In an interview following the recent 2026 ASCO Annual Meeting, Harold J. Burstein, MD, PhD, discussed how new data may help refine treatment intensity for patients with HR+/HER2- early-stage breast cancer. He highlighted the OPTIMA and lidERA trials, chemotherapy deescalation, oral SERDs, endocrine therapy tolerability, and emerging research on GLP-1 agonists and breast cancer incidence.

Following these presentations, featured expert Harold J. Burstein, MD, PhD, was interviewed by Conference Reporter Associate Editor-in-Chief Christopher Ontiveros, PhD. Clinical perspectives from Dr Burstein on these findings are presented here.

An important theme at ASCO 2026 in HR+/HER2- early-stage breast cancer was how we continue to individualize treatment intensity. Several studies asked different versions of the same practical questions: who needs more treatment, who can safely receive less treatment, and how do we help patients tolerate the therapy they need?

One of the highlights at ASCO 2026 was the presentation by Robert C. Stein, PhD, MBBChir, FRCP, on the OPTIMA trial, a phase 3 study in the design style of the TAILORx and RxPONDER trials, asking which patients with ER+/HER2- early-stage breast cancer might still need chemotherapy (abstract 500). TAILORx and RxPONDER were built around the Oncotype DX Breast Recurrence Score (Abbott, Inc), while the OPTIMA trial used the PAM50-based Prosigna Breast Risk of Recurrence (ROR) Test score (Veracyte, Inc). In OPTIMA, patients were randomized to standard chemotherapy plus endocrine therapy or to assay-guided treatment. In the assay-guided arm, patients with an ROR score of greater than 60 received chemotherapy plus endocrine therapy, whereas those with an ROR score of 60 or less received endocrine therapy alone. Patients with lower ROR scores had a very low ROR, and the assay-directed strategy met the prespecified noninferiority margin, with a 5-year invasive breast cancer–free survival of 90.4% vs 91.5% in the control arm.

There were a couple of “nuggets” from the OPTIMA trial that expanded our knowledge. The first was the impact on premenopausal women. In the TAILORx and RxPONDER trials, premenopausal women did not uniformly receive ovarian function suppression, so it has been unclear whether the apparent chemotherapy benefit reflected a cytotoxic effect or chemotherapy-induced menopause. In the OPTIMA trial, younger premenopausal women were uniformly given ovarian function suppression, and there was no difference between endocrine therapy alone and chemotherapy plus endocrine therapy for the lower ROR group. This is very important because it suggests that we can probably extend genomic assays to premenopausal patients, assuming that we appropriately give ovarian function suppression.

An important question raised by the OPTIMA study is whether the various genomic signatures (eg, the Oncotype DX Breast Recurrence Score, the MammaPrint Breast Cancer Test for Risk of Recurrence index [Agendia, Inc], and the Prosigna Breast ROR Test score) can be used interchangeably. Limited data suggest that they are discordant tests, and it will be a clinical trial priority to determine which patients might warrant which tests for the best outcomes.

The second key observation was in patients with multiple positive nodes. OPTIMA included some patients with 4 or more positive nodes. There was no statistically significant difference in outcomes between those in the 4- to 9-node group who received endocrine therapy and those who received chemotherapy plus endocrine therapy, although the cohort was relatively small and the curves separated a bit. I think that we still need to be cautious about avoiding chemotherapy in patients with multiple positive axillary lymph nodes. Still, the OPTIMA trial continues to build momentum toward sparing many patients with ER+/HER2- early-stage breast cancer from chemotherapy.

Another important study at ASCO 2026 was an update on the lidERA trial presented by Peter Schmid, MD, PhD, FCRP (abstract 502). This phase 3 study evaluated adjuvant giredestrant, an oral SERD, compared with standard adjuvant endocrine therapy with tamoxifen or an aromatase inhibitor in ER+/HER2- early-stage breast cancer. The ASCO update focused on pre- and postmenopausal patients, with premenopausal women uniformly receiving ovarian function suppression. Giredestrant improved invasive disease–free survival and distant recurrence–free interval vs standard endocrine therapy, with consistent benefit irrespective of menopausal status. One important nuance is that a small fraction of patients in the control arm received tamoxifen rather than an aromatase inhibitor, and that group did not do as well with longer follow-up. These will be important discussions if giredestrant makes it to the market.

A pooled analysis of the phase 2/3 ADAPT-HR+/HER2- trial and the phase 3 PlanB trial presented at ASCO 2026 by Oleg Gluz, MD, addressed another practical chemotherapy question (abstract LBA515). The study investigators looked for patients with high-risk HR+/HER2- early-stage breast cancer who preferentially needed anthracycline-based chemotherapy rather than a nonanthracycline regimen such as anthracycline-taxane chemotherapy. Ultimately, they did not identify a group that derived a major survival benefit from anthracycline-based chemotherapy. This fits with the emerging US trend suggesting that a nonanthracycline regimen is probably appropriate for most intermediate- to somewhat higher-risk cancers that need chemotherapy, while tumors with an extraordinarily high anatomic stage or a very high genomic risk may still be candidates for anthracycline-based regimens.

There were also supportive care– and prevention-related abstracts from this year’s ASCO meeting that caught my eye. For example, the phase 3 OASIS-4 trial presented by Claudio N. Soares, MD, PhD, MBA, looked at elinzanetant, an NK-1 and NK-3 receptor antagonist, for vasomotor symptoms in patients with HR+ breast cancer who are on endocrine therapy (abstract 512). In this post hoc subgroup analysis by endocrine therapy type, elinzanetant consistently improved sleep disturbance and menopause-related quality of life, including vasomotor, psychosocial, physical, and sexual aspects, across endocrine therapy subgroups. These results serve as an important reminder that controlling symptoms such as hot flashes and night sweats can be very important for day-to-day quality of life and for helping patients remain on endocrine therapy.

Finally, there was a retrospective cohort study presented at ASCO 2026 by Elizabeth Susan McDonald, MD, PhD, looking at GLP-1 agonists and breast cancer incidence (abstract 10506). In this large observational study of women undergoing breast imaging, breast cancer diagnoses were significantly lower among women who were exposed to GLP-1 agonists. Since this was a retrospective study, these results are not definitive, but they are provocative. Whether these results reflect a direct drug effect, weight loss, improved metabolic health, or a combination is unknown, but it is a ripe area for research.

Looking ahead, the next big wave will be additional oral SERD trials. Several phase 3 trials should be reporting soon and should help define whether tamoxifen and aromatase inhibitors remain the default treatment or whether oral SERDs should be used for selected patients.