Breast Cancer Treatment Side Effects: Cardiotoxicity and Bone Health Challenges

A recent study published in the Asia-Pacific Journal of Oncology Nursing explored whether the implementation of self-management interventions could reduce cancer treatment–related cardiotoxicities among survivors of breast cancer. A team of researchers from China conducted the study and explained that cardiotoxicities induced from therapy can "lead to long-term cardiovascular complications that impair quality of life (QoL) and survival," underscoring the importance of developing strategies to manage treatment-related toxicity for the support of cardiovascular health in patients with breast cancer throughout survivorship.

The investigators selected studies that were performed between January 2004 and November 2024 from six English-language databases. Eleven randomized controlled trials were selected from the databases, involving a total of 950 patients. The investigators divided the patients from the studies into a self-management intervention group (n=516) and a control group (n=434). The intervention group received either aerobic or resistance exercise interventions and the control group received care as usual.

According to the results, "the meta-analysis indicated that exercise interventions significantly improved VO2peak (MD = 2.71, 95% CI 1.23 to 4.20, P < 0.001) and left ventricular ejection fraction (MD = 1.80, 95% CI 0.06 to 3.54, P = 0.043), although heterogeneity was substantial." However, the researchers also highlighted that "the effectiveness of exercise on secondary outcomes remains uncertain" and that the "GRADE framework rated the certainty of the evidence as very low."

The study authors emphasized that "exercise has emerged as the most frequently employed self-management strategy for mitigating therapy-induced cardiotoxicity among breast cancer survivors." They concluded that "evidence has indicated that structured exercise may help attenuate cancer therapy-induced cardiotoxicity, with VO2peak emerging as a more sensitive marker than left ventricular ejection fraction."

In a separate development, a narrative review published in Osteoporosis International by the International Osteoporosis Foundation (IOF) Committee of Scientific Advisors Working Group on Cancer-Induced Bone Disease warns that women with early-stage, estrogen receptor–positive breast cancer who discontinue denosumab after aromatase inhibitor therapy may face a significant and under-recognized risk of spontaneous vertebral fractures.

Aromatase inhibitors are a cornerstone of adjuvant therapy for hormone receptor–positive breast cancer, significantly reducing recurrence and mortality. However, by suppressing estrogen production, aromatase inhibitors can accelerate bone loss and increase fracture risk. To counter this, antiresorptive therapies such as denosumab or bisphosphonates are widely recommended.

Denosumab has strong evidence for fracture prevention during aromatase inhibitor therapy; yet, unlike bisphosphonates, its protective effects reverse rapidly once treatment is stopped. The review's authors warn that discontinuing denosumab can trigger a "rebound phenomenon" marked by rapid bone turnover, bone loss, and potentially multiple vertebral fractures—even in women without prior osteoporosis or traditional fracture risk factors.

The review highlights that bone turnover increases sharply after denosumab withdrawal, leading to rapid loss of bone mineral density. Spontaneous vertebral fractures—often multiple and clustered at the thoracolumbar spine—have been reported after denosumab discontinuation in women treated with aromatase inhibitors. Fracture risk may be underestimated because many affected women did not have osteoporosis at the start of cancer therapy.

Expert consensus supports initiating bisphosphonate therapy after denosumab discontinuation, although the optimal drug, dose, timing, and duration remain undefined. The authors emphasized that starting denosumab in women receiving aromatase inhibitors should never be viewed as a standalone decision, but rather as part of a planned therapeutic sequence that anticipates treatment discontinuation. They also highlighted practical challenges such as delayed denosumab dosing, limited access to bisphosphonates in some countries, and management difficulties in patients with contraindications to bisphosphonate therapy.

Despite growing recognition of the problem, the authors noted that there are numerous open research questions which future prospective studies will have to answer to personalize the most appropriate antiresorptive therapy for each patient.