Breast Cancer Trial Results and Real-World Results Differ Based on Treatment Abandonment

A clinical trial finding that adjuvant hormone therapy-related heat flashes predict improved treatment outcomes among patients with oestrogen receptor-positive breast cancer has been challenged by a new study by Zeng et al. published in JNCCN—Journal of the National Comprehensive Cancer Network. Patients who received treatment for hot flashes after starting adjuvant hormone therapy were actually more likely to experience negative outcomes, according to the population-based study, which examined 7,152 chemotherapy-free breast cancer patients in Sweden between 2006 and 2019. The significantly shorter duration of disease-free survival may be explained by the 14.2 per cent greater early cessation rate among patients who later received treatment for hot flashes.

According to the corresponding author Wei He, PhD, of the School of Public Health, Zhejiang University, China, and the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, "Results from clinical trials might not translate to the real world because the therapy discontinuation rates differ between these two settings." The administration of symptom-relieving medications to patients experiencing treatment-related side effects may not be sufficient to avoid treatment termination, cancer care providers need to be aware.

The relationship between using hot flash medication and stopping adjuvant hormone therapy was weaker among patients with a family history of cancer, according to lead author Erwei Zengt. This might be due to the fact that patients with cancer-related family members were more motivated to finish adjuvant hormone therapy, despite any negative side effects.

Hot Flashes and Stopping Treatment

According to studies listed in the article, randomised clinical trials have shown that adjuvant hormone therapy for oestrogen receptor-positive breast cancer, including tamoxifen and aromatase inhibitors, decreases breast cancer mortality by 30% and 40%, respectively. One of the most frequent adverse effects, hot flashes only caused 8 to 28 per cent of patients to stop their medication. The percentage of patients who discontinued their care earlier than was initially recommended ranged from 31% to 73 per cent in real-world settings.

According to lead author Kamila Czene, PhD, also of the Karolinska Institutet, "Precision medicine based on the patient's genetic background may help to prevent treatment discontinuation." For some patients, reducing the dosage of adjuvant hormone therapy could be a further therapeutic option to lessen treatment-related side effects.

A lower disease-free survival rate (adjusted hazard ratio [HR] = 1.67, 95 per cent confidence interval [CI] = 1.11-2.52) and a higher treatment discontinuation rate (adjusted HR = 1.47, 95 per cent CI = 1.21-1.78) were observed in the study for patients who started taking hot flash medications for the first time soon after beginning adjuvant hormone therapy. According to patient characteristics, there were different associations between hot flash medications and stopping adjuvant hormone therapy, with lower-income patients having stronger associations (HR = 1.91, 95 per cent CI = 1.41-2.59) and patients without first-degree relatives who had cancer having stronger associations (HR = 1.81, 95 per cent CI = 1.39-2.35) or passing away from cancer having stronger associations (HR = 1.71, 95 per cent CI = 1.37-2.12).

Commentary

"According to Jame Abraham, MD, FACP, Chairman of the Department of Hematology and Medical Oncology at the Cleveland Clinic Taussig Cancer Institute and Member of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Panel for Breast Cancer, 20% of patients with breast cancer stop anti-estrogen therapy too soon.

There could be a number of causes for this, including side effects, said Dr. Abraham, who was not involved in the study. It's intriguing to note that patients experiencing hot flashes have worse outcomes in real-world data, which probably results in more early endocrine medication discontinuations. The treatment of side effects and adherence to medication are crucial areas that doctors must continue to focus on."

The researchers did note that because this research was conducted in a nation with a single healthcare system, generalisations concerning the United States may be complicated.

The authors of the study came to the following conclusion: "Hot flashes associated with adjuvant hormone therapy predict poorer, rather than better, breast cancer outcomes among patients in clinical routine practise. A subset of individuals with more severe hot flashes who are more likely to stop adjuvant hormone therapy and require more assistance for treatment adherence may be identified as having adverse effects by the introduction of hot flash medicines.