ER Status Measured by FISH Is a Better Predictor of Prognosis in ER Positive, Postmenopausal Breast Cancer Patients Treated with Adjuvant Tamoxifen Than ER Status Measured by RT-qPCR or IHC.

Author(s):  
M. Lyng ◽  
K. Vang ◽  
A. Knoop ◽  
H. Ditzel ◽  
A. Lykkesfeldt ◽  
...  
1997 ◽  
Vol 15 (4) ◽  
pp. 1385-1394 ◽  
Author(s):  

PURPOSE Adjuvant tamoxifen has been shown to reduce relapse and mortality among node-positive post-menopausal breast cancer patients. The value of adding chemotherapy to tamoxifen is controversial. PATIENTS AND METHODS Between July 1986 and April 1993, 1,266 postmenopausal breast cancer patients with node-positive disease were randomly assigned to receive one of four adjuvant therapy regimens: (A) tamoxifen alone for 5 years; (B) tamoxifen plus three courses of early cyclophosphamide, methotrexate, and fluorouracil (CMF) on months 1, 2, and 3; (C) tamoxifen plus delayed single courses of CMF on months 9, 12, and 15; (D) tamoxifen plus early and delayed CMF on months 1, 2, 3, 9, 12, and 15. The two-by-two factorial design allowed two direct comparisons: early CMF (B and D) versus no early CMF (A and C), and delayed CMF (C and D) versus no delayed CMF (A and B). Estrogen receptor (ER) status was known for all patients and was used to stratify the randomization. A total of 1, 212 patients (96%) were eligible and assessable. The median follow-up duration was 60 months. RESULTS The results of the two-by-two factorial comparisons were as follows: (1) early CMF added to tamoxifen significantly improved 5-year disease-free survival (DFS; 64% v 57%; hazards ratio [HR], 0.79; 95% confidence interval [CI], 0.66 to 0.95; P = .01); and (2) delayed CMF added to tamoxifen did not improve DFS (5-year DFS, 61% v 60%; HR, 0.97; 95% CI, 0.81 to 1.17; P = .77). For patients with ER-positive tumors, the addition of CMF, either early or delayed or both, reduced the relative risk of relapse by 22% to 36%. In contrast, for patients with ER-negative tumors, tamoxifen with delayed CMF was associated with a nonsignificant increased risk of relapse (HR, 1.27; 95% CI, 0.92 to 1.76; P = .15). CONCLUSION Postmenopausal patients with node-positive breast cancer should be offered combination chemotherapy in addition to tamoxifen. Tamoxifen should not be initiated before CMF, as this might be detrimental, especially for patients with ER-negative tumors.


1996 ◽  
Vol 60 (3) ◽  
pp. 409-411 ◽  
Author(s):  
Silvia Cecchini ◽  
Stefano Ciatto ◽  
Rita Bonardi ◽  
Antonia Mazzotta ◽  
Grazia Grazzini ◽  
...  

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 562-562
Author(s):  
Karin J. Beelen ◽  
Mark Opdam ◽  
Rutger H.T. Koornstra ◽  
Andrew D. Vincent ◽  
Jan Baptist Vermorken ◽  
...  

562 Background: The sensitivity of the estrogen receptor (ERα) to anti-estrogen therapy can be affected by phosphorylation events. In premenopausal breast cancer patients, phosphorylation of the ERα at serine 118 (ERαS118-p) is predictive for benefit from adjuvant tamoxifen. Since ERαS118-p represents the common hallmark of different signaling cascades that differ in E2 dependency, the resulting effect on estrogen sensitivity may differ between pre- and postmenopausal patients. Phosphorylation of serine 167 (ERαS167-p) has been associated with favorable disease outcome, but whether ERαS167-p can predict tamoxifen sensitivity is currently unknown. We tested the predictive value of both ERαS118-p and ERαS167-p for benefit from adjuvant tamoxifen in postmenopausal breast cancer patients. Methods: We collected primary tumor blocks from 563 ERα positive (stage I-III) postmenopausal patients who had been randomized between tamoxifen (1 to 3 years) vs. no adjuvant therapy (IKA trial). The median follow-up of patients without a recurrence event was 9.4 years. Immunohistochemistry was performed on a TMA using monoclonal antibodies for ERαS118-p and ERαS167-p. The percentage of positive nuclei was scored and a score of ≥ 10 % was considered as positive. Multivariate Cox models were used to assess hazard ratios (HRs) for recurrence free interval and the interaction between these phosphorylations and tamoxifen treatment. Results: We did not find a significant interaction between either ERαS118-p (p=0.99) or ERαS167-p (p=0.44) and tamoxifen, suggesting that the relative benefit from adjuvant tamoxifen in postmenopausal patients is not dependent on the presence of one of these phosphorylations. Both tamoxifen treated patients as well as control patients had a better prognosis when their tumor was positive for ERαS118-p (adjusted HR 0.60 p=0.02) or ERαS167-p (adjusted HR 0.62, p=0.02) compared to patients whose tumor did not express these ERα phosphorylations. Conclusions: In postmenopausal patients ERαS118-p and ERαS167-p are both associated with better prognosis, but do not predict differential benefit from tamoxifen.


2013 ◽  
Vol 35 ◽  
pp. 207-212 ◽  
Author(s):  
Roman Hrstka ◽  
Veronika Brychtova ◽  
Pavel Fabian ◽  
Borivoj Vojtesek ◽  
Marek Svoboda

Endocrine resistance is a significant problem in breast cancer treatment. Thus identification and validation of novel resistance determinants is important to improve treatment efficacy and patient outcome. In our work, AGR2 expression was determined by qRT-PCR in Tru-Cut needle biopsies from tamoxifen-treated postmenopausal breast cancer patients. Our results showed inversed association of AGR2 mRNA levels with primary treatment response (P=0.0011) and progression-free survival (P=0.0366) in 61 ER-positive breast carcinomas. As shown by our experimental and clinical evaluations, elevated AGR2 expression predicts decreased efficacy of tamoxifen treatment. From this perspective, AGR2 is a potential predictive biomarker enabling selection of an optimal algorithm for adjuvant hormonal therapy in postmenopausal ER-positive breast cancer patients.


QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
H M Abdelaziz ◽  
K Naguib ◽  
D Moussa ◽  
N Mohammad

Abstract Background Breast cancer (BC) is a major health problem in Egypt and worldwide. Its prognosis depends not only on tumor stage but also on tumor biology. Aim of the Work To correlate the percentage of expression of Ki67 with the clinical outcomes of early hormone-receptor positive for postmenopausal breast cancer patients who are receiving adjuvant tamoxifen Material and Methods we retrospectively reviewed 52 patients treated for non-metastatic postmenopausal breast cancer with adjuvant tamoxifen at Ain-Shams University hospital, Clinical Oncology department between January 2010 and December 2015. Ki67 value and other clinicopathological data were retrieved. Results Out of 52 patients fulfilling research criteria, the age rannged from 45 to 71 years.All patients were stage0-ΙΙΙ. Stage II was the most common represented 38.5 %, while Stage 0 was the least common presents 3.8%. Using a ki67cut-off value of 20, patients were stratified into two risk groups; the low risk group had ki67 <20 % and represented (67.3%) of cases and the high risk group were ≥ 20% and represented 32.7%. The median Ki67 value was 12.00 (IQR 5 – 20).Median DFS was 42.5 months (IQR 31.2 – 57). Median of OS was 49 moths (IQR 34 – 58).Among multiple prognostic factors Stage, luminal A subtype was significantly related to better OS and DFS In our study, there was no difference regarding OS and DFS between low and high ki67 group’s results ρ = 0.308 and ρ = 0.064 respectively. Conclusion Ki67 is not a predictive factor for resistance to adjuvant tamoxifen in post-menopausal female breast cancer patients.


1998 ◽  
Vol 84 (1) ◽  
pp. 21-23 ◽  
Author(s):  
Silvia Cecchini ◽  
Stefano Ciatto ◽  
Rita Bonardi ◽  
Antonia Mazzotta ◽  
Paolo Pacini ◽  
...  

Aims To evaluate the relative risk of endometrial cancer with respect to the expected underlying incidence in breast cancer patients undergoing long-term adjuvant tamoxifen therapy. Methods A total of 1010 postmenopausal breast cancer patients receiving adjuvant tamoxifen and with a first negative endometrial ultrasonography (cutoff for abnormal endometrial thickness >5 mm) were followed by annual transvaginal ultrasonography. Abnormal endometrial thickness prompted an outpatient endometrial biopsy or curettage under anesthesia in the case of cervical stenosis and increasing endometrial thickness. The standardized incidence ratio (SIR) with respect to underlying incidence was determined. Results A total of 1,010 eligible subjects who had been receiving tamoxifen for an average of 51 months were enrolled and followed for a total of 2,361 patient-years between January 1993 and December 1996. Five cases of endometrial cancer were observed in the study period: 1 was detected at screening, and 4 were diagnosed for vaginal bleeding in the interval between screening examinations. SIR was 4.0 (95% confidence interval, 1.39.4) and increased to 4.8 (CI, 1.6-10.5) when the single cancer detected at first screening was considered as incident. Conclusions This study adds evidence to the hypothesis that long-term tamoxifen treatment may be responsible for a relevant increase in the risk of developing endometrial cancer. Surveillance based on endometrial ultrasonography was poorly sensitive, but the favorable stage at diagnosis of screen-detected or interval endometrial cancers does not support a more aggressive screening approach.


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