Test-directed chemo de-escalation in clinically high-risk, node-positive HR+/HER2- early breast cancer - UK NIHR / UCL / Warwick CTU
Discover KOL Sentiment on OPTIMA →Design - Phase 3 Prosigna PAM50 (ROR) test-directed chemotherapy de-escalation vs chemotherapy-for-all, clinically high-risk node-positive HR+/HER2- early breast cancer (NCT02027441); primary invasive breast cancer-free survival (non-inferiority).
Primary result (on-page result-block) - Non-inferiority met - 5-yr invasive breast cancer-free survival 91.8% (control) vs 90.3% (test-directed), HR 1.03 (90% CI 0.85-1.25); within the pre-specified 3% non-inferiority margin (median follow-up ~4 years).
Clinical reach - Roughly two-thirds (~68%) of clinically high-risk, node-positive patients were classified as biologically low-risk (Prosigna ROR-low) and could potentially avoid adjuvant chemotherapy.
Open questions - The pN2 (4-9 node) subgroup has a low event count and is the principal interpretive caveat; the headline result is most robust in the 1-3-node population.
Regulatory - Investigational strategy trial - not a drug approval; Prosigna is an FDA-cleared test (Veracyte).
Sponsor - UK NIHR / UCL / Warwick Clinical Trials Unit; Prosigna PAM50 assay (Veracyte).
Compiled and reviewed by the KOL Pulse research team, led by Brian Shields, Founder, KOL Pulse. Last updated July 21, 2026.
Latest KOL reactions surfaced first, then top tweets by impressions — click to view on X
#OPTIMA addresses a real and long-standing tension in how we treat premenopausal node-positive ER+ breast cancer. The signal is meaningful: PAM50 ROR<60 patients who received adequate OFS did not appear to benefit from chemotherapy. That is a hypothesis worth taking seriously.
Such important information answering an important question. Question I have is how these results will guide our choice of genomic assay going forward in this patient population.
🚨 The OncoAlert #BreastCancer faculty’s TOP 10 abstracts for #ASCO26 — selected by our leads and finalized through a Delphi voting process with senior breast cancer experts. 1️⃣ 500 — OPTIMA Test-directed chemotherapy in high-risk ER+/HER2- early BC 2️⃣ LBA1006 — PERSEVERA BC https://t.co/FJSHDjv3Ln
#ASCO26 | We've been sparing node-negative #breastcancer patients from chemo using #Oncotype. #OPTIMA just did it in the population we've been most afraid to touch. 4,400+ patients. ER+/HER2−. Node-positive, up to pN2. #Prosigna_ROR: ≤60 → no chemo. 5-year IBCFS: 90.4% vs
💫🌟🚨 Top 10 #BreastCancer abstracts for #ASCO26 — selected by our leads and finalized via a Delphi voting process 🗳️🔬 1️⃣ 500 — OPTIMA 2️⃣ LBA1006 — PERSEVERA BC 3️⃣ 507 — KEYNOTE-522 final analysis 4️⃣ LBA1007 — SERENA-6 5️⃣ 502 — LIDERA BC 6️⃣ LBA1000 — ASCENT-04 7️⃣ 501 — NATALEE https://t.co/3BPHgMO1ct
#ASCO26 Can genomic testing safely spare chemotherapy in high-risk ER+/HER2- early breast cancer? The phase III OPTIMA trial says yes. 🧬 4,429 pts 🧪 Prosigna (PAM50)-guided strategy 🎯 Majority node-positive disease Key finding: Low-risk ROR (≤60) patients had excellent https://t.co/22ZadcSpgb https://t.co/cL8NHWlJqh
🧬 OPTIMA is a major de-escalation signal in mostly node-positive HR+/HER2− early breast cancer. In >4,400 pts, Prosigna/PAM50-guided chemotherapy decisions met non-inferiority vs standard chemo for 5-year IBCFS: 90.4% vs 91.5%, HR 0.99. This included premenopausal pts on OFS
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. #ASCO26 Abstract Preview https://t.co/vm2tCjbnd8 The OPTIMA trial evaluated Prosigna https://t.co/tLC2NO2dw9
#asco26. Stein presents data from optima. Using Prosigna to determine chemo benefit in early HR+ BC. Premenopausal women <40 where we stillneed info excluded. Shows Prosigna identifies N+ pts unlikely to benefit from chemo. IMP! 1500 older premen pts included. @OncoAlert https://t.co/MeAaes5bL9
Dr Piccart reinforces that OPTIMA for the first time prospectively shows the chemo benefit for premenopausal low GEP women, is mostly due to chemotherapy induced ovarian suppression. https://t.co/QNSOtlyjqm
#ASCO26 OPTIMA does not teach us a completely new biology; it reinforces the Oncotype DX-era message with Prosigna/PAM50 at a phase III level. What makes it important is the population: clinically high-risk ER+/HER2− EBC, frequent nodal positivity, 19% pN2 disease, and 37% https://t.co/qaIrXJTs0P
How will OPTIMA change our practice ? #ASCO26 @OncoAlert @ASCO https://t.co/c0yCb5l39T https://t.co/vzmDSkv0ZO
OPTIMA Trial #ASCO26 The 50-gene Prosigna test identifies ~2/3 of ER+/HER2− early breast cancer patients — including those with node-positive disease & premenopausal women ≥40 — who derive no meaningful benefit from adjuvant chemotherapy. 5-yr IBCFS: 90.3% vs 91.8% → https://t.co/8TRrnqdsBK
OPTIMA asks a long-standing clinical de-escalation question: can biology-guided genomic testing safely spare adjuvant chemotherapy in women with clinically high-risk, node-positive ER+/HER2- early breast cancer — a population where adjuvant chemo has historically been the default? Earlier de-escalation trials (TAILORx, RxPONDER) addressed node-negative and limited node-positive disease using Oncotype DX. OPTIMA extends the question into a higher-risk, more chemotherapy-committed population (up to nine involved nodes, including pN2) and uses a different assay — the 50-gene Prosigna PAM50 ROR (Risk of Recurrence) test — to identify a low-risk biology subgroup that may not benefit from chemotherapy.
The trial is a UK NIHR-funded, investigator-led Phase III non-inferiority study coordinated by the Warwick Clinical Trials Unit and University College London, with Robert Stein (UCL) presenting first results at the ASCO 2026 Plenary Session on May 30, 2026. Roughly 4,400 clinically high-risk patients were randomised. Patients found to be Prosigna ROR-low were randomised to omit adjuvant chemotherapy and receive endocrine therapy alone, versus the conventional standard of chemotherapy followed by endocrine therapy. The primary question is whether the test-directed (chemo-sparing) strategy is non-inferior to standard-of-care chemo-plus-endocrine therapy at 5 years.
The result is being discussed by KOLs as a potential practice-changing chemo de-escalation signal for a much larger, higher-risk population than previous genomic tests have validated — while also drawing nuanced commentary from Martine Piccart, Dr Sarah Sammons, Yakup Ergün and others on subgroup limits (particularly N2 disease, where event counts remain low) and on the practical question of how widely the strategy will be adopted given existing competing assays.
UK NIHR-funded, investigator-led, multicentre Phase III randomised non-inferiority trial (NCT02027441). Coordinated by Warwick Clinical Trials Unit and UCL. Eligible patients had Prosigna PAM50 testing performed on the primary tumour; those with a ROR score ≤60 ("low-risk" by PAM50 biology) were randomised 1:1 to test-directed therapy (omit adjuvant chemotherapy → endocrine therapy alone) versus standard-of-care (adjuvant chemotherapy followed by endocrine therapy). Patients with high-ROR tumours received chemotherapy and were not randomised.
Clinically high-risk, ER+/HER2- early breast cancer, age ≥40, node-positive disease (1-9 involved nodes, including pN2). Both pre- and post-menopausal women were eligible. Approximately 4,400 patients enrolled across UK sites. Notably, this is a substantially higher-risk and more node-positive population than TAILORx or RxPONDER.
Prosigna 50-gene PAM50 Risk of Recurrence (ROR) signature (Veracyte). Test performed on primary tumour. Low-risk threshold pre-specified as ROR ≤60. Per the trial slides, approximately two-thirds of clinically high-risk patients were identified as Prosigna low-risk and therefore eligible for chemotherapy omission.
5-year invasive breast cancer-free interval / distant disease-free survival in the ROR-low randomised cohort, with a pre-specified non-inferiority margin. Key secondary endpoints: distant recurrence, overall survival, quality of life, and treatment-related toxicity.
At a median follow-up of 4 years, the 5-year IBCFS (invasive breast cancer-free survival) from the Kaplan-Meier curves was 91.8% control vs 90.3% test-directed, hazard ratio 1.03 (90% CI 0.85-1.25, p=0.006 non-inferiority) — meeting the pre-specified 3% non-inferiority margin. In the Prosigna ROR-low cohort (ROR ≤ 60, the population randomised to omit chemo), 5-year IBCFS was 94.8% control vs 93.6% test-directed, HR 1.06 (90% CI 0.80-1.40, p=0.003). Source: Stein et al., ASCO 2026 oral (Abstract #500); numbers per @stolaney1's verbatim post from the live presentation. The trial therefore supports the interpretation that, in clinically high-risk node-positive HR+/HER2- early breast cancer with a Prosigna low-ROR profile, adjuvant chemotherapy can be safely omitted in this biology subgroup.
According to the trial slides shared by multiple KOLs (Nozawa, Griguolo, Lucarecco), the Prosigna ROR-low result identified roughly two-thirds (~68%) of clinically high-risk, node-positive ER+/HER2- patients as biologically low-risk — meaning a majority of this previously "obligate-chemo" population could potentially be spared adjuvant chemotherapy under a test-directed strategy. This is the headline that KOLs are pointing to as the practice-changing element of OPTIMA: not the absolute survival numbers, but the size of the population the trial reclassifies.
Multiple KOLs (Dr Sarah Sammons, Martine Piccart in the discussion, Yakup Ergün) flagged the still-low event count in the pN2 (4-9 nodes) subgroup as the principal interpretive caveat — the headline non-inferiority result is most robust in the 1-3-node population. Piccart's invited discussion framed OPTIMA as the first prospective demonstration that Prosigna can de-escalate chemotherapy in node-positive disease, but emphasised continued follow-up, longer-term recurrence data, and direct comparison with competing assays as outstanding questions. Several US-based KOLs (Hamilton, Tolaney) raised the practical question of how rapidly the Prosigna ROR-guided strategy will be adopted in a US market where Oncotype DX already dominates node-positive decision-making.
Source: Stein et al., ASCO 2026 oral presentation (Abstract #500), May 30 2026; OPTIMA trial slides shared on X by Rugo, Nozawa, Griguolo, Lucarecco, Y. Abdou, To Be Elizabeth.OPTIMA is a Phase 3 UK randomized trial (NCT02027441) that tests whether a Prosigna PAM50 (Recurrence-of-Risk, ROR) test-directed strategy can safely de-escalate adjuvant chemotherapy in clinically high-risk, node-positive HR-positive, HER2-negative early breast cancer. Patients randomized to the test-directed arm received chemotherapy only if their tumor was biologically high-risk; the primary endpoint was invasive breast cancer-free survival, tested for non-inferiority.
Per the trial's own result slides shared by KOLs, the test-directed strategy met non-inferiority: at a median follow-up of about 4 years, 5-year invasive breast cancer-free survival was 91.8% in the control arm versus 90.3% in the test-directed arm (HR 1.03; 90% CI 0.85-1.25), within the pre-specified 3% non-inferiority margin.
OPTIMA is a biomarker-guided strategy trial, not a drug-approval study. It evaluates the Prosigna PAM50 (ROR) assay - an FDA-cleared, CE-marked test from Veracyte - as a tool to direct which clinically high-risk, node-positive patients need adjuvant chemotherapy. No new drug is being tested or approved.
According to trial slides shared by multiple KOLs, the Prosigna ROR-low result identified roughly two-thirds (about 68%) of clinically high-risk, node-positive ER-positive/HER2-negative patients as biologically low-risk - meaning a majority of this previously chemotherapy-recommended population could potentially avoid adjuvant chemotherapy without compromising outcomes.
The principal caveat, flagged by KOLs including Sarah Sammons and Martine Piccart, is the still-low event count in the pN2 (4-9 node) subgroup, where the non-inferiority conclusion is less robust. The headline result is most reliable in the 1-3-node population, and longer follow-up is needed before extending de-escalation to higher nodal burden.
Primary publications, sponsor & institutional press releases, and major oncology media coverage around the Stein/UCL ASCO 2026 oral presentation.
“OPTIMA addresses a long-standing challenge in breast cancer care: identifying who truly benefits from chemotherapy and who does not. Our findings show that many patients can safely avoid chemotherapy without compromising their outcomes.”Source: EurekAlert / UCL · May 30 2026 ↗
“I will now recommend a genomic assay for all post- and premenopausal women (≥40 y) with any number of positive nodes. A low-risk genomic result triggers shared decision-making.”
All 31 curated OPTIMA-related tweets from #ASCO26 and pre-conference commentary, sorted positive → neutral → negative. Text is verbatim from each KOL.
On August 5, the Oncology Brothers asked how to adopt OPTIMA in practice. Seven physicians answered. The full exchange, verbatim and in order:
Still trying to figure out how to adopt the data from OPTIMA trial in my practice (and how to use OncotypeDx vs. PAM50 scoring/test). Who is the right patient? Should I pivot completely from other tests and just rely on PAM50? @ErikaHamilton9 @PTarantinoMD @hoperugo @DrSGraff
I feel most comfortable for postmenopausal node positive.
I would continue to use Oncotype as the default assay in standard node-negative disease and in postmenopausal patients with 1–3 positive nodes. In OPTIMA-eligible premenopausal patients aged ≥40 years who will receive optimal ovarian suppression, and in selected patients with 4–9 positive nodes, I would prefer Prosigna as the de-escalation assay. However, in an otherwise eligible patient whose chemotherapy I de-escalate, I would not yet omit an adjuvant CDK4/6 inhibitor.
Only thing I’d say about this is the 4-9 node group was a small minority of folks in the trial. I’m not ready to use it in this group but 1-3 nodes I think I’ll start moving in that direction.
I do not think the number of N2 patients is that low (20%). What concerns me more is that the follow-up remains too short for HR-positive breast cancer.
True, agree shorter term follow up.
I completely agree @dr_yakupergun that this is strictly for adj chemo and not using this tool to decide on adj CDK4/6i! @drsarahsam for postmenopausal women node positive, do you mean N1 or N2? Or are you using this over OncotypeDx in any N+ postmenopausal women?
Results of OPTIMA Trial are important but follow up data reported is at 5 years only; however, we know that 50% of Patients with HR+ HER2- disease recurrences occur after 5 years. We may be comfortable applying it for patients with 4-5 involved LN and strongly positive ER.
I would be more likely to use in an N2 patient motivated to avoid chemotherapy.
Agree with @dr_yakupergun's approach. I would use in N2 especially when tumor characteristics are very Luminal-A(esque).
