title: Letrozole plus GnRH analogue as preoperative and adjuvant therapy in premenopausal women with ER positive locally advanced breast cancer.
abstract: Patients with large ER positive tumors candidate to preoperative chemotherapy may also benefit from a concurrent endocrine intervention, but this issue has been scarcely investigated due to concerns arising from unfavorable results emerged from an adjuvant trial of concurrent tamoxifen and chemotherapy. We retrospectively investigated the activity of letrozole plus GnRH analogue (GnRH-a) administered concurrently with preoperative chemotherapy and as adjuvant treatment in premenopausal women with locally advanced ER positive breast cancer consecutively admitted at the European Institute of Oncology. Results were compared with those of a non-randomized unmatched control group of premenopausal women with locally advanced ER positive breast cancer receiving preoperative chemotherapy, followed by tamoxifen and GnRH-a after surgery. Primary endpoints were pathological complete response (pCR) rate, decrease of Ki67 and disease free survival (DFS). One-hundred and nineteen women constituted the study group, while 95 patients served as controls. The pCR rate was 5.0 vs 1.1% in the study and control group, respectively. A statistically significant greater suppression of Ki67 was observed in patients receiving chemoendocrine therapy as compared with controls (P = 0.003). At a median follow up of 59 months, 26 events occurred in the chemoendocrine group and 48 in the control group. Five-year DFS was 78 vs 41% in the study and in the control group, respectively [adjusted HR 0.46, 95% CI 0.27-0.79, P = 0.0047]. The concurrent administration of letrozole and GnRH-a with preoperative chemotherapy was highly effective in premenopausal women with large ER positive breast cancer in terms of decreased proliferation and of improved DFS. Randomized studies are warranted to establish the role of the addition of endocrine therapy to chemotherapy as standard preoperative approach for ER positive locally advanced breast cancer as well as of letrozole in combination with GnRH-a for the treatment of premenopauasal women with early breast cancer.
authors.affiliation: Research Unit of Medical Senology at the Department of Medicine, European Institute of Oncology, Milano, Italy. rosalba.torrisi@humanitas.it
authors.forename: Rosalba
authors.initials: R
authors.lastname: Torrisi
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Bagnardi
authors.forename: Nicole
authors.initials: N
authors.lastname: Rotmensz
authors.forename: Eloise
authors.initials: E
authors.lastname: Scarano
authors.forename: Monica
authors.initials: M
authors.lastname: Iorfida
authors.forename: Paolo
authors.initials: P
authors.lastname: Veronesi
authors.forename: Alberto
authors.initials: A
authors.lastname: Luini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Viale
authors.forename: Armando
authors.initials: A
authors.lastname: Santoro
authors.forename: Marco
authors.initials: M
authors.lastname: Colleoni
authors.forename: Aron
authors.initials: A
authors.lastname: Goldhirsch
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000628:therapy*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000401:mortality / Q000628:therapy*; D018275:Carcinoma, Lobular / Q000378:metabolism / Q000401:mortality / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D004958:Estradiol / Q000378:metabolism; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D000077289:Letrozole; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009570:Nitriles / Q000008:administration & dosage; D017697:Premenopause; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism; D012189:Retrospective Studies; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage
chemical_list: D004958:Estradiol; D007987:Gonadotropin-Releasing Hormone; D019394:Ki-67 Antigen; D000077289:Letrozole; D009570:Nitriles; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014230:Triazoles; C083781:LHRH, Ala(6)-Gly(10)-ethylamide-; C508053:ERBB2 protein, human