In this podcast, experts review 2 of the most important studies presented at the ASCO 2026 annual conference that inform treatment decisions for patients with early-stage hormone receptor–positive/HER2-negative breast cancer. The discussion focuses on the phase III OPTIMA trial, which evaluated Prosigna PAM50-guided chemotherapy selection and the potential for chemotherapy de-escalation in selected patients, with stimulating insights on the role of ovarian function suppression with endocrine therapy in premenopausal women. Their discussion also examines the NATALEE PAM50 biomarker analysis, which demonstrated benefit from adjuvant ribociclib across intrinsic molecular breast cancer subtypes without a significant treatment-by-subtype interaction. Together, these findings help clarify how genomic risk assessment, menopausal status, tumor biology, and adjuvant CDK4/6 inhibitor therapy may be integrated into individualized treatment planning and shared decision-making.
In this podcast episode, Hope S. Rugo, MD, FASCO, and Nerea Lopetegui-Lia, MD, discuss practice-informing data presented at ASCO 2026 for patients with early-stage hormone receptor (HR)–positive/HER2-negative breast cancer, including:
Presenters:
Hope S. Rugo, MD, FASCO
Director, Women’s Cancer Program
Division Chief, Breast Medical Oncology
Professor, Department of Medical Oncology & Therapeutics Research
City of Hope Comprehensive Cancer Center
Professor Emeritus and Emeritus Winterhof Family Distinguished Professor of Breast Oncology
University of California, San Francisco
San Francisco, California
Nerea Lopetegui-Lia, MD
Assistant Professor
Division of Medical Oncology, Breast Section
Department of Internal Medicine
The Ohio State University
Columbus, Ohio
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Link to full program:
https://bit.ly/4x4u5AT
This transcript was automatically generated from the audio recording and may contain inaccuracies, including errors or typographical mistakes.
ASCO 2026 Updates in Early Hormone Receptor–Positive Breast Cancer
Hello and welcome to the Decera Clinical Education Oncology Podcast. I’m your host, Sharif Morsalin. Today’s podcast features Dr. Hope Rugo from City of Hope Comprehensive Cancer Center and Dr. Nerea Lopetegui-Lia from The Ohio State University Comprehensive Cancer Center. They will discuss key early-stage breast cancer findings presented at the 2026 ASCO Annual Meeting.
For more information on our presenters, along with a link to the full educational program, please visit the show notes for this episode.
Now, let’s get started and hear what the experts have to say.
Dr. Rugo: It is great to discuss these potentially practice‑changing abstracts with you. We have really chosen just two abstracts to discuss, although there was a lot of data presented at ASCO 2026. Longer‑term follow‑up of KEYNOTE‑522 and survival. However, two studies stood out in the hormone receptor‑positive area in terms of how we think about treating patients. There was also an update from the lidERA study, looking at an oral SERD in early‑stage breast cancer in premenopausal women.
Although we will focus on two studies, there were a number of other studies that were of interest at ASCO. When we were all thinking about ASCO 2026 and what was the single biggest surprise was OPTIMA study. The OPTIMA study was an international trial and partially blinded, which is interesting.
What they did in this randomized phase III noninferiority trial was to look at using the Prosigna gene expression assay which patients with early‑stage hormone receptor‑positive breast cancer needed chemotherapy or not. A familiar question for us. However, this trial had some unique aspects to it which were particularly important to us.
Tell us about those aspects, and what did you think of the data?
Dr. Lopetegui‑Lia: Yes, it is a very interesting study. The study did include patients that were 40 years or older. I think about 37% were premenopausal women. It included patients with zero to nine positive lymph nodes. It was a predominantly node‑positive population. There were 19% that had between 4 to 9 positive lymph nodes. This was, as you mentioned, a test‑directed study looking at noninferiority for choosing chemotherapy or not in patients with the Prosigna PAM 50 risk of recurrence score of 60 or less can be used to consider de‑escalating chemotherapy in these higher‑risk patients. Therefore, in a way, it extends the genomic decision‑making beyond the Oncotype‑defined populations that we know of in TAILORx and RxPONDER.
One of the aspects that is worth highlighting is in the premenopausal patient population, those who avoided chemotherapy did receive ovarian function suppression. If we are thinking about a chemo‑sparing strategy, it really does hinge on delivering OFS plus endocrine therapy. Not simply dropping chemotherapy without escalating the endocrine backbone. I thought that was a very interesting aspect that was included in the study.
Dr. Rugo: Yes, I agree. We have been in a bit of a quandary from RxPONDER, the randomized trial, which asked an appropriate question using the Oncotype test, whether or not we could define a group of patients who had one to three positive nodes who did not need chemotherapy. That did work for patients who were postmenopausal. For the premenopausal group, everybody seemed to benefit from chemo, which was a big surprise. It still remains.
It turned out that less than 20% of these young women received ovarian function suppression, which we know for higher‑risk cancers does improve outcome based on the SOFT and TEXT trials. It was thought that potentially the chemotherapy was really playing an ovarian suppression role in the RxPONDER trial, and that is now being studied in the OFSET trial, a big cooperative group trial in the US.
OPTIMA really tried to answer that question by requiring that all premenopausal women received ovarian function suppression. I agree with you. This is really intriguing. I have ordered the test now a few times. I think that we might be able to find, using this test, a group of younger patients who do not need chemotherapy.
Not under 40. I am not yet comfortable with the 4 to 9 positive nodes. We have to individualize this for our individual patients, where we do think they may be able to avoid chemotherapy, but they need to go on ovarian function suppression and generally an aromatase inhibitor as tolerated. Only four years of follow‑up. Now we are going to need a longer‑term follow‑up of this trial, and that will help us.
We also saw some really interesting data. Of course, what we do in the early‑stage setting for our high‑risk patients now is give CDK4/6 inhibitors, and we have plenty to choose from, from NATALEE and monarchE.
The NATALEE trial, I actually did a very interesting biomarker analysis based on some data in the metastatic setting, where they looked to see what was the PAM 50 subtype in the different groups. What they saw, as you might expect, is that two‑thirds of the patients were Luminal A, a little more than a quarter Luminal B, and then 3%, both HER2‑enriched and basal‑like. Then they looked at what did ribociclib do.
Tell us what ribociclib did and what you think of that.
Dr. Lopetegui‑Lia: Yes. We know that NATALEE did establish the three years of adjuvant ribociclib in combination with endocrine therapy for stage II–III hormone receptor‑positive HER2‑negative population, including node‑negative patients with high‑risk features. The eligibility criteria was broader than monarchE, which included node‑positive high‑risk criteria. The invasive disease‑free survival benefit was sustained and deepened over time.
The ASCO 2026 gene expression analysis showed that ribociclib did benefit across all PAM 50 subtypes with no significant subtype in treatment interactions, so intrinsic subtype should not currently be used to select patients.
In patients with early‑stage high‑risk hormone receptor‑positive breast cancer, when we do have both ribociclib and abemaciclib approved, I tend to present both options to my patients, talk about toxicities, duration of therapy, and do shared decision‑making. I would be curious to hear what your practice is, or if there was anything specific from the gene expression analysis that you would want to highlight.
Dr. Rugo: Thanks. I agree with what you have said entirely. I will say that what was surprising to me was that in the metastatic setting, it appeared that patients who had basal‑like disease did not benefit from endocrine therapy, much less adding a CDK4/6 inhibitor. This was strikingly different. It was only 3% of the patient population. Really small numbers, less than 100 patients in each group of basal‑like and HER2‑enriched. However, there was a big separation of the curves, so although not definitive, it does suggest that when you have early‑stage disease and you are less likely to have multiple mechanisms of resistance and be losing PR and then ER, that regardless of whether you have high proliferative disease or not, that you benefit from the addition of a CDK4/6 inhibitor when you fit the higher‑risk or intermediate risk criteria.
Luminal A and Luminal B also benefited, but it is interesting looking at the curves because the hazard ratios were good 0.71, 0.77 for Luminal B and Luminal A. However, for basal‑like and HER2‑enriched, they were around 0.4 or 0.5. Even more, it is just that overall, the patient population did not do as well. The curves were just lower. It tells us about the biology. These patients need chemotherapy, but that the importance of hormone therapy afterwards is not to be ignored here, along with the combination of a CDK4/6 inhibitor for what we think of as more endocrine‑resistant disease.
Choosing between CDK4/6 inhibitors, I agree, is a shared decision process. Then, of course, we switch for toxicity as well.
This has been a really interesting conversation about these two really important abstracts that were presented at ASCO 2026 this year. It has been fun talking with you.
Dr. Lopetegui‑Lia: Thank you.
Thank you, Dr. Rugo and Dr. Lopetegui-Lia, for an informative discussion and for sharing your perspectives on these important ASCO 2026 findings. And many thanks to you, our listeners, for joining us today.
Be sure to visit the show notes for additional educational resources and check back for more episodes on important topics in oncology.