Elsevier

ESMO Open

Volume 7, Issue 4, August 2022, 100531
ESMO Open

Original Research
Characterization of the HER2 status in BRCA-mutated breast cancer: a single institutional series and systematic review with pooled analysis

https://doi.org/10.1016/j.esmoop.2022.100531Get rights and content
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open access

Highlights

  • Prevalence of HER2 positivity in BRCA1/2-mutated breast cancer is poorly described.

  • In our series we found a 7% HER2 positivity rate among all first BRCA1/2 BCs.

  • Following the systematic review, the pooled rate of BRCAmut/HER2-positive BCs is ∼9%.

  • Compared with BRCA1, prevalence of HER2 positivity among BRCA2 is higher.

  • More research is needed to better characterize this subgroup of patients.

Background

Pathogenic variants (PVs) in BRCA1/2 genes account for ∼6% of breast and 20% of ovarian cancers. Most breast tumors developed by BRCA1 carriers are triple negative. BRCA2 tumors have similar rates of estrogen receptor positivity as sporadic controls but are less likely to be human epidermal growth factor receptor 2 (HER2)-positive. Prevalence of HER2 positivity among breast cancers (BCs) in BRCA1/2 mutation carriers is poorly and variably described, ranging from 0% to 10% and 0% to 13% in BRCA1 and BRCA2 carriers, respectively.

Patients and methods

We assessed the prevalence of HER2 positivity among a single institutional cohort of 398 BCs developed in carriers of BRCA1/2 PVs (240 BRCA1, 158 BRCA2). Subsequently, a systematic review of the literature and pooled analysis was carried out.

Results

In our series we found a 7% HER2 positivity rate among all first BRCA1/2 BCs overall. In BRCA1 carriers, 5.4% of BCs were HER2-positive compared with 9.5% in BRCA2-mutated patients. Among bilateral BCs, HER2-positive cases were 15.2% in the BRCA1 group and 23.1% in the BRCA2 group. Notably, six BRCA1 and eight BRCA2 carriers showed discordant HER2 status between BC and bilateral BC (23.7%, 14/59). The systematic review included 21 083 BRCA1/2 patients from 73 eligible studies. The pooled rate of BRCAmut/HER2-positive BCs is 9.1% (95% confidence interval 7.3% to 11.2%). BRCA1 and BRCA2 when reported as separate data ranged from 0% to 33.3% (mean 8.3%) and from 0% to 86% (mean 10.3%), respectively.

Conclusions

As compared with sporadic cases, BCs occurring in BRCA1 and/or BRCA2 PVs carriers are less frequently HER2-positive. Prevalence of HER2 positivity in our series was consistent with pooled analysis and did not exceed 10%. Although not common, co-existence of BRCA mutations and HER2 overexpression and/or gene amplification should be acknowledged. More research is needed to better characterize this subgroup of patients who should not be excluded a priori from clinical trials of targeted therapy for BRCA1/2-driven cancers.

Key words

breast cancer
HER2-positive
BRCA1
BRCA2

Cited by (0)

These authors contributed equally to this work and should be considered co-first authors.

These authors contributed equally to this work and should be considered co-senior authors.