title: Pathologic complete response as a potential surrogate for the clinical outcome in patients with breast cancer after neoadjuvant therapy: a meta-regression of 29 randomized prospective studies.
abstract: OBJECTIVE
  To assess the role of pathologic complete response (pCR) after neoadjuvant therapy as surrogate end point of disease-free survival (DFS) and overall survival (OS) in patients with breast cancer, we performed a trial-based meta-regression of randomized studies comparing different neoadjuvant systemic treatments.
  
  
  METHODS
  The systematic literature search included electronic databases and proceedings of oncologic meetings. Endocrine therapy trials were excluded. Treatment effects on DFS and OS were expressed as hazard ratios (HRs), and treatment effects on pCR were expressed as odds ratios (ORs). A weighted regression analysis was performed on log-transformed treatment effect estimates to test the association between treatment effects on the surrogate outcome and treatment effects on the clinical outcome.
  
  
  RESULTS
  Twenty-nine trials, 59 arms, and 30 comparisons, for a total of 14,641 patients, were included in the analysis. Using the complete set of data, the regression of either the log(HR) for DFS or the log(HR) for OS on the log(OR) for pCR demonstrated only weak associations (R(2) = 0.08; 95% CI, 0 to 0.47; and R(2) = 0.09; 95% CI, 0.01 to 0.41, respectively). Better associations were found in an exploratory analysis assessing a subset of trials comparing intensified/dose-dense chemotherapy versus standard-dose regimens (DFS: R(2) = 0.79; 95% CI, 0.26 to 0.95; P = .003; and OS: R(2) = 0.57; 95% CI, 0.19 to 0.93; P = .03).
  
  
  CONCLUSIONS
  This meta-regression analysis of 29 heterogeneous neoadjuvant trials does not support the use of pCR as a surrogate end point for DFS and OS in patients with breast cancer. However, pCR may potentially meet the criteria of surrogacy with specific systemic therapies.
authors.affiliation: Alfredo Berruti, Vito Amoroso, and Laura Ferrari, University of Brescia at Spedali Civili Hospital; Edda Simoncini and Rebecca Pedersini, Spedali Civili Hospital, Brescia; Fabio Gallo and Maria Pia Sormani, University of Genoa; Paolo Bruzzi, Istituto di Ricovero e Cura a Carattere Scientifico San Martino, Istituto Nazionale per la Ricerca sul Cancro, Genoa; Valentina Bertaglia, University of Turin, at San Luigi Gonzaga Hospital, Orbassano; and Alberto Bottini, Istituti Ospitalieri Hospital, Cremona, Italy. alfredo.berruti@gmail.com.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Berruti
authors.affiliation: Alfredo Berruti, Vito Amoroso, and Laura Ferrari, University of Brescia at Spedali Civili Hospital; Edda Simoncini and Rebecca Pedersini, Spedali Civili Hospital, Brescia; Fabio Gallo and Maria Pia Sormani, University of Genoa; Paolo Bruzzi, Istituto di Ricovero e Cura a Carattere Scientifico San Martino, Istituto Nazionale per la Ricerca sul Cancro, Genoa; Valentina Bertaglia, University of Turin, at San Luigi Gonzaga Hospital, Orbassano; and Alberto Bottini, Istituti Ospitalieri Hospital, Cremona, Italy.
authors.forename: Vito
authors.initials: V
authors.lastname: Amoroso
authors.affiliation: Alfredo Berruti, Vito Amoroso, and Laura Ferrari, University of Brescia at Spedali Civili Hospital; Edda Simoncini and Rebecca Pedersini, Spedali Civili Hospital, Brescia; Fabio Gallo and Maria Pia Sormani, University of Genoa; Paolo Bruzzi, Istituto di Ricovero e Cura a Carattere Scientifico San Martino, Istituto Nazionale per la Ricerca sul Cancro, Genoa; Valentina Bertaglia, University of Turin, at San Luigi Gonzaga Hospital, Orbassano; and Alberto Bottini, Istituti Ospitalieri Hospital, Cremona, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Gallo
authors.affiliation: Alfredo Berruti, Vito Amoroso, and Laura Ferrari, University of Brescia at Spedali Civili Hospital; Edda Simoncini and Rebecca Pedersini, Spedali Civili Hospital, Brescia; Fabio Gallo and Maria Pia Sormani, University of Genoa; Paolo Bruzzi, Istituto di Ricovero e Cura a Carattere Scientifico San Martino, Istituto Nazionale per la Ricerca sul Cancro, Genoa; Valentina Bertaglia, University of Turin, at San Luigi Gonzaga Hospital, Orbassano; and Alberto Bottini, Istituti Ospitalieri Hospital, Cremona, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Bertaglia
authors.affiliation: Alfredo Berruti, Vito Amoroso, and Laura Ferrari, University of Brescia at Spedali Civili Hospital; Edda Simoncini and Rebecca Pedersini, Spedali Civili Hospital, Brescia; Fabio Gallo and Maria Pia Sormani, University of Genoa; Paolo Bruzzi, Istituto di Ricovero e Cura a Carattere Scientifico San Martino, Istituto Nazionale per la Ricerca sul Cancro, Genoa; Valentina Bertaglia, University of Turin, at San Luigi Gonzaga Hospital, Orbassano; and Alberto Bottini, Istituti Ospitalieri Hospital, Cremona, Italy.
authors.forename: Edda
authors.initials: E
authors.lastname: Simoncini
authors.affiliation: Alfredo Berruti, Vito Amoroso, and Laura Ferrari, University of Brescia at Spedali Civili Hospital; Edda Simoncini and Rebecca Pedersini, Spedali Civili Hospital, Brescia; Fabio Gallo and Maria Pia Sormani, University of Genoa; Paolo Bruzzi, Istituto di Ricovero e Cura a Carattere Scientifico San Martino, Istituto Nazionale per la Ricerca sul Cancro, Genoa; Valentina Bertaglia, University of Turin, at San Luigi Gonzaga Hospital, Orbassano; and Alberto Bottini, Istituti Ospitalieri Hospital, Cremona, Italy.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Pedersini
authors.affiliation: Alfredo Berruti, Vito Amoroso, and Laura Ferrari, University of Brescia at Spedali Civili Hospital; Edda Simoncini and Rebecca Pedersini, Spedali Civili Hospital, Brescia; Fabio Gallo and Maria Pia Sormani, University of Genoa; Paolo Bruzzi, Istituto di Ricovero e Cura a Carattere Scientifico San Martino, Istituto Nazionale per la Ricerca sul Cancro, Genoa; Valentina Bertaglia, University of Turin, at San Luigi Gonzaga Hospital, Orbassano; and Alberto Bottini, Istituti Ospitalieri Hospital, Cremona, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Ferrari
authors.affiliation: Alfredo Berruti, Vito Amoroso, and Laura Ferrari, University of Brescia at Spedali Civili Hospital; Edda Simoncini and Rebecca Pedersini, Spedali Civili Hospital, Brescia; Fabio Gallo and Maria Pia Sormani, University of Genoa; Paolo Bruzzi, Istituto di Ricovero e Cura a Carattere Scientifico San Martino, Istituto Nazionale per la Ricerca sul Cancro, Genoa; Valentina Bertaglia, University of Turin, at San Luigi Gonzaga Hospital, Orbassano; and Alberto Bottini, Istituti Ospitalieri Hospital, Cremona, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Bottini
authors.affiliation: Alfredo Berruti, Vito Amoroso, and Laura Ferrari, University of Brescia at Spedali Civili Hospital; Edda Simoncini and Rebecca Pedersini, Spedali Civili Hospital, Brescia; Fabio Gallo and Maria Pia Sormani, University of Genoa; Paolo Bruzzi, Istituto di Ricovero e Cura a Carattere Scientifico San Martino, Istituto Nazionale per la Ricerca sul Cancro, Genoa; Valentina Bertaglia, University of Turin, at San Luigi Gonzaga Hospital, Orbassano; and Alberto Bottini, Istituti Ospitalieri Hospital, Cremona, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Bruzzi
authors.affiliation: Alfredo Berruti, Vito Amoroso, and Laura Ferrari, University of Brescia at Spedali Civili Hospital; Edda Simoncini and Rebecca Pedersini, Spedali Civili Hospital, Brescia; Fabio Gallo and Maria Pia Sormani, University of Genoa; Paolo Bruzzi, Istituto di Ricovero e Cura a Carattere Scientifico San Martino, Istituto Nazionale per la Ricerca sul Cancro, Genoa; Valentina Bertaglia, University of Turin, at San Luigi Gonzaga Hospital, Orbassano; and Alberto Bottini, Istituti Ospitalieri Hospital, Cremona, Italy.
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Sormani
mesh_terms: D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D018572:Disease-Free Survival; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D020360:Neoadjuvant Therapy; D016017:Odds Ratio; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome