Study challenges traditional breast cancer classification methods

Breast cancer is often classified as either estrogen receptor-positive (hormone-sensitive) or not. However, a new study from Karolinska Institutet suggests that this simplified classification may overlook important biological differences between patients that could affect treatment decisions. The results are published in The Lancet Regional Health – Europe.

Breast cancer tumors that express estrogen receptors are known as estrogen receptor-positive (ER-positive) or hormone-sensitive breast cancer and, on average, have a better prognosis than ER-negative breast cancer. ER-positive tumors can grow in response to estrogen and can therefore be treated with drugs that block the effects of this hormone.

It is a spectrum

Internationally, tumors in which at least one per cent of the tumor cells express the estrogen receptor are classified as ER-positive, whereas in Sweden the threshold is ten per cent.

Rather than talking about ER-positive or ER-negative breast cancer, we need to view it as a spectrum. Our study shows that a more detailed classification can provide important information about the tumor's biological characteristics and the patient's prognosis."

Balazs Acs, Associate Professor, Department of Oncology-Pathology, Karolinska Institutet

The researchers analyzed data from over 75,000 women in Sweden who, between 2007 and 2023, had been diagnosed with HER2-negative breast cancer, a type of cancer that does not have elevated levels of the HER2 protein. The patients were divided into five groups based on the percentage of tumor cells expressing the estrogen receptor: 0, 1–9, 10–29, 30–59 or 60–100 per cent. The tumor characteristics, treatments and survival rates were then compared across the groups. The researchers also analyzed molecular data from almost 4,800 tumors to study biological differences.

May guide treatment

Women whose tumors had low or moderate levels of estrogen receptors (up to 59 per cent) had poorer survival rates than those whose tumors had high levels (over 60 per cent). These differences remained even when the researchers took into account other important factors such as tumor stage, age and treatment. tumors in which 10 to 29 per cent of the tumor cells expressed estrogen receptors were biologically and clinically similar to tumors with very low levels or no estrogen receptors at all.

"We also observed that patients with mild to moderate levels of estrogen receptors appear to benefit from a combination of chemotherapy and hormone therapy," says Balazs Acs. "This suggests that the exact level of estrogen receptors may be important when choosing a treatment."

The researchers emphasize that the results come from an observational study and that treatments were not randomly allocated among patients. Further studies are needed to investigate how the findings can best be translated into clinical practice.

The study was conducted in collaboration with Karolinska University Hospital in Sweden.