2024 SABCS Meeting Magazine - 25

For the 40% or more of adult women who have
developed obesity, a 10% reduction in weight (about
20% reduction in body fat) may be necessary to reduce
breast cancer risk. Achieving and maintaining that level
of loss is challenging, as is any long-term behavioral
modification, particularly for individuals who may be
genetically predisposed to hold on to those calories,
she continued. Consequently, many women are turning
to pharmacotherapy for help with weight loss and
maintenance. But what do we know about these newer
agents for weight loss and cancer risk?
Dr. Fabian will be the moderator for the Risk Reduction
and Early Detection: Mechanisms of Obesity
Related Risk for Breast Cancer and Approaches to
Risk Reduction on Tuesday, December 10, at noon in
Hemisfair Ballroom 1-2. Panelists will address lifestyle,
genetic, and epigenetic interactions in predicting the
development of obesity and response to calorie restriction
and physical activity; how fat loss and metabolic
improvement affect cancer risk; and the impact
of types of exercise and pharmacotherapy,
including nutrient-stimulated hormone
(NUSH)-based therapeutics. The NUSHbased
therapeutics include drugs
with glucagon-like peptide-1 (GLP-1)
+/- glucose-dependent insulinotropic
polypeptide (GIP) receptor agonist properties.
For women at higher risk especially
There is much to be optimistic
about looking to the future of
breast cancer prevention through
pharmacology, fueled by a deeper
understanding of the lived experience of
people at risk for developing breast cancer,
Dr. Fabian said.
" We are beginning to accept that women
without cancer are likely to take riskreducing
agents over a protracted period
of time if they address other ongoing symptoms
or problems such that they improve rather than
adversely impact quality of life, " Dr. Fabian said.
Interventions such as metformin used to correct
metabolic dysfunction, combinations of SERMs and
low-dose estrogen for peri- and post-menopausal
women with vasomotor symptoms or the NUSH agents
discussed earlier are all being studied for their effects
on risk for breast cancer.
Not having an easily accessed quantifiable
and objectively measured biomarker
that can predict outcome from an
intervention has also been an obstacle
to breast cancer prevention.
" Heart disease has LDL cholesterol,
type 2 diabetes has A1C, but breast
Carol Fabian, MD
currently in a metabolically normal range
additions to healthy behaviors may be
desirable. However, women are reluctant to take a drug
with potential side effects for a disease that they may not
have. These concerns have been a significant challenge to
breast cancer risk reduction through pharmacotherapy.
" We are addressing this by testing lower doses of
drugs like tamoxifen, which has been found to minimize
side effects but reduces risk for breast cancer by about
two-thirds in postmenopausal women, " Dr. Fabian said.
" However, risk reduction in premenopausal women was
much less and not significant. "
Consequently, current early phase trials are looking
into which premenopausal women might benefit from
lower doses.
December 10-13, 2024 | San Antonio, Texas
cancer risk? To some extent, the new fully
automated measures of change in area
or volume of mammographic density is
serving as a biomarker of response to
selective estrogen receptor modulators (SERMS)
like tamoxifen in clinical trials, but it may be
premature to use this as an individual assessment
of response, " Dr. Fabian said. " Reversible blood
biomarkers of risk, such as circulating miRNA,
would also be most helpful. "
In the future, a variety of affordable interventions that
are life phase- and risk-appropriate and address other
common symptoms or problems will be available for
breast cancer risk reduction. These will be paired with
easy-to-perform test measuring biomarkers associated
with risk/response, she explained.
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2024 SABCS Meeting Magazine

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