Obeng-Gyasi Elucidates on How Allostatic Load Could Play a Role in Treatment Completion and Survival in Breast Cancer

Contemporary Concepts | <b>Contemporary Concepts in Breast Cancer</b>

Samilia Obeng-Gyasi discussed the connection between stress and allostatic load and chemotherapy completion in patients with breast cancer.

A higher allostatic load among patients with lymph node–positive or high-risk lymph node–negative breast cancer was associated with lower odds of completing chemotherapy and lower survival rates, according to Samilia Obeng-Gyasi, MD, MPH.

This was assessed as part of the phase 3 E5103 trial (NCT00433511) by the ECOG-ACRIN Cancer Research Group, which examined whether doxorubicin hydrochloride, cyclophosphamide, and paclitaxel with or without bevacizumab (Avastin) would improve outcomes for patients with lymph-node positive or high-risk lymph-node negative breast cancer. Investigators reported that, after adjusting for genetic ancestry, every 1 unit increase of elevated allostatic load was associated with a 15% reduction in odds of completing chemotherapy (OR, 0.85; 95% CI, 0.72-0.99) and a 14% increase in risk of death (HR, 1.14; 95% CI, 1.02-1.29). Additionally, there was no association found between ancestry and chemotherapy completion.

“Our long-term goal really is to create a validated allostatic load composite. This would include multiple biomarkers across multiple physiologic systems,” according to Obeng-Gyasi. “Then when a patient presents to an oncology provider, we will collect their allostatic load score, and hopefully that will help us better understand how they may respond to treatment, it will give us an idea about their long-term survival.”

In an interview with CancerNetwork®, Obeng-Gyasi, a surgical oncology specialist from The Ohio State University Comprehensive Cancer Center-The James (OSUCCC), discussed how these findings may guide future clinical research and the importance of reducing allogenic load in patients with breast cancer.

CancerNetwork®: What was the rationale behind investigating the impact of allostatic load and genetic ancestry on outcomes in patients with breast cancer?

Obeng-Gyasi: There have been prior studies looking at the relationship between allostatic load and outcomes among patients with cancer, and those studies have shown that patients who have an elevated allostatic load at baseline are more likely to have a worse cancer specific mortality, and a worse overall mortality. Independently, there have been studies that have looked at genetic ancestry and we have discovered specifically in this E5103 cohort that we use, that women of African ancestry have worse clinical outcomes than women of European ancestry.1 We wanted to see if we could look at both those factors within a study population to see if the relationships that have been [observed] in other studies concerning survival, and chemotherapy completion with regard to genetic ancestry were consistent in this study cohort.

When looking at the key findings, how did allostatic load appear to affect patient outcomes?

What we saw was mostly what I would call a signal. We were interested in seeing if there was a relationship between allostatic load and chemotherapy completion, and allostatic load and survival. We did find that there was an association between allostatic load and chemotherapy completion, and there appears to be a relationship with survival. This study was a preliminary study looking at this dataset. We’re obviously going to run much more granular studies looking at various modifications of allostatic load and the relationship between the outcomes, but at least the study gave us an idea that there is a relationship that is there; we just have to explore it a little bit further.

How did genetic ancestry impact patient survival and treatment completion?

In the previous studies that looked at genetic ancestry and outcomes, they didn’t include allostatic load as one of the variables within their analysis. It appears in this population of patients, when you look at both allostatic load and genetics in a model, the previous relationship that they found between ancestry and survival is not there. This has led us to speculate that there might be an interaction or a way in which allostatic load and genetic ancestry may either mediate or moderate each other and have an effect on some of the clinical outcomes that we've seen in other studies.

After reviewing the findings from this trial, do you feel that the research uncovered any notable disparities?

What we found is what we expected to find. When you think of allostatic load, the way that it’s being operationalized here is that it’s your body’s response to chronic external challenges of chronic stressors. Studies have shown that individuals who face a stressful life or working conditions are more likely to have a higher risk of developing certain illnesses like hypertension, insomnia, obesity, or diabetes because of dysregulation secondary to these stressors. As you can anticipate individuals who have more comorbidities are more likely to have poorer outcomes than people who have less comorbidities.

The findings from these studies are important because we looked at a clinical trial population where everybody was getting similar access to care. A lot of times when talking about disparities, one of the biggest disparities that we have is that there are differences in the quality of oncologic care that patients have received. Here you have a situation where access to care is equivalent, and what our results essentially show is that these socio-environmental factors that people face, even within the setting of equal access to care are still significant.

How do you think this research can be used to better care for patients?

Our long-term goal really is to create a validated allostatic load tool. This would include multiple biomarkers across multiple physiologic systems. Then when a patient presents to an oncology provider, we would collect biomarkers for their allostatic load score, and hopefully, that will help us better understand how they may respond to treatment. It will give us an idea about their long-term survival.

For patients who have significant psychosocial issues, you might be able to use strategies that have been shown to work like patient navigation, where up front they receive resources, or at least they have access to resources that might mitigate some of the adverse social determinants of health that they face. It may help us in our treatment decision and in how we deliver that treatment. Essentially, our goal is to have this allostatic load score, or concept be integrated in the cancer continuum from the etiology of cancer all the way through survivorship.

How do you think oncologists can help guide patients in terms of stress management?

It's important to understand that when we’re talking about stress in this study, we’re conceptualizing it as a physiological response to external stressors. In terms of how mitigating stress can improve outcomes, there have been some studies looking at patients with metastatic breast cancer in China, where they did do a psychosocial intervention for some of the patients.2 What they discovered was that patients who underwent the intervention had their allostatic load score lower. We know that at least based on that study, that there are interventions that might be amenable to reducing one’s allostatic load score.

Also, other studies have looked other concepts that are similar to allostatic load and have used cognitive behavioral therapy as an avenue to reduce some of those stressors and have also shown some good outcomes. What this information tells us is that there are possible interventions that we might be able to utilize among patients who have allostatic load, and that might help mitigate some of the poor outcomes that they face.

Where do you feel future research efforts should be focused?

The next big thing is understanding how allostatic load works. Right now, we are hypothesizing that it may either work as a mediator between social determinants of health and outcomes, or it could possibly also be a moderator of that relationship. As of now we’re uncertain. I think the key thing is to find out how allostatic load exerts its effects. Once we have that kind of information, we can also talk about interventions to mitigate that, in addition to what I’ve discussed to mitigate that.

Is there anything else you wanted to add?

It’s important to recognize that social environmental factors have significant implications on patients’ lives. They have implications on the types of cancers people develop and how they interact with the health system and how they interface or how they respond to treatment. I think trying to better understand how people live, where people live, and where people work is very important for us as clinicians so that people just don’t show up and then everything else stops. Everything else going on in a patient's life still happens as they are going through treatment, and I think this kind of work is important in terms of helping us recognize and understand that.

References

1. Obeng-Gyasi S. The implications of genetic ancestry and allostatic load on clinical outcomes in the ECOG-ACRIN adjuvant breast cancer trial E5103. Presented at the 14th Annual American Association for Cancer Research. October 6-8, 2021; Virtual.

2. Lu W, Cui Y, Zheng Y, et al. Impact of newly diagnosed breast cancer on quality of life among Chinese women. Breast Cancer Res Treat. 2007;102(2):201-210. doi:10.1007/s10549-006-9318-5