– If the results can be confirmed in further studies, it would be relevant to review the mutations we have already seen in the diagnosis (breast cancer). And then consider other treatment options that work better, says Lao Saal, one of the cancer researchers behind the study, which is the world’s largest conducted on estrogen receptor resistance mutations in primary breast cancer.
Breast cancer is the most common form of cancer in women, and in Sweden alone it affects about 10,000 women a year. Most breast tumors contain the so-called estrogen receptor (ESR1), and after surgery the most important treatment for these women are hormonal drugs that reduce the activity of the estrogen receptor and thus reduce the risk of recurrence.
Mutations in breast cancer recurrence
What the researchers looked at more closely were some mutations in the estrogen receptor gene that were discovered a few years ago in women who received anti-estrogen treatment and then returned to their cancer. Mutations have made the tumor resistant to hormonal treatment. Recent studies, however, have shown that the frequency of these resistance mutations was negligible in patients at baseline.
But that didn’t stop the curiosity of Lund researchers and they are now analyzing sequencing data with more than 3,000 breast tumors in a large SCAN-B research database, in samples taken before drug treatment.
Among the 2720 tumors that had an estrogen receptor and were therefore relevant for hormonal treatment, 29 tumors with any of the resistance mutations were found. They all occurred in patients older than 50 years.
The SCAN-B research database, the Swedish Breast Cancer Analysis Network, currently has about 16,000 registered breast cancer patients, with about 120 patients added each month.
Higher risk of dying from breast cancer
– We investigated whether resistant mutations before cancer treatment affected patients’ prognosis, and then we saw that patients with a primary tumor mutation had three times the risk of recurrence and 2.5 times the risk of dying. The link between mutations and poor survival was also seen after statistical corrections for age or for other factors that may affect a patient’s outcome, says doctoral student Malin Dahlgren.
– This confirms what previous studies have shown, that mutations are unusual, but now we know that these resistant mutations occur in about 1 percent of breast cancer cases and we are the first to show that these patients seem to respond less well to hormonal treatment. If the results can be verified in further studies, it may be important to consider other treatment options for these patients, Lao Saal says.
Pre-existing somatic mutations in estrogen receptor alpha (ESR1) in early-stage primary breast cancer (Malin Dahlgren, Anthony M. George, Christian Brueffer, Sergii Gladchuk, Yilun Chen, Johan Vallon-Christersson, Cecilia Hegardt, Jari Häkkinen, Lisa Rydén, Martin Malmberg, Christer Larsson, Sofia K. Gruvberger-Saal, Anna Ehinger, Niklas Loman , Åke Borg, Lao H. Saal) JNCI spectrum of cancer
Lao Saal, researcher at LUCC – Lund University University Cancer Center, [email protected]