HER2-low breast cancer is associated with a lower likelihood of response to chemotherapy but an improved overall survival rate, especially for metastatic cases.

At the 2022 San Antonio Breast Cancer Symposium, Daniel Peiffer, MD, PhD, and colleagues discussed “Epidemiology and Prognosis of HER2-Low Breast Cancer (BC) in the National Cancer Data Base (NCDB),” their retrospective cohort study that included more than 1.19 million patients (including 394,937 HER2-0 and 796,452 HER2-low) in the NCDB who were diagnosed with invasive BC classified as HER2-negative from 2010 to 2019 who also had HER2 immunohistochemistry results available.

The study authors compared clinical characteristics and demographics of HER2-0 vs HER2-low (defined as immunohistochemistry score of 1+ or 2+) cases in the cohort.

To quantify the independent association of demographic and clinical factors with HER2-low status, the study authors used a logistic regression and reported odds ratios (OR) and 95% confidence intervals (CI).

The authors compared overall survival (OS) by receptor subtype and stage. In addition, in patients who received neoadjuvant chemotherapy (NAC), the authors used a logistic regression to determine whether pathological complete response (pCR) rate was different between HER2 0 and HER2-low patients.

Hispanic ethnicity was associated with a lower likelihood of HER2-low (OR 0.89, 95% CI 0.87-0.91), whereas Black patients had a slightly increased likelihood of HER2-low status (OR 1.06, 95% CI 1.04-1.08).

In multivariable survival analysis of TNBC patients, HER2-low breast cancer was associated with improved OS for stage 2 (hazard ratio [HR] 0.93, 95% CI 0.90-0.96), stage 3 (HR 0.92, 95% CI 0.88-0.96), and stage 4 (HR 0.92, 95% CI 0.87-0.97) cancer. “By contrast, survival analysis of hormone receptor-positive cancer showed that HER2-low BC was associated with improved OS only for stage 4 disease (HR 0.96, 95% CI 0.92-0.99),” the authors wrote.

In conclusion, HER2-low breast cancer is associated with a lower response to chemotherapy but has improved OS, especially in metastatic cases. Additionally, “There are racial/ethnic differences in the incidence of HER2-low BC, largely mediated by differences in rates of TNBC, and fewer Black and Hispanic patients will be candidates for therapies targeting low level HER2 expression,” the authors concluded.

Peiffer D, Howard F, Chen N, et al. Epidemiology and prognosis of HER2-low breast cancer (bc) in the National Cancer Data Base (NCDB). Presented at: 2022 San Antonio Breast Cancer Symposium. December 6-10, 2022. Poster HER2-11.