title: Tumor-infiltrating lymphocytes and molecular response after neoadjuvant therapy for HR+/HER2- breast cancer: results from two prospective trials.
abstract: The aim was to evaluate the role of tumor-infiltrating lymphocytes (TIL) in predicting molecular response after preoperative endocrine or cytotoxic treatment for HR+/HER2- patients who do not achieve a pathological complete response.
  
  
  
  Stromal (Str) TIL were centrally evaluated on samples from diagnostic core-biopsies of HR+/HER2- patients included in two prospective randomized trials: the LETLOB trial (neoadjuvant endocrine-based treatment) and the GIOB trial (neoadjuvant chemotherapy-based treatment). Pre- and post-treatment Ki67 was centrally assessed.
  
  
  
  StrTIL were evaluable in 111 cases (n = 73 from the LETLOB trial and n = 38 from the GIOB trial). Median StrTIL was 2%. Patients with high StrTIL (StrTIL ≥10%, n = 28) had more frequently breast cancer of ductal histology (p = 0.02), high grade (p = 0.049), and high Ki67 (p = 0.02). After neoadjuvant endocrine treatment (LETLOB cohort), a significant Ki67 suppression (p < 0.01) from pre- to post-treatment was observed in both the low and high StrTIL groups. High StrTIL patients achieve more frequently a relative Ki67 suppression ≥50% from baseline as compared to low StrTIL patients (55 vs. 35%, p non significant). After neoadjuvant chemotherapy (GIOB cohort), a significant Ki67 suppression was observed only for low StrTIL patients (Wilcoxon p = 0.001) and not in the high StrTIL group (p = 0.612). In this cohort, the rate of patients achieving a relative Ki67 suppression ≥50% from baseline was significantly higher in the low vs high StrTIL group (64% vs 10%, p = 0.003). Geometric mean Ki67 suppression was evaluated in each cohort according to StrTIL: the lowest value (-41%) was observed for high StrTIL cases treated with chemotherapy.
  
  
  
  This hypothesis-generating study suggests that in HR+/HER2- breast cancer StrTIL at baseline may influence the achievement of a molecular response after neoadjuvant treatment. Further evaluation in large studies is needed, and interaction with the type of treatment warrants to be explored.
authors.affiliation: Department of Surgery, Oncology and Gastroenterology, University of Padova, via Giustiniani 2, 35128, Padua, Italy.|Division of Medical Oncology 2, Istituto Oncologico Veneto IRCCS, via Gattamelata 64, 35128, Padua, Italy.
authors.forename: M V
authors.initials: MV
authors.lastname: Dieci
authors.affiliation: Division of Clinical Oncology, S. Anna University Hospital, via Moro 8, 44100, Cona, Ferrara, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Frassoldati
authors.affiliation: Breast UnitASST Cremona, viale Concordia 1, 26100, Cremona, Italy.|Department of Medical, Surgery & Health Sciences, University of Trieste, Piazza Ospitale 1, 34129, Trieste, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Generali
authors.affiliation: Division of Medical Oncology, Azienda Ospedaliera ASMN, IRCSS, Viale Umberto I 50, 42123, Reggio Emilia, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Bisagni
authors.affiliation: Department of Medical and Surgical Sciences of Mother, Child and Adult, University of Modena and Reggio Emilia, Modena, Italy.|Division of Medical Oncology, Modena University Hospital, via del Pozzo 71, 41124, Modena, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Piacentini
authors.affiliation: Division of Oncology, "Guglielmo da Saliceto" Hospital, via Taverna 49, 29121, Piacenza, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Cavanna
authors.affiliation: Division of Medical Oncology, "B.Ramazzini" Hospital, Via Molinari 2, 41012, Carpi, Italy.
authors.forename: K
authors.initials: K
authors.lastname: Cagossi
authors.affiliation: Department of Medical and Biological Sciences, University of Udine, Udine, Italy.|Department of Oncology, University Hospital of Udine, Piazzale Santa Maria della Misericordia 15, 33010, Udine, Italy.|UO Oncologia Medica I, Azienda Ospedaliera Universitaria Pisana, Santa Chiara Hospital, via Roma 67, 56126, Pisa, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Puglisi
authors.affiliation: Division of Medical Oncology, Università Politecnica delle Marche, Ospedali Riuniti Umberto I, via Conca 71, 60126, Ancona, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Michelotti
authors.affiliation: Division of Medical Oncology, Università Politecnica delle Marche, Ospedali Riuniti Umberto I, via Conca 71, 60126, Ancona, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Berardi
authors.affiliation: Division of Medical Oncology, Cannizzaro Hospital, via Messina 829, 95126, Catania, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Banna
authors.affiliation: ICR Clinical Trials and Statistics Unit, 15 Cotswold Road, Sutton, SM2 5NG, UK.
authors.forename: A
authors.initials: A
authors.lastname: Goubar
authors.affiliation: Division of Pathology, Modena University Hospital, via del Pozzo 71, 41124, Modena, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Ficarra
authors.affiliation: Department of Surgery, Oncology and Gastroenterology, University of Padova, via Giustiniani 2, 35128, Padua, Italy.|Division of Medical Oncology 2, Istituto Oncologico Veneto IRCCS, via Gattamelata 64, 35128, Padua, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Griguolo
authors.affiliation: Department of Surgery, Oncology and Gastroenterology, University of Padova, via Giustiniani 2, 35128, Padua, Italy. pierfranco.conte@unipd.it.|Division of Medical Oncology 2, Istituto Oncologico Veneto IRCCS, via Gattamelata 64, 35128, Padua, Italy. pierfranco.conte@unipd.it.
authors.forename: Pierfranco
authors.initials: P
authors.lastname: Conte
authors.affiliation: Department of Surgery, Oncology and Gastroenterology, University of Padova, via Giustiniani 2, 35128, Padua, Italy.|Division of Medical Oncology 2, Istituto Oncologico Veneto IRCCS, via Gattamelata 64, 35128, Padua, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Guarneri
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D000077341:Lapatinib; D000077289:Letrozole; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009570:Nitriles / Q000008:administration & dosage; D011446:Prospective Studies; D011799:Quinazolines / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage
chemical_list: D014408:Biomarkers, Tumor; D000077341:Lapatinib; D000077289:Letrozole; D009570:Nitriles; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D011956:Receptors, Cell Surface; D014230:Triazoles; C508053:ERBB2 protein, human
keywords: Chemotherapy; Endocrine therapy; Ki67; Neoadjuvant; Tumor-infiltrating lymphocytes