dc.contributor.author | Dowsett, M | |
dc.contributor.author | Kilburn, L | |
dc.contributor.author | Rimawi, MF | |
dc.contributor.author | Osborne, CK | |
dc.contributor.author | Pogue-Geile, K | |
dc.contributor.author | Liu, Y | |
dc.contributor.author | Jacobs, SA | |
dc.contributor.author | Finnigan, M | |
dc.contributor.author | Puhalla, S | |
dc.contributor.author | Dodson, A | |
dc.contributor.author | Martins, V | |
dc.contributor.author | Cheang, M | |
dc.contributor.author | Perry, S | |
dc.contributor.author | Holcombe, C | |
dc.contributor.author | Turner, N | |
dc.contributor.author | Swift, C | |
dc.contributor.author | Bliss, JM | |
dc.contributor.author | Johnston, S | |
dc.contributor.author | PALLET trialists, | |
dc.date.accessioned | 2021-11-23T14:13:11Z | |
dc.date.available | 2021-11-23T14:13:11Z | |
dc.date.issued | 2022-01-01 | |
dc.identifier.citation | Clinical cancer research : an official journal of the American Association for Cancer Research, 2021 | |
dc.identifier.issn | 1078-0432 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4893 | |
dc.identifier.eissn | 1557-3265 | |
dc.identifier.doi | 10.1158/1078-0432.ccr-21-1628 | |
dc.description.abstract | 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 <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. | |
dc.format | Print-Electronic | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | AMER ASSOC CANCER RESEARCH | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0 | |
dc.title | Biomarkers of Response and Resistance to Palbociclib Plus Letrozole in Patients With ER+/HER2- Breast Cancer. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2021-10-07 | |
rioxxterms.version | AM | |
rioxxterms.versionofrecord | 10.1158/1078-0432.ccr-21-1628 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by-nc-nd/4.0 | |
rioxxterms.licenseref.startdate | 2021-10-13 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Clinical cancer research : an official journal of the American Association for Cancer Research | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical Trials & Statistics Unit | |
pubs.publication-status | Published | |
pubs.embargo.terms | Not known | |
icr.researchteam | Clinical Trials & Statistics Unit | |
dc.contributor.icrauthor | Kilburn, Lucy | |
dc.contributor.icrauthor | Cheang, Chon | |
dc.contributor.icrauthor | Turner, Nicholas | |
dc.contributor.icrauthor | Bliss, Judith | |