Transcriptomic stratification of breast carcinomas with double-equivocal HER2 status

Background

The evaluation of HER2 overexpression and amplification in breast cancer (BC) provides a validated predictor of response to anti-HER2 agents. However, the algorithm based on immunohistochemistry (IHC) and in situ hybridization (ISH) still identifies a category of carcinomas that remain equivocal after ISH testing (“double equivocal” carcinomas). These carcinomas represent a real challenge for oncologists, who have to face the dilemma “to treat or not to treat”. The ASCO/CAP guidelines stress the need for data defining their biology and clinical behavior. Our aim was to stratify double-equivocal BCs by using transcriptomics.

Methods

We retrieved a series of 28 formalin fixed paraffin embedded double-equivocal BCs, i.e. showing HER2/CEP17 ratio 

Results

All cases were estrogen receptor positive and 68% showed progesterone receptor expression in more than 20% of tumor cells. The large majority of double equivocal BCs were classified by Prosigna as pertaining to the Luminal B molecular subgroup (23/28, 82%); three cases (11%) were classified as Luminal A and two cases (7%) as HER2-enriched. These carcinomas frequently (23/28, 82%) showed a high risk of recurrence (ROR) even when the analysis was restricted to node negative BCs showing a tumor size

Conclusions

Double equivocal BCs preferentially pertain to the Luminal B rather than to the HER2-enriched molecular subgroup. Nevertheless, our data show that these luminal B carcinomas, even when node negative and of small tumor size, preferentially harbor a high risk of recurrence. This transcriptomic stratification may help in the treatment decision making of this controversial category of BC.

Clinical trial identification

Legal entity responsible for the study

University of Turin

Funding

Italian Association for Cancer Research

Disclosure

All authors have declared no conflicts of interest.