Mutational analysis of triple-negative breast cancers within the International Breast Cancer Study Group (IBCSG) Trial 22-00

Elisabetta Munzone, Kathryn P. Gray, Caterina Fumagalli, Elena Guerini-Rocco, István Láng, Thomas Ruhstaller, Lorenzo Gianni, Roswitha Kammler, Giuseppe Viale, Angelo Di Leo, Alan S. Coates, Richard D. Gelber, Meredith M. Regan, Aron Goldhirsch, Massimo Barberis, Marco Colleoni

Research output: Contribution to journalArticle

Abstract

Purpose: We investigated the occurrence and the prognostic and predictive relationship of a selected number of somatic mutations in triple-negative breast cancer (TNBC) patients having known clinical outcomes treated within the IBCSG Trial 22-00. Methods: A matched case–control sampling selected patients enrolled in the IBCSG Trial 22-00 who had TNBC tumors, based on local assessment. Cases had invasive breast cancer recurrence (at local, regional, or distant site) according to the protocol definition. Matched controls had not recurred. Mutational analysis was performed with OncoCarta panel v1.0 using Mass Array System. The panel includes 19 genes belonging to different functional pathways as PI3K pathway, receptor tyrosine kinase, and cell cycle-metabolic group. Conditional logistic regression assessed the association of mutation status with breast cancer recurrence. Results: Mutation assessment was successful for 135 patients (49 cases, 86 controls). A total of 37 (27.4%) of the 135 patients had at least one mutation in the selected genes. PIK3CA was the most common mutated gene (18/135; 13.3%), followed by BRAF, KIT and PDGFRA (each 4/135, 3.0%) and AKT1 (3/135; 2.2%). TNBC patients with at least one mutation had increased odds of recurrence compared with those with wild-type tumors (odds ratio (OR) 2.28; 95% CI 0.88–5.92), though this difference was not statistically significant (p = 0.09). We found no evidence that these mutations were predictive for the value of maintenance metronomic chemotherapy. Conclusions: Mutations in the tested oncogenes were not associated with breast cancer recurrence in this TNBC subset of patients. The question of whether any of these mutated genes (e.g., PIK3CA) may represent a useful therapeutic target in TNBC may be answered by ongoing clinical trials and/or larger dataset analysis.

Original languageEnglish
Pages (from-to)351-360
Number of pages10
JournalBreast Cancer Research and Treatment
Volume170
Issue number2
DOIs
Publication statusPublished - Jul 1 2018

Fingerprint

Triple Negative Breast Neoplasms
Breast Neoplasms
Mutation
Recurrence
Genes
Maintenance Chemotherapy
Receptor Protein-Tyrosine Kinases
Phosphatidylinositol 3-Kinases
Oncogenes
Cell Cycle
Logistic Models
Odds Ratio
Clinical Trials

Keywords

  • Mass array system
  • PIK3CA
  • Prognosis
  • Somatic mutation
  • Triple-negative breast cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Mutational analysis of triple-negative breast cancers within the International Breast Cancer Study Group (IBCSG) Trial 22-00. / Munzone, Elisabetta; Gray, Kathryn P.; Fumagalli, Caterina; Guerini-Rocco, Elena; Láng, István; Ruhstaller, Thomas; Gianni, Lorenzo; Kammler, Roswitha; Viale, Giuseppe; Di Leo, Angelo; Coates, Alan S.; Gelber, Richard D.; Regan, Meredith M.; Goldhirsch, Aron; Barberis, Massimo; Colleoni, Marco.

In: Breast Cancer Research and Treatment, Vol. 170, No. 2, 01.07.2018, p. 351-360.

Research output: Contribution to journalArticle

Munzone, Elisabetta ; Gray, Kathryn P. ; Fumagalli, Caterina ; Guerini-Rocco, Elena ; Láng, István ; Ruhstaller, Thomas ; Gianni, Lorenzo ; Kammler, Roswitha ; Viale, Giuseppe ; Di Leo, Angelo ; Coates, Alan S. ; Gelber, Richard D. ; Regan, Meredith M. ; Goldhirsch, Aron ; Barberis, Massimo ; Colleoni, Marco. / Mutational analysis of triple-negative breast cancers within the International Breast Cancer Study Group (IBCSG) Trial 22-00. In: Breast Cancer Research and Treatment. 2018 ; Vol. 170, No. 2. pp. 351-360.
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abstract = "Purpose: We investigated the occurrence and the prognostic and predictive relationship of a selected number of somatic mutations in triple-negative breast cancer (TNBC) patients having known clinical outcomes treated within the IBCSG Trial 22-00. Methods: A matched case–control sampling selected patients enrolled in the IBCSG Trial 22-00 who had TNBC tumors, based on local assessment. Cases had invasive breast cancer recurrence (at local, regional, or distant site) according to the protocol definition. Matched controls had not recurred. Mutational analysis was performed with OncoCarta panel v1.0 using Mass Array System. The panel includes 19 genes belonging to different functional pathways as PI3K pathway, receptor tyrosine kinase, and cell cycle-metabolic group. Conditional logistic regression assessed the association of mutation status with breast cancer recurrence. Results: Mutation assessment was successful for 135 patients (49 cases, 86 controls). A total of 37 (27.4{\%}) of the 135 patients had at least one mutation in the selected genes. PIK3CA was the most common mutated gene (18/135; 13.3{\%}), followed by BRAF, KIT and PDGFRA (each 4/135, 3.0{\%}) and AKT1 (3/135; 2.2{\%}). TNBC patients with at least one mutation had increased odds of recurrence compared with those with wild-type tumors (odds ratio (OR) 2.28; 95{\%} CI 0.88–5.92), though this difference was not statistically significant (p = 0.09). We found no evidence that these mutations were predictive for the value of maintenance metronomic chemotherapy. Conclusions: Mutations in the tested oncogenes were not associated with breast cancer recurrence in this TNBC subset of patients. The question of whether any of these mutated genes (e.g., PIK3CA) may represent a useful therapeutic target in TNBC may be answered by ongoing clinical trials and/or larger dataset analysis.",
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T1 - Mutational analysis of triple-negative breast cancers within the International Breast Cancer Study Group (IBCSG) Trial 22-00

AU - Munzone, Elisabetta

AU - Gray, Kathryn P.

AU - Fumagalli, Caterina

AU - Guerini-Rocco, Elena

AU - Láng, István

AU - Ruhstaller, Thomas

AU - Gianni, Lorenzo

AU - Kammler, Roswitha

AU - Viale, Giuseppe

AU - Di Leo, Angelo

AU - Coates, Alan S.

AU - Gelber, Richard D.

AU - Regan, Meredith M.

AU - Goldhirsch, Aron

AU - Barberis, Massimo

AU - Colleoni, Marco

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N2 - Purpose: We investigated the occurrence and the prognostic and predictive relationship of a selected number of somatic mutations in triple-negative breast cancer (TNBC) patients having known clinical outcomes treated within the IBCSG Trial 22-00. Methods: A matched case–control sampling selected patients enrolled in the IBCSG Trial 22-00 who had TNBC tumors, based on local assessment. Cases had invasive breast cancer recurrence (at local, regional, or distant site) according to the protocol definition. Matched controls had not recurred. Mutational analysis was performed with OncoCarta panel v1.0 using Mass Array System. The panel includes 19 genes belonging to different functional pathways as PI3K pathway, receptor tyrosine kinase, and cell cycle-metabolic group. Conditional logistic regression assessed the association of mutation status with breast cancer recurrence. Results: Mutation assessment was successful for 135 patients (49 cases, 86 controls). A total of 37 (27.4%) of the 135 patients had at least one mutation in the selected genes. PIK3CA was the most common mutated gene (18/135; 13.3%), followed by BRAF, KIT and PDGFRA (each 4/135, 3.0%) and AKT1 (3/135; 2.2%). TNBC patients with at least one mutation had increased odds of recurrence compared with those with wild-type tumors (odds ratio (OR) 2.28; 95% CI 0.88–5.92), though this difference was not statistically significant (p = 0.09). We found no evidence that these mutations were predictive for the value of maintenance metronomic chemotherapy. Conclusions: Mutations in the tested oncogenes were not associated with breast cancer recurrence in this TNBC subset of patients. The question of whether any of these mutated genes (e.g., PIK3CA) may represent a useful therapeutic target in TNBC may be answered by ongoing clinical trials and/or larger dataset analysis.

AB - Purpose: We investigated the occurrence and the prognostic and predictive relationship of a selected number of somatic mutations in triple-negative breast cancer (TNBC) patients having known clinical outcomes treated within the IBCSG Trial 22-00. Methods: A matched case–control sampling selected patients enrolled in the IBCSG Trial 22-00 who had TNBC tumors, based on local assessment. Cases had invasive breast cancer recurrence (at local, regional, or distant site) according to the protocol definition. Matched controls had not recurred. Mutational analysis was performed with OncoCarta panel v1.0 using Mass Array System. The panel includes 19 genes belonging to different functional pathways as PI3K pathway, receptor tyrosine kinase, and cell cycle-metabolic group. Conditional logistic regression assessed the association of mutation status with breast cancer recurrence. Results: Mutation assessment was successful for 135 patients (49 cases, 86 controls). A total of 37 (27.4%) of the 135 patients had at least one mutation in the selected genes. PIK3CA was the most common mutated gene (18/135; 13.3%), followed by BRAF, KIT and PDGFRA (each 4/135, 3.0%) and AKT1 (3/135; 2.2%). TNBC patients with at least one mutation had increased odds of recurrence compared with those with wild-type tumors (odds ratio (OR) 2.28; 95% CI 0.88–5.92), though this difference was not statistically significant (p = 0.09). We found no evidence that these mutations were predictive for the value of maintenance metronomic chemotherapy. Conclusions: Mutations in the tested oncogenes were not associated with breast cancer recurrence in this TNBC subset of patients. The question of whether any of these mutated genes (e.g., PIK3CA) may represent a useful therapeutic target in TNBC may be answered by ongoing clinical trials and/or larger dataset analysis.

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KW - Prognosis

KW - Somatic mutation

KW - Triple-negative breast cancer

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