Investigators have found that estrogen levels measured through blood tests may be predictive of which individuals at high risk of breast cancer will benefit from aromatase inhibitors, according to a recent study presented by Cuzick et al at the 2023 San Antonio Breast Cancer Symposium (Abstract PS10-03) and simultaneously published in The Lancet Oncology. These findings may lead to improved strategies for identifying postmenopausal patients who may respond positively to therapy.
Background
About one-seventh of women in the United Kingdom are expected to develop breast cancer, with almost 56,000 new cases per year. Postmenopausal patients with higher concentrations of estrogen in their blood may have an increased risk of developing breast cancer.
Aromatase inhibitors are currently the most effective preventive agent for estrogen receptor–positive breast cancer. However, their use may be increased by identifying those who may benefit most from the therapy.
Aromatase inhibitors such as anastrozole are recommended by the National Institute of Clinical Care and Excellence as preventive therapy in postmenopausal patients at high risk for breast cancer. Anastrozole has also been licensed by the Medicines and Healthcare products Regulatory Agency for breast cancer prevention.
Study Methods and Results
In this study, an international team of investigators analyzed data from the IBIS-II prevention trial with the goal of determining whether measuring estrogen levels in the blood may be an effective strategy for identifying postmenopausal patients at an increased risk for breast cancer who may benefit most from preventive therapy with aromatase inhibitors. The investigators noted that in the international IBIS-II trial, patients were randomly assigned to receive anastrozole between 2003 and 2012.
In an analysis of a case-control study involving 212 patients—72 of whom were at risk for breast cancer and 140 of whom were controls—the investigators found the patients in the placebo group with higher estrogen levels had an increased risk of developing breast cancer; however, this association was not observed in the anastrozole group. Further, about 75% of patients who received anastrozole saw a 55% reduction in the risk of developing breast cancer, whereas those in the bottom 25% of estrogen levels saw a much lower reduction in the risk of breast cancer.
Conclusions
These findings suggested that inexpensive blood tests capable of measuring hormone levels could be used to identify postmenopausal patients who may benefit most from preventive therapy with aromatase inhibitors. This personalization would allow patients to receive the drugs that would offer them the best balance of mitigating their risk of breast cancer and anastrozole side effects.
“These results are very exciting and can refine how we choose preventive medication for postmenopausal [patients] at high risk of breast cancer. In our study, the 25% of these women with the lowest estradiol 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 postmenopausal [patients] at high breast cancer risk before prescribing anastrozole to identify those who are at greatest risk and will respond well,” underscored lead study author Jack Cuzick, PhD, of the Wolfson Institute of Population Health at the Queen Mary University of London.
“It was really exciting when anastrozole was approved by [the National Institute of Clinical Care and Excellence] as a preventive treatment for some [patients] at high risk of breast cancer. This research now gives us some clues about which [patients] would benefit most from the drug, while identifying [those] who won’t benefit and can be spared [the] unnecessary side effects,” reiterated David Crosby, PhD, Head of Prevention and Early Detection at Cancer Research UK. “Cancer Research UK carried out some of the key work on developing these drugs. 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,” he concluded.
Disclosure: The research in the IBIS-II trial was funded by Cancer Research UK and the National Health and Medical Research Council in Australia. Biobank and hormone assays in this study were funded by the Breast Cancer Research Foundation, and additional hormone assays were funded by The Royal Marsden Cancer Charity. For full disclosures of the study authors, visit thelancet.com.
