||5R01CA246592-02 Interpret this number
||Metabolite Profiles and Mammographic Density in Premenopausal Women
In 2019, approximately 268,600 women in the US will be diagnosed with breast cancer, making it the leading
cause of cancer in women. About 25% of these cases occurred in premenopausal women. The annual
incidence of breast cancer among women under age 50 has been increasing slowly since the mid-1990s, in
contrast to what is observed in women aged over 50 years, where the incidence has remained stable over
time. This persistent increase in the incidence among younger women indicates that new approaches to
primary prevention in premenopausal women are needed. Mammographic breast density is one of the
strongest risk factors for breast cancer, especially in premenopausal women, where an estimated 39% of
breast cancer cases is attributable to having dense breasts. A decrease in breast density leads to a reduction
in breast cancer incidence. Nevertheless, the molecular basis of mammographic breast density and the
mechanisms through which dense breast increases breast cancer risk are poorly understood. A greater
understanding of these mechanisms is crucial, and will uncover new biological pathways and actionable
biomarkers that can be targeted to prevent breast cancer development. Metabolomics is a promising tool to
provide novel insights into disease etiology, biological mechanisms, and pathways. Metabolomics has,
however, not been applied to study mammographic breast density. Our pilot analyses show differences in
metabolite levels between women with fatty breasts compared to women with dense breasts. Building on these
novel findings, we will apply state-of-the art metabolomics platforms to 1) investigate the metabolome of
mammographic breast density in premenopausal women; 2) quantify the variation in mammographic breast
density explained by the metabolome; 3) determine whether the metabolome of mammographic breast density
predicts breast cancer development in premenopausal women. Our overarching hypothesis is that we will
leverage metabolomics to uncover the molecular mechanisms, biological pathways, as well as novel actionable
biomarkers that are associated with mammographic breast density in premenopausal women. Our study
population will consist of premenopausal women recruited during annual screening mammogram at the Joanne
Knight Breast Health Center at the Washington University School of Medicine, St. Louis, MO. Mammographic
breast density is quantitatively assessed using Volpara. Fasting blood samples are collected on the same day
the women have their mammograms. The women also complete a questionnaire with detailed information on
breast cancer risk factors and determinants of mammographic density. In conclusion, we will build on our
exciting preliminary data to uncover novel, actionable biomarkers associated with mammographic breast
density, and also breast cancer development in premenopausal women. These biomarkers could be targeted
in breast cancer prevention in future studies.
Reply to Hopper, Nguyen, and Li.
, Toriola A.T.
JNCI cancer spectrum, 2021 Aug; 5(4), p. pkab052.
Refining the Focus on Early Life and Adolescent Pathways to Prevent Breast Cancer.
, Toriola A.T.
Journal of the National Cancer Institute, 2021-06-01; 113(6), p. 658-659.
Chemoprevention Agents to Reduce Mammographic Breast Density in Premenopausal Women: A Systematic Review of Clinical Trials.
, Rakhmankulova M.
, Simon L.E.
, Toriola A.T.
JNCI cancer spectrum, 2021 Feb; 5(1), p. pkaa125.