Dataset Information

Intrinsic Subtype and Therapeutic Response Among HER2-Positive Breaty st Tumors from the NCCTG (Alliance) N9831 Trial.

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 from trastuzumab (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.

SUBMITTER: Perez EA

PROVIDER: S-EPMC5903647 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Publications

Intrinsic Subtype and Therapeutic Response Among HER2-Positive Breaty st Tumors from the NCCTG (Alliance) N9831 Trial.

Perez Edith A EA Ballman Karla V KV Mashadi-Hossein Afshin A Tenner Kathleen S KS Kachergus Jennifer M JM Norton Nadine N Necela Brian M BM Carr Jennifer M JM Ferree Sean S Perou Charles M CM Baehner Frederick F Cheang Maggie Chon U MC Thompson E Aubrey EA

Journal of the National Cancer Institute 20161028 2

<h4>Background</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 27794124

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Project description:Purpose: Recent trials have shown potential benefit of extended adjuvant endocrine therapy and relatively high risk of recurrence (RoR) after 5 years in hormone receptor-positive (HR+) human epidermal growth factor receptor 2-negative (HER2-) breast cancer. Although risk of late relapse in HR+ HER2- breast cancer is fairly well defined, the risk in HER2-positive (HER2+) breast cancer treated with adjuvant trastuzumab-based chemotherapy remains largely unknown.Methods: We included 3,177 patients with HER2+ breast cancer treated with adjuvant chemotherapy alone or with trastuzumab from the North Central Cancer Treatment Group N9831 (ClinicalTrials.gov identifier: NCT00005970) and National Surgical Adjuvant Breast and Bowel Project B-31 (ClinicalTrials.gov identifier: NCT00004067) trials.Results: Overall, HR+ breast cancer was significantly associated with improved recurrence-free survival (RFS) during the first 5 years (hazard ratio, 0.65; 95% CI, 0.56 to 0.77; P < .001). Among patients treated with trastuzumab, cumulative hazard for RFS was lower in patients with HR+ HER2+ breast cancer during the first 5 years (10.96% v 17.48%; hazard ratio, 0.60; 95% CI, 0.45 to 0.79; P < .001). However, there was no significant difference in RFS based on HR status during years 5 to 10 (hazard ratio, 1.32; 95% CI, 0.93 to 1.88; P = .12). A comparable degree of trastuzumab benefit was observed in HR+ and HR- breast cancers ( P for interaction = .87). Furthermore, we observed low RoR in years 5 to 10 among patients with HR+ HER2+ breast cancer: 3.23% in patients without lymph node involvement (N0) and 6.39% in patients with involvement of one to three lymph nodes (N1).Conclusion: The benefit of adjuvant trastuzumab persists for a long time. A distinct pattern of recurrence was observed between HR+ and HR- HER2+ disease but with similar degree of benefit from adjuvant trastuzumab. RoR in years 5 to 10 in HR+ HER2+ breast cancer is low, particularly in patients with N0 or N1 disease.

Dataset Information

Intrinsic Subtype and Therapeutic Response Among HER2-Positive Breaty st Tumors from the NCCTG (Alliance) N9831 Trial.

Background

Methods

Results

Conclusions

Publications

Intrinsic Subtype and Therapeutic Response Among HER2-Positive Breaty st Tumors from the NCCTG (Alliance) N9831 Trial.

Similar Datasets

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