Breast Cancer

, Volume 27, Issue 1, pp 77–84 | Cite as

Histological features of skin and subcutaneous tissue in patients with breast cancer who have received neoadjuvant chemotherapy and their relationship to post-treatment edema

  • Ayako Nakagawa
  • Hiroshi FujimotoEmail author
  • Takeshi Nagashima
  • Takafumi Sangai
  • Mamoru Takada
  • Takahito Masuda
  • Ryotaro Teranaka
  • Satoshi Ota
  • Jun Matsushima
  • Shinsuke Akita
  • Masayuki Ohtsuka
Original Article



Lymphedema is a major complication of treatment for breast cancer. Although chemotherapy can cause lymphedema, there have been few reports about histological changes in skin and subcutaneous tissue after chemotherapy. The aim of our study was to determine whether chemotherapy affects blood and lymphatic vessels in the skin and subcutaneous fat and to investigate the relationship between these changes and extent of post-chemotherapy edema.


We compared histological findings in skin and subcutaneous fat of mastectomy specimens from 38 patients who had received NAC (neoadjuvant chemotherapy) and 56 who had not (non-NAC) attending our institution from 2007 to 2016. Patients whose tumor may have affected the area examined were excluded. Blood and lymphatic vessels were identified by CD31 and D2-40, respectively. We assessed microvessel density (MVD), lymphatic microvessel density (MLVD), lumen cross-sectional area (LA), and amount of endothelium (AE) in blood and lymphatic vessels. To minimize surgical effects, we measured edema, defined as ≥ 15% thicker dorsal subcutaneous tissue than baseline, on the contralateral side.


MVD, LA, and AE of blood vessels were greater and MLVD not significantly different in the skin of NAC patients than in that of non-NAC patients. MVD was greater and AE of blood vessels less in subcutaneous fat of NAC patients than in that of non-NAC patients. Patients with edema had significantly less AE of blood vessels in skin than did those without it.


These pathological findings can help to identify patients who will develop edema and improve their treatment.


Microvessel density Angiogenesis CD31 D2-40 Neoadjuvant chemotherapy 



The authors acknowledge the generous contributions of the staff of the Department of Pathology and Ms. Hiroko Kawamura for their slide preparation and wish to thank Dr. Rikiya Nakamura, Department of Breast Surgery, Chiba Cancer Center for advice on experimental design. We also thank Dr. Trish Reynolds, MBBS, FRACP, from Edanz Group ( for editing a draft of this manuscript.

Compliance with ethical standards

Conflict of interest

This work was supported by Grants from Chiba Foundation for Health Promotion & Disease Prevention. There are no other potential conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all study participants.


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Copyright information

© The Japanese Breast Cancer Society 2019

Authors and Affiliations

  • Ayako Nakagawa
    • 1
  • Hiroshi Fujimoto
    • 1
    Email author
  • Takeshi Nagashima
    • 1
  • Takafumi Sangai
    • 1
  • Mamoru Takada
    • 1
  • Takahito Masuda
    • 1
  • Ryotaro Teranaka
    • 1
  • Satoshi Ota
    • 2
  • Jun Matsushima
    • 3
  • Shinsuke Akita
    • 4
  • Masayuki Ohtsuka
    • 1
  1. 1.Department of General SurgeryChiba University Graduate School of MedicineChibaJapan
  2. 2.Department of PathologyChiba University HospitalChibaJapan
  3. 3.Department of Diagnostic PathologyChiba University Graduate School of MedicineChibaJapan
  4. 4.Department of Plastic, Reconstructive, and Aesthetic SurgeryChiba University Graduate School of MedicineChibaJapan

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