title: Antitumour and biological effects of letrozole and GnRH analogue as primary therapy in premenopausal women with ER and PgR positive locally advanced operable breast cancer.
abstract: Preoperative endocrine therapy is effective in postmenopausal patients with breast cancers expressing oestrogen receptor. We investigated the activity of primary therapy with letrozole in combination with GnRH analogue in premenopausal women with T2-T4 N0-N2 breast cancer, whose tumours expressed oestrogen and progesterone receptors. We measured the expression of molecular factors involved in responsiveness to endocrine agents including ERalpha, EGFR, HER2, MAP kinases (and phosphorylated forms) ER-beta1, both at initial biopsy and at the time of surgery. Thirty-five patients were included and 32 patients were evaluable for response. Sixteen patients (50%, 95% CI 32-68%) obtained a partial response, 16 patients were stable. One patient showed pathological complete response (3%, 95% CI 0-16%). Response was significantly associated with younger age (P<0.05) and a longer duration of treatment (P<0.05). Treatment significantly decreased ERalpha-p-Ser(118) and upregulated ER-beta1, independently of response. No or negligible overexpression of EGFR was observed at baseline or after treatment in this population. Preoperative letrozole and GnRH analogue are effective in premenopausal women. A biological response in terms of downregulation of phosphorylated ERalpha was observed in all patients. Future investigations might focus on treatments of longer duration.
authors: Research Unit of Medical Senology, European Institute of Oncology Milan, via Ripamonti 435, Milan, Italy. rosalba.torrisi@ieo.it
authors: R
authors: R
authors: Torrisi
authors: V
authors: V
authors: Bagnardi
authors: G
authors: G
authors: Pruneri
authors: R
authors: R
authors: Ghisini
authors: L
authors: L
authors: Bottiglieri
authors: E
authors: E
authors: Magni
authors: P
authors: P
authors: Veronesi
authors: C
authors: C
authors: D'Alessandro
authors: A
authors: A
authors: Luini
authors: S
authors: S
authors: Dellapasqua
authors: G
authors: G
authors: Viale
authors: A
authors: A
authors: Goldhirsch
authors: M
authors: M
authors: Colleoni
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D047072:Aromatase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D015536:Down-Regulation / Q000187:drug effects; D066246:ErbB Receptors / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000627:therapeutic use*; D006801:Humans; D000077289:Letrozole; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009367:Neoplasm Staging; D009570:Nitriles / Q000494:pharmacology* / Q000627:therapeutic use; D017697:Premenopause; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D013997:Time Factors; D016896:Treatment Outcome; D014230:Triazoles / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D066246:ErbB Receptors; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D007987:Gonadotropin-Releasing Hormone; D000077289:Letrozole; D020928:Mitogen-Activated Protein Kinases; D009570:Nitriles; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014230:Triazoles; C508053:ERBB2 protein, human
references: Eur Urol. 2006 Jan;49(1):54-8; discussion 58
references: 16314038
references: Cancer Chemother Pharmacol. 2005 Nov;56 Suppl 1:21-6
references: 16273360
references: J Clin Oncol. 2006 Mar 1;24(7):1037-44
references: 16505422
references: Br J Cancer. 2006 Apr 10;94(7):1051-6
references: 16538221
references: J Clin Oncol. 2006 Apr 20;24(12):1940-9
references: 16622270
references: J Steroid Biochem Mol Biol. 2006 Apr;99(1):19-32
references: 16533599
references: Onkologie. 2006 May;29(5):210-7
references: 16679783
references: J Steroid Biochem Mol Biol. 2006 Dec;102(1-5):232-40
references: 17055257
references: J Clin Oncol. 2007 Jun 20;25(18):2509-15
references: 17577027
references: Ann Oncol. 2001 May;12(5):685-91
references: 11432629
references: Ann Oncol. 2001 Nov;12(11):1527-32
references: 11822750
references: J Steroid Biochem Mol Biol. 2001 Dec;79(1-5):103-7
references: 11850213
references: Oncogene. 2002 Jul 25;21(32):4921-31
references: 12118371
references: Steroids. 2003 Jan;68(1):1-9
references: 12475718
references: N Engl J Med. 2003 Jun 12;348(24):2431-42
references: 12802030
references: Br J Cancer. 2004 Feb 9;90(3):590-4
references: 14760369
references: Clin Cancer Res. 2004 Feb 15;10(4):1354-9
references: 14977836
references: Clin Cancer Res. 2004 Sep 1;10(17):5769-76
references: 15355905
references: Clin Cancer Res. 2004 Sep 1;10(17):5902-6
references: 15355923
references: Clin Cancer Res. 2004 Oct 1;10(19):6622-8
references: 15475452
references: Eur J Cancer. 1992;28(2-3):415-20
references: 1591054
references: J Clin Oncol. 1999 Feb;17(2):460-9
references: 10080586
references: Anticancer Res. 1999 May-Jun;19(3B):2261-8
references: 10472341
references: Breast Cancer Res Treat. 1999 Jul;56(1):25-34
references: 10517340
references: Clin Cancer Res. 2004 Nov 15;10(22):7490-9
references: 15569979
references: Br J Cancer. 2004 Dec 13;91(12):2012-7
references: 15558072
references: Endocr Relat Cancer. 2004 Dec;11(4):761-70
references: 15613450
references: Lancet Oncol. 2005 Jun;6(6):383-91
references: 15925816
references: J Clin Oncol. 2005 Aug 1;23(22):5108-16
references: 15998903
references: J Steroid Biochem Mol Biol. 2005 May;95(1-5):41-8
references: 15967659
references: Endocr Relat Cancer. 2005 Jul;12 Suppl 1:S113-7
references: 16113087
references: Breast. 2006 Feb;15(1):9-19
references: 16230013