{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T21:58:49Z","timestamp":1785189529335,"version":"3.55.0"},"posted":{"date-parts":[[2026,7,1]]},"group-title":"Oncology","reference-count":50,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"National Cancer Institute of the National Institutes of Health","award":["UH3CA262221"],"award-info":[{"award-number":["UH3CA262221"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Purpose<\/jats:title>\n                  <jats:p>There are no clinically validated biomarkers to assess recurrence risk and guide treatment de-escalation in Basal-like and HER2-enriched breast cancer. Taxane-based chemotherapy remains a cornerstone of treatment despite significant toxicity. We evaluated the prognostic and predictive utility of the MHCII Immune Activation Score (IA Score) in these subtypes.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Experimental Design<\/jats:title>\n                  <jats:p>We retrospectively analyzed Basal-like and HER2-enriched breast cancers from the NCIC CTG MA.21 trial, which randomized patients with node-positive or high-risk node-negative disease to adjuvant chemotherapy with or without taxanes. MA.21 predated immune checkpoint inhibitors and routine HER2-targeted therapy. Subtype was previously assigned by PAM50. The 36-gene MHCII-IA assay used RNA from formalin-fixed, paraffin-embedded tissue. Multivariable Cox and Kaplan-Meier analyses evaluated associations between IA Score, clinicopathologic variables, tumor-infiltrating lymphocytes (TILs), relapse-free survival (RFS), and taxane benefit.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Among Basal-like (N=317) and HER2-enriched (N=155) tumors, higher IA Score was associated with improved RFS independent of lymph node status and provided stronger prognostic discrimination than TILs. Node-negative patients with high IA Score had excellent outcomes (8-year RFS &gt;90%) versus those with low IA Score (8-year RFS &lt;76%). In node-positive disease, high IA Score increased 8-year RFS by &gt;10% relative to low IA Score. IA Score stratified taxane benefit: node-positive IA-low patients benefited, whereas IA-high tumors had favorable outcomes regardless of regimen.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>MHCII Immune Activation Score is a prognostic and predictive biomarker in Basal-like and HER2-enriched breast cancer. High IA Score identified patients with excellent outcomes before pembrolizumab, trastuzumab, and taxane-based treatment escalation, providing a rationale for prospective risk-adapted de-escalation strategies.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.06.24.26356102","type":"posted-content","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T15:01:49Z","timestamp":1783090909000},"source":"Crossref","is-referenced-by-count":0,"title":["The MHCII Immune Activation Score predicts risk of recurrence and benefit of taxanes in Basal-like and HER2-enriched breast cancer"],"prefix":"10.64898","author":[{"given":"Philip S.","family":"Bernard","sequence":"first","affiliation":[{"name":"Department of Pathology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingshu E.","family":"Chen","sequence":"additional","affiliation":[{"name":"Canadian Cancer Trials Group, Queen\u2019s 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