title: Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: German Breast Group, c/o GBG Forschungs GmbH, Martin-Behaim-Straße 12, 63263 Neu-Isenburg, Germany. gunter.vonminckwitz@germanbreastgroup.de
authors.forename: Gunter
authors.initials: G
authors.lastname: von Minckwitz
authors.forename: Michael
authors.initials: M
authors.lastname: Untch
authors.forename: Jens-Uwe
authors.initials: JU
authors.lastname: Blohmer
authors.forename: Serban D
authors.initials: SD
authors.lastname: Costa
authors.forename: Holger
authors.initials: H
authors.lastname: Eidtmann
authors.forename: Peter A
authors.initials: PA
authors.lastname: Fasching
authors.forename: Bernd
authors.initials: B
authors.lastname: Gerber
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Eiermann
authors.forename: Jörn
authors.initials: J
authors.lastname: Hilfrich
authors.forename: Jens
authors.initials: J
authors.lastname: Huober
authors.forename: Christian
authors.initials: C
authors.lastname: Jackisch
authors.forename: Manfred
authors.initials: M
authors.lastname: Kaufmann
authors.forename: Gottfried E
authors.initials: GE
authors.lastname: Konecny
authors.forename: Carsten
authors.initials: C
authors.lastname: Denkert
authors.forename: Valentina
authors.initials: V
authors.lastname: Nekljudova
authors.forename: Keyur
authors.initials: K
authors.lastname: Mehta
authors.forename: Sibylle
authors.initials: S
authors.lastname: Loibl
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018943:Anthracyclines / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000737:chemistry / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D002278:Carcinoma in Situ / Q000737:chemistry / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D016009:Chi-Square Distribution; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008408:Mastectomy / Q000009:adverse effects / Q000401:mortality; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D043823:Taxoids / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018943:Anthracyclines; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; C508053:ERBB2 protein, human