Research led by Jack Cuzick shows that blood hormone levels are an important indicator of whether women will benefit from recently licensed medication, Anastrozole, for the prevention of breast cancer. The study results have been presented by Professor Cuzick in his William L. McGuire Memorial Lecture at the San Antonio Breast Cancer Symposium (SABCS), and simultaneously published in Lancet Oncology on 6 December.
Anastrozole is recommended by the National Institute of Clinical Care and Excellence (NICE) as an option for preventive therapy in post-menopausal women at high risk of breast cancer, and is now also licensed by the Medicines and Healthcare products Regulatory Agency (MHRA) for breast cancer prevention. The study in Lancet Oncology, could lead to better ways to identify those post-menopausal women who would most benefit from these drugs.
1 in 7 women in the UK will develop breast cancer, with almost 56,000 cases diagnosed every year. Post-menopausal women with higher blood concentrations of the hormone oestrogen are at higher risk of developing breast cancer. Aromatase inhibitors stop the production of oestrogen and reduce the amount made in the body. They are currently the most effective preventive agent for oestrogen-receptor positive breast cancer, but their utility could be increased by identifying those who stand to benefit most by taking these drugs.
An international team of authors from the UK, Australia, Finland, Germany, Italy, and the USA tested whether measuring oestrogen in the blood could identify which women at increased risk of breast cancer will benefit most from the preventive effects of an aromatase inhibitor. They analysed data from the IBIS-II prevention trial, an international randomised controlled trial of anastrozole in high-risk post-menopausal women conducted from 2003 to 2012.
Their analysis of a case-control study of 212 women (72 cases, 140 controls) showed a clear trend of increasing risk with increasing hormone levels in the placebo group, but not in the anastrozole group. A 55% reduction of risk of developing cancer was seen in three quarters of the women receiving anastrozole, but a much lower reduction was seen in those in the bottom 25% of oestradiol levels.
These data suggest that inexpensive blood tests to measure hormones could be used to identify women who will benefit most from preventive therapy with an aromatase inhibitor. This personalisation would allow for women to receive the medication that would offer them the best balance of managing cancer risk and side effects.
Professor Cuzick said: ‘These results are very exciting, and can refine how we choose preventive medication for post-menopausal women at high risk of breast cancer. In our study the 25% of these women with the lowest oestradiol measurements benefitted little from taking anastrozole, while still suffering from the side effects of the drug. A simple blood hormone test could improve the benefit of anastrozole if we use it to select the patients best suited to take it. We now need to routinely assess hormone levels in post-menopausal women at high breast cancer risk before prescribing anastrozole, to identify those who are at greatest risk and will respond well.’
Head of prevention and early detection at Cancer Research UK, Dr David Crosby said: ‘It was really exciting when anastrozole was approved by NICE as a preventive treatment for some woman at high risk of breast cancer. This research now gives us some clues about which women would benefit most from the drug, while identifying women who won’t benefit and can be spared unnecessary side effects. Cancer Research UK carried out some of the key work on developing these drugs, known as aromatase inhibitors. It's an area with a lot of potential, and larger trials building on the results in this study will be key to further understanding who is most likely to benefit.’
Jack Cuzick, Kim Chu, Brian Keevil, Adam R Brentnall, Anthony Howell, Nicholas Zdenkowski, Bernardo Bonanni, Sibylle Loibl, Kaija Holi, D. Gareth Evans, Steve Cummings, Mitch Dowsett on behalf of IBIS-II collaborators. Impact of baseline oestradiol and testosterone serum levels on the effectiveness of anastrozole in preventing breast cancer in high risk postmenopausal women - a case control study. Lancet Oncology 6 December 2023. DOI: 10.1016/S1470-2045(23)00578-8