Hot flashes related to adjuvant hormone therapy were predictive of worse breast cancer outcomes, according to research on disease-free survival and treatment discontinuation in patients with and without hot flashes.
A real-world study in Sweden found that hot flashes related to adjuvant hormone therapy (AHT) were predictive of worse breast cancer outcomes among patients in routine clinical practice, in contrast to outcomes in randomized clinical trials.1 Investigators compared disease-free survival (DFS) and treatment discontinuation among patients with and without hot flashes. The 5-year DFS rate was 95.8% but among patients who used agents to treat hot flashes shortly after AHT initiation; DFS was significantly shorter (TABLE 11 ; HR, 1.67; 95% CI, 1.11-2.52) and the treatment discontinuation rate was higher (adjusted HR, 1.47; 95% CI, 1.21-1.78).
Historically, several studies have explored the relationship between hot flashes, AHT, and outcomes, which resulted in conflicting findings. In addition, the investigators noted that previous studies were conducted in the confines of clinical trials evaluating other aims.2,3
In research cited within the article, tamoxifen and aromatase inhibitors reduced mortality by 30% and 40%, respectively, in randomized clinical trials. Hot flashes associated with these treatments led to an 8% to 28% discontinuation. In real-world settings, discontinuation rates had been reported in the 31% to 73% range.1
Erwei Zeng, MSc, and colleagues1 linked the National Quality Registry for Breast Cancer to the Swedish Prescribed Drug Register (SPDR), a national database that records dispersed prescription drugs. Investigators identified 15,197 women who received a breast cancer diagnosis between 2006 and 2019 and who initiated AHT with 1 or more prescriptions of tamoxifen or aromatase inhibitors.
Patients were excluded if the investigators noted the presence of distant metastases at diagnosis. To further exclude women whose hot flashes were caused by AHT, patients with a previous breast cancer event (eg, local recurrence), patients treated with chemotherapy, and those who used drugs to relieve hot flashes within 1 year of AHT initiation were not enrolled.
7152 Women Evaluated
After exclusion criteria were applied, 7152 women were evaluated in the final cohort. After a median follow-up for DFS of 6.8 years (interquartile range, 3.9-10.0), the 5-year and 10-year DFS rates were 95.8% and 91.0%, respectively. Among patients using tamoxifen and aromatase inhibitors, the associations were similar and did not reach statistical significance.
The median treatment discontinuation rate at 5 years was 48.9% (interquartile range, 25%-75%) and the median follow-up for discontinuation of AHT was 3.5 years (range, 1.7-5.0). Patients who started using agents to treat hot flashes were more likely to discontinue AHT. Additional analysis showed that patients who discontinued AHT were more likely to have shorter DFS, with a multivariable-adjusted HR of 1.46 (95% CI, 1.18- 1.80). Similar associations were observed for patients who used tamoxifen and aromatase inhibitors (TABLE 21 ).
When characteristics were stratified, the use of drugs for hot flashes was associated with a higher risk of AHT discontinuation. These observations were stronger among women with low incomes, those with no family history of cancer among first-degree relatives, and those with no first-degree relatives who had died of cancer.
Investigators emphasized that this trial is the first population-based study to investigate the long-term treatment outcome among women with treatment-related hot flashes with the use of drugs for hot flashes serving as an objective indicator.
Although the investigators’ findings suggest that differences in treatment discontinuation should be considered before results from clinical trials can be generalized to clinical practice, they caution that their results do not necessarily invalidate results from clinical trials.
Limitations of the current trial include prescriptions in the SPDR lacking indication information, so the investigators could not rule out that some use of drugs for hot flashes may be for other conditions. Further, a prescription refill indicated in the SPDR is not a verification that the patient is taking the medication; also, because Sweden has a unified health care system, generalizations to other countries should be avoided.
1. Zeng E, He W, Smedby KE, Czene K. Adjuvant hormone therapy–related hot flashes predict treatment discontinuation and worse breast cancer prognosis. J Natl Compr Canc Netw. 2022;1-7. doi:10.6004/ jnccn.2021.7116
2. Mortimer JE, Flatt SW, Parker BA, et al; WHEL Study Group. Tamoxifen, hot flashes and recurrence in breast cancer. Breast Cancer Res Treat. 2008;108(3):421-426. doi:10.1007/s10549-007-9612-x
3. Cuzick J, Sestak I, Cella D, Fallowfield L; ATAC Trialists’ Group. Treatment-emergent endocrine symptoms and the risk of breast cancer recurrence: a retrospective analysis of the ATAC trial. Lancet Oncol. 2008;9(12):1143-1148. doi:10.1016/S1470-2045(08)70259-6