A UNICANCER-sponsored phase 3 interventional trial is now recruiting premenopausal women with HR+/HER2− early breast cancer to assess whether PAM50 genomic scoring (Prosigna®) can safely guide omission of adjuvant chemotherapy in favor of optimized endocrine therapy with ovarian function suppression. The primary endpoint is invasive disease-free survival compared against systematic chemo-endocrine therapy.
UNICANCER has initiated a phase 3 randomized trial (NCT07106632) examining whether Prosigna® (PAM50)-directed treatment allocation can match the oncologic outcomes of standard systematic adjuvant chemotherapy in premenopausal women with hormone receptor-positive, HER2-negative invasive breast cancer. The experimental arm assigns chemo-endocrine therapy or endocrine therapy alone based on centrally assessed PAM50 risk-of-recurrence scores, while the control arm follows current standard-of-care chemo-endocrine therapy. The primary endpoint captures invasive disease-free survival, encompassing locoregional recurrence, distant metastasis, contralateral breast cancer, and all-cause mortality.
The scientific rationale centers on a recognized gap in evidence: genomic assays have successfully guided chemotherapy decisions in postmenopausal HR+/HER2− disease, but premenopausal women have historically been excluded from de-escalation strategies due to their elevated relapse risk. Prior risk-stratification trials in this population were confounded by suboptimal endocrine therapy—most enrolled women did not receive ovarian function suppression (OFS), a regimen now considered standard for high-risk premenopausal disease. Investigators hypothesize that a portion of chemotherapy's benefit in this group may be attributable to treatment-induced amenorrhea rather than direct cytotoxic effect, suggesting that optimized endocrine therapy incorporating OFS could be sufficient for patients with low PAM50 scores.
Approximately 70% of enrolled participants are expected to have low Prosigna® scores and would therefore be allocated to endocrine therapy alone in the experimental arm. Secondary objectives include head-to-head comparison of recurrence rates, quality-of-life outcomes over five years, health-economic analysis, and qualitative assessment of patient attitudes toward therapeutic de-intensification. Eligible participants are premenopausal women with confirmed ER+/HER2− invasive breast cancer who have completed breast and axillary surgery and have tumor tissue available for PAM50 analysis; those with stage IV disease, prior adjuvant systemic therapy, or active pregnancy are excluded.
The trial addresses a clinically meaningful unmet need, as younger women with HR+/HER2− breast cancer bear a disproportionate burden of chemotherapy-related toxicity—including effects on fertility, cognitive function, and occupational capacity—relative to their postmenopausal counterparts. Definitive evidence supporting genomic-guided omission of chemotherapy in this population remains absent, and results from this trial could meaningfully reshape adjuvant treatment algorithms for premenopausal early breast cancer.
Key points
- Phase 3 randomized trial (NCT07106632) is actively recruiting premenopausal women with HR+/HER2− invasive early breast cancer to evaluate Prosigna® (PAM50)-guided adjuvant chemotherapy de-escalation.
- Experimental arm assigns chemo-endocrine therapy or endocrine therapy plus OFS based on centrally assessed PAM50 score; control arm receives standard systematic chemo-endocrine therapy.
- Primary endpoint is invasive disease-free survival; secondary endpoints include recurrence rates, quality of life, health economics, and patient perception of de-escalation.
- Approximately 70% of participants are anticipated to have low PAM50 scores and would receive endocrine therapy alone in the experimental arm.
- Prior trials in premenopausal populations were limited by inadequate endocrine therapy; this trial mandates OFS to address that confound.
Why it matters
No validated evidence currently supports omitting adjuvant chemotherapy in high-risk premenopausal HR+/HER2− breast cancer, leaving clinicians without genomic guidance tools analogous to those used in postmenopausal disease. This trial could establish whether Prosigna®-directed de-escalation with optimized OFS-based endocrine therapy is non-inferior, potentially sparing a substantial proportion of younger women from chemotherapy toxicity.