Chemotherapy linked to physical decline in older women with high-risk breast cancer

A UCLA-led study suggests women who are 65 years old or older with high-risk breast cancer and are treated with chemotherapy are more likely to develop a substantial decline in physical function.

The study, published in a special issue of the Journal of Cancer Survivorship, found over 30% of older women who have early-stage breast cancer and underwent chemotherapy experienced a significant decline in their ability to perform daily tasks like walking or climbing stairs compared to those who didn't have chemotherapy and women without cancer who were the same age. 

This is the first study to compare functional decline in older adults with early-stage breast cancer receiving chemotherapy to breast cancer patients who did not receive chemotherapy and age-matched women without cancer. 

We have previously shown that chemotherapy can contribute to a decline in physical function in breast cancer survivors, but it wasn't fully understood if the decline was primarily driven by the cancer, chemotherapy or both. It's important to have this comparison to determine whether or not this decline represents an acceleration of the aging process itself."

Dr. Mina Sedrak, first author of the study associate professor of medicine at the David Geffen School of Medicine at UCLA and director of the Cancer and Aging Program at the UCLA Health Jonsson Comprehensive Cancer Center

Breast cancer, especially in older women, can often lead to faster aging and declining of physical abilities. This phenomenon, known as accelerated aging, can have an effect on people's quality of life, independence, and even lifespan. Given the expected rise in the number of older survivors with breast cancer -;more than 6 million by 2040-; understanding the mechanisms of accelerated aging and finding ways to prevent it is imperative.

To better understand the impact of breast cancer treatment on aging-related decline in physical function, the team performed a multicenter prospective study that compared the changes in physical function over time in women over the age of 65. Participants included 444 women with early-stage breast cancer receiving chemotherapy, 98 women with early-stage breast cancer not receiving chemotherapy, and 100 women without cancer of the same age. 

Participants underwent two evaluations. The first evaluation included completing questionnaires about demographics, health status, and a geriatric assessment. For women with breast cancer, additional data on cancer-specific and treatment-related characteristics were gathered from medical records. The second evaluation, which included another round of the geriatric assessment, occurred within 30 days of ending chemotherapy for the group of women who received chemotherapy group or at matched time points for the other two groups.

In the analysis, the researchers found that 30% of older adults who received chemotherapy for breast cancer experienced a significant decline in physical function, compared to 8% of those who didn't receive chemotherapy and 5% of those without cancer.

Among the participants who experienced a substantial decline, the activity most adversely affected was climbing several stairs (75.7%), followed by walking one mile (73.0%) and engaging in moderate activity (68.6%).

These findings suggest that the combination of high-risk breast cancer, which includes higher stages and less favorable molecular characteristics, and chemotherapy contributes to accelerated decline in older adults with early-stage breast cancer.

"Our findings emphasize the impact that cancer and cancer treatment can have on physical function in older women," said Sedrak. "Physical function is essential for maintaining independence, mobility, and overall quality of life and there needs to be a more urgent effort to develop interventions to develop strategies to preserve physical function for women, before, during and after cancer treatment."

The team is now focusing on understanding the biological mechanisms underlying the interaction between cancer treatment and fundamental aging processes. They are specifically looking at cellular senescence and identifying mechanisms that can be targeted by drugs to potentially reverse these processes.

The study's senior author is Jingran Ji from City of Hope. Other authors are Can-Lan Sun, Marie Bae, Rachel A. Freedman, Allison Magnuson, Tracey O'Connor, Beverly Moy, Tanya M. Wildes, Heidi D. Klepin, Andrew E. Chapman, William P. Tew, Efrat Dotan, Mary Anne Fenton, Heeyoung Kim, Vani Katheria, Hyman B. Muss, Harvey J. Cohen and Cary P. Gross.

The study was funded in part by the National Institute of Aging and the Breast Cancer Research Foundation.