The Role of Ultrasound in the Detection of Endometrial Pathologies in Asymptomatic Postmenopausal Breast Cancer Patients With Tamoxifen Treatment

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.

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AGR2 Predicts Tamoxifen Resistance in Postmenopausal Breast Cancer Patients

Disease Markers ◽

10.1155/2013/761537 ◽

2013 ◽

Vol 35 ◽

pp. 207-212 ◽

Cited By ~ 17

Author(s):

Roman Hrstka ◽

Veronika Brychtova ◽

Pavel Fabian ◽

Borivoj Vojtesek ◽

Marek Svoboda

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Optimal Algorithm ◽

Endocrine Resistance ◽

Postmenopausal Breast Cancer ◽

Progression Free Survival ◽

Tamoxifen Treatment ◽

Mrna Levels ◽

Breast Cancer Patients ◽

Er Positive

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.

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Risk of Endometrial Cancer in Breast Cancer Patients under Long-Term Adjuvant Treatment with Tamoxifen

Tumori Journal ◽

10.1177/030089169808400104 ◽

1998 ◽

Vol 84 (1) ◽

pp. 21-23 ◽

Cited By ~ 9

Author(s):

Silvia Cecchini ◽

Stefano Ciatto ◽

Rita Bonardi ◽

Antonia Mazzotta ◽

Paolo Pacini ◽

...

Keyword(s):

Breast Cancer ◽

Endometrial Cancer ◽

Cancer Patients ◽

Endometrial Thickness ◽

Postmenopausal Breast Cancer ◽

Cancer Surveillance ◽

Tamoxifen Treatment ◽

Adjuvant Tamoxifen ◽

Breast Cancer Patients

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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