Evidence has emerged showing that external stressors adversely affect cancer outcomes

A measure of environmental stress had a significant association with mortality risk in patients with breast cancer, a large retrospective cohort study showed.

Patients with high allostatic load (AL) had an almost 50% higher risk of all-cause mortality than patients with low AL. Stratification of AL scores showed that patients in the highest (fourth) quartile had an almost 80% greater risk than those in the lowest (first) quartile. Patients in the third quartile had a 56% higher relative risk compared to the first quartile.

“There was a significant dose-dependent association between increased AL and an increased risk of all-cause mortality,” report Samilia Obeng-Gyasi, MD, MPH, Ohio State University in Columbus, and co-authors in open JAMA network. “In addition, AL remained significantly associated with higher all-cause mortality after adjusting for the Charlson comorbidity index.”

“These findings suggest that increased AL reflects socioeconomic marginalization and is associated with all-cause mortality in patients with breast cancer,” they concluded.

The results add to a growing body of evidence that external stressors can adversely affect outcomes in cancer and other diseases.

“The authors are to be commended for creating a measure of allostatic load that can be derived from routine biomarkers in an institutional breast cancer cohort,” said Anurag Singh, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, New York. Withpage today via email. “The correlation of these findings with socioeconomic factors is fascinating and consistent with our data, showing that household income was significantly associated with gene-based recurrence scores and breast cancer survival. Likewise, we found that socioeconomic factors can affect methylation of the DNA”.

AL reflects cumulative physiological damage secondary to cognitive-emotional responses to socioenvironmental stressors, such as low socioeconomic status. Early researchers in the field defined AL as the “cost of chronic exposure to fluctuating or heightened neural or neuroendocrine response resulting from a chronic or repeated environmental challenge to which an individual responds as being particularly stressful.”

AL combines primary mediators of the hypothalamic-pituitary-adrenal axis (such as cortisol) and medullary adrenal sympathetic pathway, secondary outcomes of the hypothalamic-pituitary-adrenal axis and medullary adrenal sympathetic pathway (such as C-reactive protein), and tertiary outcomes (such as cancer) in a composite score. Emerging literature suggests that elevated LA (an indicator of physiological dysregulation) is associated with exposure to adverse socio-environmental stressors, increased risk of chronic disease, and worse all-cause mortality.

In cancer patients, elevated AI was associated with worse all-cause and disease-specific mortality and other adverse outcomes. Obeng-Gyasi and colleagues previously reported an association between elevated AL at diagnosis of metastatic lung cancer and worse all-cause mortality. The same study showed associations between high LA and stressors, such as limited mobility, worse self-care, problems engaging in social and daily activities, and a greater number of stressful life events.

With regard to breast cancer, high versus low AL was associated with larger tumor size and unfavorable tumor characteristics. In addition, high LA has been associated with marital dissolution, low education and unhealthy behaviors.

No previous studies have shown an association between high AL and all-cause mortality in patients with breast cancer. To examine the question, investigators consulted an institutional electronic medical record and a cancer registry at the National Cancer Institute Comprehensive Cancer Center. They identified patients with newly diagnosed stage I-III breast cancer from January 2012 to December 2020.

Currently, there is no reference standard for biomarkers to include in the AL calculation, the authors noted. For their study, they limited data collection to biomarkers collected routinely in clinical practice and frequently used in the LA literature. The biomarkers represented four physiological systems: cardiovascular, metabolic, renal and immune. AL scores ranged from 0-10, and AL values ​​were stratified into quartiles.

The primary outcome was all-cause mortality, defined as the time from breast cancer diagnosis to the date of death. Data analysis included 4459 patients, mean age 59 years; 87% were non-Hispanic whites. The global average for the AL was 2.6 and the median was 2.0. A high NA was defined as a value that exceeded the median.

Patients with high NA were older and more likely to be single (relative ratio [RR] 2.76), widowed/separated/divorced (RR 2.78), have government insurance (Medicaid RR 2.8; Medicare RR 2.9), and identify as non-Hispanic black (RR 3.08).

Data showed that 2257 patients had a low NA and 99 died during follow-up, translating to a mortality per 100 person-years of 1.04. The remaining 2202 patients had a high NA and 180 died during follow-up, which translated to a mortality of 1.99 per 100 person-years. Mortality increased linearly with AL quartiles:

• Q1: 0.89 per 100 person-years
• Q2: 1.22
• Q3: 1.78
• Q4: 2.59

“These results support existing studies suggesting that patients suffering from persistent socioeconomic marginalization…

“This study shows that vital signs…and routine laboratory assessments…collected in clinical practice can be used to calculate a robust measure of AL,” they added.