Five years on, many HER2-positive breast cancer patients still do well without chemo

Five-year PHERGain data show a PET-guided, chemotherapy-free path held up for patients whose tumors responded, though the trial was small and non-comparative.

Five-year results from PHERGain, a randomized phase 2 trial (NCT03161353), suggest that some patients with HER2-positive early breast cancer can skip chemotherapy without a clear loss of long-term outcomes. The paper appeared in Nature Medicine on 29 October 2026.

The trial enrolled patients with operable, stage I–IIIA HER2-positive tumors of at least 1.5 cm. Most (randomized 1:4) went to group B, which received trastuzumab and pertuzumab, with or without endocrine therapy, and no chemotherapy at first. An 18F-FDG-PET scan after two cycles identified responders. Non-responders, and responders who lacked a pathological complete response (pCR) at surgery, also received docetaxel and carboplatin. Group A received the full chemotherapy combination.

At a median follow-up of 5.6 years, group B (n=267) had 5-year invasive disease-free survival of 89.5% (95% CI 85.7–93.4). Among 86 PET responders who reached pCR and never had chemotherapy, the figure was 92.4% (95% CI 86.7–98.5), with one distant recurrence. Earlier work found that 37.9% of group B PET responders reached pCR on the chemo-free regimen. Circulating tumor DNA (ctDNA) detectable at baseline or during treatment tracked with worse outcomes, and clearance tracked with higher pCR rates and better survival.

This matters for abundance because HER2-positive disease makes up roughly 15–20% of breast cancers. Every patient who can safely skip chemotherapy avoids its toxicity, the cost of drugs and managing side effects, and time lost to treatment. A scan-guided approach could free up oncology capacity and make effective care easier to deliver widely.

The caveats are real. The trial is non-comparative, so it can't show that group B did as well as group A. The 92.4% figure comes from a subgroup defined after randomization, and the authors call it descriptive, not proof that omitting chemotherapy caused the result. The ctDNA analyses are exploratory. Hormone receptor subgroup results weren't in our source material. Watch for larger comparative trials.

Source: Nature Medicine