Lung Metastasis of HER2-positive Breast Cancer with Squamous Cell Differentiation Phenotype: A Case Report

Yu Qiu; Yuanzhi Lu

doi:doi:10.11648/j.ajcem.20251306.12

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Lung Metastasis of HER2-positive Breast Cancer with Squamous Cell Differentiation Phenotype: A Case Report

Yu Qiu

, Yuanzhi Lu^*

Published in American Journal of Clinical and Experimental Medicine (Volume 13, Issue 6)

Received: 10 November 2025 Accepted: 24 November 2025 Published: 17 December 2025

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Abstract

Drug resistance, recurrence, and metastasis are the main challenges that can lead to treatment failure and deteriorate outcomes of patients with breast cancer. Breast cancer metastasizes to different organs and may present with different phenotypic features. However, the underlying mechanisms of phenotypic plasticity of breast cancer still remain unclear. We herein report a case of HER2-positive breast cancer in which the patient developed acquired therapeutic resistance following standard postoperative adjuvant chemotherapy combined with anti-HER2 targeted therapy. The patient initially responded to treatment; however, one year after completion of therapy, new bilateral pulmonary nodules emerged. Subsequent pathological examination confirmed metastatic carcinoma with a transdifferentiated squamous cell phenotype. Comprehensive biomarker analyses, including immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and next-generation sequencing (NGS), were performed on matched samples from the primary breast tumor and the corresponding lung metastatic lesions. Integrated diagnostic results confirmed that the pulmonary lesions were metastatic in origin from the breast, harboring HER2 amplification as well as PIK3CA and TP53 mutations. In contrast to the primary lesion, the metastatic lung lesions demonstrated acquisition of a squamous phenotype, accompanied by multiple chromosomal heterozygous/homozygous deletions and copy-number gain that may have contributed to this phenotypic transformation. Despite HER2 amplification, the pulmonary metastases showed negative HER2 protein expression, possibly reflecting tissue-specific gene expression differences. These findings provide new insights for the clinical management of HER2-positive breast cancer.

Published in	American Journal of Clinical and Experimental Medicine (Volume 13, Issue 6)
DOI	10.11648/j.ajcem.20251306.12
Page(s)	170-176
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2025. Published by Science Publishing Group

Keywords

Metaplastic Breast Cancer, Lung Metastasis, Squamous Cell Metaplasia, Case Report

References

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[13]	Wang H, Xiang D, Liu B, et al. Inadequate DNA damage repair promotes mammary transdifferentiation, leading to brca1 breast cancer [J]. Cell, 2019, 178(1): 135-151. e119. https://doi.org/10.1016/j.cell.2019.06.002
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APA Style

Qiu, Y., Lu, Y. (2025). Lung Metastasis of HER2-positive Breast Cancer with Squamous Cell Differentiation Phenotype: A Case Report. American Journal of Clinical and Experimental Medicine, 13(6), 170-176. https://doi.org/10.11648/j.ajcem.20251306.12

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ACS Style

Qiu, Y.; Lu, Y. Lung Metastasis of HER2-positive Breast Cancer with Squamous Cell Differentiation Phenotype: A Case Report. Am. J. Clin. Exp. Med. 2025, 13(6), 170-176. doi: 10.11648/j.ajcem.20251306.12

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AMA Style

Qiu Y, Lu Y. Lung Metastasis of HER2-positive Breast Cancer with Squamous Cell Differentiation Phenotype: A Case Report. Am J Clin Exp Med. 2025;13(6):170-176. doi: 10.11648/j.ajcem.20251306.12

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@article{10.11648/j.ajcem.20251306.12,
  author = {Yu Qiu and Yuanzhi Lu},
  title = {Lung Metastasis of HER2-positive Breast Cancer with Squamous Cell Differentiation Phenotype: A Case Report},
  journal = {American Journal of Clinical and Experimental Medicine},
  volume = {13},
  number = {6},
  pages = {170-176},
  doi = {10.11648/j.ajcem.20251306.12},
  url = {https://doi.org/10.11648/j.ajcem.20251306.12},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajcem.20251306.12},
  abstract = {Drug resistance, recurrence, and metastasis are the main challenges that can lead to treatment failure and deteriorate outcomes of patients with breast cancer. Breast cancer metastasizes to different organs and may present with different phenotypic features. However, the underlying mechanisms of phenotypic plasticity of breast cancer still remain unclear. We herein report a case of HER2-positive breast cancer in which the patient developed acquired therapeutic resistance following standard postoperative adjuvant chemotherapy combined with anti-HER2 targeted therapy. The patient initially responded to treatment; however, one year after completion of therapy, new bilateral pulmonary nodules emerged. Subsequent pathological examination confirmed metastatic carcinoma with a transdifferentiated squamous cell phenotype. Comprehensive biomarker analyses, including immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and next-generation sequencing (NGS), were performed on matched samples from the primary breast tumor and the corresponding lung metastatic lesions. Integrated diagnostic results confirmed that the pulmonary lesions were metastatic in origin from the breast, harboring HER2 amplification as well as PIK3CA and TP53 mutations. In contrast to the primary lesion, the metastatic lung lesions demonstrated acquisition of a squamous phenotype, accompanied by multiple chromosomal heterozygous/homozygous deletions and copy-number gain that may have contributed to this phenotypic transformation. Despite HER2 amplification, the pulmonary metastases showed negative HER2 protein expression, possibly reflecting tissue-specific gene expression differences. These findings provide new insights for the clinical management of HER2-positive breast cancer.},
 year = {2025}
}

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TY  - JOUR
T1  - Lung Metastasis of HER2-positive Breast Cancer with Squamous Cell Differentiation Phenotype: A Case Report
AU  - Yu Qiu
AU  - Yuanzhi Lu
Y1  - 2025/12/17
PY  - 2025
N1  - https://doi.org/10.11648/j.ajcem.20251306.12
DO  - 10.11648/j.ajcem.20251306.12
T2  - American Journal of Clinical and Experimental Medicine
JF  - American Journal of Clinical and Experimental Medicine
JO  - American Journal of Clinical and Experimental Medicine
SP  - 170
EP  - 176
PB  - Science Publishing Group
SN  - 2330-8133
UR  - https://doi.org/10.11648/j.ajcem.20251306.12
AB  - Drug resistance, recurrence, and metastasis are the main challenges that can lead to treatment failure and deteriorate outcomes of patients with breast cancer. Breast cancer metastasizes to different organs and may present with different phenotypic features. However, the underlying mechanisms of phenotypic plasticity of breast cancer still remain unclear. We herein report a case of HER2-positive breast cancer in which the patient developed acquired therapeutic resistance following standard postoperative adjuvant chemotherapy combined with anti-HER2 targeted therapy. The patient initially responded to treatment; however, one year after completion of therapy, new bilateral pulmonary nodules emerged. Subsequent pathological examination confirmed metastatic carcinoma with a transdifferentiated squamous cell phenotype. Comprehensive biomarker analyses, including immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and next-generation sequencing (NGS), were performed on matched samples from the primary breast tumor and the corresponding lung metastatic lesions. Integrated diagnostic results confirmed that the pulmonary lesions were metastatic in origin from the breast, harboring HER2 amplification as well as PIK3CA and TP53 mutations. In contrast to the primary lesion, the metastatic lung lesions demonstrated acquisition of a squamous phenotype, accompanied by multiple chromosomal heterozygous/homozygous deletions and copy-number gain that may have contributed to this phenotypic transformation. Despite HER2 amplification, the pulmonary metastases showed negative HER2 protein expression, possibly reflecting tissue-specific gene expression differences. These findings provide new insights for the clinical management of HER2-positive breast cancer.
VL  - 13
IS  - 6
ER  -

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Author Information

Yu Qiu

Department of Pathology, The First Affiliated Hospital of Jinan University, Guangzhou, China

Contact Email

http://orcid.org/0009-0006-3444-7371
Yuanzhi Lu

Department of Pathology, The First Affiliated Hospital of Jinan University, Guangzhou, China

Contact Email

http://orcid.org/0000-0003-2946-643X

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APA Style

Qiu, Y., Lu, Y. (2025). Lung Metastasis of HER2-positive Breast Cancer with Squamous Cell Differentiation Phenotype: A Case Report. American Journal of Clinical and Experimental Medicine, 13(6), 170-176. https://doi.org/10.11648/j.ajcem.20251306.12

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ACS Style

Qiu, Y.; Lu, Y. Lung Metastasis of HER2-positive Breast Cancer with Squamous Cell Differentiation Phenotype: A Case Report. Am. J. Clin. Exp. Med. 2025, 13(6), 170-176. doi: 10.11648/j.ajcem.20251306.12

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AMA Style

Qiu Y, Lu Y. Lung Metastasis of HER2-positive Breast Cancer with Squamous Cell Differentiation Phenotype: A Case Report. Am J Clin Exp Med. 2025;13(6):170-176. doi: 10.11648/j.ajcem.20251306.12

Copy | Download

@article{10.11648/j.ajcem.20251306.12,
  author = {Yu Qiu and Yuanzhi Lu},
  title = {Lung Metastasis of HER2-positive Breast Cancer with Squamous Cell Differentiation Phenotype: A Case Report},
  journal = {American Journal of Clinical and Experimental Medicine},
  volume = {13},
  number = {6},
  pages = {170-176},
  doi = {10.11648/j.ajcem.20251306.12},
  url = {https://doi.org/10.11648/j.ajcem.20251306.12},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajcem.20251306.12},
  abstract = {Drug resistance, recurrence, and metastasis are the main challenges that can lead to treatment failure and deteriorate outcomes of patients with breast cancer. Breast cancer metastasizes to different organs and may present with different phenotypic features. However, the underlying mechanisms of phenotypic plasticity of breast cancer still remain unclear. We herein report a case of HER2-positive breast cancer in which the patient developed acquired therapeutic resistance following standard postoperative adjuvant chemotherapy combined with anti-HER2 targeted therapy. The patient initially responded to treatment; however, one year after completion of therapy, new bilateral pulmonary nodules emerged. Subsequent pathological examination confirmed metastatic carcinoma with a transdifferentiated squamous cell phenotype. Comprehensive biomarker analyses, including immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and next-generation sequencing (NGS), were performed on matched samples from the primary breast tumor and the corresponding lung metastatic lesions. Integrated diagnostic results confirmed that the pulmonary lesions were metastatic in origin from the breast, harboring HER2 amplification as well as PIK3CA and TP53 mutations. In contrast to the primary lesion, the metastatic lung lesions demonstrated acquisition of a squamous phenotype, accompanied by multiple chromosomal heterozygous/homozygous deletions and copy-number gain that may have contributed to this phenotypic transformation. Despite HER2 amplification, the pulmonary metastases showed negative HER2 protein expression, possibly reflecting tissue-specific gene expression differences. These findings provide new insights for the clinical management of HER2-positive breast cancer.},
 year = {2025}
}

Copy | Download

TY  - JOUR
T1  - Lung Metastasis of HER2-positive Breast Cancer with Squamous Cell Differentiation Phenotype: A Case Report
AU  - Yu Qiu
AU  - Yuanzhi Lu
Y1  - 2025/12/17
PY  - 2025
N1  - https://doi.org/10.11648/j.ajcem.20251306.12
DO  - 10.11648/j.ajcem.20251306.12
T2  - American Journal of Clinical and Experimental Medicine
JF  - American Journal of Clinical and Experimental Medicine
JO  - American Journal of Clinical and Experimental Medicine
SP  - 170
EP  - 176
PB  - Science Publishing Group
SN  - 2330-8133
UR  - https://doi.org/10.11648/j.ajcem.20251306.12
AB  - Drug resistance, recurrence, and metastasis are the main challenges that can lead to treatment failure and deteriorate outcomes of patients with breast cancer. Breast cancer metastasizes to different organs and may present with different phenotypic features. However, the underlying mechanisms of phenotypic plasticity of breast cancer still remain unclear. We herein report a case of HER2-positive breast cancer in which the patient developed acquired therapeutic resistance following standard postoperative adjuvant chemotherapy combined with anti-HER2 targeted therapy. The patient initially responded to treatment; however, one year after completion of therapy, new bilateral pulmonary nodules emerged. Subsequent pathological examination confirmed metastatic carcinoma with a transdifferentiated squamous cell phenotype. Comprehensive biomarker analyses, including immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and next-generation sequencing (NGS), were performed on matched samples from the primary breast tumor and the corresponding lung metastatic lesions. Integrated diagnostic results confirmed that the pulmonary lesions were metastatic in origin from the breast, harboring HER2 amplification as well as PIK3CA and TP53 mutations. In contrast to the primary lesion, the metastatic lung lesions demonstrated acquisition of a squamous phenotype, accompanied by multiple chromosomal heterozygous/homozygous deletions and copy-number gain that may have contributed to this phenotypic transformation. Despite HER2 amplification, the pulmonary metastases showed negative HER2 protein expression, possibly reflecting tissue-specific gene expression differences. These findings provide new insights for the clinical management of HER2-positive breast cancer.
VL  - 13
IS  - 6
ER  -

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