ID of Biomarkers May Improve Life for Breast Cancer Survivors
Thinking and Living With Cancer (TLC) Clinical Trial findings may help older breast cancer survivors reduce risks for cognitive decline and hastened aging.
The Challenge
Decades of scientific innovation have led to a decrease in deaths from breast cancer. Of course, surviving longer may have its own challenges. Many of the 3.9 million breast cancer survivors in the United States have long-term effects resulting from both the cancer and its treatment, which can make life more difficult.
One issue, for instance, is cancer-related cognitive decline (CRCD). For years, scientists have recognized that treatment for breast cancer, which may include surgery and possibly one or more systemic therapies (like chemotherapy, targeted therapy, and hormonal therapy), may adversely affect the mind.
Although these treatments kill cancer cells, they may also damage cells and stimulate inflammatory biomarkers to circulate and cross into the brain cells, causing harm.
That damage to the brain can potentially lead to declines in a survivor’s daily functioning, work performance, and social and emotional well-being.
But research about the role of inflammatory markers has had inconsistent findings.?
See the Cancer Research?Glossary for NonScientists
Improve your understanding of these cancer research terms - and others.?
- Biologic age/epigenetic aging
- C-reactive protein (CRP)
- Epigenetics
- Interleukin-6 (IL-6)?
The Research
The Thinking and Living With Cancer (TLC) study examines the effect of systemic treatments for breast cancer on cognitive decline and quality of life in women age 60 and older.
TLC researchers particularly focus on how cognition (attention, processing speed, learning and memory, and executive function, like filtering distractions and switching tasks) may be affected by genetics, inflammatory biomarkers, sleep, and physical measures like walking speed and grip strength.
The Thinking and Living With Cancer (TLC) Study In Brief
Three factors in the design of the TLC study set it apart from previous similar ones. It was one of the first studies to:
- Focus specifically on breast cancer survivors who are age 60 and older (who make up the majority of breast cancer survivors).
- Include a control group of women the same age who don’t have cancer.
- Follow-up with participants for multiple years, rather than just immediately before and after treatment.
From its start in 2010 to its close at the end of 2023, the TLC study will follow an estimated enrollment of 1,700 participants from 6 cancer centers across the United States for up to 5 years.
Participants are divided into 2 approximately equal groups of women ages 60 to 90. One group includes those recently diagnosed with breast cancer, while women in the other group (the control group) are cancer free. Women in both groups were similar in age, education level, and race. None of the women had dementia or a psychiatric or neurological disorder at the beginning of the study.
Results from the TLC study will help improve the quality of care for the growing number of older women with breast cancer by:
Within the last 5 years, 绿帽社 research grants have helped fund three scientists who have co-authored several studies using data from TLC participants:
- Sunita Patel, PhD, from the City of Hope, Duarte, CA, focuses her research on risk and protective factors (especially from inflammation biomarkers) for cancer-related neurocognitive conditions that affect thinking, reasoning, and memory related to cancer. She’s had 2 ACS grants, with the most recent ending in June 2022.
- Judith Carroll, PhD, from the University of California Los Angeles (UCLA), had an ACS grant from 2016 to 2020 focused on biobehavioral vulnerability to accelerated aging in breast cancer survivors.
- Kathleen Van Dyk, PhD, from UCLA, had an ACS grant from 2017 to 2019 focused on cognitive decline in breast cancer survivors.?
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TLC Study “1:” High blood levels of an inflammation biomarker - c-reactive protein ?- may signal later cognitive decline in breast cancer survivors.
A 2022 study described in the was supported by an ACS grant awarded to neuropsychologist Patel and included previous ACS grantees Carroll and Van Dyke as co-authors. Using longitudinal TLC data, this study is one of the first to examine the long-term relationship between chronic inflammation and cognition in a large group of older breast cancer survivors and to compare these effects with those observed in a control group of women in the same age range without a personal history of cancer.
“This study used data from TLC participants to evaluate a specific inflammation biomarker called c-reactive protein (CRP). We wanted to learn 3 things:
(1) If higher CRP levels in the blood predict later changes to thinking and memory caused by cancer treatments.
(2) If higher CRP has stronger effects on cognition? in the TLC group of breast cancer survivors than they are in the TLC control group of women without cancer.
(3) Whether CRP could be useful to identify older breast cancer survivors at risk for cognitive problems."
Sunita Patel, PhD
City of Hope in Duarte, CA
ACS Research Grantee and Co-author of Several TLC Studies
The researchers evaluated neuropsychological tests and questionnaires at each visit and measured C-reactive protein (CRP) – a key marker of inflammation – from participants’ blood samples.
Levels of CRP increase with inflammatory conditions like rheumatoid arthritis, some heart diseases, and infection. The levels increase rapidly with severe tissue damage from injury or progressive cancer.
Their results showed that the cancer survivors:
- Had higher inflammation levels (as measured by circulating levels of CRP) before they began systemic cancer therapy.
- Were significantly more likely to report cognitive problems compared with