Highlights
- •We report the change of the hormone receptors (HRs) and HER2 in lobular breast cancer.
- •We describe the discordance in HR and HER2 between primary cancer and metastasis.
- •The majority of discordances regarded a reduced expression or loss of HR.
- •We observed a shift from luminal-like to triple-negative and to HER2-low cancers.
- •HR but not HER2-low changes have prognostic implications.
Abstract
Background
Invasive lobular carcinoma (ILC) has unique clinical-biological features. Phenotypical
differences between primary tumours (PTs) and metastases (M) have been described for
invasive ductal carcinoma, but data on ILC are limited.
Methods
We retrospectively analysed patients with recurrent ILC from our institution from
2013 to 2020. We evaluated the discordance of the oestrogen receptor (ER), progesterone
receptor (PgR) and HER2 between PT and M, to understand prognostic and therapeutic
implications.
Results
Thirteen percent (n = 91) of all patients had ILC. We observed 15%, 44% and 5% of
ER, PgR and HER2 status discordance between PT and M. ER/PgR discordance was related
to receptor loss and HER2 mainly due to gain. PT presented a luminal-like phenotype
(93%); 6% and 1% were triple-negative (TNBC) and HER2-positive. In M, there was an
increase in TNBC (16%) and HER2-positive (5%). Metastasis-free survival and overall
survival (OS) were different according to clinical phenotype, with poorer prognosis
for HER2+ and TNBC (p < 0.001); OS after metastatic progression did not differ across
phenotypes (p = 0.079). In luminal-like ILC (n = 85) at diagnosis, we found that OS
after relapse was poorer in patients experiencing a phenotype switch to TNBC but improved
in patients with HER2 gain (p = 0.0028). Poorer survival was reported in patients
with a PgR and/or ER expression loss of ≥25%. There was HER2-low enrichment in M1
(from 37% to 58%): this change was not associated with OS (p > 0.05).
Conclusion
Our results suggest that phenotype switch after metastatic progression may be associated
with patients’ outcomes. Tumour biopsy in recurrent ILC could drive treatment decision-making,
with prognostic implications.
Keywords
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Article info
Publication history
Published online: March 07, 2023
Accepted:
February 27,
2023
Received in revised form:
February 24,
2023
Received:
January 10,
2023
Publication stage
In Press Uncorrected ProofIdentification
Copyright
© 2023 Elsevier Ltd. All rights reserved.
