UCCCC breast program researchers and clinicians have long been committed to better understanding and addressing health disparities, and to improving care to underserved populations. One example of such endeavors is UChicago’s Center for Interdisciplinary Health Disparities Research (CIHDR), which has coordinated its research with the infrastructure of the university’s Specialized Program of Research Excellence (SPORE) in Breast Cancer.
In their efforts to uncover the reasons behind cancer health disparities, CIHDR and SPORE investigators are advancing research into prevention, early detection, and treatment—all while fostering trust between UChicago and its neighbors through a wide range of outreach activities. Research efforts are focused on the interplay of genes and the environment in the development of triple-negative breast cancer, with a multidisciplinary team of scientists working to identify genes relevant to the cancer’s development, determine their role in inherited susceptibility, and perform genetic epidemiologic analyses that can be used in the clinic.
The interplay between environment and genetics is of particular interest to professor of Medicine Suzanne Conzen, MD, who, along with her colleagues in the laboratory, is examining the ways in which environmental factors might affect the development and growth of malignancies— and, ultimately, response to treatment and likelihood of recurrence. Using a mouse model, Conzen and David Lee Shillinglaw Distinguished Service Professor in Psychology Martha McClintock, PhD, have shown that social isolation is associated with altered gene expression in the animals’ mammary glands; in isolated animals, systemic glucocorticoid levels were higher and triplenegative tumors grew larger. Specifically, three enzymes critical to glycolysis have been found to be significantly elevated in the isolated female animals’ mammary adipose tissue. The next step is to determine whether such changes favor breast cancer cell proliferation and increased resistance to chemotherapy effectiveness.
Suzanne Conzen, MD
“In this setting, social isolation is a model for exposure to unrelenting stressors over which the individual has no control,” Conzen said. “And while we can’t say that these findings can be extrapolated to humans, there certainly is a growing understanding of the physiologic impact of chronic stress in a wide range of disease states.”
Conzen, who is also the co-leader of the UCCCC’s Molecular Mechanisms of Cancer (MMC) Program, notes that larger translational studies have demonstrated a link between tumor glucocorticoid receptor overexpression and poor outcomes in women with early-stage breast cancer, a relationship that appears specific to estrogennegative tumors.
In a phase I trial, UCCCC and Evanston Hospital- NorthShore University Health System investigators are examining the use of a glucocorticoid receptor antagonist in conjunction with chemotherapy. Once safety is established, the goal will be to evaluate the protocol to determine if blocking glucocorticoid receptor activity might enhance the effectiveness of chemotherapy in women with non-estrogen-sensitive tumors whose disease is resistant to treatment.
Lessons to Be Learned
Conzen is quick to point out that it’s the physiologic response to stress, rather than the stress itself, that produces the altered hormonal milieu leading to changes in gene expression. “As clinicians, we need to adopt a proactive approach with regard to assessing our patients’ levels of stress, and determining what, if any, mechanisms are in place (or will be needed) to help them to deal with that stress effectively,” she said. Conzen went on to note that social stressors may be especially prevalent in underserved populations, since feelings of isolation and societal discrimination are reported with greater frequency by women in such populations.
She cited a small but excellent randomized trial, in which supportive therapy involving stress reduction and mood improvement was shown to lower recurrence rates in women with early-stage breast cancer.1
“This is also a trust issue,” Conzen said, “that becomes highly relevant to treatment and recurrence once a woman is diagnosed with cancer.” She said that investigators, including Cathy P. Hall, MSN, RN, OCN®, et al, suggest that training healthcare workers in cultural sensitivity and, therefore, more effective communication with patients, could increase participation in breast cancer screening.2