scholarly journals High IKKα expression is associated with reduced time to recurrence and cancer specific survival in oestrogen receptor (ER)-positive breast cancer

2017 ◽  
Vol 140 (7) ◽  
pp. 1633-1644 ◽  
Author(s):  
Lindsay Bennett ◽  
Jean Quinn ◽  
Pamela McCall ◽  
Elizabeth A. Mallon ◽  
Paul G. Horgan ◽  
...  
2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 612-612
Author(s):  
B. M. Syed ◽  
S. J. Johnston ◽  
D. W. M. Wong ◽  
D. A. L. Morgan ◽  
I. O. Ellis ◽  
...  

612 Background: A recent Cochrane review of seven randomised trials involving 1,446 elderly women (unselected for oestrogen receptor (ER) status) has shown no significant difference in overall survival between surgery (with or without adjuvant tamoxifen) and primary endocrine therapy using tamoxifen. We now report results of a large series from a single centre with a dedicated elderly breast cancer service, with long term follow-up. Methods: During a period of > 20 years, 1,031 elderly (> 70 years) women with ER positive (H-score >50) early operable primary breast cancer received either surgery (with or without adjuvant endocrine therapy) (N = 436) or primary endocrine therapy (N = 595) (>80% using tamoxifen) as initial treatment, with complete follow-up information till deaths. The initial treatment was decided based on fitness for surgery and patient choice. Analysis was carried out on breast cancer specific survival and degree of ER positivity. Results: After a median follow up of 49 months (range 0 - 261 months), patients between 70 - 80 years, treated by surgery, had better 5-year breast cancer specific survival compared to their counterparts treated by primary endocrine therapy (95% versus 85%; p < 0.001). For patients > 80 years, there was however no statistical difference between the two groups (90% versus 90%; p = 0.813). The median survival has not reached yet in all groups. Patients in the latter group (> 80 years) were found to have a higher chance of having strongly ER positive tumours (57% versus 50% in patients between 70 - 80 years with H-score >200; p- < 0.02). Conclusions: In a selected group of elderly women (> 80 years) who tend to have strongly ER positive tumours, surgery and primary endocrine therapy did not appear to produce any difference in breast cancer specific survival. This subject is currently being investigated in a national randomised trial in the UK. No significant financial relationships to disclose.


Author(s):  
Juliet Richman ◽  
Alistair Ring ◽  
Mitch Dowsett ◽  
Ivana Sestak

Abstract Purpose Clinical Treatment Score at 5 years (CTS5) is a prognostic tool to estimate distant recurrence (DR) risk after 5 years of endocrine therapy for postmenopausal women with oestrogen receptor-positive (ER-positive) breast cancer. Methods The validity of CTS5 was tested in a retrospective cohort of patients diagnosed with early ER-positive breast cancer. The primary endpoint was DR in years 5–10. The primary analysis cohort consisted of postmenopausal women, with premenopausal women as a secondary analysis cohort. Cox regression models were used to determine the prognostic value of CTS5 and Kaplan–Meier curves were used with associated 10-year DR risks (%). Results 2428 women were included with a median follow-up of 13.4 years. The CTS5 was significantly prognostic in both postmenopausal (N = 1662, HR = 2.18 95% CI (1.78–2.67)) and premenopausal women (N = 766, HR = 1.84 95% CI (1.32–2.56)). The 10-year DR risks were 2.9% (1.9–4.5), 7.2% (5.3–9.9), and 12.9% (10.0–16.7) for low, intermediate and high risk in postmenopausal women and 3.8% (2.2–6.7), 6.9% (4.4–10.8), and 11.1% (7.4–16.5) in premenopausal women, respectively. The number of observed DRs was significantly greater than expected in those predicted to be at high risk by CTS5 but this discordance was lost when those receiving more than 60 months of endocrine therapy were excluded. Conclusions The CTS5 demonstrated clinical validity for predicting late DR within a large cohort of unselected postmenopausal patients but less so in premenopausal patients. Calibration of the CTS5 was good in patients who did not receive extended endocrine therapy. The CTS5 low-risk cohort has risk of DR so low as to not warrant extended endocrine therapy.


2005 ◽  
Vol 34 (2) ◽  
pp. 553-566 ◽  
Author(s):  
L C Murphy ◽  
B Peng ◽  
A Lewis ◽  
J R Davie ◽  
E Leygue ◽  
...  

To investigate the effect of altered oestrogen receptor (ER)α and ERβ expression on oestrogen and anti-oestrogen action in breast cancer, we have stably expressed an inducible ERβ1 in MCF7 breast cancer cells. Stably expressing clones were isolated and over-expression of ERβ1 correlated with increased levels of specific radiolabelled oestradiol (E2) binding. Increased ERβ1 did not affect endogenous levels of ERα but increased progesterone receptor (PR) levels. Over-expression of ERβ1 reduced growth responses to E2 in contrast to little if any effect of over-expression of ERα. In oestrogen-replete conditions, over-expression of ERβ1 but not ERα reduced proliferation. Over-expression of ERβ1 did not result in anti-oestrogen resistance but was associated with increased sensitivity to 4-hydroxytamoxifen. Our results suggested that over-expression of ERβ1 in the presence of an endogenously expressed ERα was associated with tamoxifen sensitivity but may negatively modulate ERα-mediated growth. However, not all ERα activities were inhibited since endogenous PR expression was increased by both ERα and ERβ1 over-expression. These data paralleled those seen in some in vivo studies showing a relationship between PR and ERβ expression as well as ERβ expression and tamoxifen sensitivity of ER-positive breast cancer patients. These models are relevant and will be useful for dissecting the role of ERβ1 expression in ER-positive breast cancer.


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