When Sandra was diagnosed with breast cancer, her doctors had a powerful tool: tamoxifen, a drug that fights hormone-sensitive tumors by blocking estrogen. But years later, her neighbor Linda, facing a seemingly similar diagnosis, didn't respond to the same treatment the same way. Why? A groundbreaking study from Sweden may finally hold some answers.
Researchers at the Karolinska Institutet in Stockholm have discovered that the cells surrounding a breast tumor the so-called tumor microenvironment may play a major role in determining whether tamoxifen works well over the long term. Their study, published in the journal BMC Medicine, followed 513 postmenopausal women for up to 25 years and found that patients with certain types of surrounding cells benefited far more from the drug than others.
The study focused on women with a common form of breast cancer called estrogen receptor-positive, HER2-negative. These patients took part in the randomized Stockholm Tamoxifen trial, where some received tamoxifen and others did not. The researchers then examined the types of immune cells, connective tissue cells, and blood vessel cells present within and around each tumor to see if their composition affected treatment outcomes.
The results were striking. Patients who had a low abundance of immune cells in the tumor microenvironment experienced the greatest long-term benefit from tamoxifen compared to those who did not receive the treatment. Different levels of blood vessel-related cells and connective tissue cells were also linked to how much benefit patients gained.
"Today, breast tumors are assessed mainly on the basis of the characteristics of the cancer cells themselves," said Nick Tobin, a researcher at Karolinska Institutet's Department of Oncology-Pathology and the study's senior author. "Our findings suggest that the cells surrounding the tumor may also provide important information about how patients respond to treatment."
Paula Camargo-Romera, the study's first author, said the findings could eventually help explain why patients with the same type of breast cancer sometimes respond so differently to hormone therapy. "In the longer term, this knowledge may help researchers investigate whether treatments can be tailored more effectively to the biological characteristics of individual tumors," she said.
The researchers caution that the study is based on patients treated according to older standards of care, so the findings need to be confirmed in modern patient populations before being used in everyday clinical practice. Still, the work represents a meaningful step toward understanding the complex neighborhood around a tumor and how it influences a patient's journey through treatment. By looking beyond the cancer cells themselves, scientists may one day help more patients like Sandra and Linda get the right therapy the first time.
The study was published as DOI: 10.1186/s12916-026-05091-5.