There are “minimal prognostic differences” between HER2-low breast cancer and HER2-negative breast cancer, according to researchers. They reported these findings in JAMA Oncology.

The researchers did find differences in pathologic complete response (pCR) rates and overall survival (OS) between patients with HER2-low disease and those with HER2-negative disease. However, the differences between the groups were small, likely mediated by other factors, and of questionable clinical relevance, according to the researchers.

“HER2-low breast cancer does not appear to be a biologically distinct group,” said study author Frederick M. Howard, MD, of the University of Chicago in Illinois.

Continue Reading

Dr Howard and colleagues evaluated data from 1,136,016 patients in the National Cancer Database who were diagnosed with invasive breast cancer between 2010 and 2019. A majority of patients (65.5%) had HER2-low disease, and 34.5% had HER2-negative disease.

Of the patients who received neoadjuvant chemotherapy, 99,783 were evaluable for pCR. The pCR rate was 23.6% in the HER2-negative group and 16.3% in the HER2-low group.

In a multivariable analysis, HER2-low status was associated with a slightly lower likelihood of pCR (adjusted odds ratio [aOR], 0.89; 95% CI, 0.86-0.92; P <.001). The effect size was similar when patients were divided into HER2 1+ (aOR, 0.89; 95% CI, 0.85-0.92; P <.001) and HER2 2+ groups (aOR, 0.89; 95% CI, 0.84-0.93; P <.001).

The researchers also found similar results when they looked only at patients with triple-negative breast cancer (TNBC; aOR, 0.89; 95% CI, 0.85-0.93; P <.001) or hormone receptor-positive disease (aOR, 0.92; 95% CI, 0.86-0.98; P =.008).

HER2-low status was also associated with small improvements in OS. In a multivariable analysis of 987,934 evaluable patients, HER2-low status was positively associated with OS (adjusted hazard ratio [aHR], 0.98; 95% CI, 0.97-0.99; P <.001).

The association between HER2-low status and OS was stronger for patients with stage III TNBC (aHR, 0.92; 95% CI, 0.89-0.96; P <.001) or stage IV TNBC (aHR, 0.91; 95% CI, 0.87-0.96; P <.001). However, the improvements in 5-year OS were small — 2.0% for stage III TNBC and 0.4% for stage IV TNBC.

“There were some slightly higher trends toward improved prognosis in patients with HER2-low breast cancer, particularly in more advanced stage disease and in those with triple-negative disease, but these differences were still fairly small in magnitude,” Dr Howard said.

“I think it’s likely that these small associations we’re seeing with survival and pCR are not due to the fact that these cancers are HER2-low but are due to the fact that these cancers are more likely to have a hormone receptor-positive luminal biology, or more likely to be luminal androgen receptor-positive, or due to other reasons and not solely due to the low level of HER2 expression on the cancer cell surface,” he added. “I think more study is needed on larger scales to determine how much of the difference in prognosis and pCR seen with HER2-low breast cancer is mediated by some of these other factors.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Peiffer DS, Zhao F, Chen N, et al. Clinicopathologic characteristics and prognosis of ERBB2-low breast cancer among patients in the National Cancer Database. JAMA Oncol. Published online February 23, 2023. doi:10.1001/jamaoncol.2022.7476