RESOLVING THE LEDGER
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0 Share Newsweek is a Trust Project member See more of our trusted coverage when you search. Prefer Newsweek on Google to see more of our trusted coverage when you search. A new study into breast cancer classification has suggested the standard currently used may overlook important differences that may impact treatment decisions.
Not all breast cancers are the same, and healthcare professionals classify the type using tests to determine which treatment options are most likely to help a patient .
One check is whether the cancer cells are fueled by hormones. An estrogen receptor (ER) positive breast cancer has receptors for the hormone estrogen, meaning treatment with hormone or endocrine therapy can block the growth of the cancer cells.
Progesterone receptor (PR) positive has receptors for the hormone progesterone, and a hormone receptor (HR) negative breast cancer does not have hormone receptors, according to the Mayo Clinic.
On average, ER positive breast cancer tumors have a better prognosis than ER negative breast cancer, as the tumors grow in response to estrogen, and can be treated with therapy that blocks the effects of estrogen.
Certain breast cancer cells also make too much of a protein called human epithelial growth factor-receptor 2, known as HER2. Classifications of breast cancer can be HER2 positive, HER2 low, or HER2 negative, and impacts on whether a targeted therapy can control the breast cancer.
However, researchers from the Karolinska Institutet in Sweden now believe these classifications should be treated as a spectrum.
Researcher Balazs Acs, associate professor at the department of oncology-pathology, told Newsweek that their study found that ER expression "behaves as a spectrum rather than a simple positive-versus-negative biomarker."
The team analyzed data from more than 75,000 women in Sweden diagnosed with HER2-negative breast cancer between 2007 and 2023, dividing them into groups based on the percentage of tumor cells expressing the estrogen receptor. They then compared tumor characteristics, treatments and survival rates across the groups, while also studying molecular data from around 4,800 tumors to study the biological differences.
Acs said: "Notably, tumors with ER expression between 10 percent and 29 percent had survival outcomes and molecular characteristics more similar to ER-low and ER-negative breast cancers than to strongly ER-positive tumors, suggesting that the current classification system may not fully capture clinically relevant biological differences."
He said they found that patients with ER expression between 10 and 59 percent "had poorer survival than those with strongly ER-positive disease," and that patients receiving both chemotherapy and endocrine therapy "had improved survival compared with patients treated with endocrine therapy alone in these intermediate ER groups."
The differences remained even when accounting for factors including tumor stage, age of the patient, and treatment.
"These findings support reporting ER as a percentage and considering ER expression as a continuum in clinical decision-making," Acs said.
Further research is required to investigate how the findings can be translated into clinical practice, as the results were from an observational study and treatment was not allocated randomly among patients.
Acs told Newsweek that their future research "will focus on better understanding the biology of these intermediate ER-expressing tumors and identifying additional biomarkers that may refine risk stratification and treatment selection."
"We are particularly interested in exploring the role of progesterone receptor expression and other molecular features to determine how these findings can be translated into more personalized treatment approaches for patients with breast cancer," he said.
Yang Q, Boyaci C, Zerdes I et al. Patient characteristics, treatment patterns, and survival across estrogen receptor expression subgroups in HER2-negative breast cancer: a population-based cohort study. The Lancet Regional Health – Europe, 2026; 0 DOI: http://dx.doi.org/10.1016/j.lanepe.2026.101826
Contact Newsweek editors on this story: Kara Dolman and Emma Lee-Sang
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