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

Breast Cancer. 2020 Jan;27(1):77-84. doi: 10.1007/s12282-019-00996-x. Epub 2019 Jul 25.

Abstract

Background: 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.

Methods: 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.

Results: 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.

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

Keywords: Angiogenesis; CD31; D2-40; Microvessel density; Neoadjuvant chemotherapy.

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms / complications
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Chemotherapy, Adjuvant / adverse effects
  • Edema / chemically induced
  • Edema / pathology*
  • Endothelium, Vascular / pathology
  • Female
  • Humans
  • Microvessels / pathology
  • Middle Aged
  • Neoadjuvant Therapy / adverse effects
  • Neovascularization, Pathologic / chemically induced
  • Neovascularization, Pathologic / pathology
  • Skin / blood supply
  • Skin / pathology*
  • Subcutaneous Tissue / blood supply
  • Subcutaneous Tissue / pathology*