Exploring Genomic Assays for Early-Stage Breast Cancer Treatment
During a live event, Heather L. McArthur, MD, MPH, reviewed genomic assays for early-stage breast cancer.
Heather L. McArthur, MD, MPH
Genomic assays play a critical role in guiding treatment decisions for patients with early-stage invasive breast cancer by providing prognostic and predictive insights. In a live Community Case Forum in Fort Worth, Texas, Heather L. McArthur, MD, MPH, an associate professor in the Department of Internal Medicine and clinical director of the Breast Cancer Program at UT Southwestern Medical Center in Dallas, Texas, highlighted key assays such as Oncotype DX, MammaPrint, and Endopredict, emphasizing their unique gene targets and clinical applications. Additionally, she reviewed NCCN and ASCO (American Society of Clinical Oncology) guidelines, noting their recommendations for assay use in different patient subgroups, including node-negative and node-positive cases.
Targeted OncologyTM: What are the genomic assays currently available for use in patients with early-stage invasive breast cancer?
Heather L. McArthur, MD, MPH: It's been a busy space in terms of genomic assays over the last 25 years. When I was at Memorial Sloan Kettering Cancer Center in New York, we were involved in the development of the Oncotype DX assay, so it's remarkable to me that there are so many options on offer now. The genomic assays available include MammaPrint, which looks at 70 gene areas; Oncotype DX, which looks at 21 gene areas—16 cancer-specific gene areas and 5 reference genes—PAM-50, which looks at 50 gene areas; Endopredict, which looks at 12; and then Breast Cancer Index, which is in a class by itself in my mind, because it speaks to late recurrences and benefit from extended therapy.1
Formalin-fixed, paraffin-embedded [samples] can be used to do any of these assays. The actual profiling method is a little bit different depending on which assay you choose; quantitative PCR [polymerase chain reaction] is common, although microarray for MammaPrint, for example, is another option. The scores are all different, so they're very specific to the specific assay. Most of the tests are available centrally, particularly in the United States, but there are also some local options too, from PAM-50 and for Endopredict.
Do the NCCN guidelines for breast cancer include all of these assays?
The NCCN guidelines were recently updated at version 4.2025. All of the assays Oncotype DX, MammaPrint, Endopredict and Breast Cancer Index have prognostic information, but it's not particularly useful to know that someone is at high risk of recurrence but there's nothing you can do about it. It's that predictive impact that tells you that you can pivot and make a different treatment choice that will have a favorable impact for your patient. So the predictive impact is the power of these assays. Oncotype DX has predictive impact in the node negative and in the N1 space, and Breast Cancer Index has predictive impact in attending to extended therapy.2
What other guidelines are available to determine the use of the assays?
ASCO has generated an algorithm on biomarkers to help guide these decisions. They're a little bit controversial, so if we hone down, the HER2 negative and ER positive, premenopausal or age less than or equal to 50 years, node negative, it endorses using Oncotype DX. For [the same population but] node positive, it says insufficient evidence to recommend a biomarker for use, but that's come into question a bit recently.3
In postmenopausal women who have node-negative disease, Oncotype DX is the favorite approach per NCCN guidelines, but MammaPrint is also on that list, as are others, but only if locally validated and together with other parameters and patients without access to genomic tests for the IHC4 test. Then in the postmenopausal, node positive space, 1 to 3 nodes, it has all the same options listed. For 4 or more lymph nodes involved, that space hasn't really been evaluated yet. Breast Cancer Index may be offered to patients who've received 5 years of adjuvant endocrine therapy without evidence of recurrence.
What is in the Oncotype DX 21-gene assay?
There are 5 reference genes and there are 16 cancer-specific genes.4 [This includes] progesterone receptor and Ki67, so a lot of things that we look at in conventional pathology reports are captured here, so you see it on a DNA level. And then there are others that look at not just HER2, but invasion and other impactful markers. So it started out with hundreds of different gene areas that they interrogated, but they paired it down to these critical 21. In evaluating this specific assay, in the TAILORx trial [NCT00310180], in node-negative patients, we have 3 different spaces.5 We have low, intermediate, and high risk. Then in the RxPONDER trial [NCT01272037], or node-positive population, we have a binary output of less than 25, so low risk or high risk, particularly for postmenopausal women.6
DISCLOSURES: McArthur previously reported a consulting or advisory role with Merck, Lilly, Immunomedics, Pfizer, Genentech, Bristol Myers Squibb, AstraZeneca, Daiichi Sankyo, Seattle Genetics, Genomic Health, Puma Biotechnology; research funding from Bristol Myers Squibb, ZIOPHARM Oncology, Lilly, Merck; travel, accommodations, or expenses from Merck, Spectrum Pharmaceuticals, Lilly, Amgen, Puma Biotechnology, Immunomedics, Genentech, Pfizer, AstraZeneca, Bristol Myers Squibb, DAVA Pharmaceuticals; and other relationships with Lilly, Genomic Health.
