Fred Hutchinson Cancer Center is advancing breast cancer research through new funding initiatives targeting various aspects of the disease, from prevention to treatment response prediction and genetic underpinnings.
ADVac: Targeting Obesity-Related Breast Cancer
Dr. Mary Disis, director of the UW Medicine Cancer Vaccine Institute, is leading research on ADVac, an adipose-directed vaccine designed to address the link between obesity and breast cancer. Obesity, particularly in postmenopausal women, elevates breast cancer risk by 20-40%. Metabolic syndrome, characterized by obesity, type 2 diabetes, and high blood pressure, further exacerbates this risk.
Obesity triggers the infiltration of CD8+ T-cells into fat, initiating an adaptive immune response that leads to sustained inflammation. This chronic inflammation results in metabolic dysfunction in fat tissue and T cells, a condition that persists even after weight loss. "These inflammatory T cells persist even after weight loss," Dr. Disis noted.
ADVac aims to counteract adipose-driven inflammation by eliciting a response from Type II anti-inflammatory T cells. Preclinical studies have demonstrated that ADVac can reverse metabolic dysfunction at the tumor site and prevent breast cancer development. Mass spectrometry analysis revealed that the vaccine induced "a metabolic reprogramming in adipose tissue of obese mice to resemble the metabolic profile seen in lean mice," potentially inhibiting breast cancer growth, according to Dr. Disis.
Ongoing research focuses on optimizing vaccine dosing and delivery schedules, as well as determining the necessary number of booster doses. The ultimate goal is to improve measures of metabolic dysfunction by 60% or better in obese mice, with or without metformin. If the toxicity profile is favorable, the research will support an Investigational New Drug Application to the FDA for clinical trials. ADVac could potentially be used to help those with metabolic syndrome, type 2 diabetes, fatty liver disease and other disorders associated with adipose inflammation.
FFNP-PET/CT: Predicting Endocrine Therapy Response
Dr. Hannah Linden is investigating FFNP (21 [18F] fluorofuranylnorprogesterone), a PET/CT progesterone tracer, to improve the prediction of response to endocrine therapy combined with the CDK4/6 inhibitor abemaciclib (Verzenio). A multi-center clinical trial will assess the accuracy of FFNP-PET for predicting treatment response. Participants will undergo baseline PET/CT scans using the FFNP tracer, followed by estradiol administration and another scan. They will then receive abemaciclib twice daily for 28 days, along with endocrine therapy chosen by their physician. PET/CT scans using the glucose tracer FDG will also be conducted at baseline, with additional diagnostic imaging every three cycles.
"We’re hoping that the use of FFNP as an imaging agent will provide more precise information about the location of tumors than a PET scan alone can provide," Dr. Linden explained. The trial (NCT06179303) is being run in conjunction with Washington University in St. Louis, Missouri.
Uncovering Genetic Mutations in Breast Cancer
Dr. Mary-Claire King is continuing her research on inherited breast cancer, focusing on families with a high incidence of the disease but no identified genetic cause. One project utilizes a new technology platform to sequence long strands of DNA, enabling the discovery of complex mutations that are otherwise undetectable. The second project explores dysregulation of gene expression, particularly subtle changes in estrogen receptor expression, as a basis for inherited breast cancer.
"For many families severely affected with breast cancer, no genetic reason for their illness has been discovered," Dr. King said. "Our goal is to understand inherited breast cancer in these families."
Dr. King is also collaborating with Israeli and Palestinian researchers to analyze the inherited bases of breast cancer in Palestinian women and to establish an infrastructure for comprehensive cancer genetics services.
