Prospective evaluation of estrogen receptor-beta in predicting response to neoadjuvant antiestrogen therapy in elderly breast cancer patients.
It has been proposed that knowledge of estrogen receptor beta (ER-beta) expression may refine estrogen receptor alpha (ER-alpha) predictivity of response to endocrine therapy. We challenged this hypothesis in ER-alpha-positive breast cancers subjected to preoperative antiestrogen treatment. Forty-seven elderly (> or =65 years old) women with nonmetastatic, ER-alpha-positive (by immunohistochemistry) primary breast cancers (> 2 cm in diameter) entered a neoadjuvant hormone therapy protocol (60 mg/day toremifene for 3 months). ER-alpha and ER-beta (ERs) mRNA was determined by semiquantitative RT-PCR, before (on core needle biopsy) and after (on surgical specimens) neoadjuvant treatment. Study end points included: (1) relation between treatment response and ER mRNA expression; and (2) changes in ER expression after treatment. The response was clinically assessed as tumor size change at the end of the preoperative treatment. ER mRNA expression was assessable before and after treatment in 38 and 20 cases respectively. ER-beta was co-expressed with ER-alpha at variable levels and significantly correlated only with progesterone receptor (P = 0.0285). Objective clinical response, including patients with minor change (> or =25-<50% tumor shrinkage after treatment), was documented in 68.4% of cases and was independent of ER-beta levels or changes. ER-alpha levels were higher in tumors from patients in complete remission than in those from women achieving partial response or minor change compared with non-responsive patients (median expression values: 801 versus 516 versus 320 arbitrary units) and were consistently down-regulated by preoperative treatment. We conclude that in this elderly patient population with ER-alpha-positive tumors, ER-beta mRNA was neither predictive of response to preoperative toremifene nor provided additional information to the knowledge of ER-alpha mRNA levels, which, conversely, were directly correlated with likelihood of response.
Cappelletti
Vera
V
Department of Experimental Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy. vera.cappelletti@istitutotumori.mi.it
Celio
Luigi
L
Bajetta
Emilio
E
Allevi
Arianna
A
Longarini
Raffaella
R
Miodini
Patrizia
P
Villa
Raffaella
R
Fabbri
Alessandra
A
Mariani
Luigi
L
Giovanazzi
Riccardo
R
Galante
Emanuele
E
Greco
Marco
M
Grazia Daidone
Maria
M
D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D004965:Estrogen Antagonists / Q000627:therapeutic use; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020360:Neoadjuvant Therapy; D012333:RNA, Messenger / Q000096:biosynthesis; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use*; D017312:Toremifene / Q000627:therapeutic use*; D016896:Treatment Outcome; D047368:Tumor Burden
D018931:Antineoplastic Agents, Hormonal; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D012333:RNA, Messenger; D020845:Selective Estrogen Receptor Modulators; D017312:Toremifene