Clinical outcomes based on multigene profiling in metastatic breast cancer patients

Reva K. Basho, Debora de Melo Gagliato, Naoto T. Ueno, Chetna Wathoo, Huiqin Chen, Maryam Shariati, Caimiao Wei, Ricardo H. Alvarez, Stacy L. Moulder, Aysegul A. Sahin, Sinchita Roy-Chowdhuri, Mariana Chavez-MacGregor, Jennifer K. Litton, Vincent Valero, Raja Luthra, Jia Zeng, Kenna R. Shaw, John Mendelsohn, Gordon Mills, Debu TripathyFunda Meric-Bernstam

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

BACKGROUND: Identifying the clinical impact of recurrent mutations can help define their role in cancer. Here, we identify frequent hotspot mutations in metastatic breast cancer (MBC) patients and associate them with clinical outcomes. PATIENTS AND METHODS: Hotspot mutation testing was conducted in 500 MBC patients using an 11 gene (N = 126) and/or 46 or 50 gene (N = 391) panel. Patients were stratified by hormone receptor (HR) and human epidermal growth factor 2 (HER2) status. Clinical outcomes were retrospectively collected. RESULTS: Hotspot mutations were most frequently detected in TP53 (30%), PIK3CA (27%) and AKT1 (4%). Triple-negative breast cancer (TNBC) patients had the highest incidence of TP53 (58%) and the lowest incidence of PIK3CA (9%) mutations. TP53 mutation was associated with shorter relapse-free survival (RFS) (median 22 vs 42months; P < 0.001) and overall survival (OS) from diagnosis of distant metastatic disease (median 26 vs 51months; P < 0.001). Conversely, PIK3CA mutation was associated with a trend towards better clinical outcomes including RFS (median 41 vs 30months; P = 0.074) and OS (52 vs 40months; P = 0.066). In HR-positive patients, TP53 mutation was again associated with shorter RFS (median 30 vs 46months; P = 0.017) and OS (median 30 vs 55months; P = 0.001). When multivariable analysis was performed for RFS and OS, TP53 but not PIK3CA mutation remained a significant predictor of outcomes in the overall cohort and in HR-positive patients. CONCLUSIONS: Clinical hotspot sequencing identifies potentially actionable mutations. In this cohort, TP53 mutation was associated with worse clinical outcomes, while PIK3CA mutation did not remain a significant predictor of outcomes after multivariable analysis.

Original languageEnglish (US)
Pages (from-to)76362-76373
Number of pages12
JournalOncotarget
Volume7
Issue number47
DOIs
StatePublished - Jan 1 2016
Externally publishedYes

Fingerprint

Breast Neoplasms
Mutation
Survival
Recurrence
Hormones
Triple Negative Breast Neoplasms
Incidence
Genes
Neoplasms

Keywords

  • Genomics
  • Metastatic breast cancer
  • PIK3CA
  • TP53

ASJC Scopus subject areas

  • Oncology

Cite this

Basho, R. K., Gagliato, D. D. M., Ueno, N. T., Wathoo, C., Chen, H., Shariati, M., ... Meric-Bernstam, F. (2016). Clinical outcomes based on multigene profiling in metastatic breast cancer patients. Oncotarget, 7(47), 76362-76373. https://doi.org/10.18632/oncotarget.12987

Clinical outcomes based on multigene profiling in metastatic breast cancer patients. / Basho, Reva K.; Gagliato, Debora de Melo; Ueno, Naoto T.; Wathoo, Chetna; Chen, Huiqin; Shariati, Maryam; Wei, Caimiao; Alvarez, Ricardo H.; Moulder, Stacy L.; Sahin, Aysegul A.; Roy-Chowdhuri, Sinchita; Chavez-MacGregor, Mariana; Litton, Jennifer K.; Valero, Vincent; Luthra, Raja; Zeng, Jia; Shaw, Kenna R.; Mendelsohn, John; Mills, Gordon; Tripathy, Debu; Meric-Bernstam, Funda.

In: Oncotarget, Vol. 7, No. 47, 01.01.2016, p. 76362-76373.

Research output: Contribution to journalArticle

Basho, RK, Gagliato, DDM, Ueno, NT, Wathoo, C, Chen, H, Shariati, M, Wei, C, Alvarez, RH, Moulder, SL, Sahin, AA, Roy-Chowdhuri, S, Chavez-MacGregor, M, Litton, JK, Valero, V, Luthra, R, Zeng, J, Shaw, KR, Mendelsohn, J, Mills, G, Tripathy, D & Meric-Bernstam, F 2016, 'Clinical outcomes based on multigene profiling in metastatic breast cancer patients', Oncotarget, vol. 7, no. 47, pp. 76362-76373. https://doi.org/10.18632/oncotarget.12987
Basho RK, Gagliato DDM, Ueno NT, Wathoo C, Chen H, Shariati M et al. Clinical outcomes based on multigene profiling in metastatic breast cancer patients. Oncotarget. 2016 Jan 1;7(47):76362-76373. https://doi.org/10.18632/oncotarget.12987
Basho, Reva K. ; Gagliato, Debora de Melo ; Ueno, Naoto T. ; Wathoo, Chetna ; Chen, Huiqin ; Shariati, Maryam ; Wei, Caimiao ; Alvarez, Ricardo H. ; Moulder, Stacy L. ; Sahin, Aysegul A. ; Roy-Chowdhuri, Sinchita ; Chavez-MacGregor, Mariana ; Litton, Jennifer K. ; Valero, Vincent ; Luthra, Raja ; Zeng, Jia ; Shaw, Kenna R. ; Mendelsohn, John ; Mills, Gordon ; Tripathy, Debu ; Meric-Bernstam, Funda. / Clinical outcomes based on multigene profiling in metastatic breast cancer patients. In: Oncotarget. 2016 ; Vol. 7, No. 47. pp. 76362-76373.
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AU - Gagliato, Debora de Melo

AU - Ueno, Naoto T.

AU - Wathoo, Chetna

AU - Chen, Huiqin

AU - Shariati, Maryam

AU - Wei, Caimiao

AU - Alvarez, Ricardo H.

AU - Moulder, Stacy L.

AU - Sahin, Aysegul A.

AU - Roy-Chowdhuri, Sinchita

AU - Chavez-MacGregor, Mariana

AU - Litton, Jennifer K.

AU - Valero, Vincent

AU - Luthra, Raja

AU - Zeng, Jia

AU - Shaw, Kenna R.

AU - Mendelsohn, John

AU - Mills, Gordon

AU - Tripathy, Debu

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N2 - BACKGROUND: Identifying the clinical impact of recurrent mutations can help define their role in cancer. Here, we identify frequent hotspot mutations in metastatic breast cancer (MBC) patients and associate them with clinical outcomes. PATIENTS AND METHODS: Hotspot mutation testing was conducted in 500 MBC patients using an 11 gene (N = 126) and/or 46 or 50 gene (N = 391) panel. Patients were stratified by hormone receptor (HR) and human epidermal growth factor 2 (HER2) status. Clinical outcomes were retrospectively collected. RESULTS: Hotspot mutations were most frequently detected in TP53 (30%), PIK3CA (27%) and AKT1 (4%). Triple-negative breast cancer (TNBC) patients had the highest incidence of TP53 (58%) and the lowest incidence of PIK3CA (9%) mutations. TP53 mutation was associated with shorter relapse-free survival (RFS) (median 22 vs 42months; P < 0.001) and overall survival (OS) from diagnosis of distant metastatic disease (median 26 vs 51months; P < 0.001). Conversely, PIK3CA mutation was associated with a trend towards better clinical outcomes including RFS (median 41 vs 30months; P = 0.074) and OS (52 vs 40months; P = 0.066). In HR-positive patients, TP53 mutation was again associated with shorter RFS (median 30 vs 46months; P = 0.017) and OS (median 30 vs 55months; P = 0.001). When multivariable analysis was performed for RFS and OS, TP53 but not PIK3CA mutation remained a significant predictor of outcomes in the overall cohort and in HR-positive patients. CONCLUSIONS: Clinical hotspot sequencing identifies potentially actionable mutations. In this cohort, TP53 mutation was associated with worse clinical outcomes, while PIK3CA mutation did not remain a significant predictor of outcomes after multivariable analysis.

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KW - Metastatic breast cancer

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