Characteristics, Clinical Differences and Outcomes of Breast Cancer Patients with Negative or Low HER2 Expression

High expression of HER2 receptor in Immunohistochemistry (IHC) sections or amplification of its gene in In Situ Hybridization (ISH) assays define a subset of breast cancers that have an aggressive natural history but respond to treatments blocking HER2. In contrast, patients with lower HER2 expression, not meeting the criteria for clinical positivity, are currently treated similarly to completely HER2 negative patients. However, emerging data suggest that patients with low HER2 expression may benefit from newer, more potent antibody-drug conjugates. Thus, this investigation sought to clarify the characteristics of HER2 low expressors and compare them with patients with no HER2 expression.

We undertook a retrospective analysis of all breast cancer patients seen in our cancer center over a 6-year period and been classified as HER2 negative. Patients were categorized as HER2 negative when they had a score of 0 in IHC and as HER2 low if they had a score of 1 + or 2 + in IHC and no amplification by ISH. Characteristics of the patients and tumors in the 2 groups were compared.

A total of 391 HER2 negative and low patients have been included. Among them, 130 patients (33.2%) were HER2 negative (score 0 by IHC) and 261 patients (66.8%) were HER2 low (score 1 + and 2 + by IHC/ ISH non-amplified). There were no differences in age, menopause status, mode of detection of cancer (clinical or screening) and clinical stage at diagnosis between the 2 groups. Patients in the HER2 low group had less commonly high-grade cancers than HER2 negative patients (25.35 vs. 34.6%, x²P = .04). In addition, The HER2 low group had higher ER Histoscore (> 240) in 88.1% of cases compared with 69.2% in the HER2 negative group (x²P < .000). Similarly, a higher percentage of HER2 low cases than HER2 negative ones expressed the progesterone receptor (PR, x²P < .000). HER2 low patients were rarely (3.8%) classified as triple negative, while this percentage was 21.5% in HER2 negative patients. The Overall Survival (OS) of patients with HER2 low cancers was longer than the OS of their HER2 negative counterparts (LogRank P =.001).

HER2 negative staining (IHC score 0) is associated with adverse tumor characteristics compared with clinically HER2 negative patients with low HER2 expression (score 1 + and 2 +/ ISH non-amplified).