Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jun 27;61(7):1168.
doi: 10.3390/medicina61071168.

Pathologic Response and Survival Outcomes on HER2-Low vs. HER2-Zero in Breast Cancer Receiving Neoadjuvant Chemotherapy

Rumeysa Colak  1 , Caner Kapar  1 , Ezgi Degerli  1 , Seher Yildiz Tacar  1 , Aysegul Akdogan Gemici  2 , Nursadan Gergerlioglu  3 , Serdar Altinay  4 , Mesut Yilmaz  1
Affiliations

Pathologic Response and Survival Outcomes on HER2-Low vs. HER2-Zero in Breast Cancer Receiving Neoadjuvant Chemotherapy

Rumeysa Colak et al. Medicina (Kaunas). .

Abstract

Background and Objectives: The clinical value of HER2-low breast cancer (BC), defined by immunohistochemistry (IHC) scores of 1+ or 2+/ISH-negative without HER2 amplification, remains unclear in the neoadjuvant setting. This study aimed to determine whether HER2-low and HER2-zero tumors differ in pathological complete response (pCR) rates and disease-free survival (DFS) among early-stage breast cancer patients undergoing neoadjuvant chemotherapy (NAC). Materials and Methods: We retrospectively analyzed 134 early BC patients treated with NAC between 2017 and 2023. Patients were categorized as HER2-zero (IHC 0) or HER2-low (IHC 1+ or 2+/ISH-). The primary endpoint was total pCR (tpCR); secondary endpoints included breast (bpCR), nodal (npCR), and radiologic complete response (rCR), alongside DFS analysis stratified by hormone receptor (HR) status. Results: Of the cohort, 91 patients (67.9%) were HER2-zero and 43 (32.1%) were HER2-low. There was no statistically significant difference in tpCR (26.4% vs. 27.9%, p = 0.852), bpCR (28.6% vs. 30.2%, p = 0.843), npCR (37.4% vs. 32.6%, p = 0.588), and rCR (23.1% vs. 30.2%, p = 0.374) between HER2-zero and HER2-low groups. DFS did not significantly differ between HER2-zero and HER2-low groups overall (p = 0.714), nor within HR-positive (p = 0.540) or TNBC (p = 0.523) subgroups. Conclusions: HER2-low tumors demonstrated similar pathological responses and survival outcomes compared to HER2-zero tumors. While a HER2-low status does not appear to define a distinct biological subtype in early BC, it remains a relevant classification for emerging HER2-targeted therapies, needing further investigation in prospective studies.

Keywords: HER2-low; breast cancer; disease-free survival; hormone receptor status; neoadjuvant chemotherapy; pathologic complete response.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Pathologic and Radiologic Response by HER2 status.
Figure 2
Figure 2
Total pCR (A), Radiologic CR (B), Breast pCR (C) and Axilla pCR (D) by HER2 Status and HR Subgroups.
Figure 3
Figure 3
DFS Rates According to HER2 Status in All Group (A), HR-Positive Subgroup (B), and TNBC Subgroups (C).
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Sung H., Ferlay J., Siegel R.L., Laversanne M., Soerjomataram I., Jemal A., Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2021;71:209–249. doi: 10.3322/caac.21660. - DOI - PubMed
    1. Carter P., Presta L.E.N., Gorman C.M., Ridgway J.B., Henner D., Wong W.L., Rowland A.M., Kotts C., E Carver M., Shepard H.M. Humanization of an anti-p185HER2 antibody for human cancer therapy. Proc. Natl. Acad. Sci. USA. 1992;89:4285–4289. doi: 10.1073/pnas.89.10.4285. - DOI - PMC - PubMed
    1. Schettini F., Pascual T., Conte B., Chic N., Brasó-Maristany F., Galván P., Martínez O., Adamo B., Vidal M., Muñoz M., et al. HER2-enriched subtype and pathological complete response in HER2-positive breast cancer: A systematic review and meta-analysis. Cancer Treat. Rev. 2020;84:101965. doi: 10.1016/j.ctrv.2020.101965. - DOI - PMC - PubMed
    1. Denkert C., Seither F., Schneeweiss A., Link T., Blohmer J.U., Just M., Wimberger P., Forberger A., Tesch H., Jackisch C., et al. Clinical and molecular characteristics of HER2-low-positive breast cancer: Pooled analysis of individual patient data from four prospective, neoadjuvant clinical trials. Lancet Oncol. 2021;22:1151–1161. doi: 10.1016/S1470-2045(21)00301-6. - DOI - PubMed
    1. Agostinetto E., Rediti M., Fimereli D., Debien V., Piccart M., Aftimos P., Sotiriou C., de Azambuja E. HER2-low breast cancer: Molecular characteristics and prognosis. Cancers. 2021;13:2824. doi: 10.3390/cancers13112824. - DOI - PMC - PubMed