Prognostic or predictive biomarkers in HER2-positive early breast cancer (EBC) may inform treatment optimization. The ADAPT HER2-positive/hormone receptor-positive phase II trial (NCT01779206) demonstrated pathological complete response (pCR) rates of ~40% following de-escalated treatment with 12 weeks neoadjuvant ado-trastuzumab emtansine (T-DM1) ± endocrine therapy. In this exploratory analysis, we evaluated potential early predictors of response to neoadjuvant therapy. The effects of PIK3CA mutations and immune (CD8 and PD-L1) and apoptotic markers (BCL2 and MCL1) on pCR rates were assessed, along with intrinsic BC subtypes. Immune response and pCR were lower in PIK3CA-mutated tumors compared with wildtype. Increased BCL2 at baseline in all patients and at Cycle 2 in the T-DM1 arms was associated with lower pCR. In the T-DM1 arms only, the HER2-enriched subtype was associated with increased pCR rate (54% vs. 28%). These findings support further prospective pCR-driven de-escalation studies in patients with HER2-positive EBC.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:84985 |
| Date | 26 April 2023 |
| Creators | Harbeck, Nadia, von Schumann, Raquel, Kates, Ronald Ernest, Braun, Michael, Kuemmel, Sherko, Schumacher, Claudia, Potenberg, Jochem, Malter, Wolfram, Augustin, Doris, Aktas, Bahriye, Forstbauer, Helmut, Tio, Joke, Grischke, Eva-Maria, Biehl, Claudia, Liedtke, Cornelia, De Haas, Sanne Lysbet, Deurloo, Regula, Wuerstlein, Rachel, Kreipe, Hans Heinrich, Gluz, Oleg |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 2072-6694, 4884 |
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