Heterogeneity of the Estrogen Receptor and Risk of Death in Breast Cancer

Key Points

  • Patients with high intratumor heterogeneity of the estrogen receptor were twice as likely to die up to 25 years after their diagnoses, compared to patients with low heterogeneity.
  • This finding was independent of whether patients had received tamoxifen and of other known tumor markers.
  • The greater risk of death for patients with high intratumor heterogeneity also applied to patients with luminal A breast cancer, though these patients are generally thought to have a good prognosis. 

Researchers at Karolinska Institutet in Sweden have discovered that the risk of death from breast cancer is twice as high for patients with high heterogeneity of the estrogen receptor within the same tumor, compared to patients with low heterogeneity. The study, published by Lindström et al in the Journal of the National Cancer Institute, showed that the higher risk of death over a span of 25 years is independent of other known tumor markers and also holds true for luminal A breast cancer, a subtype with a generally good prognosis.

Women who develop estrogen receptor (ER)-positive breast cancer have a remaining long-term risk of dying of the disease. It is also known that the estrogen receptor can change when a breast cancer tumor spreads, which affects survival. The cause of this is unknown, but a possible explanation is that there are tumor cells with varying degrees of expression of the estrogen receptor—ie, intratumor heterogeneity.

In the present study, Swedish and American researchers sought to discover if breast cancer patients with high heterogeneity of the estrogen receptor in their breast cancer tumor have a higher long-term risk of dying. To this end, they examined the records of 593 patients in a clinical study who had been either treated with tamoxifen or not treated with systemic therapy after surgery. All women had been diagnosed with postmenopausal ER-positive breast cancer between 1976 and 1990.

Study Findings

“Our study shows that patients with high intratumor heterogeneity of the estrogen receptor were twice as likely to die up to 25 years after their diagnoses as compared to patients with low heterogeneity,” said Linda Lindström, MSc, PhD, a researcher in the Department of Biosciences and Nutrition at the Karolinska Institutet. “And this was independent of whether or not they'd received tamoxifen and of other known tumor markers.”

The researchers also discovered that the greater risk of death for patients with high intratumor heterogeneity applied to patients with luminal A breast cancer. “Patients with luminal A breast cancer and high intratumor heterogeneity of the estrogen receptor were also twice as likely to die from the disease,” continued Dr. Lindström. “This is interesting, given that patients with luminal A breast cancer subtype are generally thought to have a good prognosis. We believe that if validated, these new findings should be usable within the near future.”

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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