| Autor: |
Stephen Johnston, Judith M. Bliss, Claire Swift, Nick Turner, Chris Holcombe, Sophie Perry, Maggie Cheang, Vera Martins, Andrew Dodson, Shannon Puhalla, Melanie Finnigan, Samuel A. Jacobs, Yuan Liu, Katherine Pogue-Geile, C. Kent Osborne, Mothaffar F. Rimawi, Lucy Kilburn, Mitch Dowsett |
| Rok vydání: |
2023 |
| DOI: |
10.1158/1078-0432.c.6531375.v1 |
| Popis: |
Purpose:To determine (i) the relationship between candidate biomarkers of the antiproliferative (Ki67) response to letrozole and palbociclib alone and combined in ER+/HER2− breast cancer; and (ii) the pharmacodynamic effect of the agents on the biomarkers.Experimental Design:307 postmenopausal women with ER+/HER2− primary breast cancer were randomly assigned to neoadjuvant treatment with letrozole for 14 weeks; letrozole for 2 weeks, then letrozole+palbociclib to 14 weeks; palbociclib for 2 weeks, then letrozole+palbociclib to 14 weeks; or letrozole+palbociclib for 14 weeks. Biopsies were taken at baseline, 2 and 14 weeks and surgery at varying times after stopping palbociclib. Immunohistochemical analyses were conducted for Ki67, c-PARP, ER, PgR, RB1, CCNE1, and CCND1.Results:Higher baselines ER and PgR were significantly associated with a greater chance of complete cell-cycle arrest (CCCA: Ki67 ESR1 mutations were found in 2/4 tumors for which surgery took place ≥6 months after starting treatment.Conclusions:High CCNE1 levels were confirmed as a biomarker of resistance to letrozole+palbociclib. Ki67 recovery within 3–9 days of discontinuing palbociclib indicates incomplete suppression of proliferation during the “off” week of its schedule. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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