NEW YORK (Reuters Health) – The results of a phase III Italian study indicate that the risk of breast cancer in postmenopausal women who use hormone replacement therapy (HRT) is not attenuated by the addition of low-dose tamoxifen.

“However, we noted beneficial trends in some subgroups which may deserve a larger study,” the investigators report.

In their paper in the Annals of Oncology online July 17, they point out that while HRT reduces menopausal symptoms and may decrease mortality, it increases breast cancer risk. On the other hand, breast cancer prevention trials have shown fewer breast cancers occurred among HRT users who were assigned to tamoxifen or raloxifene rather than placebo.

The team therefore conducted a randomized trial involving 1884 recently postmenopausal women on HRT, assigning them to either 5 mg/day tamoxifen or placebo for 5 years. The tamoxifen dose had previously been shown to retain antiestrogen activity without promoting endometrial proliferation in HRT users.

Dr. Andrea DeCensi, at Ospedali Galliera in Genoa, and colleagues found that, after an average follow-up of 6.2 years, 19 breast cancers had occurred in the tamoxifen group (annual rate 3.3/1000) compared to 24 in the placebo group(annual rate 4.1/1000). This translated to a rate ratio (RR) of 0.80, which was not statistically significant.

However, the RR among women who had been on HRT for less than 5 years was significant at 0.35. Tamoxifen also showed a favorable trend in estrogen-only users (RR, 0.26), and among women who remained on treatment for at least a year (RR, 0.49).

Compared to placebo, tamoxifen was associated with a significantly greater frequency of hot flashes (RR, 1.78), night sweats (RR, 1.62), vaginal discharge (2.13) and vaginal dryness (RR, 1.49), the report indicates.

Regarding safety, there was no difference in serious adverse events between the two arms of the study.

Summing up, Dr. DeCensi and colleagues conclude, “The addition of low-dose tamoxifen to HRT did not significantly reduce breast cancer risk and increased climacteric symptoms.”

Nonetheless, noting that important limitations precluded reliable conclusions, they add: “However, our trial suggests that the addition of low-dose tamoxifen to HRT may reduce the risk of breast cancer in recently postmenopausal women. This hypothesis should be assessed in a larger study.”

Source: A phase-III prevention trial of low-dose tamoxifen in postmenopausal hormone replacement therapy users: the HOT study
Ann Oncol 2013.