Standard breast cancer classification may overlook important differences
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 tumours 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 tumours 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, tumours in which at least one per cent of the tumour 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,” says Balazs Acs, associate professor at the Department of Oncology-Pathology, Karolinska Institutet. “Our study shows that a more detailed classification can provide important information about the tumour’s biological characteristics and the patient’s prognosis.”
The researchers analysed 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 tumour cells expressing the estrogen receptor: 0, 1–9, 10–29, 30–59 or 60–100 per cent. The tumour characteristics, treatments and survival rates were then compared across the groups. The researchers also analysed molecular data from almost 4,800 tumours to study biological differences.
May guide treatment
Women whose tumours had low or moderate levels of estrogen receptors (up to 59 per cent) had poorer survival rates than those whose tumours had high levels (over 60 per cent). These differences remained even when the researchers took into account other important factors such as tumour stage, age and treatment.
Tumours in which 10 to 29 per cent of the tumour cells expressed estrogen receptors were biologically and clinically similar to tumours 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 emphasise 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. See the scientific article for information on funding and conflicts of interest.
Publication
“Patient characteristics, treatment patterns, and survival across estrogen receptor expression subgroups in HER2-negative breast cancer: a population-based cohort study”, Qiao Yang, Ceren Boyaci, Ioannis Zerdes, Irma Fredriksson, Xinsong Chen, Johan Hartman, Balazs Acs, The Lancet Regional Health – Europe, online 26 August 2026, doi: 10.1016/j.lanepe.2026.101826.