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.
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.
Torrisi
R
R
Research Unit of Medical Senology, European Institute of Oncology Milan, via Ripamonti 435, Milan, Italy. rosalba.torrisi@ieo.it
Bagnardi
V
V
Pruneri
G
G
Ghisini
R
R
Bottiglieri
L
L
Magni
E
E
Veronesi
P
P
D'Alessandro
C
C
Luini
A
A
Dellapasqua
S
S
Viale
G
G
Goldhirsch
A
A
Colleoni
M
M
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
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
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