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. 2019 Nov 6;14(11):e0224726.
doi: 10.1371/journal.pone.0224726. eCollection 2019.

Mutation and immune profiling of metaplastic breast cancer: Correlation with survival

Michelle Afkhami  1 , Daniel Schmolze  1 , Susan E Yost  2 , Paul H Frankel  3 , Andrew Dagis  3 , Idoroenyi U Amanam  2 , Milhan Telatar  1 , Kim Nguyen  1 , Kim Wai Yu  4 , Thehang Luu  2 , Raju Pillai  1 , Patricia A Aoun  1 , Joanne Mortimer  2 , Yuan Yuan  2
Affiliations

Mutation and immune profiling of metaplastic breast cancer: Correlation with survival

Michelle Afkhami et al. PLoS One. .

Abstract

The goal of this study is to characterize the genomic and immune profiles of metaplastic breast cancer (MpBC) and identify the association with survival through an analysis of archived tumor tissue. A next-generation sequencing-based mutational assay (Onco-48) was performed for 21 MpBC patients. Clinicopathologic characteristics were captured, including relapse free survival (RFS) and overall survival (OS). Immunohistochemistry (IHC) for CD3, CD4, CD8, and programmed death-ligand 1 (PD-L1) was also performed. Recurrence free survival (RFS) at 5 years was 57% (95% CI 0.34-0.75) and overall survival (OS) at 5 years was 66% (95% CI 0.41-0.82). The most commonly altered genes were TP53 (68.4%, 13/19), PIK3CA (42.1%, 8/19), and PTEN (15.8%, 3/19. For patients with PIK3CA mutations, RFS and OS were significantly worse than for those without (HR 5.6, 95% CI 1.33-23.1 and HR 8.0, 95% CI 1.53-41.7, respectively). Cox regression estimated that PD-L1 expression was associated with worse RFS and OS (HR 1.08, 95% CI 1.01-1.16 and HR 1.05, 95% CI 1.00-1.11, respectively, for an absolute increase in PD-L1 expression of 1%). In conclusion, PIK3CA mutation and PD-L1 expression confer poor prognosis in this cohort of patients with MpBC.

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Conflict of interest statement

YY has contracted clinical trials and research projects sponsored by Merck, Eisai, Novartis, Genentech, and Pfizer, independent of the study presented in this manuscript. There are no patents, products in development or marketed products associated with this research to declare. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials. The other authors declare that they have no competing interests.

Figures

Fig 1
Fig 1. The most frequently altered genes in MpBC.
Alterations include substitutions, amplifications, and deletions in MpBC patient cohort (n = 19).
Fig 2
Fig 2. Kaplan Meier survival analysis for MpBC patients.
A) RFS for patients with PIK3CA mutation (red) vs. no mutation (blue) (p = 0.009); B) OS for patients with PIK3CA mutation (red) vs. no mutation (blue) (p = 0.004).
Fig 3
Fig 3. Representative IHC stain of CD3, CD4, CD8 and PD-L1.
(A) H&E stained image of representative metaplastic carcinoma (spindle cell subtype) (original magnification 40X). (B) CD3 immunostain, highlighting T cells (original magnification 40X). (C) Combined CD8 (brown chromogen) and CD4 (red chromogen) immunostain (original magnification 40X). (D) PD-L1 immunostain (original magnification 40X).
Fig 4
Fig 4. Photomicrographs of lung biopsy demonstrating metastatic MpBC with squamous differentiation invading lung parenchyma.
(A) Hematoxylin-eosin staining (original magnification 4X), (B) Hematoxylin-eosin staining (original magnification 20X), (C) IHC showing tumor cells are positive for GCDFP-15 (original magnification 20X), and (D) IHC showing tumor cells are negative for TTF-1 (original magnification 20X), consistent with MpBC. MpBC, metaplastic breast cancer; IHC, immunohistochemistry; GCDFP-15, gross cystic disease fluid protein 15; TTF-1, thyroid transcription factor-1.
Fig 5
Fig 5. Treatment response by PET-CT.
(A) Baseline imaging demonstrating pulmonary metastases (February 2015); (B) Imaging after 2 months of treatment with everolimus, demonstrating tumor regression (April 2015); (C, D) Persistent responses; (E, F) Disease progression.
See this image and copyright information in PMC

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