Impact on Survival of Intratumor Heterogeneity of the Estrogen Receptor
Estrogen receptor positive breast cancer has a long-term risk of systemic and ultimately fatal recurrence. In a recently published study in the Journal of the National Cancer Institute (see full text link at end of article, IntrTumHet), Lindström et al examine the impact of estrogen receptor intratumor heterogeneity and other biologic factors on the risk of fatal breast cancer in patients with ER positive, node negative breast cancer.
The STO-3 trial enrolled 1780 postmenopausal ER+, node negative patients randomly assigned to receive tamoxifen vs not. ER heterogeneity was calculated by pathologists and classified as either high or low. The study found a statistically significant difference in long-term survival by high vs low for low tumor heterogeneity and for luminal A subtype tumors. Those with high intratumor heterogeneity had a two-fold increase in long-term risk compared with patients with low heterogeneity and a similar difference favoring luminal A tumors. IntrTumHet
Intuitively, this study confirms not only the heterogeneity of the estrogen receptor within individual breast tumors but also that increasing heterogeneity is associated with a poorer prognosis. Several years ago, this data would have been extremely important potentially leading to a change in the way that ER is evaluated and reported. However, one now wonders whether tumor genomics might be identifying this same difficult patient population?