Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes

J Clin Oncol. 2012 May 20;30(15):1796-804. doi: 10.1200/JCO.2011.38.8595. Epub 2012 Apr 16.

Abstract

Purpose: The exact definition of pathologic complete response (pCR) and its prognostic impact on survival in intrinsic breast cancer subtypes is uncertain.

Methods: Tumor response at surgery and its association with long-term outcome of 6,377 patients with primary breast cancer receiving neoadjuvant anthracycline-taxane-based chemotherapy in seven randomized trials were analyzed.

Results: Disease-free survival (DFS) was significantly superior in patients with no invasive and no in situ residuals in breast or nodes (n = 955) compared with patients with residual ductal carcinoma in situ only (n = 309), no invasive residuals in breast but involved nodes (n = 186), only focal-invasive disease in the breast (n = 478), and gross invasive residual disease (n = 4,449; P < .001). Hazard ratios for DFS comparing patients with or without pCR were lowest when defined as no invasive and no in situ residuals (0.446) and increased monotonously when in situ residuals (0.523), no invasive breast residuals but involved nodes (0.623), and focal-invasive disease (0.727) were included in the definition. pCR was associated with improved DFS in luminal B/human epidermal growth factor receptor 2 (HER2) -negative (P = .005), HER2-positive/nonluminal (P < .001), and triple-negative (P < .001) tumors but not in luminal A (P = .39) or luminal B/HER2-positive (P = .45) breast cancer. pCR in HER2-positive (nonluminal) and triple-negative tumors was associated with excellent prognosis.

Conclusion: pCR defined as no invasive and no in situ residuals in breast and nodes can best discriminate between patients with favorable and unfavorable outcomes. Patients with noninvasive or focal-invasive residues or involved lymph nodes should not be considered as having achieved pCR. pCR is a suitable surrogate end point for patients with luminal B/HER2-negative, HER2-positive (nonluminal), and triple-negative disease but not for those with luminal B/HER2-positive or luminal A tumors.

Trial registration: ClinicalTrials.gov NCT00288002 NCT00544232 NCT00544765 NCT00793377 NCT00795899.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anthracyclines / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / analysis
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy*
  • Carcinoma in Situ / chemistry
  • Carcinoma in Situ / mortality
  • Carcinoma in Situ / pathology
  • Carcinoma in Situ / therapy*
  • Carcinoma, Ductal, Breast / chemistry
  • Carcinoma, Ductal, Breast / mortality
  • Carcinoma, Ductal, Breast / pathology
  • Carcinoma, Ductal, Breast / therapy*
  • Chemotherapy, Adjuvant
  • Chi-Square Distribution
  • Disease-Free Survival
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Mastectomy* / adverse effects
  • Mastectomy* / mortality
  • Middle Aged
  • Neoadjuvant Therapy*
  • Neoplasm Invasiveness
  • Proportional Hazards Models
  • Randomized Controlled Trials as Topic
  • Receptor, ErbB-2 / analysis
  • Taxoids / administration & dosage
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Anthracyclines
  • Biomarkers, Tumor
  • Taxoids
  • ERBB2 protein, human
  • Receptor, ErbB-2

Associated data

  • ClinicalTrials.gov/NCT00288002
  • ClinicalTrials.gov/NCT00544232
  • ClinicalTrials.gov/NCT00544765
  • ClinicalTrials.gov/NCT00793377
  • ClinicalTrials.gov/NCT00795899