Oestrogen receptor β and neoadjuvant therapy with tamoxifen: prediction of response and effects of treatment

Abstract

In order to elucidate the relative importance of oestrogen receptor (ER)a, ERb and an ERb variant (ERb2/bcx) in the response of breast cancers to tamoxifen, tumour levels of each receptor were assessed in 36 patients before and after 3 months of neoadjuvant treatment with tamoxifen (20 mg daily). All patients were postmenopausal women presenting with large ERa-positive breast cancers. Clinical response to treatment was assessed by tumour volume changes as determined from sequential ultrasounds and pathological response by comparison of the tumour morphology before and after treatment. Of 33 cases, 23 (70%) were classified as having a clinical response and 16 (48%) as having a response pathologically. All tumours stained positively for ERa and ERb and 15 out of 33 (45%) for ERb2/bcx. There were no significant differences in quantitative expression of any receptor between tumours that subsequently responded and that did not, whether response was assessed clinically or pathologically. Tamoxifen treatment was associated with a decrease in ERa, but an increase was the most frequent change (17 out of 33) in ERb, and no consistent change was evident in staining of the ERb2/bcx variant. In summary, ERb1 and ERb2/bcx variant protein are detected in ERa-positive breast tumours but their expression is not associated with a response to tamoxifen. Differential changes in ERa and ERb were seen with treatment.

ERβ in breast cancer—Onlooker, passive player, or active protector?

“…We found fifteen studies investigating ERβ expression and response to endocrine therapy. Of these, thirteen examined ERβ protein expression using primarily IHC [82,86,87,93,94,97,104,105,107,[111][112][113][114]. Only three of these studies [82,97,107] separate ERβ tumor populations based on ERα status, although the majority of tumors typically contain both subtypes.…”

“…Of the thirteen studies examining ERβ protein expression (Table 1), one reported no significant correlation between ERβ levels and the response to TAM therapy in ERα+ only tumors [111]. Another group looked exclusively at ERα− tumors from patients treated with hormonal therapy, chemotherapy, or radiotherapy, either alone or in combination [87].…”

“…The role of ERβcx has also been investigated in seven studies [18,83,87,105,110,111,114] analyzing protein expression levels (Table 1). Two observed no significant correlation between ERβcx protein expression and response to TAM [111,114], and a third showed no difference in RFS or OS between patients with ERα− only tumors expressing high versus low ERβcx levels [87].…”

“…Two observed no significant correlation between ERβcx protein expression and response to TAM [111,114], and a third showed no difference in RFS or OS between patients with ERα− only tumors expressing high versus low ERβcx levels [87]. However, three studies have utilized ERβcx-specific C-terminal antibodies to show that ERβcx expression significantly correlates with increased OS [105], increased RFS [83], and a longer survival rate [110] in a total of 314 patients treated with adjuvant or neoadjuvant endocrine therapy.…”

Evaluation of ERα, PR and ERβ isoforms in neoadjuvant treated breast cancer

“…Rody and colleagues observed in a neoadjuvant study that Her-2 seems to be highly predictive for chemotherapy outcome (24). Concerning ERß Miller and colleagues focused on ERß expression with neoadjuvant tamoxifen therapy and observed a decrease of ERß1 (28). Possible effects of aromatase inhibitors or chemotherapy on ERß or a possible predictive value of ERß for cytotoxic drugs remain to be investigated.…”