Low doses of the investigational medicinal product endoxifen reduce breast density to the same extent as the standard treatment tamoxifen, but without causing such troublesome side effects. This is shown by a new study from Karolinska Institutet published in the Journal of the National Cancer Institute. The results may have implications for future preventive treatment of breast cancer.
Tamoxifen is a well-established drug that has been used for more than 40 years to reduce the risk of recurrence in patients with breast cancer. The drug is also approved for prevention of breast cancer in women at increased risk.
However, the side effects of tamoxifen are a major problem. Many women experience menopausal-like symptoms, such as hot flushes, which means that many do not complete the treatment.
Endoxifen is the most active metabolite formed when tamoxifen is broken down in the body. The new study investigated whether endoxifen in tablet form could provide the same biological impact and a more predictable effect than tamoxifen.
A total of 240 healthy, premenopausal women were randomised to receive a placebo or 1 or 2 mg of endoxifen daily for six months. The researchers then measured mammographic breast density. High mammographic density can contribute to an increased risk of breast cancer but a reduction during treatment can be a good measure of therapeutic outcome.
"Both 1 and 2 milligrams of endoxifen resulted in a clear reduction in breast density compared with the placebo," says Mattias Hammarström, co-author and PhD candidate at the Department of Medical Epidemiology and Biostatistics at Karolinska Institutet.
The results show that 1 mg of endoxifen reduced breast density by an average of 19 per cent and 2 mg by 26 per cent. Data from a previous study show that 20 mg of tamoxifen reduces density by approximately 18.5 per cent. The effect of low-dose endoxifen thus corresponded to that seen with tamoxifen.
Participants who received 2 mg of endoxifen reported a greater worsening of hot flushes and night sweats compared with the lower-dose group, whilst the 1 mg group had a safety profile similar to that of the placebo with respect to serious side effects and biomarkers.
"Our results suggest that a lower dose may be sufficient to affect breast density, whilst also appearing to be better tolerated," says Mattias Hammarström.
The study is a so-called proof-of-concept trial, meaning it is designed to demonstrate that a treatment produces the expected biological effect before larger and longer trials are conducted. However, the study cannot show whether endoxifen reduces the risk of breast cancer or recurrence.
