The importance of reporting discrete HER2 IHC scores

In this case, the patient presented with a primary breast cancer classified as HER2-negative. This was a referral case and the discrete HER2 IHC score was not reported from the outside institution. Following progression of the disease, the patient’s metastatic sample was found to be HER2 IHC 2+ (equivocal), with negative CISH, which also categorized the metastatic sample as HER2-negative. From primary to metastatic disease, the change in HER2 IHC score was unknown; the score may have changed from either IHC 0 to IHC 2+, or IHC 1+ to IHC 2+. This case highlights the importance of reporting discrete HER2 IHC scores, as opposed to binary HER2-positive or -negative results.

A biopsy and subsequent left breast lumpectomy were performed at an outside institution on a 58-year-old female, and she was found to have invasive ductal carcinoma with lobular features. After HER2 IHC evaluation, the tumor was reported to be HER2-negative with no subsequent reflex ISH testing. No discrete IHC score was provided in the referral report, and therefore, it was not possible to determine whether the sample was HER2 0 or 1+ by IHC. The patient was then treated with radiotherapy as well as hormone therapy; however, hormone therapy was stopped secondary to side effects.

Two years later, a PET/CT scan showed multiple enlarged left internal mammary lymph nodes with increased FDG avidity, suggestive of metastatic disease. A CT-guided biopsy of a left internal mammary node was performed. The biopsy identified metastatic carcinoma of the breast (positive CK7 and GATA3 by IHC). The tumor was scored as HER2 IHC 2+. FISH could not be performed due to insufficient sample. Chemotherapy was initiated.

Following treatment with chemotherapy, a CT-guided biopsy of the left chest wall again showed metastatic disease of breast origin (positive CK7 and GATA3 by IHC). HER2 IHC evaluation was performed and was scored as IHC 2+ with negative CISH.

The specimen from CT-guided biopsy of the left chest wall metastatic breast cancer (Figure 1) shows complete membrane staining of moderate intensity in >10% of tumor cells, and therefore, was scored as HER2 IHC 2+. CISH was performed and was negative (HER2/CEP17 ratio = 1.26, HER2 copy = 2.40, and CEP17 copy = 1.90).

The interpretation was made following the 2018 ASCO-CAP HER2 guidelines, which state that equivocal IHC (2+) is weak-to-moderate complete membrane staining in >10% of tumor cells, or complete/circumferential membrane staining that is intense in ≤10% of the invasive tumor cells.¹

A supporting visual guide for HER2 differentiation can help with HER2 IHC assessment in clinical practice. The guide can be found here.

In this case, although both primary and metastatic samples were HER2-negative, the difference in HER2 IHC score was unknown; the score may have changed from either IHC 0 to IHC 2+, or IHC 1+ to IHC 2+. This case highlights the importance of reporting discrete HER2 IHC scores as opposed to binary HER2-positive or -negative results. Reporting the discrete score provides a higher level of information, which is especially helpful to compare with if further testing occurs in a patient’s disease course.

As we now recognize the full spectrum of HER2 expression, providing discrete IHC scores in the pathology report is key to gaining a better overall understanding of a patient’s disease. Having detailed biomarker information at all stages of a patient’s journey with breast cancer may help to better inform clinical care and treatment decisions.

• HER2 IHC scores can differ between primary and metastatic samples. According to the 2023 ASCO-CAP guideline update, HER2 IHC testing should be repeated on metastatic specimens¹


• Include discrete HER2 IHC scores in the pathology report*

You can find more information on how to approach similar challenging cases in the e-learning series titled Interpreting HER2 in breast cancer: A full spectrum of possibilities, found in the Breast Tumors Resources.

*These practice considerations represent the opinions of the Breast Pathology Faculty. Members of the Breast Pathology Faculty have been contracted as paid advisors through Daiichi Sankyo and AstraZeneca and have received compensation for their time.