Impact of estrogen receptor α on the tamoxifen response and prognosis in luminal-A-like and luminal-B-like breast cancer

Бабышкина, Н. Н.; Вторушин, С. В.; Dronova, T.; Patalyak, S.; Slonimskaya, Е. М.; Kzhyshkowska, Julia; Чердынцева, Н. В.; Choynzonov, E. L.

doi:10.1007/s10238-019-00583-6

Cited by 11 publications

(8 citation statements)

References 20 publications

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“…Our findings are supported by an earlier report describing a prolonged survival of women whose tumors exhibited ESR1 amplification among the 175 patients who had undergone tamoxifen treatment ( 2 ). They are also in line with findings by Babyshkina and colleagues who recently found that in tamoxifen-treated luminal tumors, a significant decrease in ESR1 mRNA expression levels and a heterogeneous ERα protein expression pattern were both associated with a significantly shorter PFS ( 29 ).…”

Section: Discussionsupporting

confidence: 91%

Estrogen Receptor Alpha Gene Amplification Is an Independent Predictor of Long-Term Outcome in Postmenopausal Patients with Endocrine-Responsive Early Breast Cancer

Singer

Holst

Steurer

et al. 2022

Clinical Cancer Research

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Purpose: Estrogen receptor (ER) expression is a prognostic parameter in breast cancer, and a prerequisite for the use of endocrine therapy. In ER+ early breast cancer, however, no receptor-associated biomarker exists that identifies patients with a particularly favorable outcome. We have investigated the value of ESR1 amplification in predicting the long-term clinical outcome in tamoxifen-treated postmenopausal women with endocrine-responsive breast cancer. Patients and Methods: 394 patients who had been randomized into the tamoxifen-only arm of the prospective randomized ABCSG-06 trial of adjuvant endocrine therapy with available formalin-fixed, paraffin-embedded tumor tissue were included in this analysis. IHC ERα expression was evaluated both locally and in a central lab using the Allred score, while ESR1 gene amplification was evaluated by FISH analysis using the ESR1/CEP6 ratio indicating focal copy number alterations. Results: Focal ESR1 copy-number elevations (amplifications) were detected in 187 of 394 (47%) tumor specimens, and were associated with a favorable outcome: After a median follow-up of 10 years, women with intratumoral focal ESR1 amplification had a significantly longer distant recurrence-free survival [adjusted HR, 0.48; 95% confidence interval (CI), 0.26–0.91; P = 0.02] and breast cancer–specific survival (adjusted HR 0.47; 95% CI, 0.27–0.80; P = 0.01) as compared with women without ESR1 amplification. IHC ERα protein expression, evaluated by Allred score, correlated significantly with focal ESR1 amplification (P < 0.0001; χ2 test), but was not prognostic by itself. Conclusions: Focal ESR1 amplification is an independent and powerful predictor for long-term distant recurrence-free and breast cancer–specific survival in postmenopausal women with endocrine-responsive early-stage breast cancer who received tamoxifen for 5 years.

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Section: Discussionsupporting

confidence: 91%

Estrogen Receptor Alpha Gene Amplification Is an Independent Predictor of Long-Term Outcome in Postmenopausal Patients with Endocrine-Responsive Early Breast Cancer

Singer

Holst

Steurer

et al. 2022

Clinical Cancer Research

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“…The subtype of breast cancer was established by the immunohistochemical study of tissue samples after surgery (expression of receptors for estrogen (ER) and progesterone (PR)), HER-2 status and the level of proliferative activity (expression of Ki67) in accordance with the St. Gallen Consensus Recommendation [ 48 ]. IHC was prepared as described [ 49 ]. For ER and PR expressions, the cases were classified as positive when nuclear immunoreactivity was in ≥1% of tumor cells according to the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines [ 50 ].…”

Section: Methodsmentioning

confidence: 99%

Size and Methylation Index of Cell-Free and Cell-Surface-Bound DNA in Blood of Breast Cancer Patients in the Contest of Liquid Biopsy

Тамкович

Tupikin

Kozyakov³

et al. 2022

IJMS

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Aberrantly methylated circulating DNA (cirDNA) has proven to be a good cancer marker, but its detection is limited by low concentrations, fragmentation, and insufficiency. Since the methylated cirDNA was shown to be more stable in circulation than the unmethylated one and was shown to bind with the blood cell surface, we studied the concentration, representation, and fragmentation of tumor-derived methylated DNA in cell-free and cell-surface-associated DNA. We found that long DNA fragments (more than 10 kb) are mainly associated with the surface of blood cells. However, in plasma short DNA fragments (100–1000 bp) were also found along with long DNA fragments. Isolation of short fragments after separation of cirDNA in 6% PAGE followed by quantitative PCR (L1 element) has shown that short DNA fragments in healthy females represent 22% versus 0.5–4.4% in breast cancer patients. The methylated form of the RARβ2 gene was detected only in long DNA fragments by Real-time TaqMan PCR of bisulfite-converted DNA. The methylation index of cirDNA from healthy women was estimated at 0%, 9%, and 7% in plasma, PBS-EDTA, and trypsin eluates from the surface of blood cells, respectively. The methylation index of breast cancer patients’ DNA was found to be 33%, 15%, and 61% in the same fractions confirming the overrepresentation of methylated DNA in csbDNA.

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“…Determination of the molecular subtype of breast cancer was carried out after assessing the receptor status in the operating material (expression of receptors for estrogen (ER) and progesterone (PR)), HER-2 status and the level of proliferative activity (expression of Ki67) in accordance with the St. Gallen Consensus Recommendation [42]. IHC was prepared as described [43]. For ER and PR expressions, the cases were classified as positive when nuclear immunoreactivity was in ≥1% of tumor cells according to the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines [44].…”

Section: Immunohistochemistrymentioning

confidence: 99%

Plasma Exosomes of Patients with Breast and Ovarian Tumors Contain an Inactive 20S Proteasome

et al. 2021

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Exosomes are directly involved in governing of physiological and pathological conditions of an organism through the transfer of information from producing to receiving cells. It can be assumed that exosomes are one of the key players of tumor dissemination since they are very stable and small enough to penetrate from various tissues into biological fluids and then back, thus interacting with tissue target cells. We evaluated the enzymatic activity and the level of 20S proteasome in tissue and exosomes of healthy females (n = 39) and patients with ovarian (n = 50) and breast (n = 108) tumors to reveal the critical role of exosomal cargo in the mediation of different types of metastases. Exosomes from plasma and ascites were isolated and characterized in according to International Society for Extracellular Vesicles guidelines. The level of 20S proteasome in tissue and exosomes was determined using Western blot analysis. Chymotrypsin- and caspase-like (ChTL and CL, respectively) peptidase activities of the proteasomes were determined using fluorogenic Suc-LLVY-AMC and Cbz-LLG-AMC substrates, respectively. We observed increased levels of 20S proteasome in ovarian cancer tissue and luminal B subtype breast cancer tissue as well as in plasma exosomes from cancer patients. Moreover, the level of the 20S proteasome in plasma exosomes and ascites exosomes in patients with ovarian tumors is comparable and higher in ovarian cancer patients with low volume ascites than in patients with moderate and high-volume ascites. We also found increased ChTL and CL activities in breast cancer and ovarian cancer tissues, as well as in peritoneal metastases in ovarian cancer, while proteasomal activity in exosomes from plasma of healthy females and all patients, as well as from ascites of ovarian tumor patients were lower than detection limit of assay. Thus, regardless of the type of tumor metastasis (lymphogenous or peritoneal), the exosomes of cancer patients were characterized by an increased level of 20S proteasome, which do not exhibit enzymatic activity.

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Impact of estrogen receptor α on the tamoxifen response and prognosis in luminal-A-like and luminal-B-like breast cancer

Cited by 11 publications

References 20 publications

Estrogen Receptor Alpha Gene Amplification Is an Independent Predictor of Long-Term Outcome in Postmenopausal Patients with Endocrine-Responsive Early Breast Cancer

Estrogen Receptor Alpha Gene Amplification Is an Independent Predictor of Long-Term Outcome in Postmenopausal Patients with Endocrine-Responsive Early Breast Cancer

Size and Methylation Index of Cell-Free and Cell-Surface-Bound DNA in Blood of Breast Cancer Patients in the Contest of Liquid Biopsy

Plasma Exosomes of Patients with Breast and Ovarian Tumors Contain an Inactive 20S Proteasome

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