Are There More HER2 FISH in the Sea? An Institution’s Experience in Identifying HER2 Positivity Using Fluorescent In Situ Hybridization in Patients with HER2 Negative Immunohistochemistry

Sep 24, 2026

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Study evaluates true HER2-positive rates in invasive breast cancer under an institutional workflow performing both HER2 immunohistochemistry (IHC) and reflex fluorescent in situ hybridization (FISH) for all cases. Using a retrospective chart review from 2015–2021, investigators quantified HER2 positivity and examined patient and tumor characteristics. Among 1835 cases, 289 were HER2 positive by IHC and FISH (15.7%), and an additional 38 initially IHC-negative tumors were reclassified as HER2 positive after reflex FISH, increasing total positivity to 327 (17.8%).

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages6

Reading Time15 min

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Background

Patients and Methods

Results

Conclusions

Keywords

Ann Surg Oncol (2024) 31:376–381 [https://doi.org/10.1245/s10434-023-14439-7](https://doi.org/10.1245/s10434-023-14439-7) ORIGINAL ARTICLE – BREAST ONCOLOGY Are There More HER2 FISH in the Sea? An Institution’s Experience in Identifying HER2 Positivity Using Fluorescent In Situ Hybridization in Patients with HER2 Negative Immunohistochemistry Camille Suydam, MD1, Fairouz Chibane, MD, MBA2, Nicole Brown, MD2, Madeleine Schlafly, BS2, Alicia H. Arnold, DO2, Intisar Ghleilib, MD3, Melissa Easley, MD2, and Joseph White, DO3 1Department of Surgery, Eisenhower Army Medical Center, Fort Gordon, GA; 2Department of Surgery, Medical College of Georgia at Augusta Health, Augusta, GA; 3Department of Pathology, Medical College of Georgia at Augusta Health, Augusta, GA ABSTRACT Background. Approximately 20% of breast cancers express HER2-positive receptors in the USA. HER2 receptor immunohistochemistry (IHC) staining with equivocal (2+) results commonly undergoes fluorescence in-situ hybridization (FISH) for further classification. Current guidelines do not recommend routine FISH testing in IHC-negative (0 or 1+) cases. This study investigates an institution that performs both IHC and FISH testing on all cases to identify the true HER2-positive rate. Patients and Methods. A retrospective chart review from 2015 to 2021 was conducted at an institution where both HER2 IHC and FISH testing were performed at the time of diagnosis for all invasive breast cancers. The rate of true HER2-positive patients was determined, and patient and tumor characteristics were further explored. Results. A total of 1835 invasive breast cancer cases were primarily treated at this institution. A total of 289 cases were HER2 positive on IHC and FISH testing (15.7%) . An additional 38 cases were identified as HER2 negative on IHC, but reclassified as HER2 positive on reflex FISH testing. Total HER2 positive cases increased from 289 (15.7%) to 327 cases (17.8%) with reflex FISH testing. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2023 First Received: 4 April 2022 Accepted: 27 September 2023 Published online: 7 November 2023 C. Suydam, MD e-mail: Camille.r.suydam.mil@health.mil Conclusions. The additional HER2-positive cases after completing FISH testing on IHC-negative tumors suggests there may be a role for routine FISH testing in addition to standard IHC staining to determine HER2 status for breast cancer. The ethical, prognostic and even benefits of a correct diagnosis outweigh the added expense of FISH testing. Keywords HER2 · FISH · IHC · False negative · Reflex testing In the USA, breast cancer is the most commonly diagnosed cancer and the second most common cause of cancer death in women. 1 Breast cancer is a diverse disease with several biologic subtypes that have distinct behavior, each necessitating a different treatment. One of these subtypes is defined by an overexpression of the human epidermal growth factor receptor 2 (HER2) gene, previously called HER2/neu or ERBB-2 . This gene plays a critical role in controlling epithelial cell growth, differentiation,2,3 and possibly angiogenesis.4,5 Approximately 15–20% of primary invasive breast cancers are HER2 positive.6 HER2 gene amplification is associated with a relatively poor prognosis with increased risk of recurrence and metastasis,7 but is also a predictive factor for response to anthracycline-based chemotherapy and treatment benefit with anti-HER2 therapies such as trastuzumab, lapatinib, and pertuzumab.8 Since the development of anti-HER2 therapy, outcomes for HER2-positive patients have improved significantly.9, 10 The accurate identification of HER2 status and initiation of disease-specific therapy can decrease the risk of death and alter the prognosis of a patient who has HER2-positive breast cancer.9 HER2 status is assessed in all newly diagnosed, invasive, or recurrent breast tumors. How

FAQs

Why do clinicians perform FISH after equivocal HER2 IHC results?

HER2 immunohistochemistry (IHC) with equivocal (2+) staining commonly triggers fluorescence in situ hybridization (FISH) to refine HER2 classification and guide appropriate therapy.

How was the study conducted and which time period was analyzed?

A retrospective chart review analyzed invasive breast cancer cases diagnosed between 2015 and 2021, at an institution where both HER2 IHC and FISH testing were performed at diagnosis for all cases.

What effect did reflex FISH testing have on the final HER2-positive rate?

Reflex FISH identified additional HER2-positive cases initially classified as IHC-negative, increasing total HER2 positivity from 289 (15.7%) to 327 (17.8%).

What conclusion does the study draw about routine reflex FISH testing?

The additional HER2-positive cases detected after completing FISH testing on IHC-negative tumors suggest a potential role for routine FISH alongside standard IHC to determine HER2 status, with diagnostic accuracy benefits outweighing added cost.

Sep 24, 2026

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