Considering How TAILORx Transformed Node-Negative Breast Cancer Treatment

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During a live event, Heather L. McArthur, MD, MPH, discussed the TAILORx trial in node-negative hormone receptor–positive/HER2-negative breast cancer.

Heather L. McArthur, MD, MPH

Heather L. McArthur, MD, MPH

Node-negative, hormone receptor–positive/HER2-negative breast cancer represents a subset of patients where treatment decisions often hinge on genomic risk stratification. 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, discussed key insights from the TAILORx trial (NCT00310180) during a live Community Case Forum in Fort Worth, Texas. The trial revealed that chemotherapy provided no significant benefit for intermediate-risk patients, allowing for de-escalation to endocrine therapy alone, though higher scores in younger women may warrant reconsideration.


This article is part 2 of a 2-part series from a Community Case Forum event.

Targeted Oncology: What are the data supporting assays in the node-negative breast cancer space?

Heather L. McArthur, MD, MPH: The TAILORx study was designed to determine whether chemotherapy is beneficial for mid-range recurrence scores. When I was at Memorial Sloan Kettering, we participated in this study. It was such a long time ago now. Essentially, patients who had low risk scores automatically got endocrine therapy. Patients who had high risk scores automatically got chemotherapy and endocrine therapy. But the question was this intermediate group with recurrence scores in the range of 11 to 25. The default—and that's important in thinking about TAILORx—the default, the standard of care in that space at the time was endocrine therapy and chemotherapy. So it's the endocrine therapy alone arm, arm B, that's the experimental arm. Can you safely de-escalate in this mid-range population?

There are a number of stratification factors in this study: tumor size, menopausal status, planned chemotherapy, planned radiation, and recurrence score. But in my mind, it was the first de-escalation study where the default was escalated therapy, and they were looking bravely for the first time at whether everyone truly needed chemotherapy in that space. Key eligibility criteria included node negative [and] hormone receptor positive were the criteria. The disease could be estrogen-receptor and/or progesterone-receptor positive and HER2 negative. This is a lower-risk population, T1c and T2 tumors primarily, although there was an allowance based on high-risk features to allow for high-risk T1b tumors, but predominantly T1c and T2 tumors.

What were the end results of TAILORx?

In node-negative, HR-positive, HER2-negative breast cancer, the primary end point for this intermediate-risk group of invasive disease-free survival [showed] there was absolutely no difference with the addition of chemotherapy to endocrine therapy. These were the first data that allowed us to de-escalate. Of course, we've seen more recent follow-up, including overall survival at 9 years, showing exactly the same outcomes for the endocrine therapy vs the endocrine therapy with chemotherapy group, so no advantage with chemotherapy in that intermediate group. That changed our practice.

For patients who were older than 50 who participated in the trial, there was no difference in terms of recurrence risk in that population. There was a bit more divergence [between endocrine therapy only vs endocrine plus chemotherapy], especially when you look at the higher recurrence scores. So there's a suggestion that maybe on the higher end of that 11 to 25 range, there might be differences, but it was not statistically significant.

We've had updates in these women who were under 50 years, with 12-year rates of recurrence. The low-risk group, so that's the under 10 [score], does extremely well with endocrine therapy alone, 98.5% at 9 years. The high-risk group does as you would expect. That's the group that was assigned automatically to get chemotherapy with endocrine therapy. Of course, more recently, we can probably improve upon these numbers, because we have access to adjuvant CDK4/6 inhibitors. It was almost 90% in that group. For these younger women, there wasn't a significant difference between endocrine therapy vs chemotherapy and endocrine therapy in patients who had scores of 11 to 15 or 16 to 20. But it's that 20 to 25 range, that upper limit, that wasn't statistically significant, at 85.5% vs 93.3%. That suggests that maybe there's a population in that group for whom you might consider chemotherapy, and of course, it doesn't tell us which chemotherapy specifically to prescribe.

Can we incorporate clinical risk to try and refine our decision making in this space?

I would suggest that you can. Data from TAILORx showed freedom from distant recurrence, incorporating clinical risk plus Oncotype DX score.2 So can you combine that composite of information to further refine decisions? Patients who have low clinical risk and a moderate recurrence score don't derive benefit from chemotherapy. But as the clinical risk is heightened in those higher recurrence score areas, the 21 to 25; there was an 11.7% difference in that space. That's why RSClin and other resources were developed to help us refine our thinking about patients who are in this space, who fall within that intermediate risk by genomics, but who are high risk. You can plug in numbers and get that calculation.

What about anthracycline therapy for patients with node-negative breast cancer?

We've been facing a battle around anthracyclines for the treatment of breast cancer in general for several years now. Is there a benefit with anthracyclines in patients with high genomic risk, who are node negative, HR positive, and for patients with high recurrence score? Data were presented at the 2024 San Antonio Breast Cancer Symposium showing the Kaplan-Meier curve for patients who have a very high recurrence score, so greater than or equal to 31.3 It's a range of 0 to 100 overall. Patients who had a recurrence score greater than or equal to 31 and are node negative definitely derived benefit from anthracycline therapy. So anthracycline therapy should not be omitted in that very high-risk population.

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.

REFERENCES:
1. Sparano JA, Gray RJ, Makower DF, et al. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. N Engl J Med. 2018;379(2):111-121. doi:10.1056/NEJMoa1804710
2. Sparano JA, Crager M, Gray RJ, et al. Clinical and genomic risk for late breast cancer recurrence and survival. NEJM Evid. 2024;3(8):EVIDoa2300267. doi:10.1056/EVIDoa2300267
3. Chen N, Freeman JQ, Yarlagadda S, et al. Abstract GS3-03: Impact of anthracyclines in high genomic risk node-negative HR+/HER2- breast cancer. Clin Cancer Res. 2025;31(suppl 12):GS3–03. doi:10.1158/1557-3265.SABCS24-GS3-03

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