Data and metadata supporting the article: Clinical, pathological and PAM50 gene expression features of HER2-low breast cancer

Due to the recent and increased interest
in the HER2-low group, there is an urgent need to better understand its
clinicopathological and molecular features. Thus, the authors of the current study,
decided to collect clinicopathological and PAM50 gene expression data from
multiple datasets of HER2-negative disease and compare many features between
HER2-low and HER2 0. Analyses were focused on the overall population and
according to hormone receptor (HR) status and HER2 immunohistochemistry (IHC)
expression.

Data description and data access: This study involved the collection and analysis of clinicopathological and
PAM50 gene expression data from multiple publicly available datasets. The following
cBioPortal datasets were used: https://identifiers.org/cbioportal:breast_msk_2018,
https://identifiers.org/cbioportal:bfn_duke_nus_2015,
https://identifiers.org/cbioportal:brca_mskcc_2019,
https://identifiers.org/cbioportal:brca_bccrc_xenograft_2014,
https://identifiers.org/cbioportal:brca_bccrc,
https://identifiers.org/cbioportal:brca_broad,
https://identifiers.org/cbioportal:brca_sanger,
https://identifiers.org/cbioportal:brca_tcga,
https://identifiers.org/cbioportal:brca_igr_2015,
https://identifiers.org/cbioportal:brca_metabric,
https://identifiers.org/cbioportal:brca_mbcproject_wagle_2017
and https://identifiers.org/cbioportal:acbc_mskcc_2015.
Data from the internal studies of the Hospital Clinic of Barcelona, and patient data
from the SOLTI and GEICAM trials included in this study, are not publicly
available to protect patient privacy, but will be made available on reasonable
request from the corresponding author. Corresponding author details: Prof.
Aleix Prat, Translational Genomic and Targeted Therapeutics in Solid Tumors,
August Pi i Sunyer Biomedical Research Institute (IDIBAPS) and Department of Medical
Oncology, Hospital Clinic, Carrer de Villarroel, 170, 08036, Barcelona, Spain.
Email: [e-mail]. The data file
Database for genomic analyses.xlsx, is publicly available in the figshare
repository, as part of this data record. The aforementioned anonymised file
contains all PAM50 normalised gene expression data used for the genomic
analyses of this study. In the data file, patients were also categorised
according to hormone receptor status, HER2-low status, HER2 immunohistochemical
status and PAM50 intrinsic subtype. The complete version of the data file used
and/or analyzed during the current study, Db complete 31_08_2020.xlsx, is available
upon reasonable request from the corresponding author, as described above.

Study approval: All studies from which
patient data were used had received proper ethical approval.

Study aims and methodology: Novel antibody-drug conjugates against HER2 are showing high activity
in HER2-negative breast cancer (BC) with low HER2 expression (i.e. 1+ or 2+ and
lack of ERBB2 amplification). However, the clinical and molecular
features of HER2-low BC are yet to be elucidated. To better understand the
clinicopathological and molecular features of HER2-low breast cancer, and to
emphasize the need to implement reproducible and sensitive assays to measure
low HER2 expression, the authors collected retrospective clinicopathological
and PAM50 data from 3,689 patients with HER2-negative disease.

All
non-overlapping publicly available breast datasets (i.e. 12 studies and 6,477
patients) were interrogated from the cBio Cancer Genomics Portal
(http://cbioportal.org). From these databases, HER2-negative tumors with known
IHC and HER2 amplification status were extracted. Other patients were extracted
from internal databases from the Hospital Clinic (Barcelona, Spain), from two
SOLTI clinical trials (SOLTI 1501-VENTANA and SOLTI 1402-CORALEEN), from the Spanish
Cancer Research Group (GEICAM)/CIBOMA study and from a previously published collaboration
between Hospital Clinic (Barcelona, Spain), Hospital Vall d’Hebron (Barcelona,
Spain), University Campus Bio-Medico (Roma, Italy) and GEICAM.

Patients
were included if they were HER2-negative with known IHC and HER2 amplification
status and if they had at least one of the following information available: 1)
clinicopathological features, 2) PAM50 gene expression data and 3) PAM50
intrinsic subtype identified. The following clinical pathological features were
evaluated, when available: Ki67 IHC, histological grade, estrogen receptor and
progesterone receptor status, age at diagnosis, menopausal status, tumor sample
origin (primary versus metastatic), histological subtype and TILs.

IHC-based classification, PAM50 subtypes and gene expression data and
statistical analysis, are described in more detail in the published article.