Early-stage HR+/HER2- breast cancer is the most common subtype of breast cancer and is typically characterized by slower growth, hormone-driven biology, and a favorable prognosis when treated with appropriately tailored therapies. A study presented at the recent 2025 ASCO Annual Meeting emphasized a role for gene expression profiling (GEP) in this patient population.

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Following this presentation, featured expert Melinda L. Telli, MD, FASCO, was interviewed by Conference Reporter Associate Editor-in-Chief Christopher Ontiveros, PhD. Clinical perspectives from Dr Telli on these findings are presented here.

The GEP tests that we use in early-stage breast cancer, and specifically for patients with HR+/HER2- breast cancer, look at messenger RNA expression in the tumor (ie, ER-, proliferation-, and HER2-related genes) to obtain information related to genomic risk of the breast cancer. In practice and historically, we have looked at clinical risk factors such as patient age, tumor size, absence or presence of lymph node involvement, and tumor grade to make decisions regarding adjuvant treatment. However, these messenger RNA GEP tests allow us to get more specific when considering the genomic risk of breast cancer.

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We have really come a long way in applying these tests. In the early days, we had retrospective data from completed clinical trials for which long-term outcomes were available to help guide our treatment approach. But we now have prospective GEP data that have been incredibly compelling that give the clinician the ability to make a treatment decision for or against the use of adjuvant chemotherapy based on a patient’s GEP risk score. While many GEP assays provide good information on prognosis, the assay for which we have the highest level of evidence in terms of its ability to help us decide for or against the use of adjuvant chemotherapy is the Oncotype DX assay (Exact Sciences). The Oncotype DX readout is based on a continuous score of 0 to 100, where patients with scores of 26 to 100 are recommended to receive adjuvant chemotherapy.

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These findings were first supported by the TAILORx trial, which looked at patients with early-stage lymph node–negative HR+/HER2- breast cancer and provided high-level evidence that there is no significant adjuvant chemotherapy benefit for patients with low- and intermediate-risk scores on the Oncotype DX assay. Subsequently, the RxPONDER trial in patients with early-stage lymph node–positive HR+/HER2- breast cancer who had surgical resection with 1, 2, or 3 positive lymph nodes showed that there was no chemotherapy benefit in postmenopausal patients with Oncotype DX scores in the 0 to 25 range. GEP has been a big advance and has certainly brought us to a place where we can use genomic risk to guide our decisions regarding the use of adjuvant chemotherapy.

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We have increasingly been seeing real-world evidence studies on GEP at ASCO meetings, which, in general, I find quite interesting. At ASCO 2025, there were not many presentations on GEP in patients with HR+/HER2- breast cancer. However, there was one very large real-world study presented by Marija Sullivan, MD, from The University of Texas MD Anderson Cancer Center looking at patterns of Oncotype DX testing and adjuvant chemotherapy use in more than 300,000 patients with early-stage HR+/HER2- breast cancer from 2018 to 2021 (abstract 528). The investigators found that, in clinical practice, 54% of patients received Oncotype DX testing. Of the patients who received the test, 16% went on to receive chemotherapy. One might wonder, “Why is that percentage not higher than that?”

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Certainly, there was variation with Black and Hispanic patients. The test was less likely to be ordered for these patients when they had a diagnosis of early-stage HR+/HER2- breast cancer compared with White patients. Dr Sullivan and colleagues also found that, among Black and Hispanic women, those without an Oncotype DX test were more likely to have chemotherapy. However, Black women who had the test and had a high-risk score were less likely to receive the recommended course of chemotherapy compared with White women.

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I think that these real-world data experiences are interesting because they give us a view into how these data and tests are being used more broadly in patient populations that are typically not captured in clinical trials. I also think that studies like this one from ASCO 2025 provide an opportunity for targeted intervention, improving the use of these tests and adherence to clinical practice guidelines. GEP tests are incredibly important. They have allowed us to reduce the number of patients who receive chemotherapy today compared with 15 or 20 years ago.