Researchers at the Karolinska Institute 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 as compared to patients with low heterogeneity. The institute’s study also shows 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.
The most common form of breast cancer is estrogen-receptor-positive—so-called ‘hormone-sensitive’ breast cancer. This means that the tumor needs the female hormone estrogen to grow. Women who develop this kind of breast cancer have a continuous long-term risk of dying from the disease.
It is also known that the estrogen receptor can change when a breast cancer tumor spreads, which affects survival. It is not known why this is the case, but a possible explanation is that there are tumor cells in one and the same tumor with varying degrees of expression of the estrogen receptor. This is known as intratumor heterogeneity.
In the Karolinska Institute study, Swedish and American researchers sought to discover whether breast cancer patients with high heterogeneity of the estrogen receptor in their breast cancer tumors have a higher long-term risk of dying. To this end, they analyzed data from a previous clinical study to review the fates of 593 patients who had been either treated with tamoxifen or not treated with systemic therapy after surgery. All women had been diagnosed with post-menopausal estrogen-receptor-positive breast cancer between 1976 and 1990.
Linda Lindström, PhD, Karolinska Institute.
“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,” says Linda Lindström, PhD, researcher in the department of biosciences and nutrition at the Karolinska Institute. “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 also applied to patients with luminal A breast cancer, a subtype of estrogen-receptor-positive breast cancer that is considered to have a good prognosis.
“Patients with luminal A breast cancer and high intratumour heterogeneity of the estrogen receptor were also twice as likely to die from the disease,” says 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 useable within the near future.”
The study was financed by the California Breast Cancer Research Program, the Cancer Society in Stockholm, the Gösta Milton Donation Fund, and the Swedish Research Council.
REFERENCE
- Lindström LS, Yau C, Czene K, et al. Intratumor heterogeneity of the estrogen receptor and the long-term risk of fatal breast cancer. J Natl Cancer Inst. Published online in advance, January 19, 2018; doi: 10.1093/jnci/djx270.
