Chemotherapy May Speed Biological Aging in Breast Cancer Survivors

Breast cancer survivors treated with anthracycline-based chemotherapy may lose a median of 9.4 years of remaining life to chemotherapy-induced biological age acceleration, according to a population-level simulation study published in JAMA Network Open.¹ The model projected that the more cytotoxic regimen improved breast cancer survival but moved up the point at which death from other causes overtook breast cancer as the dominant risk. The investigators noted that treatment decisions should not change based on these findings, but that clinicians should be aware of possible age acceleration in survivorship care.¹

The study, led by Swarnavo Sarkar, PhD, of Georgetown Lombardi Comprehensive Cancer Center in Washington, DC, is the first to estimate the lifetime balance between the survival benefit of chemotherapy and accelerated biological aging using population-based simulation modeling, according to a news release from the cancer center.²

“Female breast cancer survivors comprise the single largest segment of the 18.6 million cancer survivors in the United States,” senior author Jeanne Mandelblatt, MD, MPH, director of the Institute for Cancer and Aging Research at Georgetown Lombardi, said in the release.² She added that some forms of chemotherapy that extend survival have “triggered a secondary crisis: treatment-induced molecular damage to the body’s cells and organs, causing acceleration of biological age.”

How did investigators model chemotherapy-related aging?

The investigators adapted an established Cancer Intervention and Surveillance Modeling Network (CISNET) breast cancer model to include a systems biology module based on p16INK4a, a blood biomarker of cellular senescence.¹ Senescent cells stop dividing but resist cell death, and they promote further aging through changes in tissue modeling and inflammation.¹

“Senescent cells secrete biological molecules that cause several aging-related diseases,” Sarkar said in the release.²

Published data on increases in p16INK4a levels after chemotherapy were used to assign each simulated survivor a biological age, which replaced chronological age in determining the risk of non–breast cancer death. The simulated population included 400 million US women diagnosed with breast cancer at ages 30 to 79 years between 1990 and 2030, followed until death.¹

Two scenarios were run: one in which all women with breast cancer received anthracycline-based chemotherapy (more cytotoxic) and one in which all received nonanthracycline chemotherapy (less cytotoxic). The model assumed that chemotherapy-induced senescence lasted for the rest of a survivor’s life and affected only non–breast cancer mortality.¹

To validate the approach, the investigators compared model output with 8-year results from the Anthracyclines in Early Breast Cancer (ABC) trials, in which the anthracycline regimen was anthracycline plus taxane and the comparator was cyclophosphamide plus taxane.^1,3 The model reproduced the trials’ pattern: higher breast cancer survival with the anthracycline-based regimen but no difference in all-cause mortality through 8 years of follow-up.¹

“The key to our methodology is accounting for the fact that while chemotherapy improves breast cancer survival, treatment can also increase damage to normal tissues,” Sarkar said.²

How many life-years could survivors lose to accelerated aging?

At the median (50th percentile) of biological aging, the model projected the following losses in remaining life-years compared with expectations based on chronological age:¹

• Anthracycline-based chemotherapy, all ages: 9.4 (IQR, 7.6-11.2) life-years lost (25.0 vs 34.4 expected)
• Nonanthracycline chemotherapy, all ages: 1.8 life-years lost (29.7 vs 31.5 expected)
• Difference between more and less cytotoxic regimens: median 7.6 (IQR, 7.0-8.0) life-years
• Women diagnosed at ages 30 to 39 years: 11.7 life-years lost with anthracycline (38.7 vs 50.4 expected) vs 2.1 (IQR, 1.1-4.1) with nonanthracycline, a median difference of 9.6 (IQR, 8.0-10.0) years

The projected effect shrank with age at diagnosis because older women have shorter remaining life expectancy. Among women diagnosed at ages 70 to 79 years, the median loss was 6.0 life-years with anthracycline and 1.4 with nonanthracycline therapy.¹

When does the risk of death from other causes overtake breast cancer?

Based on chronological age alone, the risk of non–breast cancer death was projected to exceed the risk of breast cancer death 33 years after diagnosis. Among anthracycline recipients, biological age acceleration moved that crossover a median of 16 (IQR, 12-19) years earlier. For women diagnosed at ages 40 to 49 years, it occurred a median of 19 (IQR, 16-23) years earlier; the effect was smaller for women diagnosed at ages 60 to 69 years.¹

Differences in overall survival took years to appear. During the first 5 to 10 years after chemotherapy, all-cause survival for the 2 regimens was within 5%. After 20 years, all-cause mortality was 10% to 25% higher among survivors who received the more cytotoxic regimen, driven by competing non–breast cancer deaths.¹

“Chemotherapy-induced biologic aging can persist for years, and the effects of this acceleration are not visible for many years,” Mandelblatt said.²

What are the limitations of the study?

The authors described the results as illustrative of how simulation modeling can be used to study cancer and aging. Biological age was based on a single biomarker, p16INK4a, which, like other aging biomarkers, is not routinely used in clinical practice. The 2 regimens were modeled as hypothetical scenarios in the same population, which does not capture the clinical and social factors that shape real-world treatment selection. Data were insufficient to model hormonal therapy, immunotherapy, or newer regimens, and the model assumed biological aging persisted without recovery after chemotherapy. Existing senescence data were also not stratified by social or environmental exposures.¹

The study was funded by the National Cancer Institute and other National Institutes of Health grants, with additional support from organizations including the American Cancer Society and the Breast Cancer Research Foundation.¹

Sarkar said the team plans to expand the methodology to other treatments. “There are two next steps we are planning, the first being expanding the scope of this methodology for other types of breast cancer treatments, such as radiotherapy, immunotherapies, targeted therapies and hormonal treatments, which also appear to speed up aging, with effects potentially lasting for many years after treatment,” he said. “We also plan to include information about survivor characteristics to help guide future conversations about individual outcomes.”²

How does this fit with other research on aging after breast cancer?

Most prior research on accelerated aging in cancer survivors has focused on survivors of childhood, adolescent, and young adult cancers, with fewer longitudinal studies in breast cancer.¹ Oncology Nursing News has previously reported on a JAMA Network Open cohort study in which breast cancer survivors who received chemotherapy experienced prolonged declines in physical health compared with those treated with endocrine therapy alone.⁴ At the 2026 Oncology Nursing Society Congress, findings from the EPICC trial suggested that biological age acceleration and neighborhood deprivation may shape the cognitive benefits of aerobic exercise in postmenopausal women with breast cancer.⁵

According to the release, Mandelblatt noted that physical activity, as well as medications being used for other purposes, may help slow accelerated aging in breast and other cancer survivors.²

What are the key takeaways for oncology nurses?

• Keep the treatment message clear. The authors stated that oncologists should not modify treatment decisions based on the potential for accelerated aging, because the goal of chemotherapy is to improve breast cancer survival.¹ Patients who ask about the findings can be told that the results are population-level projections, not individual predictions.
• Pay attention to younger survivors. The greatest projected losses occurred among women treated at ages 30 to 39 years, and younger women are more likely to receive highly cytotoxic therapy because of aggressive tumor subtypes.¹
• Plan survivorship care for the long term. Survival differences between regimens did not emerge for years after treatment, which supports ongoing monitoring for aging-related conditions such as cardiovascular disease, diabetes, and functional decline well beyond active treatment.¹
• Reinforce healthy behaviors. Physical activity and good sleep, which slow age acceleration in general populations, are recommended for all breast cancer survivors, and awareness of aging risks may help motivate lifestyle changes.^1,6
• Set expectations about testing. Biomarkers of aging such as p16INK4a are not yet used in routine care, and senolytic and other antiaging drugs remain under study.¹

References

1. Sarkar S, Sedrak MS, Carroll JE, Schechter C, Muss HB, Mandelblatt JS. Chemotherapy-induced biological age acceleration and lifetime outcomes in breast cancer survivors. JAMA Netw Open. 2026;9(11):e2643008. doi:10.1001/jamanetworkopen.2026.43008

2. Chemotherapy for breast cancer linked to accelerated biological aging. News release. Georgetown Lombardi Comprehensive Cancer Center. November 10, 2026. Accessed November 12, 2026. https://lombardi.georgetown.edu/news-release/chemotherapy-for-breast-cancer-linked-to-accelerated-biological-aging/

3. Geyer CE Jr, Blum JL, Yothers G, et al. Long-term follow-up of the anthracyclines in early breast cancer trials (USOR 06-090, NSABP B-46-I/USOR 07132, and NSABP B-49 [NRG Oncology]). J Clin Oncol. 2024;42(12):1344-1349. doi:10.1200/JCO.23.01428

4. Cortese T. Chemotherapy linked to persistent physical health decline in breast cancer survivors. Oncology Nursing News. March 22, 2025. Accessed November 12, 2026. https://www.oncnursingnews.com/view/chemotherapy-linked-to-persistent-physical-health-decline-in-breast-cancer-survivors

5. Attobrah Q. Exercise’s cognitive benefits in breast cancer survivors may vary by aging and neighborhood factors. Oncology Nursing News. May 16, 2026. Accessed November 12, 2026. https://www.oncnursingnews.com/view/exercise-related-cognitive-benefits-may-differ-by-biologic-aging-and-neighborhood-deprivation

6. Runowicz CD, Leach CR, Henry NL, et al. American Cancer Society/American Society of Clinical Oncology breast cancer survivorship care guideline. CA Cancer J Clin. 2016;66(1):43-73. doi:10.3322/caac.21319