ASCO 2026 HR+ and HER2+ Breast Cancer Preview: Read up on the Insights to Know Before You Go

Preparations for the 2026 ASCO Annual Meeting are in full swing, and we’ve been hearing a ton of buzz about the highly anticipated breast cancer updates. Read on for exclusive insights on the meeting’s top presentations to watch from:

• Yara Abdou, MD, MSCR, an associate professor of medicine and the Breast Cancer Clinical Trial Program leader in the Division of Oncology in the Department of Medicine at the University of North Carolina (UNC) School of Medicine and the UNC Lineberger Comprehensive Cancer Center in Chapel Hill
• VK Gadi, MD, PhD, deputy director of the University of Illinois (UI) Cancer Center and a medical oncologist at UI Health, as well as an assistant professor of clinical medicine and director of Medical Oncology in the Division of Hematology and Oncology at the UI College of Medicine in Chicago
• Erika Hamilton, MD, FASCO, the Late Phase chief development officer and director of Breast Cancer Research at Sarah Cannon Research Institute in Nashville, Tennessee
• Kevin Kalinsky, MD, MS, FASCO, professor and director of the Division of Medical Oncology in the Department of Hematology and Medical Oncology at the Emory University School of Medicine, as well as the Louisa and Rand Glenn Family Chair in Breast Cancer Research and the director of the Glenn Family Breast Center at the Winship Cancer Institute of Emory University in Atlanta, Georgia
• Alexis LeVee, MD, a breast medical oncologist at UCLA Health in Santa Monica, California
• Jane L. Meisel, MD, FASCO, a professor and co-director of Breast Medical Oncology in the Department of Hematology and Medical Oncology, as well as a professor in the Department of Gynecology & Obstetrics at the Emory University School of Medicine

First results from the OPTIMA phase III randomized non-inferiority trial of test-directed chemotherapy in patients with high clinical risk ER-positive HER2-negative early breast cancer.

Presentation time: May 30, 2026, 1:15 pm CT

Kalinsky: This is a study that I've been eager to see with the Prosigna Breast Cancer Prognostic Gene Signature Assay in clinic for patients with hormone receptor [HR]–positive, HER2-negative disease. [In everyday practice], we use the 21-gene recurrence score. We also use the 70-gene MammaPrint test. However, this [study] is evaluating Prosigna with a different design. This study also included a subset of patients with N2 disease, so those with 4 to 9 lymph nodes involved. If patients were premenopausal and had high-risk disease, they were required to undergo 3 years of ovarian suppression. I'm eager to see what those data look like.

Abdou: This study focuses on a higher-risk patient population, including patients with node-positive disease, where uncertainty around chemotherapy benefit remains. I’m interested in its prospective, test-directed design using Prosigna and how it may help refine treatment decisions in patients who fall into these more ambiguous, clinically higher-risk groups.

Prognostic and predictive impact of baseline gene expression (exp) in the NATALEE trial of adjuvant (adj) ribociclib (RIB) + nonsteroidal aromatase inhibitor (NSAI) in HR+/HER2− early breast cancer (EBC)

Presentation time: May 30, 2026, 1:27 pm CT

Meisel: The phase 3 NATALEE trial [NCT03701334] led to the approval of adjuvant ribociclib [Kadcyla] for patients with medium- and high-risk HR-positive breast cancer. I am hopeful that this abstract will give us information about which patients, potentially based on gene expression, might benefit most from that approach. If we could identify the patients who wouldn't benefit, then we wouldn't have to subject those patients to the toxicity and challenge of an additional treatment. It's the idea of personalizing therapy a little more. Now that we have the opportunity to give more [therapy] for certain patients, who are the patients who we can potentially pull back on?

Efficacy and safety of giredestrant (GIRE) in patients (pts) with estrogen receptor– positive, HER2-negative early breast cancer (ER+, HER2– eBC) in the phase III lidERA BC clinical trial: Results by menopausal status.

Presentation time: May 30, 2026, 1:39 pm CT

Abdou: We saw encouraging results [from the phase 3 lidERA Breast Cancer trial (NCT04961996)] presented at the 2025 San Antonio Breast Cancer Symposium, and I’m interested in the subgroup analyses by menopausal status. Understanding how oral selective estrogen receptor degraders [SERDs] perform across biologically distinct patient populations will be critical as we consider tailoring endocrine therapy in the early-stage setting.

Meisel: Giredestrant is a drug that was studied and recently shown to be beneficial as monotherapy for adjuvant management of estrogen receptor [ER]–positive breast cancer in the early-stage setting. It is the first new endocrine therapy in the adjuvant setting that we've seen show benefit in a couple decades. Does the efficacy of that drug differ between premenopausal and postmenopausal women? [This analysis will] also shed insight into which patients will benefit the most if this drug gets approved in that setting.

Anbenitamab plus albumin-bound docetaxel (nab-docetaxel) ± carboplatin (Cb) versus trastuzumab and pertuzumab plus docetaxel (THP) ± Cb as neoadjuvant therapy for HER2- positive early or locally advanced breast cancer: A randomized, open-label, multicenter, phase 3 trial.

Presentation time: May 30, 2026, 3:39 pm CT

Gadi: The comparator arm in this study was docetaxel plus carboplatin, trastuzumab [Herceptin], and pertuzumab [Perjeta; TCHP]; that's a standard regimen in the United States [US]. Another interesting trial that came out at the 2025 ESMO Congress, which was the phase 3 DESTINY-Breast11 study [NCT05113251], used a neoadjuvant regimen of dose-dense doxorubicin and cyclophosphamide plus THP [ddAC-THP] vs the investigational agent, fam-trastuzumab deruxtecan-nxki [T-DXd; Enhertu]. Some criticism of that trial was that [ddAC-THP is] not a regimen we use in the US. In ASCO 2026 LBA660, the comparator arm is the same [regimen] we use in the US. The investigational arm is interesting because of the drugs involved. Anbenitamab [KN026] is a dual HER2-targeting therapeutic antibody. It's not an antibody-drug conjugate [ADC] or a bispecific antibody; it's something we call biparatopic. It binds 2 different epitopes on the same protein and serves as a different logic gate to make sure we get good binding to the target on the cancer cells. One of the targets inhibits the activity, and the other target leads to the degradation of HER2 on the cell surface. This is combined with nab-docetaxel [HB1801] and carboplatin. It's a more accurate one-to-one comparison [with a clinically relevant] comparator arm. The primary end point of this study is pathologic complete response [pCR] rate, and it's reported to be superior [with the anbenitamab-based regimen]. We'll have to see the data. One of the appealing things about this type of strategy is, outside of the chemotherapy itself, it may be associated with a lot less toxicity than ADCs, and if the pCR rate is similar [to that reported with ADCs], then that offers an advantage regarding its applicability to patient care. It's a purely Chinese study, so we don't know what barriers we're going to face trying to get [anbenitamab] in the US and other Western countries.

Abstract LBA514: Neoadjuvant rilvegostomig (R) + trastuzumab deruxtecan (T-DXd) in high-risk HER2- negative breast cancer: Results from the I-SPY 2.2 trial.

Presentation time: June 1, 2026, 10:45 am CT

LeVee: It will be interesting to see what this trial shows. The drug is a bispecific antibody targeting PD-1 and TIGIT. It's a novel immunotherapy combined with an ADC, T-DXd. This may be our future regarding combining immunotherapies and ADCs.

Giredestrant (GIRE) + palbociclib (PALBO) vs letrozole (LET) + PALBO as first-line (1L) therapy in patients (pts) with estrogen receptor–positive, HER2-negative locally advanced or metastatic breast cancer (ER+, HER2– LA/mBC): Primary analysis of the phase III persevERA BC trial.

Presentation time: June 2, 2026, 11:45 am CT

Hamilton: I am eager to see the results of this abstract, as we have seen in a news release that it is negative.¹ This comes on the heels of positive data in the adjuvant setting for giredestrant in ER-positive high-risk breast cancer [regardless of] ESR1 mutation [status]. We have long thought that perhaps in combination with CDK4/6 inhibition, the endocrine backbone may matter less. Is this true? Or perhaps this study was too small to see a difference in combination with palbociclib [Ibrance]? There are other, larger trials like the phase 3 SERENA-4 trial [NCT04711252] that may be better powered to see the benefit of an improved endocrine therapy backbone in combination with CDK4/6 inhibition, but I still believe a patient should not need an ESR1 mutation to derive benefit from oral SERDs.

First-line (1L) camizestrant (CAMI) for emergent ESR1 mutations (ESR1m) in advanced breast cancer (ABC): Final progression-free survival 2 (PFS2) from the phase III SERENA-6 trial.

Presentation time: June 2, 2026, 11:57 am CT

LeVee: There was a notice [reported on April 30, 2026], that the FDA did not [vote in favor of the clinical benefit of] camizestrant in HR-positive metastatic breast cancer based on the phase 3 SERENA-6 study [NCT04964934].² I'm interested to see the time to second progression updates are from that study.

A randomized, open-label, phase 3 study of gedatolisib + fulvestrant ± palbociclib vs standard of care in HR+/HER2−/PIK3CA-mutant (MT) advanced breast cancer (VIKTORIA-1 Study 2).

Presentation time: June 2, 2026, 12:09 pm CT

Kalinsky: We'll get updated data from the phase 3 VIKTORIA-1 study [NCT05501886], which is investigating intravenous therapy with the PI3K/mTOR inhibitor in patients with PIK3CA-mutant tumors. We've seen previously reported exciting data comparing [gedatolisib] doublets and triplets [vs fulvestrant (Faslodex) monotherapy] in PIK3CA wild-type disease. Now we'll see data—and we just saw a news release reporting that there was a [PFS] advantage—with gedatolisib in patients with PIK3CA-mutant tumors.³

Abdou: We already know this study is positive, and I’m excited to see the full dataset. Patients with PIK3CA-mutant disease continue to represent an important population with evolving therapeutic options, and this trial adds another promising strategy that could further expand and refine our treatment paradigm.

Gadi: It will probably be imminently practice-changing depending on the quality of the data that are presented on the podium. This is a trial that has been half presented already at ESMO 2025 [with the PIK3CA wild-type population]; that portion of the trial was also positive. That portion focused on patients with advanced metastatic breast cancer that was HR-positive and HER2-negative who had received at least 1 prior line of anti-estrogen–based therapy with a CDK4/6 inhibitor. The portion of the trial that was presented evaluated this new drug added to fulvestrant plus palbociclib in one-third of patients, or [in combination with] just fulvestrant in one-third of patients, vs fulvestrant by itself, which, for many patients, would have been considered standard of care [SOC]. This showed meaningful improvements in PFS [with the gedatolisib-based regimens] and an acceptable toxicity profile. This is now sitting in front of the FDA waiting for an approval [for patients with PIK3CA wild-type disease].

What's being presented at ASCO 2026 is the second half of this study. It will be interesting to see whether we have a new SOC for patients who have a PIK3CA mutation, as well. What's nice about this is the tolerability of the drug is decent. I've been able to give it in my own practice as a phase 1 trialist at my prior institution. Lots of people are bullish as to whether this will change practice.

References

1. Genentech provides update on phase III persevErA study in ER-positive advanced breast cancer. News release. Genentech. March 8, 2026. Accessed May 6, 2026. https://www.gene.com/media/press-releases/15106/2026-03-08/genentech-provides-update-on-phase-iii-p
2. April 30, 2026 meeting of the Oncologic Drugs Advisory Committee (ODAC). FDA. Accessed May 6, 2026. https://www.youtube.com/live/taCx7enN7hk
3. Celcuity’s phase 3 VIKTORIA-1 Trial achieves primary end point with clinically meaningful improvement in progression-free survival in PIK3CA mutant cohort. News release. Celcuity Inc. May 1, 2026. Accessed May 6, 2026. https://ir.celcuity.com/news-releases/news-release-details/celcuitys-phase-3-viktoria-1-trial-achieves-primary-endpoint