title: Changes in PgR and Ki-67 in residual tumour and outcome of breast cancer patients treated with neoadjuvant chemotherapy.
abstract: BACKGROUND
  Limited data are available on the prognostic value of changes in the biological features of residual tumours following neoadjuvant therapies in breast cancer patients.
  
  
  METHODS
  We collected information through the institutional clinical database on all consecutive breast cancer patients treated with neoadjuvant chemotherapy at the European Institute of Oncology (IEO), Milan, Italy, between 1999 and 2011. We selected patients who did not achieve pathological complete response at final surgery. All patients had a pathological evaluation, including ER, PgR, HER2 protein and Ki-67 expression carried out at the IEO both at diagnostic core biopsy and at final surgery.
  
  
  RESULTS
  We identified a total of 904 patients. The 5% of patients who were ER positive at diagnostic biopsy had ER-negative residual tumour at final surgery. For PgR expression, 67% of the patients, whose tumours had a PgR >20% at diagnostic biopsy had a PgR <20% at final surgery. The Ki-67 expression changed from >20% to <20% in 40% of the patients. At the multivariate analysis, the decrease of PgR-immunoreactive cells correlated with improved outcome in terms of disease-free survival (DFS) [hazard ratio (HR) 0.73; 95% confidence interval (CI) 0.54-1.00, P 0.046]. In addition, the decrease of Ki-67 expression to <20% of the cells at final surgery was found to be associated with better outcome both in terms of DFS (HR 0.52; 95% CI 0.40-0.68 P < 0.0001) and overall survival (HR 0.45; 95% CI 0.32-0.64, P < 0.0001).
  
  
  CONCLUSIONS
  The decrease of PgR and Ki-67 expression after preoperative chemotherapy has a prognostic role in breast cancer patients with residual disease.
authors.affiliation: Division of Medical Senology, European Institute of Oncology, Milan emilia.montagna@ieo.it.
authors.forename: E
authors.initials: E
authors.lastname: Montagna
authors.affiliation: Department of Quantitative Methods and Statistics, University of Milan-Bicocca, Milan Division of Epidemiology and Biostatistics.
authors.forename: V
authors.initials: V
authors.lastname: Bagnardi
authors.affiliation: Department of Pathology, European Institute of Oncology, Milan School of Medicine, University of Milan, Milan.
authors.forename: G
authors.initials: G
authors.lastname: Viale
authors.affiliation: Division of Epidemiology and Biostatistics.
authors.forename: N
authors.initials: N
authors.lastname: Rotmensz
authors.affiliation: Division of Medical Senology, European Institute of Oncology, Milan.
authors.forename: A
authors.initials: A
authors.lastname: Sporchia
authors.affiliation: Division of Medical Senology, European Institute of Oncology, Milan.
authors.forename: G
authors.initials: G
authors.lastname: Cancello
authors.affiliation: Division of Medical Senology, European Institute of Oncology, Milan.
authors.forename: A
authors.initials: A
authors.lastname: Balduzzi
authors.affiliation: Division of Senology.
authors.forename: V
authors.initials: V
authors.lastname: Galimberti
authors.affiliation: Division of Senology.
authors.forename: P
authors.initials: P
authors.lastname: Veronesi
authors.affiliation: Division of Senology.
authors.forename: A
authors.initials: A
authors.lastname: Luini
authors.affiliation: Department of Pathology, European Institute of Oncology, Milan.
authors.forename: M G
authors.initials: MG
authors.lastname: Mastropasqua
authors.affiliation: Department of Pathology, European Institute of Oncology, Milan.
authors.forename: C
authors.initials: C
authors.lastname: Casadio
authors.affiliation: Division of Medical Senology, European Institute of Oncology, Milan.
authors.forename: C
authors.initials: C
authors.lastname: Sangalli
authors.affiliation: Program of Senology (Breast Health), European Institute of Oncology, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Goldhirsch
authors.affiliation: Division of Medical Senology, European Institute of Oncology, Milan.
authors.forename: M
authors.initials: M
authors.lastname: Colleoni
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D017024:Chemotherapy, Adjuvant / Q000379:methods*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000032:analysis / Q000096:biosynthesis; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D018365:Neoplasm, Residual / Q000378:metabolism*; D011379:Prognosis; D016016:Proportional Hazards Models; D011960:Receptors, Estrogen / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000032:analysis / Q000096:biosynthesis; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone
keywords: HER2; breast cancer; chemotherapy; hormonal receptors; neoadjuvant therapy; surgery