HER2 borderline is a negative prognostic factor for primary malignant breast cancer



HER-(human epidermal growth factor receptor 2) gene amplification and protein overexpression are important predictive, prognosis markers, and therapeutic target for breast cancer, emphasizing the importance of categorizing patients into HER2 positive and negative. However, from immunohistochemistry scores, 2% patients are neither HER2 + nor -ve, but borderline called HER2B. To make informed treatment decisions of these patients, it is important to know how different this group is compared to HER-2 positive/negative.


We analyzed n = 104,668 breast cancer patient samples from Surveillance, Epidemiology, and End Results (SEER) database. Survival analysis was performed using open source R (Cran project R version 3.5.0) “survival” package. Hazard ratio with confidence intervals was computed using coxph function.


Of n = 104,668, 2239 (2.13%) patients were HER2 borderline, 87,157 (83.26%) HER2-negative, and 15,272 (14.6%) HER2-positive. The breast cancer as primary malignancy was observed in 84,944 (81.16%) patients. In primary malignant breast cancer (PMBC) patients, the hazard ratio among HER2-negative patients was significantly higher than HER2-positive patient samples (HR = 0.772, 95% CI 0.715–0.833, p =  < .001), whereas HER2 negative status was not significantly favorable in PMBC negative patients in HER2-positive (HR = .919, 95% 0.797–1.06, p = .248). Most importantly in PMBC patients, the HR for HER2-borderline was poor in comparison to HER2 negative (HR = 1.354, 95% CI 1.126–1.627, p =  < .001).


This is the first report with large cohort of patient samples and significant statistical power to demonstrate that HER2 borderline represents a negative prognostic factor for PMBC. Thus providing rationale for controlled clinical trial for HER2-targeted therapies in HER2-borderline patients.

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Correspondence to Shilpee Dutt.

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Atanu Bhattacharjee declares that he has no conflict of interest. Jacinth Rajendra declares that she has no conflict of interest. Rakesh Dikshit declares that he has no conflict of interest. Shilpee Dutt declares that she has no conflict of interest.

Ethical approval

No formal approval of IRB is required as data were collected from a source that was publicly available (SEER database) and did not contain unique patient identifiers.

Human and animal studies

This article does not contain any studies with animals performed by any of the authors.

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Given that these data from SEER database are de-identified and ethics approval is waived, the study did not require informed consent.

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Bhattacharjee, A., Rajendra, J., Dikshit, R. et al. HER2 borderline is a negative prognostic factor for primary malignant breast cancer. Breast Cancer Res Treat 181, 225–231 (2020). https://doi.org/10.1007/s10549-020-05608-3

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  • Primary malignancy breast cancer
  • HER-2 borderline
  • SEER