Higher TILs marked who gained most from pertuzumab in HER2-positive early breast cancer

Design

Secondary biomarker analysis of a phase 3 randomised trial (APHINITY)

Population

4,262 tumour samples from patients with early HER2-positive breast cancer

Primary outcome

Invasive disease-free survival by TIL level and scoring method

Effect

Higher TILs HR 0.41–0.93 for iDFS; pertuzumab HR 0.36–0.48 at high TILs; 12.1-point gain in node-positive TILs ≥70%

This secondary analysis of the APHINITY trial (4,805 patients with early HER2-positive breast cancer randomised to chemotherapy and trastuzumab with pertuzumab or placebo; median follow-up 74 months) scored stromal tumour-infiltrating lymphocytes (TILs) on 4,262 slides by manual, digital and AI methods.

Manual scoring was reproducible between pathologists (intraclass correlation 0.84). Higher TILs were associated with better invasive disease-free survival by every method (HR 0.41 to 0.93). Pertuzumab benefit was greater at higher TIL levels (HR 0.36 to 0.48), with the largest six-year absolute gain, 12.1 percentage points, in node-positive disease with TILs of 70% or more. AI scoring reclassified 11.6% of node-positive tumours from immune-low to immune-high, and these patients showed greater pertuzumab benefit.

TILs are cheap to score on the H&E slide already made for diagnosis. This supports reporting them routinely in HER2-positive cancer, though they do not yet decide who receives pertuzumab.

• Ask pathology to report stromal TILs on HER2-positive breast cancer biopsies.
• Higher TILs indicate better prognosis across all scoring methods.
• The largest absolute pertuzumab benefit was seen in node-positive disease with high TILs (exploratory).
• TIL level is not yet a validated basis for withholding pertuzumab.

Why it matters

A cheap marker on the existing slide may help decide who needs dual HER2 blockade most.

Don't overread it

These are secondary, exploratory analyses; TILs have not been validated to select patients for pertuzumab.

The statistics, in plain English

Subgroup and interaction analyses in a trial are less reliable than the main result; they generate hypotheses. The AI reclassification finding is from 120 tumours and needs validation in another cohort.

Read the rest in the app

You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.

Get Daily Doctor — free

Scan to keep reading on your phone. No account needed to start.