In real life, one-quarter of patients with hormone receptor-positive metastatic breast cancer receive chemotherapy as initial palliative therapy: a study of the Southeast Netherlands Breast Cancer Consortium

Lobbezoo, D.J.A.; Kampen, Roel J.W. van; Voogd, Adri C.; Dercksen, M. Wouter; Berkmortel, Franchette van den; Smilde, TJ; Wouw, Agnès J. van de; Peters, F. P. J.; Riel, J.M.G.H. van; Peters, Natascha A. J. B.; Boer, Maaike de; Peer, Petronella G. M.; Tjan-Heijnen, Vcg

doi:10.1093/annonc/mdv544

Cited by 71 publications

(91 citation statements)

References 27 publications

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“…All breast cancer guidelines concur with this recommendation but unfortunately real life data studies show that most of these patients still receive chemotherapy as their first treatment, despite the lower efficacy [37]. …”

Section: Er Positive/her-2 Negative (Luminal) Abcmentioning

confidence: 99%

3rd ESO–ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 3)

Cardoso¹,

et al. 2017

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Section: Er Positive/her-2 Negative (Luminal) Abcmentioning

confidence: 99%

3rd ESO–ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 3)

Cardoso¹,

et al. 2017

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“…A second potential bias may come from our inability to identify those mutations leading to a disease so aggressive that the patients will not be eligible for trial recruitment, preventing an exhaustive picture of the mutational profiles of mBC. However, recent studies on first-line therapies for advanced breast cancer have shown that early death is limited [32,33], and it is therefore unlikely that it has dramatically impacted the analysis. Additionally, there is a chance that mutations enriched in metastasis might be subclonal driver events and therefore might not be such good drug targets.…”

Section: Discussionmentioning

confidence: 99%

Mutational Profile of Metastatic Breast Cancers: A Retrospective Analysis

et al. 2016

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BackgroundMajor advances have been achieved in the characterization of early breast cancer (eBC) genomic profiles. Metastatic breast cancer (mBC) is associated with poor outcomes, yet limited information is available on the genomic profile of this disease. This study aims to decipher mutational profiles of mBC using next-generation sequencing.Methods and FindingsWhole-exome sequencing was performed on 216 tumor–blood pairs from mBC patients who underwent a biopsy in the context of the SAFIR01, SAFIR02, SHIVA, or Molecular Screening for Cancer Treatment Optimization (MOSCATO) prospective trials. Mutational profiles from 772 primary breast tumors from The Cancer Genome Atlas (TCGA) were used as a reference for comparing primary and mBC mutational profiles. Twelve genes (TP53, PIK3CA, GATA3, ESR1, MAP3K1, CDH1, AKT1, MAP2K4, RB1, PTEN, CBFB, and CDKN2A) were identified as significantly mutated in mBC (false discovery rate [FDR] < 0.1). Eight genes (ESR1, FSIP2, FRAS1, OSBPL3, EDC4, PALB2, IGFN1, and AGRN) were more frequently mutated in mBC as compared to eBC (FDR < 0.01). ESR1 was identified both as a driver and as a metastatic gene (n = 22, odds ratio = 29, 95% CI [9–155], p = 1.2e-12) and also presented with focal amplification (n = 9) for a total of 31 mBCs with either ESR1 mutation or amplification, including 27 hormone receptor positive (HR+) and HER2 negative (HER2−) mBCs (19%). HR+/HER2− mBC presented a high prevalence of mutations on genes located on the mechanistic target of rapamycin (mTOR) pathway (TSC1 and TSC2) as compared to HR+/HER2− eBC (respectively 6% and 0.7%, p = 0.0004). Other actionable genes were more frequently mutated in HR+ mBC, including ERBB4 (n = 8), NOTCH3 (n = 7), and ALK (n = 7). Analysis of mutational signatures revealed a significant increase in APOBEC-mediated mutagenesis in HR+/HER2− metastatic tumors as compared to primary TCGA samples (p < 2e-16). The main limitations of this study include the absence of bone metastases and the size of the cohort, which might not have allowed the identification of rare mutations and their effect on survival.ConclusionsThis work reports the results of the analysis of the first large-scale study on mutation profiles of mBC. This study revealed genomic alterations and mutational signatures involved in the resistance to therapies, including actionable mutations.

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“…[11][12][13][14] Nevertheless, chemotherapy-based regimens are still widely used as upfront therapy, sometimes without strict clinical justification. [15][16][17][18] To date, few data are available from randomised controlled trials directly comparing hormone therapies to chemotherapy-based treatment regimens in this disease subset. Indeed, in the past three decades, only two randomised controlled trials addressing this issue have been published (appendix pp 3, 18).…”

Section: Discussionmentioning

confidence: 99%

“…[11][12][13][14] Nevertheless, real-world data suggest that upfront use of chemotherapy is still common, even in the absence of visceral crisis. [15][16][17][18] This treatment approach might be partly due to the paucity of direct comparisons among hormone therapies and chemo therapy-based regimens for this subtype of metastatic breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Endocrine treatment versus chemotherapy in postmenopausal women with hormone receptor-positive, HER2-negative, metastatic breast cancer: a systematic review and network meta-analysis

Giuliano

Schettini

Rognoni

et al. 2019

The Lancet Oncology

136

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Background Although international guidelines support the administration of hormone therapies with or without targeted therapies in postmenopausal women with hormone-receptor-positive, HER2-negative metastatic breast cancer, upfront use of chemotherapy remains common even in the absence of visceral crisis. Because first-line or second-line treatments, or both, based on chemotherapy and on hormone therapy have been scarcely investigated in head-to-head randomised controlled trials, we aimed to compare these two different approaches. Methods We did a systematic review and network meta-analysis with a systematic literature search on PubMed, Embase, Cochrane Central Register of Clinical Trials, Web of Science, and online archives of the most relevant international oncology conferences. We included all phase 2 and 3 randomised controlled trials investigating chemotherapy with or without targeted therapies and hormone therapies with or without targeted therapies as firstline or second-line treatments, or both, in postmenopausal women with hormone-receptor-positive, HER2-negative metastatic breast cancer, published between Jan 1, 2000, and Dec 31, 2017. Additional recently published randomised controlled trials relevant to the topic were also subsequently added. No language restrictions were adopted for our search. A Bayesian network meta-analysis was done to compare hazard ratios (HRs) for progression-free survival (the primary outcome), and to compare odds ratios (ORs) for the proportion of patients achieving an overall response (the secondary outcome). All treatments were compared to anastrozole and to palbociclib plus letrozole. This study is registered in the Open Science Framework online public database, registration DOI 10.17605/OSF.IO/496VR. Findings We identified 2689 published results and 140 studies (comprising 50 029 patients) were included in the analysis. Palbociclib plus letrozole (HR 0•42; 95% credible interval [CrI] 0•25-0•70), ribociclib plus letrozole (0•43; 0•24-0•77), abemaciclib plus anastrozole or letrozole (0•42; 0•23-0•76), palbociclib plus fulvestrant (0•37; 0•23-0•59), ribociclib plus fulvestrant (0•48; 0•31-0•74), abemaciclib plus fulvestrant (0•44; 0•28-0•70), everolimus plus exemestane (0•42; 0•28-0•67), and, in patients with a PIK3CA mutation, alpelisib plus fulvestrant (0•39; 0•22-0•66), and several chemotherapy-based regimens, including anthracycline and taxane-containing regimens, were associated with better progression-free survival than was anastrozole alone. No chemotherapy or hormone therapy regimen was significantly better than palbociclib plus letrozole for progression-free survival. Paclitaxel plus bevacizumab was the only clinically relevant regimen that was significantly better than palbociclib plus letrozole in terms of the proportion of patients achieving an overall response (OR 8•95; 95% CrI 1•03-76•92). Interpretation In the first-line or second-line setting, CDK4/6 inhibitors plus hormone therapies are better than standard hormone therapies in terms of progression-free surv...

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In real life, one-quarter of patients with hormone receptor-positive metastatic breast cancer receive chemotherapy as initial palliative therapy: a study of the Southeast Netherlands Breast Cancer Consortium

Abstract: A high percentage of patients with HR+ disease received initial palliative chemotherapy, which was associated with worse outcome, even after adjustment of relevant prognostic factors.

Cited by 71 publications

References 27 publications

3rd ESO–ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 3)

3rd ESO–ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 3)

Mutational Profile of Metastatic Breast Cancers: A Retrospective Analysis

Endocrine treatment versus chemotherapy in postmenopausal women with hormone receptor-positive, HER2-negative, metastatic breast cancer: a systematic review and network meta-analysis

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