Higher Tumor-Infiltrating Lymphocyte Level Associated With Better Outcomes in HER2-Positive Early Breast Cancer Independent of Neoadjuvant Treatment


Key Points

  • Higher baseline tumor-infiltrating lymphocyte levels were associated with increased likelihood of pathologic complete response and improved event-free survival independent of treatment.
  • Patients with high tumor-infiltrating lymphocyte levels who did not achieve pathologic complete response had high event-free survival.

In an analysis of the NeoALTTO trial reported in JAMA Oncology, Salgado et al found that a higher level of tumor-infiltrating lymphocytes was associated with improved pathologic compete response rate and event-free survival independent of neoadjuvant treatment received in patients with HER2-positive early breast cancer.

Study Details

In NeoALTTO, 455 patients were randomly assigned to receive neoadjuvant trastuzumab (Herceptin), lapatinib (Tykerb), or the combination for 6 weeks followed by the addition of weekly paclitaxel for 12 weeks and three cycles of fluorouracil, epirubicin, and cyclophosphamide after surgery. Percentage of tumor-infiltrating lymphocytes were measured by hematoxylin-eosin stained core biopsy sections taken at diagnosis.

Pathologic Complete Response Rate

The current analysis included samples from 387 patients. The median level of tumor-infiltrating lymphocytes was 12.5%, with lower levels being found in hormone receptor–positive vs –negative patients (10.0% vs 12.5%, P = .02). Tumor-infiltrating lymphocyte levels > 5% were associated with a higher pathologic complete response rate independent of neoadjuvant treatment group (adjusted odds ratio [OR] = 2.60, P = .01), with no significant interaction being found for tumor-infiltrating lymphocyte level and combination treatment vs trastuzumab treatment (P = .51).

Event-Free Survival

After a median follow-up of 3.77 years, every 1% increase in tumor-infiltrating lymphocytes was associated with a 3% decrease in disease event rate across all treatment groups (adjusted hazard ratio = 0.97, P = .002). Patients with tumor-infiltrating lymphocyte levels greater than the median who did not achieve pathologic complete response had event-free survival similar to those who achieved pathologic complete response. Those with tumor-infiltrating lymphocyte ≥ 40% had 3-year event-free survival of 97% regardless of whether they achieved pathologic complete response.

The investigators concluded: “The presence of [tumor-infiltrating lymphocytes] at diagnosis is an independent, positive prognostic marker in HER2-positive early breast cancer treated with neoadjuvant anti-HER2 agents and chemotherapy for both [pathologic complete response] and event-free survival end points.”

Sherene Loi, MD, PhD, of Peter MacCallum Cancer Centre, University of Melbourne, is the corresponding author for the JAMA Oncology article.

The study was supported by Cancer Council Victoria and the National Health and Medical Research Council of Australia; the NeoALTTO study was funded by GlaxoSmithKline. For full disclosures of the study authors, visit

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