Language
English
Publication Date
1-1-2022
Journal
Clinical Cancer Research
DOI
10.1158/1078-0432.CCR-21-1628
PMID
34645649
PMCID
PMC9632606
PubMedCentral® Posted Date
10-13-2021
PubMedCentral® Full Text Version
Post-print
Abstract
PURPOSE: To determine (i) the relationship between candidate biomarkers of the antiproliferative (Ki67) response to letrozole and palbociclib alone and combined in ER
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 <2.7%) at 14 weeks and higher baseline Ki67, c-PARP, and CCNE1 with a lower chance. The interaction with treatment was significant only for c-PARP. CCND1 levels were decreased c.20% by letrozole at 2 and 14 weeks but showed a tendency to increase with palbociclib. CCNE1 levels fell 82% (median) in tumors showing CCCA but were unchanged in those with no CCCA. Only 2/9 tumors showed CCCA 3–9 days after stopping palbociclib. 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.
Keywords
Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Tumor, Breast Neoplasms, Female, Humans, Letrozole, Piperazines, Pyridines, Receptor, ErbB-2, Receptors, Estrogen
Published Open-Access
yes
Recommended Citation
Dowsett, Mitch; Kilburn, Lucy; Rimawi, Mothaffar F; et al., "Biomarkers of Response and Resistance to Palbociclib Plus Letrozole in Patients With ER+/HER2- Breast Cancer" (2022). Faculty and Staff Publications. 1612.
https://digitalcommons.library.tmc.edu/baylor_docs/1612