Adjuvant hormone therapy in breast cancer patients : a special focus on treatment discontinuation

Purpose: Breast cancer is the most common cancer among women, with approximately 80% of cases being estrogen-receptor (ER) positive. Adjuvant hormone therapy is a standard treatment that is recommended for ER-positive patients for a minimum of five years, but many patients discontinued it prematurely. ER-positive breast cancer also carries a risk of late recurrence, which may necessitate the use of adjuvant hormone therapy for up to ten years. This doctoral project aims to investigate the use of adjuvant hormone therapy in a real-world setting and provide insights to enhance clinical practice and patient outcomes.

Patients and Methods: Four observational studies were conducted using data from multiple Swedish health registers. The study population comprised all women diagnosed with ER-positive breast cancer who initiated adjuvant hormone therapy in the Stockholm-Gotland region. Studies I-III examined the association between patient, family, and comedication factors with the adjuvant hormone therapy discontinuation and breast cancer prognosis. Study IV assessed the real-world use and outcomes of extending adjuvant hormone therapy beyond five years.

Findings: Study I showed that hot flashes related to adjuvant hormone therapy predicted worse outcomes and discontinuation, which contrasted with findings from clinical trials. This discrepancy may be attributed to the variation in discontinuation rates between clinical practice and trials. Study II demonstrated that experiencing familial adversity, including material deprivation, negative dynamics, and loss or threat of loss of family member, also contributed to treatment discontinuation and mortality. Study III identified that discontinuation of adjuvant hormone and cardiovascular therapies often occurred concomitantly, underscoring the need for an integrated cardio-oncology approach. Finally, Study IV showed that extending adjuvant therapy beyond five years improved breast cancer outcomes in clinical practice.

Conclusions: In conclusion, the findings of this thesis emphasize the importance of continuous support for patients undergoing adjuvant hormone therapy. Additionally, the extended use of adjuvant hormone therapy beyond five years may be necessary to improve long-term breast cancer outcomes.

List of scientific papers

I. Zeng E, He W, Smedby KE, Czene K. Adjuvant Hormone Therapy-Related Hot Flashes Predict Treatment Discontinuation and Worse Breast Cancer Prognosis. Journal of the National Comprehensive Cancer Network. 2022 Apr 6; 1-7.
https://doi.org/10.6004/jnccn.2021.7116

II. Zeng E, He W, Sjölander A, Bergqvist J, Fang F, Czene K. Family-Related Factors Are Associated with Discontinuation of Adjuvant Hormone Therapy and Breast Cancer Prognosis. [Manuscript]

III. He W*, Zeng E*, Sjölander A, L. Hübbert, E. Hedayati, Czene K. Concomitant Discontinuation of Cardiovascular Therapy and Adjuvant Hormone Therapy in Breast Cancer Patients. *Equal contributions. [Submitted]

IV. Zeng E, He W, Sjölander A, Bergqvist J, Czene K. Determinants and Effectiveness of Extending the Duration of Adjuvant Hormone Therapy beyond 5 Years in Patients with Breast Cancer. Cancer Research. 2022 Oct 1; 82 (19): 3614–3621.
https://doi.org/10.1158/0008-5472.CAN-22-0900