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The mutations can prevent breast cancer treatment

The mutations can prevent breast cancer treatment

If the results could be confirmed in other studies, it would be relevant to screening for the mutations we looked at, already in diagnosing (breast cancer) and then consider other treatment options that work better, says Lau Sall, one of the cancer researchers behind these. The world’s largest study on estrogen receptor resistance mutations in primary breast cancer.

Breast cancer is the most common type of cancer among women, and in Sweden alone, about 10,000 women get sick every year. Most breast tumors contain what is called estrogen receptor 1 (ESR1) and after surgery the most important treatment for these women is hormonal drugs that reduce the activity of the estrogen receptor and thus reduce the risk of relapse.

Mutations in breast cancer recurrence

What researchers have closely studied are some of the mutations in the estrogen receptor gene that were discovered a few years ago in women who received anti-estrogen therapy and then relapsed into cancer. The mutations made the tumor resistant to hormonal therapy. However, recent studies showed that the incidence of these resistance spikes was minimal in patients at first.

But that hasn’t stopped the curiosity of the Lund researchers, and they have now analyzed sequence data for more than 3,000 breast tumors in the large SCAN-B research database, in samples taken before drug treatment.

Of the 2,720 tumors that contained estrogen receptor modules and thus were related to hormonal therapy, they found 29 tumors with none of the resistance mutations. All have occurred in patients over 50 years of age.

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Forskningsdatabasen SCAN-B, Swedish Breast Cancer Analysis NetworkThere are currently around 16,000 breast cancer patients registered and around 120 patients are added per month.

Higher risk of dying from breast cancer

We investigated whether resistant mutations, which occurred before cancer treatment, affected the prognosis of patients, and then we saw that patients with a mutation in the primary tumor had a three times higher risk of recurrence and a 2.5 times higher risk of death. The association between mutations and poor survival has also been observed after statistical corrections for age or for other factors that may affect outcome for the patient, says PhD student Malin Dahlgren.

This confirms what previous studies showed, that mutations are unusual, but we now 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 to hormonal treatment. If the results can be verified in further studies, it may be appropriate to consider other treatment options for these patients, says Lau Sall.

Scientific material:

Pre-existing somatic mutations of the estrogen receptor alpha (ESR1) in early stage primary breast cancer (Malin Dalgren, Anthony M. George, Christian Brover, Sergey Gladchuk, Yelon Chen, Johan Fallon Christerson, Cecilia Hegardt, Gary Häkkinen, Lisa Redden, Martin Malberg, Christer Larson, Sophia K., Åke Borg, Lao H. Saal) Spectrum of Cancer JNCI

Contact:

Lao Sall, Researcher at LUCC – Lund University Cancer Center, [email protected]