1. Samson, Kurt

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Stress levels rather than racial ancestry may more accurately predict treatment compliance and outcomes for women with lymph node-positive or high-risk lymph node-negative HER2-negative breast cancer, according to researchers at the 14th AACR Conference on The Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved (Abstract PO-219).

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At a press briefing, Samilia Obeng-Gyasi, MD, MPH, a surgical oncologist at The Ohio State University Comprehensive Cancer Center, said her research has found that social and environmental stressors negatively impact treatment adherence and mortality in such patients, and that Black women may be especially affected.


She presented evidence that allostatic load, or the "wear and tear" of lifelong stressors-such as social isolation, poverty, and racism-are common among racial minorities. These include high blood pressure, increased body mass index, kidney disease, inflammation, arthritis, and other conditions.


"Allostatic load describes cumulative, multisystem physiologic dysregulation secondary to repeated or chronic environmental challenges," she explained.


Elevated allostatic load has been associated with poor chemotherapy compliance in Black breast cancer patients, as well as worse disease-specific and overall survival among cancer patients in general.


Obeng-Gyasi and colleagues in the ECOG-ACRIN Cancer Research Group investigated whether allostatic load or genetic ancestry influenced patients' survival and their likelihood of completing chemotherapy in 348 patients with node-positive or high-risk lymph node-negative HER2-negative breast cancer.


Allostatic load was measured at trial entry using several biomarkers, including body mass index, systolic and diastolic blood pressure, creatinine, interleukin 6 and 10, and tumor necrosis factor-alpha. To calculate allostatic load, patients were assigned a point if their biomarker value was above the 75th percentile of the study sample.


Overall, the median allostatic load score was 2 (interquartile range, 0-6). The mean allostatic load score at study entry was higher for patients of African ancestry (2.1) and European ancestry (1.88) than for patients of other ancestries (0.91).


On adjusted analysis, a 1-unit increase in allostatic load was associated with a 15 percent reduction in the odds of completing chemotherapy per protocol (OR, 0.85; 95% CI, 0.72-0.99) and a 14 percent increase in the risk of death (HR, 1.14; 95% CI, 1.02-1.29).


"Patient behavior and clinical outcomes cannot be isolated from the effects of their social environment," Obeng-Gyasi said. "Allostatic load provides us with a way to evaluate the effects of social and environmental stressors on a patient's physiology."


While other research has suggested that allostatic load and genetic ancestry each play a role in poor breast cancer outcomes, no studies have looked at both factors together in one study population.


"We observed that people with a high allostatic load at the beginning of the study had a greater likelihood of stopping chemotherapy early and a higher risk of death," said Obeng-Gyasi. "In contrast, we did not observe an association between genetic ancestry and survival or chemotherapy completion. This suggests that allostatic load may be better than genetic ancestry at predicting chemotherapy completion and overall survival."


She and her colleagues examined data from the ECOG-ACRIN E5103 Phase III clinical trial, one of the first large breast cancer treatment trials to include both demographics and DNA. The trial examined the effect of adding bevacizumab into sequential anthracycline and paclitaxel chemotherapeutic regimens in patients with lymph node-positive or high-risk lymph node-negative HER2-negative breast cancer.


Prior evaluations of the ECOG-ACRIN adjuvant breast cancer trial E5103 suggest African ancestry is associated with a worse invasive disease-free survival and lower odds of chemotherapy completion.


Using genomic analyses and other patient information, Obeng-Gyasi and her colleagues examined allostatic load across three broad categories of genetic ancestry-African, European, and other. Among the patients included in the analysis, approximately 80 percent had European ancestry, 10 percent had African ancestry, and 10 percent had other ancestry.


They measured allostatic load using biomarkers of the cardiovascular, immune, and metabolic systems collected prior to starting treatment, including body mass index, blood pressure, creatinine, and several cytokines-immune system markers of inflammation.


After adjusting for genetic ancestry, each 1 unit increase in allostatic load score was associated with a 15 percent reduction in the likelihood of completing chemotherapy and a 14 percent increase in the risk of death.


"These results suggest that long-term exposure to chronic social and environmental stress may contribute to poor outcomes in patients with breast cancer," said Obeng-Gyasi. She explained that, with further research, measuring allostatic load may be a useful tool to predict which patients with breast cancer may be at increased risk for stopping chemotherapy early and/or having poor survival.


"Future prospective clinical trials with repeated measures of allostatic load may provide greater insight into its relationship to treatment and survival, especially if allostatic load is collected multiple times during the active treatment and survivorship phases of care," she added.


A limitation of the study is that the analyses included only a subpopulation of patients with breast cancer; therefore, the results may not apply to all patients. An additional limitation is the small sample size, she noted.


Kurt Samson is a contributing writer.