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Oestrogen receptors β1 and βcx have divergent roles in breast cancer survival and lymph node metastasis.

Rosin G, de Boniface J, Karthik GM, Frisell J, Bergh J, Hartman J - Br. J. Cancer (2014)

Bottom Line: The expression of oestrogen receptor (ER) α characterises a subset of breast cancers associated with good response to endocrine therapy.Our study reveals highly significant although antagonising roles of ERβ1 and ERβcx in breast cancer.Consequently, we suggest that the histopathological assessment of ERβ1 is of value as a prognostic and potentially predictive biomarker.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Oncology and Pathology, Karolinska Institutet, 171 77 Stockholm, Sweden [2] Department of Biosciences and Nutrition, Karolinska Institutet, Novum, 14183 Huddinge, Sweden.

ABSTRACT

Background: The expression of oestrogen receptor (ER) α characterises a subset of breast cancers associated with good response to endocrine therapy. However, the clinical significance of the second ER, ERβ1, and its splice variant ERβcx is still unclear.

Methods: We here report an assessment of ERα, ERβ1 and ERβcx by immunohistochemistry using quantitative digital image analysis of 340 primary tumours and corresponding sentinel lymph nodes.

Results: No differences were seen in ER levels in primary tumours vs lymph node metastases. ERβ1 and ERβcx were equally distributed among age groups and tumour histological grades. Loss of ERβ1 in the primary tumour was strongly associated with poor survival. Its prognostic impact was particularly evident in young patients and in high-grade tumours. The worst outcome was seen in the tumours lacking both ERα and ERβ1. ERβcx expression in the primary tumour correlated with a higher risk of lymph node metastasis, and with poor survival when expressed in sentinel node lymphocytes.

Conclusions: Our study reveals highly significant although antagonising roles of ERβ1 and ERβcx in breast cancer. Consequently, we suggest that the histopathological assessment of ERβ1 is of value as a prognostic and potentially predictive biomarker.

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Related in: MedlinePlus

Kaplan–Meier plots of overall survival and breast cancer-specific survival for ER expression in primary tumour and sentinel node lymphocytes. (A) There was a higher overall survival in patients with ERβ1-positive tumours (green) compared to ERβ1-negative (blue; log rank P=0.009). (B) The same was seen for breast cancer-specific survival for ERβ1-positive tumours (log rank P=0.011). (C) Breast cancer-specific survival was higher in patients with ERα-positive tumours (log rank P=0.048). (D) Breast cancer-specific survival did not differ between patients with ERβcx-positive or -negative tumours (log rank P=0.73). (E) There was a trend towards better overall survival in patients with ERβcx-negative tumours; however, this did not reach statistical significance (log rank P=0.18). (F) Patients with ERβcx-negative lymphocytes in the sentinel node showed a non-significant trend towards better overall survival (log rank P=0.053). Numbers at risk at each time point are given below each subfigure.
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fig2: Kaplan–Meier plots of overall survival and breast cancer-specific survival for ER expression in primary tumour and sentinel node lymphocytes. (A) There was a higher overall survival in patients with ERβ1-positive tumours (green) compared to ERβ1-negative (blue; log rank P=0.009). (B) The same was seen for breast cancer-specific survival for ERβ1-positive tumours (log rank P=0.011). (C) Breast cancer-specific survival was higher in patients with ERα-positive tumours (log rank P=0.048). (D) Breast cancer-specific survival did not differ between patients with ERβcx-positive or -negative tumours (log rank P=0.73). (E) There was a trend towards better overall survival in patients with ERβcx-negative tumours; however, this did not reach statistical significance (log rank P=0.18). (F) Patients with ERβcx-negative lymphocytes in the sentinel node showed a non-significant trend towards better overall survival (log rank P=0.053). Numbers at risk at each time point are given below each subfigure.

Mentions: Ten-year overall survival was significantly lower in women with ERβ1-negative tumours (79.7% vs 91.1%, log rank P=0.009, Figure 2A) with a HR of 2.48 (95% CI 1.23–5.01). The corresponding figures for patients receiving adjuvant endocrine treatment were 88.7% vs 92.0% and for untreated patients 48.6% vs 92.4% (endocrine treatment-adjusted log rank P=0.005). No differences were seen when controlling for different types of endocrine treatment, such as tamoxifen or aromatase inhibitors. When primary tumours were stratified according to histological grades, 10-year overall survival was significantly worse for women with ERβ1-negative tumours of high grade compared to patients with ERβ1-positive high-grade tumours (60% vs 87.8%, log rank P=0.008). There was no significant survival difference with regard to ERβ1 expression within grade 1 and grade 2 tumours. The prognostic potential of ERβ1 was also compared within the four age groups described above. Although the youngest age group included too few patients for subgroup analysis, 10-year overall survival was significantly lower in women with ERβ1-negative tumours aged 40–54 and 55–64 years than in their ERβ1-positive counterparts (80% vs 98.7%, log rank P=0.001 and 84.7% vs 91.5%, log rank P=0.042). No significant survival difference in regard to ERβ1 status was seen in elderly women (>64 years).


Oestrogen receptors β1 and βcx have divergent roles in breast cancer survival and lymph node metastasis.

Rosin G, de Boniface J, Karthik GM, Frisell J, Bergh J, Hartman J - Br. J. Cancer (2014)

Kaplan–Meier plots of overall survival and breast cancer-specific survival for ER expression in primary tumour and sentinel node lymphocytes. (A) There was a higher overall survival in patients with ERβ1-positive tumours (green) compared to ERβ1-negative (blue; log rank P=0.009). (B) The same was seen for breast cancer-specific survival for ERβ1-positive tumours (log rank P=0.011). (C) Breast cancer-specific survival was higher in patients with ERα-positive tumours (log rank P=0.048). (D) Breast cancer-specific survival did not differ between patients with ERβcx-positive or -negative tumours (log rank P=0.73). (E) There was a trend towards better overall survival in patients with ERβcx-negative tumours; however, this did not reach statistical significance (log rank P=0.18). (F) Patients with ERβcx-negative lymphocytes in the sentinel node showed a non-significant trend towards better overall survival (log rank P=0.053). Numbers at risk at each time point are given below each subfigure.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4150283&req=5

fig2: Kaplan–Meier plots of overall survival and breast cancer-specific survival for ER expression in primary tumour and sentinel node lymphocytes. (A) There was a higher overall survival in patients with ERβ1-positive tumours (green) compared to ERβ1-negative (blue; log rank P=0.009). (B) The same was seen for breast cancer-specific survival for ERβ1-positive tumours (log rank P=0.011). (C) Breast cancer-specific survival was higher in patients with ERα-positive tumours (log rank P=0.048). (D) Breast cancer-specific survival did not differ between patients with ERβcx-positive or -negative tumours (log rank P=0.73). (E) There was a trend towards better overall survival in patients with ERβcx-negative tumours; however, this did not reach statistical significance (log rank P=0.18). (F) Patients with ERβcx-negative lymphocytes in the sentinel node showed a non-significant trend towards better overall survival (log rank P=0.053). Numbers at risk at each time point are given below each subfigure.
Mentions: Ten-year overall survival was significantly lower in women with ERβ1-negative tumours (79.7% vs 91.1%, log rank P=0.009, Figure 2A) with a HR of 2.48 (95% CI 1.23–5.01). The corresponding figures for patients receiving adjuvant endocrine treatment were 88.7% vs 92.0% and for untreated patients 48.6% vs 92.4% (endocrine treatment-adjusted log rank P=0.005). No differences were seen when controlling for different types of endocrine treatment, such as tamoxifen or aromatase inhibitors. When primary tumours were stratified according to histological grades, 10-year overall survival was significantly worse for women with ERβ1-negative tumours of high grade compared to patients with ERβ1-positive high-grade tumours (60% vs 87.8%, log rank P=0.008). There was no significant survival difference with regard to ERβ1 expression within grade 1 and grade 2 tumours. The prognostic potential of ERβ1 was also compared within the four age groups described above. Although the youngest age group included too few patients for subgroup analysis, 10-year overall survival was significantly lower in women with ERβ1-negative tumours aged 40–54 and 55–64 years than in their ERβ1-positive counterparts (80% vs 98.7%, log rank P=0.001 and 84.7% vs 91.5%, log rank P=0.042). No significant survival difference in regard to ERβ1 status was seen in elderly women (>64 years).

Bottom Line: The expression of oestrogen receptor (ER) α characterises a subset of breast cancers associated with good response to endocrine therapy.Our study reveals highly significant although antagonising roles of ERβ1 and ERβcx in breast cancer.Consequently, we suggest that the histopathological assessment of ERβ1 is of value as a prognostic and potentially predictive biomarker.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Oncology and Pathology, Karolinska Institutet, 171 77 Stockholm, Sweden [2] Department of Biosciences and Nutrition, Karolinska Institutet, Novum, 14183 Huddinge, Sweden.

ABSTRACT

Background: The expression of oestrogen receptor (ER) α characterises a subset of breast cancers associated with good response to endocrine therapy. However, the clinical significance of the second ER, ERβ1, and its splice variant ERβcx is still unclear.

Methods: We here report an assessment of ERα, ERβ1 and ERβcx by immunohistochemistry using quantitative digital image analysis of 340 primary tumours and corresponding sentinel lymph nodes.

Results: No differences were seen in ER levels in primary tumours vs lymph node metastases. ERβ1 and ERβcx were equally distributed among age groups and tumour histological grades. Loss of ERβ1 in the primary tumour was strongly associated with poor survival. Its prognostic impact was particularly evident in young patients and in high-grade tumours. The worst outcome was seen in the tumours lacking both ERα and ERβ1. ERβcx expression in the primary tumour correlated with a higher risk of lymph node metastasis, and with poor survival when expressed in sentinel node lymphocytes.

Conclusions: Our study reveals highly significant although antagonising roles of ERβ1 and ERβcx in breast cancer. Consequently, we suggest that the histopathological assessment of ERβ1 is of value as a prognostic and potentially predictive biomarker.

Show MeSH
Related in: MedlinePlus