Can adverse events after hormone therapy predict survival in patients with breast cancer?

The aim of this study was to investigate the relationship between survival outcomes and specific adverse events (AEs) in patients after menopause (postmenopausal) with breast cancer treated with hormone therapy.

Most breast cancers grow in response to estrogen, the main female sex hormone. Therefore, hormone therapy which stops estrogen from reaching the cancer stops the cancer from growing. Tamoxifen (Nolvadex) and exemestane (Aromasin) are such hormone therapy drugs that have been efficient for patients with breast cancer. However, this therapy has several side effects, most of them related to low estrogen levels, resembling menopausal symptoms. The most common are hot flashes and night sweats related to the constriction or dilatation of blood vessels (called vasomotor symptoms or VMs), osteoporosis (fragile bones prone to fractures) and joint pain (called musculoskeletal adverse events or MSAEs) and vaginal dryness and pain during sexual intercourse (called vulvovaginal symptoms or VVs). This study evaluated whether there was an association between AEs after hormone therapy and survival in patients with breast cancer.

9325 postmenopausal women with breast cancer from 9 countries (559 hospitals) were included in the study. They were randomly divided in two groups, one who received exemestane 25 mg once daily for 5 years (4694 patients) and the other group who received tamoxifen 20 mg once daily for 2.5 to 3 years followed by exemestane 25 mg once daily for 2.5 years (4631 patients). All the patients were followed every 3 months in the first year and twice a year for 5 years.

The results show that younger patients were more likely to report specific AEs whereas older patients had more nonspecific AEs. Patients who reported VMs or MSAEs had a longer time without the disease than those who did not report them. Also, the overall survival (the time patients survived with or without the cancer) was higher for those who reported VMs or VVs. Furthermore, patients who had VMs and MSAEs had a lower rate of distant metastases (cancer spread to distant organs or tissues) than patients who did not report these symptoms. Patients who also received chemotherapy had a higher frequency of specific AEs in comparison with those who did not receive chemotherapy (56% versus 43%). No differences in survival were observed between the two treatment groups.

In conclusion, this study showed that postmenopausal women with breast cancer who received at least 1 year of hormone therapy and who reported at least one treatment related AE had better survival rates. The strongest effect on survival was observed for VMs. 

The main limitation of the study was that all the AEs were self-reported and no standardized symptom checklist was used.