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, have received funding from BCRF, along with the Translational Breast Cancer Research Consortium and drug maker Eli Lilly, to lead a multi-center 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 working now on FFNP, a radiotracer that images the progesterone receptor.”
For the last several years, Linden has been researching 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 is leading a study to determine if a progesterone tracer known as FFNP-PET (short for 21 [18F] fluorofuranylnorprogesterone) can be used as a better predictive marker of endocrine therapy’s efficacy.
“While FES-PET is able to quantify the presence of estrogen receptors and evaluate for tumor heterogeneity, it does not appear to be as accurate as FFNP-PET in predicting patients that will or will not respond to endocrine therapy,” Linden wrote in the proposal.
This will be the first multi-center study to test the accuracy of FFNP-PET for predicting response to endocrine therapy.
“If we’re successful,” she wrote, “it will enable the future studies of FFNP-PET as an integral and predictive imaging biomarker to inform physicians when it is reasonable to use endocrine therapy with or without novel targeted therapy that relies 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 assess the accuracy of FFNP-PET imaging to predict response to abemaciclib (also known as Verzenio) plus endocrine therapy.
“The trial is not open yet, but we are hoping we can enroll a patient before the end of the year,” Linden said.
A breast cancer vaccine that targets obesity?
Disis, director of the UW Cancer Vaccine Institute and a Fred Hutch clinical researcher, will continue her work on a vaccine designed to address obesity, an important risk factor for breast cancer, particularly when it comes to 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 secretes Type I (inflammatory) cytokines. This change in the fat results in an immune response which leads to metabolic dysfunction in both the adipose (fat) tissue and the T cells themselves. Once this happens, T cells are no longer able to maintain tumor immune surveillance. Additionally, 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 resolving even if an individual becomes normal weight.”
So the team has focused on strategies to increase Type II (anti-inflammatory) T cells in inflammatory adipose tissue, with a particular focus on creating an inflammatory adipocyte-directed (AD) vaccine.
In a preliminary experiment, ten-week-old mice were fed a high fat, high sucrose diet, then once they were obese, randomized into two cohorts. One received the ADVac, the other received an adjuvant only. Significantly, fewer CD8+ cells were observed in the breast adipose tissue of ADVac immunized mice as compared to the control obese mice. There was also significantly less leptin detected in the serum of ADVac vaccinated mice as compared to controls. Additionally, 60% of the vaccinated mice were tumor free at study termination, whereas 100% of the control mice had developed tumors.
With the new one-year, $225,000 grant, Disis and her team aim to determine the extent to which ADVac immunization can restore metabolic function at the tumor site and prevent mammary cancer development and identify the systemic effects of ADVac immunization.
“We do not mean for ADVac to replace the need for weight loss, but immunization with ADVac, if the vaccine were shown to be safe, could eliminate the risk of chronic inflammation and the development of metabolic dysfunction that leads to breast cancer,” Disis wrote in her proposal. “The systemic effects of the vaccine could bring additional significant health benefits to men and women who struggle with obesity such as restoring insulin sensitivity.”
Digging deeper into inherited breast cancer
Finally, Lasker Award winner King, the first person to determine breast cancer could be inherited, will continue to work to understand inherited breast cancer in families where genetic mutations have not yet been found. Her BCRF funding will go toward two projects.
The first involves new technology. King and her team have adapted rapidly evolving genomic technology to sequence large swaths of DNA in single very long strands, rather than thousands of short bits.
“This approach enables us to discover complex mutations in DNA that could not otherwise be detected,” King said.
With the funding, they’ll use this long-read sequencing approach to evaluate families from the New York Breast Cancer Study. The NYBCS aims to identify all the genes responsible for inherited breast cancer among women of Ashkenazi Jewish ancestry.
The second project will be an exploration of dysregulation of gene expression as a basis for inherited breast cancer.
“We are focusing particularly on inherited genetic variation that subtly alters expression of genes important to breast cancer,” King said. “These subtle effects are not mutations, but simply changes in level of expression of the gene, all within a normal range.”
King will study this variation in more detail and explore its effects on age at diagnosis of breast cancer.
The Breast Cancer Research Foundation, founded in 1993 by Evelyn H. Lauder, is dedicated to “being the end of breast cancer” by advancing the world’s most promising research.
Wise (formerly TransferWise) is the cheaper, easier way to send money abroad. It helps people move money quickly and easily between bank accounts in different countries. Convert 60+ currencies with ridiculously low fees - on average 7x cheaper than a bank. No hidden fees, no markup on the exchange rate, ever.
How to access the offer?
1- Click here
2- Select “Register''
3- Enter your email address, create a password, and select your country of residence
4- Fill out the required personal information, and the free first transfer offer will be applied automatically.
Benefits of the Multi-Currency Account:
- Free to create online
- Hold 50+ currencies
- Get multiple local bank details in one account (including EU, UK, US)
- Convert currency at the real exchange rate, even on weekends
- Spend whilst travelling on the Wise debit card without high conversion fees
Wise International Transfers:
- $1.5 billion saved by customers every year
- Send money to over 60 target currencies
- Lower fees for larger transfers
- No hidden fees. No bad exchange rates. No surprises.
- Send your money with a bank transfer, or a debit or credit card