Intrinsic subtype and therapeutic response among HER2-positive breast tumors from the NCCTG (Alliance) N9831 trial

Edith A. Perez, Karla V. Ballman, Afshin Mashadi-Hossein, Kathleen S. Tenner, Jennifer M. Kachergus, Nadine Norton, Brian M. Necela, Jennifer M. Carr, Sean Ferree, Charles M. Perou, Frederick Baehner, Maggie Chon U. Cheang, E Aubrey Thompson

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Abstract

Background: Genomic data from human epidermal growth factor receptor 2-positive (HER2+) tumors were analyzed to assess the association between intrinsic subtype and clinical outcome in a large, well-annotated patient cohort. Methods: Samples from the NCCTG (Alliance) N9831 trial were analyzed using the Prosigna algorithm on the NanoString platform to define intrinsic subtype, risk of recurrence scores, and risk categories for 1392 HER2+ tumors. Subtypes were evaluated for recurrence-free survival (RFS) using Kaplan-Meier and Cox model analysis following adjuvant chemotherapy (n=484) or chemotherapy plus trastuzumab (n=908). All statistical tests were two-sided. Results: Patients with HER2+ tumors from N9831 were primarily scored as HER2-enriched (72.1%). These individuals received statistically significant benefit fromtrastuzumab (hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.52 to 0.89, P = .005), as did the patients (291 of 1392) with luminal-type tumors (HR=0.52, 95% CI=0.32 to 0.85, P = .01). Patients with basal-like tumors (97 of 1392) did not have statistically significantly better RFS when treated with trastuzumab and chemotherapy compared with chemotherapy alone (HR=1.06, 95% CI=0.53 to 2.13, P = .87). Conclusions: The majority of clinically defined HER2-positive tumors were classified as HER2-enriched or luminal using the Prosigna algorithm. Intrinsic subtype alone cannot replace conventional histopathological evaluation of HER2 status because many tumors that are classified as luminal A or luminal B will benefit from adjuvant trastuzumab if that subtype is accompanied by HER2 overexpression. However, among tumors that overexpress HER2, we speculate that assessment of intrinsic subtype may influence treatment, particularly with respect to evaluating alternative therapeutic approaches for that subset of HER2-positive tumors of the basal-like subtype.

Original languageEnglish (US)
JournalJournal of the National Cancer Institute
Volume109
Issue number2
DOIs
StatePublished - 2017

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Breast Neoplasms
Neoplasms
Therapeutics
Confidence Intervals
Recurrence
Drug Therapy
Survival
Adjuvant Chemotherapy
Proportional Hazards Models
Trastuzumab

ASJC Scopus subject areas

  • Medicine(all)
  • Oncology
  • Cancer Research

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Intrinsic subtype and therapeutic response among HER2-positive breast tumors from the NCCTG (Alliance) N9831 trial. / Perez, Edith A.; Ballman, Karla V.; Mashadi-Hossein, Afshin; Tenner, Kathleen S.; Kachergus, Jennifer M.; Norton, Nadine; Necela, Brian M.; Carr, Jennifer M.; Ferree, Sean; Perou, Charles M.; Baehner, Frederick; Cheang, Maggie Chon U.; Thompson, E Aubrey.

In: Journal of the National Cancer Institute, Vol. 109, No. 2, 2017.

Research output: Contribution to journalArticle

Perez, EA, Ballman, KV, Mashadi-Hossein, A, Tenner, KS, Kachergus, JM, Norton, N, Necela, BM, Carr, JM, Ferree, S, Perou, CM, Baehner, F, Cheang, MCU & Thompson, EA 2017, 'Intrinsic subtype and therapeutic response among HER2-positive breast tumors from the NCCTG (Alliance) N9831 trial', Journal of the National Cancer Institute, vol. 109, no. 2. https://doi.org/10.1093/jnci/djw207
Perez, Edith A. ; Ballman, Karla V. ; Mashadi-Hossein, Afshin ; Tenner, Kathleen S. ; Kachergus, Jennifer M. ; Norton, Nadine ; Necela, Brian M. ; Carr, Jennifer M. ; Ferree, Sean ; Perou, Charles M. ; Baehner, Frederick ; Cheang, Maggie Chon U. ; Thompson, E Aubrey. / Intrinsic subtype and therapeutic response among HER2-positive breast tumors from the NCCTG (Alliance) N9831 trial. In: Journal of the National Cancer Institute. 2017 ; Vol. 109, No. 2.
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abstract = "Background: Genomic data from human epidermal growth factor receptor 2-positive (HER2+) tumors were analyzed to assess the association between intrinsic subtype and clinical outcome in a large, well-annotated patient cohort. Methods: Samples from the NCCTG (Alliance) N9831 trial were analyzed using the Prosigna algorithm on the NanoString platform to define intrinsic subtype, risk of recurrence scores, and risk categories for 1392 HER2+ tumors. Subtypes were evaluated for recurrence-free survival (RFS) using Kaplan-Meier and Cox model analysis following adjuvant chemotherapy (n=484) or chemotherapy plus trastuzumab (n=908). All statistical tests were two-sided. Results: Patients with HER2+ tumors from N9831 were primarily scored as HER2-enriched (72.1{\%}). These individuals received statistically significant benefit fromtrastuzumab (hazard ratio [HR] = 0.68, 95{\%} confidence interval [CI] = 0.52 to 0.89, P = .005), as did the patients (291 of 1392) with luminal-type tumors (HR=0.52, 95{\%} CI=0.32 to 0.85, P = .01). Patients with basal-like tumors (97 of 1392) did not have statistically significantly better RFS when treated with trastuzumab and chemotherapy compared with chemotherapy alone (HR=1.06, 95{\%} CI=0.53 to 2.13, P = .87). Conclusions: The majority of clinically defined HER2-positive tumors were classified as HER2-enriched or luminal using the Prosigna algorithm. Intrinsic subtype alone cannot replace conventional histopathological evaluation of HER2 status because many tumors that are classified as luminal A or luminal B will benefit from adjuvant trastuzumab if that subtype is accompanied by HER2 overexpression. However, among tumors that overexpress HER2, we speculate that assessment of intrinsic subtype may influence treatment, particularly with respect to evaluating alternative therapeutic approaches for that subset of HER2-positive tumors of the basal-like subtype.",
author = "Perez, {Edith A.} and Ballman, {Karla V.} and Afshin Mashadi-Hossein and Tenner, {Kathleen S.} and Kachergus, {Jennifer M.} and Nadine Norton and Necela, {Brian M.} and Carr, {Jennifer M.} and Sean Ferree and Perou, {Charles M.} and Frederick Baehner and Cheang, {Maggie Chon U.} and Thompson, {E Aubrey}",
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T1 - Intrinsic subtype and therapeutic response among HER2-positive breast tumors from the NCCTG (Alliance) N9831 trial

AU - Perez, Edith A.

AU - Ballman, Karla V.

AU - Mashadi-Hossein, Afshin

AU - Tenner, Kathleen S.

AU - Kachergus, Jennifer M.

AU - Norton, Nadine

AU - Necela, Brian M.

AU - Carr, Jennifer M.

AU - Ferree, Sean

AU - Perou, Charles M.

AU - Baehner, Frederick

AU - Cheang, Maggie Chon U.

AU - Thompson, E Aubrey

PY - 2017

Y1 - 2017

N2 - Background: Genomic data from human epidermal growth factor receptor 2-positive (HER2+) tumors were analyzed to assess the association between intrinsic subtype and clinical outcome in a large, well-annotated patient cohort. Methods: Samples from the NCCTG (Alliance) N9831 trial were analyzed using the Prosigna algorithm on the NanoString platform to define intrinsic subtype, risk of recurrence scores, and risk categories for 1392 HER2+ tumors. Subtypes were evaluated for recurrence-free survival (RFS) using Kaplan-Meier and Cox model analysis following adjuvant chemotherapy (n=484) or chemotherapy plus trastuzumab (n=908). All statistical tests were two-sided. Results: Patients with HER2+ tumors from N9831 were primarily scored as HER2-enriched (72.1%). These individuals received statistically significant benefit fromtrastuzumab (hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.52 to 0.89, P = .005), as did the patients (291 of 1392) with luminal-type tumors (HR=0.52, 95% CI=0.32 to 0.85, P = .01). Patients with basal-like tumors (97 of 1392) did not have statistically significantly better RFS when treated with trastuzumab and chemotherapy compared with chemotherapy alone (HR=1.06, 95% CI=0.53 to 2.13, P = .87). Conclusions: The majority of clinically defined HER2-positive tumors were classified as HER2-enriched or luminal using the Prosigna algorithm. Intrinsic subtype alone cannot replace conventional histopathological evaluation of HER2 status because many tumors that are classified as luminal A or luminal B will benefit from adjuvant trastuzumab if that subtype is accompanied by HER2 overexpression. However, among tumors that overexpress HER2, we speculate that assessment of intrinsic subtype may influence treatment, particularly with respect to evaluating alternative therapeutic approaches for that subset of HER2-positive tumors of the basal-like subtype.

AB - Background: Genomic data from human epidermal growth factor receptor 2-positive (HER2+) tumors were analyzed to assess the association between intrinsic subtype and clinical outcome in a large, well-annotated patient cohort. Methods: Samples from the NCCTG (Alliance) N9831 trial were analyzed using the Prosigna algorithm on the NanoString platform to define intrinsic subtype, risk of recurrence scores, and risk categories for 1392 HER2+ tumors. Subtypes were evaluated for recurrence-free survival (RFS) using Kaplan-Meier and Cox model analysis following adjuvant chemotherapy (n=484) or chemotherapy plus trastuzumab (n=908). All statistical tests were two-sided. Results: Patients with HER2+ tumors from N9831 were primarily scored as HER2-enriched (72.1%). These individuals received statistically significant benefit fromtrastuzumab (hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.52 to 0.89, P = .005), as did the patients (291 of 1392) with luminal-type tumors (HR=0.52, 95% CI=0.32 to 0.85, P = .01). Patients with basal-like tumors (97 of 1392) did not have statistically significantly better RFS when treated with trastuzumab and chemotherapy compared with chemotherapy alone (HR=1.06, 95% CI=0.53 to 2.13, P = .87). Conclusions: The majority of clinically defined HER2-positive tumors were classified as HER2-enriched or luminal using the Prosigna algorithm. Intrinsic subtype alone cannot replace conventional histopathological evaluation of HER2 status because many tumors that are classified as luminal A or luminal B will benefit from adjuvant trastuzumab if that subtype is accompanied by HER2 overexpression. However, among tumors that overexpress HER2, we speculate that assessment of intrinsic subtype may influence treatment, particularly with respect to evaluating alternative therapeutic approaches for that subset of HER2-positive tumors of the basal-like subtype.

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