Adjuvant Hormone Therapy–Related Hot Flashes Predict Treatment Discontinuation and Worse Breast Cancer Prognosis

Authors: Erwei Zeng MSc1, Wei He PhD1,2,3, Karin E. Smedby MD, PhD4, and Kamila Czene PhD1
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  • 1 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden;
  • | 2 Chronic Disease Research Institute, the Children’s Hospital, and
  • | 3 Department of Nutrition and Food Hygiene, and National Clinical Research Center for Child Health, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; and
  • | 4 Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.

Background: Clinical trials have shown that adjuvant hormone therapy (AHT)–related hot flashes can predict better breast cancer outcomes. This population-based cohort study investigated whether this result can be generalized to a real-world setting. Patients and Methods: By linking the National Quality Registry for Breast Cancer, Prescribed Drug Register, and Cause-of-Death Register, we identified 7,152 chemotherapy-free patients with breast cancer who initiated AHT in Stockholm from 2006 through 2019, and followed them until 2020. Hot flashes were defined as new use of drugs for hot flashes within 6 months after initiating AHT. We used Cox models to compare disease-free survival and treatment discontinuation among patients with and without hot flashes. Results: Patients who newly used drugs for hot flashes shortly after AHT initiation had worse disease-free survival (adjusted hazard ratio [HR], 1.67; 95% CI, 1.11–2.52) and a higher treatment discontinuation rate (adjusted HR, 1.47; 95% CI, 1.21–1.78). The association between drugs for hot flashes and discontinuation of AHT differed by patient characteristics, with stronger associations among low-income patients (HR, 1.91; 95% CI, 1.41–2.59) and those without first-degree relatives who had cancer (HR, 1.81; 95% CI, 1.39–2.35) or died from cancer (HR, 1.71; 95% CI, 1.37–2.12). Conclusions: AHT-related hot flashes predict worse, rather than better, breast cancer outcomes among patients in clinical routine practice. The identification of adverse effects by the initiation of hot flash medications may identify a subset of patients with more severe hot flashes who are more likely to discontinue AHT and need more support for treatment adherence.

Submitted September 1, 2021; final revision received November 24, 2021; accepted for publication November 29, 2021. Published online April 6, 2022.

Author contributions: Study concept and design: Zeng, He, Czene. Data curation: Zeng, He, Czene. Formal analysis: Zeng. Funding acquisition: Zeng, He, Czene. Investigation: All authors. Methodology: Zeng, He, Czene. Project administration: Czene. Resources: Czene. Software: Zeng, He. Supervision: He, Czene. Validation: Zeng. Visualization: Zeng. Writing—original draft: Zeng, He, Czene. Writing—review and editing: All authors.

Disclosures: The authors have disclosed that they have no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors.

Correspondence: Wei He, PhD, Chronic Disease Research Institute, the Children’s Hospital, and National Clinical Research Center for Child Health, School of Public Health, Zhejiang University, 866 Yu-hang-tang Road, Hangzhou, 310058 China. Email: wei.he@ki.se

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