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Do HER2-Low Tumors Have a Distinct Clinicopathologic Phenotype?

  • Breast Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Breast cancer subtypes, distinguished by hormone receptor (HR) and HER2 status, have different clinicopathologic features. With recognition of the clinical relevance of HER2-low, there is debate as to whether this is a distinct subtype. Our study aimed to determine whether HER2-low breast cancers have specific clinicopathologic features that differ from those of HER2-negative and HER2-positive cancers.

Patients and Methods

A total of 11,072 patients undergoing upfront surgery from 1998 to 2010 were identified from a single-institution prospectively maintained database. HER2 status was classified by immunohistochemistry (IHC)/fluorescence in situ hybridization (FISH) as HER2 negative (41.2%), HER2 low (45%; IHC 1+ or 2+ with negative FISH), and HER2 positive (13.7%), and stratified by HR status. Univariate (UVA) and multivariable multinomial logistic regression analysis (MVA) were performed to determine associations among variables and subtypes.

Results

Compared with HER2-negative tumors, HER2 low was associated with lymphovascular invasion [odds ratio (OR) 1.2, 95% confidence interval (CI) 1.06–1.36; p = 0.003], multifocality (OR 1.26, 95% CI 1.12–1.42; p < 0.001), nodal micrometastasis (OR 1.15, 95% CI 1.02–1.31; p = 0.024), and lower rates of ≥ 3 positive nodes (OR 0.77, 95% CI 0.66–0.90, p = 0.001). When stratified by HR expression, in both HR-positive and HR-negative tumors, age and multifocality were associated with HER2 low on UVA. On MVA, no variables were independently associated with both HR-negative and HR-positive/HER2-low tumors compared with HER2-negative tumors. In contrast, HER2-positive tumors, regardless of HR status, were associated with multifocality and an extensive intraductal component.

Conclusion

Clinicopathologic features of HER2-low tumors appear to be primarily related to HR status. Our findings do not support the characterization of HER2 low as a separate subtype.

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Acknowledgments

The preparation of this study was supported in part by NIH/NCI Cancer Center Support Grant No. P30 CA008748 to Memorial Sloan Kettering Cancer Center, and this study was presented in poster format at the 2023 American Society of Clinical Oncology Annual Meeting, 2–6 June 2023, Chicago, IL.

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Authors and Affiliations

  1. Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Natália Polidorio MD, PhD, Giacomo Montagna MD, MPH, Tiana Le BS & Monica Morrow MD

  2. Biostatistics Service, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Varadan Sevilimedu MBBS, DrPH

Authors
  1. Natália Polidorio MD, PhD
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  2. Giacomo Montagna MD, MPH
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  3. Varadan Sevilimedu MBBS, DrPH
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  5. Monica Morrow MD
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Correspondence to Monica Morrow MD.

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Polidorio, N., Montagna, G., Sevilimedu, V. et al. Do HER2-Low Tumors Have a Distinct Clinicopathologic Phenotype?. Ann Surg Oncol 31, 2231–2243 (2024). https://doi.org/10.1245/s10434-023-14800-w

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