Different Prognostic Implications of Residual Disease After Neoadjuvant Treatment: Impact of Ki 67 and Site of Response

Ann Surg Oncol. 2016 Nov;23(12):3831-3837. doi: 10.1245/s10434-016-5339-4. Epub 2016 Jun 29.

Abstract

Background: Pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) can be used as an independent prognostic factor in neoadjuvant trials. The objective of this study was to determine the impact of Ki 67 expression and site of response on overall survival (OS) and disease-free survival (DFS) across different molecular subtypes of breast cancer following NAC.

Methods: Records from 357 patients who received NAC from 2004 to 2011 were reviewed. Univariate and multivariate analyses were performed to analyze clinical and pathological factors that influence pCR and DFS.

Results: Mean follow-up time was 45 months (range 12-112). pCR was achieved in 82 patients (23 %). According to molecular subtypes, rates of pCR were significantly higher for patients with HER2-positive and triple-negative tumors (69.4 and 32.7 %, respectively; p < 0.001) compared with other molecular subtypes. pCR was a predictive factor of longer OS and DFS. The hazard ratio for DFS in patients with positive lymph nodes (ypN1) after NAC was 2.48 (95 % confidence interval 1.47-4.19). Multivariate analysis showed that molecular subtype, changes in Ki 67 expression, and axillary lymph node response were significantly predictors of OS and DFS.

Conclusions: pCR in the axilla and posttreatment changes in Ki 67 after NAC are associated with improved survival. Depending on axillary staging before NAC, detection of minimal residual disease-defined as the presence of isolated tumor cells in the SLN after NAC-may confer different prognosis. Further studies are needed to tailor treatments for patients with residual disease after NAC.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use
  • Axilla
  • Chemotherapy, Adjuvant
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Humans
  • Ki-67 Antigen / metabolism*
  • Lymphatic Metastasis
  • Middle Aged
  • Neoadjuvant Therapy
  • Neoplasm Recurrence, Local / metabolism*
  • Neoplasm, Residual
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Survival Rate
  • Triple Negative Breast Neoplasms / metabolism*
  • Triple Negative Breast Neoplasms / pathology*
  • Tumor Burden

Substances

  • Antineoplastic Agents
  • Ki-67 Antigen
  • Receptors, Estrogen
  • Receptors, Progesterone
  • ERBB2 protein, human
  • Receptor, ErbB-2