Can a progesterone tracer predict treatment response?
Breast cancer oncologist Linden, the Athena Distinguished Professor of Breast Cancer Research at the UW School of Medicine, along with nuclear medicine physician Delphine Chen, has received funding from BCRF along with the Translational Breast Cancer Research Consortium and drugmaker Eli Lilly to lead a multicenter Collaborative study with partner institutions Washington University in St. Louis, Missouri, the University of Illinois at Urbana-Champaign and the University of North Carolina.
“This study will build on our experience with FES PET — a PET scan that uses an estrogen-based tracer — and our national collaboration with the outstanding group at Washington University,” Linden said. “We are now working on FFNP, a radiotracer that maps the progesterone receptor.”
In recent years, Linden has explored the clinical utility of FES-PET, which illuminates estrogen receptors and can be used to predict whether endocrine therapy will be effective in patients. Now she’s leading a study to see if a progesterone tracer called FFNP-PET (short for 21 [18F] Fluorfuranylnorprogesterone) can be used as a better predictive marker for the effectiveness of endocrine therapy.
“While FES-PET is able to quantify the presence of estrogen receptors and assess tumor heterogeneity, it does not appear to be as accurate as FFNP in predicting patients who will or will not respond to endocrine therapy.” PET,” Linden wrote in the proposal.
This will be the first multi-center study to test the accuracy of FFNP-PET in predicting endocrine therapy response.
“If we are successful,” she wrote, “this will enable future studies of FFNP-PET as an integral and predictive imaging biomarker to inform physicians when it makes sense to use endocrine therapy, with or without novel targeted therapy that is.” on an active estrogen pathway.”
The Phase 2, multi-site study will enroll 60 patients with hormone receptor-positive, HER2-negative metastatic breast cancer to evaluate the accuracy of FFNP-PET imaging in predicting response to abemaciclib (also known as verzenio) plus endocrine therapy.
“The study is not yet open, but we hope to enroll a patient before the end of the year,” Linden said.
A breast cancer vaccine for obesity?
Disis, director of the UW Cancer Vaccine Institute and clinical researcher at Fred Hutch, will continue her work on a vaccine to combat obesity, an important risk factor for breast cancer, particularly in women with metabolic syndrome and metabolic dysfunction.
Previous research has shown that obesity triggers the infiltration of CD8 T cells into fat, which in turn secrete type I (inflammatory) cytokines. This change in fat leads to an immune response that leads to metabolic disorders in both the adipose tissue and the T cells themselves. Once this happens, T cells are no longer able to maintain tumor immune surveillance. In addition, the secretion of adipokines promotes malignant or harmful cell transformation.
“Losing weight will not solve this problem,” Disis wrote in her proposal. “Immunologic memory prevents T-cell-associated inflammation from regressing even after a person returns to normal weight.”
Therefore, the team has focused on strategies to proliferate (anti-inflammatory) type II T cells in inflammatory adipose tissue, with particular emphasis on the development of an inflammatory adipocyte (AD) vaccine.
In a preliminary experiment, ten-week-old mice were fed a high-fat, high-sucrose diet and once obese were randomly divided into two cohorts. One received the ADVac, the other only an adjuvant. Significantly, fewer CD8+ cells were observed in the mammary adipose tissue of ADVac-immunized mice compared to the obese control mice. Significantly less leptin was also detected in the serum of ADVac-vaccinated mice compared to controls. In addition, 60% of the vaccinated mice were tumor-free at the end of the study, while 100% of the control mice had developed tumors.
With the new $225,000 annual grant, Disis and her team aim to determine the extent to which ADVac immunization can restore metabolic function at the tumor site and prevent the development of breast cancer, and to identify the systemic effects of ADVac immunization.
“We do not believe ADVac is intended to replace the need for weight loss, but immunization with ADVac, if proven safe, could eliminate the risk of chronic inflammation and the development of a metabolic disorder that leads to breast cancer,” he said Disis wrote in her proposal. “The systemic effects of the vaccine could provide additional significant health benefits for men and women struggling with obesity, such as: B. restoring insulin sensitivity.”
Dig deeper into inherited breast cancer
Finally, Lasker Prize winner King, who was the first to state that breast cancer could be heritable, will continue to work to understand inherited breast cancer in families where genetic mutations have not yet been found. Your BCRF funding will flow into two projects.
The first concerns new technologies. King and her team have adapted rapidly evolving genomic technology to sequence large swaths of DNA in very long single strands, rather than thousands of short bits.
“This approach allows us to discover complex mutations in DNA that might otherwise go undetected,” King said.
With the funding, they will use this long-read sequencing approach to assess families from the New York Breast Cancer Study. The NYBCS aims to identify all of the genes responsible for inherited breast cancer in women of Ashkenazi Jewish descent.
The second project will be an exploration of gene expression dysregulation as a basis for hereditary breast cancer.
“We are particularly focused on inherited genetic variations that subtly alter the expression of genes important for breast cancer,” King said. “These subtle effects are not mutations, but simply changes in the expression level of the gene, all within a normal range.”
King will take a closer look at this variation and its impact on age at diagnosis of breast cancer.
The Breast Cancer Research Foundation, founded by Evelyn H. Lauder in 1993, is dedicated to “being the end of breast cancer” by advancing the world’s most promising research.