High estrogen receptor heterogeneity doubles breast cancer mortality risk

Postmenopausal women with breast cancer with high intratumor heterogeneity of ER had an increased long-term risk for death of breast cancer, according to results published in Journal of the National Cancer Institute.

The association also appeared among women with luminal A subtype tumors.

“The biological factors influencing the long-term risk [for] fatal breast cancer are unknown. It is, however, known that patients with ER-positive disease have a continuous long-term risk for fatal breast cancer, in contrast to patients with ER-negative cancer,” Linda Linström, MSc, PhD, researcher in the department of biosciences and nutrition at the Karolinska Institutet in Sweden, and colleagues wrote.

“Given the late onset of fatal disease in ER-positive breast cancer and the lack of clinical studies with long-term follow-up, it is difficult to predict who has a high long-term risk [for] fatal disease,” they added.

Linström and colleagues studied 1,780 postmenopausal women with lymph node-negative breast cancer from the 1976 to 1990 STO-3 trial, which randomly assigned patients to treatment with adjuvant tamoxifen or no adjuvant therapy.

Researchers used Rao’s quadratic entropy to calculate intratumor heterogeneity of ER and categorized levels as high and low heterogeneity using 67% as a cutoff at the second tertile.

The subgroups demonstrated significantly different 25-year breast cancer-specific survival:

88.3% for tamoxifen-treated women with low intratumor heterogeneity of ER;

79.6% for tamoxifen-treated women with high intratumor heterogeneity of ER;

74.3% for untreated women with low intratumor heterogeneity of ER; and

64.3% for untreated women with high intratumor heterogeneity of ER.

Results of a multivariable analysis showed patients with high vs. low intratumor heterogeneity of ER had a two times greater risk for long-term fatal breast cancer (HR = 1.98; 95% CI, 1.31-3).

This association remained regardless of treatment (tamoxifen, HR = 2.15; 95% CI, 1.07-4.34; untreated, HR = 1.91; 95% CI, 1.12-3.27).

Researchers observed a similar increased risk among patients with luminal A subtype tumors (HR = 2.43; 95% CI, 1.18-4.99).

“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 [with] patients with low heterogeneity,” Linström said in a press release. “And this was independent of whether or not they’d received tamoxifen and of other known tumor markers.” – by Cassie Homer

Disclosures: Linström reports no relevant financial disclosures. One author reports being a cofounder, stockholder and employee of Agendia.