Everolimus plus Exemestane for Hormone Receptor-Positive Advanced Breast Cancer: A PAM50 Intrinsic Subtype Analysis of BOLERO-2.
Aged
Androstadienes
/ administration & dosage
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Biomarkers, Tumor
/ metabolism
Breast Neoplasms
/ drug therapy
Double-Blind Method
Everolimus
/ administration & dosage
Female
Follow-Up Studies
Humans
International Agencies
Middle Aged
Prognosis
Receptor, ErbB-2
/ metabolism
Receptors, Estrogen
/ metabolism
Receptors, Progesterone
/ metabolism
Retrospective Studies
Survival Rate
Advanced breast cancer
Everolimus
Exemestane
Intrinsic subtype
Mammalian target of rapamycin
Journal
The oncologist
ISSN: 1549-490X
Titre abrégé: Oncologist
Pays: England
ID NLM: 9607837
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
11
07
2018
accepted:
21
12
2018
pubmed:
27
1
2019
medline:
10
7
2020
entrez:
26
1
2019
Statut:
ppublish
Résumé
The prognostic and predictive value of the two nonluminal (human epidermal growth factor receptor 2 [HER2]-enriched and basal-like) subtypes within advanced hormone receptor-positive (HR+) breast cancer is currently unknown. This study retrospectively analyzed 261 tumors (80.7% primary; 19.3% metastatic) from the BOLERO-2 study; BOLERO-2 randomized 724 patients with advanced HR+/HER2-negative breast cancer to everolimus plus exemestane or placebo plus exemestane. Tumors were classified using a PAM50 subtype predictor. Multivariable Cox regression analyses tested the independent prognostic significance of PAM50, and associations between PAM50 subtypes and treatment upon progression-free survival (PFS) were evaluated. Subtype distribution was 46.7% luminal A ( The HER2-enriched subtype was identified in a substantial proportion of advanced HR+/HER2-negative breast tumors, and was a consistent biomarker of poor prognosis. Tailored therapies are therefore needed for HER2-enriched tumors in the advanced HR+/HER2-negative breast cancer setting. Using 261 tumor samples from the BOLERO-2 phase III clinical trial, this study shows that a substantial proportion (20%-30%) of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancers do not have a luminal A or B gene expression profile. This group of patients with nonluminal disease has a poor survival outcome regardless of the addition of everolimus to exemestane. This is the second study that confirms the prognostic value of this biomarker. Overall, these findings indicate a necessity to design novel clinical trials targeting nonluminal disease within HR+/HER2-negative breast cancer.
Sections du résumé
BACKGROUND
The prognostic and predictive value of the two nonluminal (human epidermal growth factor receptor 2 [HER2]-enriched and basal-like) subtypes within advanced hormone receptor-positive (HR+) breast cancer is currently unknown.
MATERIALS AND METHODS
This study retrospectively analyzed 261 tumors (80.7% primary; 19.3% metastatic) from the BOLERO-2 study; BOLERO-2 randomized 724 patients with advanced HR+/HER2-negative breast cancer to everolimus plus exemestane or placebo plus exemestane. Tumors were classified using a PAM50 subtype predictor. Multivariable Cox regression analyses tested the independent prognostic significance of PAM50, and associations between PAM50 subtypes and treatment upon progression-free survival (PFS) were evaluated.
RESULTS
Subtype distribution was 46.7% luminal A (
CONCLUSION
The HER2-enriched subtype was identified in a substantial proportion of advanced HR+/HER2-negative breast tumors, and was a consistent biomarker of poor prognosis. Tailored therapies are therefore needed for HER2-enriched tumors in the advanced HR+/HER2-negative breast cancer setting.
IMPLICATIONS FOR PRACTICE
Using 261 tumor samples from the BOLERO-2 phase III clinical trial, this study shows that a substantial proportion (20%-30%) of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancers do not have a luminal A or B gene expression profile. This group of patients with nonluminal disease has a poor survival outcome regardless of the addition of everolimus to exemestane. This is the second study that confirms the prognostic value of this biomarker. Overall, these findings indicate a necessity to design novel clinical trials targeting nonluminal disease within HR+/HER2-negative breast cancer.
Identifiants
pubmed: 30679318
pii: theoncologist.2018-0407
doi: 10.1634/theoncologist.2018-0407
pmc: PMC6656445
doi:
Substances chimiques
Androstadienes
0
Biomarkers, Tumor
0
Receptors, Estrogen
0
Receptors, Progesterone
0
Everolimus
9HW64Q8G6G
ERBB2 protein, human
EC 2.7.10.1
Receptor, ErbB-2
EC 2.7.10.1
exemestane
NY22HMQ4BX
Types de publication
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
893-900Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Informations de copyright
© AlphaMed Press 2019.
Déclaration de conflit d'intérêts
Disclosures of potential conflicts of interest may be found at the end of this article.
Références
J Clin Oncol. 2009 Mar 10;27(8):1160-7
pubmed: 19204204
J Clin Oncol. 2009 Jun 1;27(16):2630-7
pubmed: 19380449
J Clin Oncol. 2009 Sep 20;27(27):4536-41
pubmed: 19687332
Mol Oncol. 2011 Feb;5(1):5-23
pubmed: 21147047
Steroids. 2011 Jul;76(8):736-40
pubmed: 21447351
J Clin Oncol. 2011 Jun 10;29(17):2342-9
pubmed: 21555689
N Engl J Med. 2012 Feb 9;366(6):520-9
pubmed: 22149876
Ann Oncol. 2012 Nov;23(11):2866-73
pubmed: 22532584
J Clin Oncol. 2012 Aug 1;30(22):2718-24
pubmed: 22565002
Adv Ther. 2013 Oct;30(10):870-84
pubmed: 24158787
J Natl Cancer Inst. 2014 Aug 19;106(8):null
pubmed: 25139534
Mol Oncol. 2015 Jun;9(6):1081-90
pubmed: 25687451
Breast. 2015 Nov;24 Suppl 2:S26-35
pubmed: 26253814
J Clin Oncol. 2016 Feb 10;34(5):419-26
pubmed: 26503204
BMC Med. 2015 Dec 18;13:303
pubmed: 26684470
J Clin Oncol. 2016 Sep 1;34(25):3069-103
pubmed: 27217461
JAMA Oncol. 2016 Oct 1;2(10):1287-1294
pubmed: 27281556
JAMA Oncol. 2016 Oct 1;2(10):1310-1315
pubmed: 27532364
Breast. 2017 Feb;31:244-259
pubmed: 27927580
Cancer Res. 2017 May 1;77(9):2213-2221
pubmed: 28249905
Cancer Treat Rev. 2018 Jun;67:63-70
pubmed: 29763779