declines in longer-term physical and mental health, collectively referred to as Cancer Accelerated Aging (CAA). We previously showed that both B and T lymphocytes from elderly and obese subjects are inflammatory with a poorer immune response and will test here if these cells may contribute to CAA. Elevated distress/chronic stress can promote inflammatory signaling via the sympathetic nervous system and hypothalamic pituitary axis and stress management interventions can reduce these effects in cancer patients. We created group cognitive behavioral stress management (CBSM) intervention and showed that CBSM is associated with better long-term mental and physical (longer disease-free survival, DFS) health outcomes in women with BCa and that maintaining less inflammatory signaling during primary treatment with CBSM predicted longer DFS. We also developed a remotely-delivered CBSM (R-CBSM) which showed high acceptability, and preliminary efficacy for improving psychological and immune regulation in older (>50yrs) BCa patients undergoing primary treatment. We hypothesize that CBSM’s protective effects on immune regulation during primary BCa treatment may be driven by the intervention’s ability to mitigate CAA effects on immune senescence and hyper-metabolism in B-cells and T-cells. In this proposal we will explore novel mechanisms underlying the effects of R-CBSM on inflammatory/immune senescence markers and cell metabolism in B cells and T cells from OW/OB breast cancer participants. We hypothesize R-CBSM will show greater decreases in SASP (senescence markers) and hyper-metabolism in immune cells; these will predict better influenza vaccine response and better longer-term (24-48 mos.) physical and mental health outcomes in this vulnerable population.


Dr. Jihe Zhao

University of Central Florida Research Foundation, Inc.

“Understanding Breast Cancer cell Resistance to Immunotherapy”

The 2018 Nobel Prize for Physiology and Medicine was awarded to Drs. Allison and Honjo for their discovery of the immune checkpoints. Immune checkpoints are mechanisms normal cells use to prevent selves from autoimmune attack. Cancer cells, however, can kidnap such a mechanism to protect themselves. If this kidnap can be reversed, most of aggressive cancers could be treatable by inhibiting the checkpoints. Indeed, the immunotherapy works for a few cancer types and saved the former President J. Carter's life in 2015 from very bad melanoma brain metastasis. It doesn’t work well on breast cancer (BC), however, although those few BC patients who did respond well live a much longer life. The main obstacle is the lack of knowledge about the mechanisms underlying the low responsiveness or resistance to the therapy that is the primary factor responsible for the patient death regardless of the disparities. The goal of this project is to understand the mechanisms with the long-term goal of finding ways to enhance BC patient responsiveness to such immunotherapy. KLF8 and CXCR4 proteins in BC are strongly upregulated by chemotherapies, which in turn contributes to therapy resistance and very poor patient survival. KLF8 drives CXCR4 very high in BC. This suggests a detrimental role of the KLF8-CXCR4 axis. Tumor-killing immune cells work in tissues rich for SDF-1, ligand for CXCR4. If SDF-1 is taken away, however, then the immune cells will be sent away from the battle grounds. The problem is that BC cells expressing high levels of KLF8-CXCR4 spread to the very same tissues where they can overconsume SDF-1 like sinks! Then, the immune cells will be gone and the immunotherapy will not work to kill these BC cells because the therapy relies on presence of the killer cells around the BC cells. This project is to test and prove this notion in a hope of providing new insight into BC resistance to the immunotherapy and developing effective immunotherapy for BC patients.


Sign Up for Our Newsletter