Men with hormone receptor-positive (HR+) breast cancer treated with tamoxifen had more than a two-fold increased risk of thromboembolism compared with men treated without tamoxifen, according to data from a prospective cohort study.
During 4 years of follow-up, patients treated with tamoxifen had a thromboembolic event rate of 51.9 per 1,000 person-years versus 21.5/1,000 in the men who did not receive the antiestrogen agent. The risk was greatest during the first 18 months of treatment, during which 81% of thrombotic events occurred.
Older age was the principal factor associated with increased risk of thromboembolic events, reported Holm Eggemann, MD, of Otto-von-Guericke University in Magdeburg, Germany, and colleagues in the British Journal of Cancer.
“These results will support physicians in treatment decisions of patients with male breast cancer and will sensitize them to focus their attention on the first one to two years of treatment,” the authors concluded. “In this period, an appropriate monitoring of the patients is warranted.”
The results are consistent with previous studies of female breast cancer patients treated with tamoxifen, although the rate of thromboembolism in men appeared to be somewhat higher, they added.
Male breast cancer remains a rare condition, accounting for about 1% of all breast cancers. The vast majority of the cancers in men are HR+. Eggemann and colleagues previously reported that men with breast cancer had significantly better survival if they received adjuvant tamoxifen instead of an aromatase inhibitor. Another report showed that men and women with breast cancer derive similar benefits from tamoxifen therapy.
Thromboembolism is a recognized risk of tamoxifen therapy. Studies documented that women with breast cancer have a risk of thromboembolic events two to three times greater if they receive tamoxifen as part of their treatment, and that the risk decreases after the first 2 years of treatment. In contrast, the risk of thromboembolism — and adverse events, in general — in men with breast cancer has not been studied extensively, Eggemann and colleagues noted.
The current analysis included 448 men treated for breast cancer from May 2009 to July 2017. Investigators excluded patients with undefined endocrine therapy or <6 months of follow-up, leaving 218 patients for the analysis. Of those, 177 received tamoxifen and 41 did not.
The cohort had a median age at diagnosis of 69.4, and both estrogen and progesterone receptor status was confirmed in >90% of the cases. The patients had a median follow-up of 47 months.
Overall, thromboembolic events occurred in 21 (11.9%) patients treated with tamoxifen as compared with one (2.5%) patient who did not receive tamoxifen. The tamoxifen-treated men had a 6.2% incidence of thromboembolism during the first year of treatment, declining to 3.4% in the second year, and 2.3% in the third year.
Examination of potential clinical and pathologic factors that contributed to the risk of thromboembolism revealed no significant associations in the tamoxifen-treated group. Age >71 was the only factor significantly associated with an increased risk of thrombotic events in men treated with tamoxifen.
“The most important limitation of the present study is the lack of a control group untreated with tamoxifen,” the authors acknowledged. “It is caused by the small number of patients who did not receive tamoxifen. Thus, we were unable to compare the hazard ratio of tamoxifen with the untreated population and evaluate the influence of additional risk factors on thrombotic risk.”
A recent review of adverse events in studies involving men who received tamoxifen for various indications suggested that the risk of thromboembolic events varied by the condition for which the antiestrogen was used, co-author Erik Wibowo, PhD, of the University of Otago in Dunedin, New Zealand, said in an email to MedPage Today. The review included randomized trials of men with prostate cancer treated with tamoxifen with or without antiandrogens; randomized trials of tamoxifen for gynecomastia (idiopathic or secondary to prostate cancer treatment); and nonrandomized trials of tamoxifen for men with breast cancer.
The review showed few thrombotic events in the patients who received tamoxifen for prostate cancer or gynecomastia. The studies of tamoxifen with breast cancer comprised a total of 454 patients and 49 cardiac and vascular events, 33 of which were hot flashes. Thrombotic events occurred in 11 (2.4%), and the highest rate in any of the studies was 5%, considerably less than in the rate reported by Eggemann and colleagues.
Differences in demographics and tamoxifen dosage might also explain the differences in rates of thromboembolic events in various studies, said Wibowo.
Eggemann and co-authors disclosed no relevant relationships with industry.