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Two histopathologically different diseases: hormone receptor-positive and hormone receptor-negative tumors in HER2-positive breast cancer

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Abstract

The clinical behavior of human epidermal growth factor 2 (HER2)-positive breast cancer, including pathologic complete response rate and pattern of relapse and metastasis, differs substantially according to hormone receptor (HR) status. We investigated various histopathologic features of HER2-positive breast cancer and their correlation with HR status. We retrospectively analyzed tumors of 450 HER2-positive breast cancer patients treated with chemotherapy and 1 year of trastuzumab. HR−/HER2+ tumors showed higher nuclear grade, less tubule formation, higher histologic grade, frequent apocrine features, diffuse and abundant lymphocytic infiltration, strong HER2 immunohistochemical staining (3+), higher average HER2 copy number and HER2/CEP17 ratio, the absence of HER2 genetic heterogeneity, and greater p53 expression than HR+/HER2+ tumors. An inverse correlation was observed between estrogen receptor or progesterone receptor Allred score and average HER2 copy number or HER2/CEP17 ratio. The percentage of ductal carcinoma in situ (DCIS) within the tumor was negatively correlated with ER Allred score, but positively correlated with average HER2 copy number and HER2/CEP17 ratio. Pathologic tumor size and DCIS percentage also showed a significant inverse correlation. Ratio of metastatic to total examined lymph node number was significantly correlated with average HER2 copy number and HER2/CEP17 ratio. High pT stage (hazard ratio, 2.370; p = 0.027), the presence of lymphovascular invasion (hazard ratio, 2.806; p = 0.005), and HR negativity (hazard ratio, 2.202; 1.074–4.513; p = 0.031) were found to be independent prognostic indicators of poor disease-free survival. In conclusion, HR+/HER2+ and HR−/HER2+ breast cancer showed distinct histopathologic features that may be relevant to their distinct clinical behavior.

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Acknowledgments

This study was supported by 2013 “Moon-Ho Yang” research fund from The Korean Society of Pathologists.

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, South Korea

    Hee Jin Lee, In Ah Park, Yun Chai, In Hye Song, Na Eun Kim, Joo Young Kim & Gyungyub Gong

  2. Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, South Korea

    So Yeon Park & An Na Seo

  3. Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea

    So Yeon Park

  4. Department of Hematology-Oncology, Penn State Hershey Cancer Institute, Penn State College of Medicine, Hershey, PA, USA

    Bora Lim

  5. Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea

    Jong Han Yu

  6. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea

    Jin-Hee Ahn

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  1. Hee Jin Lee
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  2. In Ah Park
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  3. So Yeon Park
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  4. An Na Seo
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  5. Bora Lim
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  6. Yun Chai
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  7. In Hye Song
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  8. Na Eun Kim
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  9. Joo Young Kim
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  10. Jong Han Yu
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  11. Jin-Hee Ahn
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  12. Gyungyub Gong
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Corresponding author

Correspondence to Gyungyub Gong.

Additional information

Hee Jin Lee and In Ah Park have contributed equally to this work.

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Lee, H.J., Park, I.A., Park, S.Y. et al. Two histopathologically different diseases: hormone receptor-positive and hormone receptor-negative tumors in HER2-positive breast cancer. Breast Cancer Res Treat 145, 615–623 (2014). https://doi.org/10.1007/s10549-014-2983-x

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  • DOI: https://doi.org/10.1007/s10549-014-2983-x

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