The more HER-2 genes a breast cancer cell has, the more HER-2 protein that cell will produce and the faster the cancer will grow. If a breast cancer patient is diagnosed with a positive HER-2 status, they typically will receive a targeted treatment such as Herceptin or Tykerb.1

However, even after treatment begins, HER-2 status remains an important top-of-mind matter. Research has shown that HER-2 status is not necessarily stable. During treatment HER-2 status can change from negative to positive2 and similarly from positive to negative3.

In one such example, researchers describe a single case study of a woman who was initially diagnosed as HER-2 negativeand treated as such. After initial chemotherapy, she underwent a subsequent mastectomy and was found to have developed a positive HER-2 status. Clinicians suggest that, when secondary biopsies are taken in cases of relapse or metastasis, the HER-2 status is rechecked in case it has changed.

In another instance, presented at the 2010 American Society of Clinical Oncology (ASCO) annual meeting, researchers showed that HER-2 status could change from positive to negative. More specifically, they showed that HER-2 status changes in about 15% of patients. This is clinically significant due to the targeted nature of the treatment used for HER-2 positive breast cancers. A change in a patient’s status, from positive to negative, renders this treatment ineffective in that patient. This tumor instability is seen between primary diagnosis and relapse as well as through tumor progression, posing a challenge in clinical decision-making and highlighting the importance of consecutive biopsies.

One possible explanation for a change in HER-2 status is tumor heterogeneity. Although a tumor may appear as singular mass, it is typically heterogeneous in nature. In other words, it is probably not a mass of identical cells but rather a mixture of different cells driven by different mutations. For example, an initial biopsy may collect cells that are HER-2 positive, and treatment with a targeted therapy would destroy these HER-2 positive cells. But the cancer may continue to grow, in which case a second biopsy might reveal HER-2 negative cells that were unaffected by the initial targeted treatment.

Related:  Monitoring Serum HER2 for Breast Cancer Prognosis

So what does all of this mean in practical terms? At least 20% of women with breast cancer will develop metastatic disease4. Disease can also continue to grow throughout treatment. Therefore, patients diagnosed with breast cancer, regardless of initial HER-2 status, should be retested and regularly monitored.

  1. Breast (2015) “HER2 Status”. Accessed at:
  1. Sivarajan, L. et al. (2011) “Change in HER-2/neu Status from Negative to Positive following Treatment in Breast Cancer: A Case Report”, Case Reports in Oncology, 4 (pp. 19-24)
  1. Lindström, L.S. et al. (2012) “Clinically used breast cancer markers such as estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 are unstable throughout tumor progression”, Journal of Clinical Oncology, 30(21) (pp. 2601-2608)
  1. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) (2011) “Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: Patient-level meta-analysis of randomised trials”, Lancet, 378 (pp. 771–784)