Expert Point of View #2: Can Molecular Profiling Identify ER-positive Patients Destined for Relapse?

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Understanding the different relapse patterns within estrogen receptor (ER)-positive breast cancer is important for guiding treatment decisions, said Laura Esserman, MD, of the University of California, San Francisco, Medical Center. Women who fall into the two separate categories may have different treatment needs, said Dr. Esserman, who has led many studies in risk assessment and molecular profiling of tumors.

“We have good predictors of early relapse. Our markers for late relapse are not so good,” she noted. Tumor cell proliferation, however, may be a means of sorting this out, she said.

Dr. Esserman and colleagues looked at timing of recurrence among 346 untreated patients from Guy’s Hospital, followed for at least 23 years.1 In ER-positive tumors of low grade, they found risk for early recurrence was very low. However, 10 years or more postdiagnosis about 20% of patients recurred. Higher-grade ER-positive, node-negative cases had an increase risk of relapse that extended ≥ 20 years, unlike hormone-negative and HER2-positive tumors where risk was confined to 5 years. Among node-positive cases, only low grade conferred late risk.

Pooling data from other datasets, the investigators found that tumor proliferative genes predicted early but not late metastatic risk in ER-positive patients. Immune-related genes were predictive for early metastatic risk in triple-negative and HER2-positive cases.

Prognostic Signatures

Breast cancer prognostic signatures need to inform both risk and timing of metastatic events and may best be applied within subsets, she said. “Current signatures predict for outcome risk within 5 years of diagnoses, but predictors of late risk for ER-positive disease are needed.”

Ultimately, she said, the best treatment decisions will be made when clinicians can dissect out the patient’s baseline risk with and without therapy, and predict their sensitivity to hormonal treatment. “It’s not simply being hormone receptor–positive. That’s only the minimum,” she pointed out.

For predicting sensitivity to endocrine therapy, at least four assays have emerged, all based on estrogen-related genes. “So there is a commonality” in this research theme, which “tells us that this approach is robust,” she added. “We are starting to ask the right questions, and to develop the kinds of tools we need.” ■

Disclosure: Dr. Esserman reported no potential conflicts of interest.


1. Esserman LJ, Moore DH, Tsing PJ, et al: Biologic markers determine both the risk and the timing of recurrence in breast cancer. Breast Cancer Res Treat 129:607-616, 2011.

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