scholarly journals Correlation of mRNA for oestrogen receptor beta splice variants ERβ1, ERβ2/ERβcx and ERβ5 with outcome in endocrine-treated breast cancer

2004 ◽  
Vol 33 (3) ◽  
pp. 773-782 ◽  
Author(s):  
M P A Davies ◽  
P A O’Neill ◽  
H Innes ◽  
D R Sibson ◽  
W Prime ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oestrogen Receptor ◽  
Splice Variants ◽  
Nodal Status ◽  
Endocrine Treatment ◽  
Breast Cancers ◽  
Treated Breast ◽  
Post Menopausal ◽  
Independent Marker ◽  
Receptor Beta

This study has been performed to test the hypothesis that different oestrogen receptor beta (ERβ) splice variants may be important determinants of clinical parameters, including outcome, in post-menopausal women with breast cancer receiving adjuvant endocrine treatment but no chemotherapy. Splice variants ERβ1, ERβ2 and ERβ5 have been analysed by semi-quantitative RT-PCR in a cohort of 105 patients with primary breast cancer. Clinical correlates included age, grade, size, nodal status, ERα, progesterone receptor, Ki67, relapse-free survival (RFS) and overall survival (OS). Seventy per cent of cases were ERβ1 positive, 69% ERβ2 positive and 70% ERβ5 positive. Within the cohort, 47% were positive for all three variants while 10% were negative for all three. ERβ1 exhibited no discernible relationship with disease outcome. ERβ2 and ERβ5 expression was significantly associated with better RFS (P<0.005), and ERβ2 with better OS (P=0.0002). In multivariate analysis, ERβ2 (P=0.006), nodal status and the level of Ki67 expression were independent predictors for RFS while ERβ2 (P=0.0008) and Ki67 status were independent predictors for OS. In the ERα-positive cases, or in the subset of those receiving adjuvant tamoxifen, ERβ2 was significantly associated with good RFS (P<0.0005) and was the only independent marker of OS. We conclude that precise identification of splice variants of ERβ are more important assessors than is ERβ1 alone of the biological status of individual breast cancers, and hence in predicting their response to endocrine therapy.

scholarly journals Wild-type oestrogen receptor beta (ERβ1) mRNA and protein expression in Tamoxifen-treated post-menopausal breast cancers

2004 ◽  
Vol 91 (9) ◽  
pp. 1694-1702 ◽  
Author(s):  
P A O'Neill ◽  
M P A Davies ◽  
A M Shaaban ◽  
H Innes ◽  
A Torevell ◽  
...  
Keyword(s):  
Protein Expression ◽  
Oestrogen Receptor ◽  
Breast Cancers ◽  
Wild Type ◽  
Mrna And Protein Expression ◽  
Post Menopausal ◽  
Receptor Beta

Endocrine treatment of breast cancer

2011 ◽  
pp. 1611-1622
Author(s):  
Amna Sheri ◽  
Stephen Johnston
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Endocrine Therapy ◽  
Oestrogen Receptor ◽  
Breast Cancer Cells ◽  
Response Duration ◽  
Endocrine Treatment ◽  
Breast Cancers ◽  
Predictors Of Response ◽  
Selective Oestrogen Receptor Modulators

Endocrine manipulation has been recognized as a treatment modality for breast cancer for over 100 years. Oestrogen is an important promoter in the pathogenesis of breast cancer and endocrine response, for the most part, is dependent on the presence of oestrogen receptor, a protein which can be detected in about 70% of primary breast cancers. Historically, treatments 30–40 years ago involved surgical removal of endocrine glands such as the ovaries, adrenal glands, or hypophysis. However, a better understanding of the mechanisms that result in oestrogenic deprivation of breast cancer cells has enabled medical therapeutics to be developed which have largely replaced surgical ablative procedures (Box 11.2.1.1). Firstly, hormonal manipulation can be achieved at a cellular level by competing for oestrogen receptor in the breast tumour, using so-called antioestrogens, such as tamoxifen which, although antioestrogenic on breast cancer cells, can have oestrogenic effects in other tissues. More antioestrogenic agents known as selective oestrogen receptor modulators (SERMs), and ‘pure’ antioestrogens such as fulvestrant have now been developed that have little or no oestrogenic effects, and these are being clinically evaluated. An alternative approach is to lower systemic oestrogen levels in premenopausal women by the use of luteinizing hormone releasing hormone (LHRH) agonists and in postmenopausal women by the use of aromatase inhibitors, which block oestrogen synthesis in nonovarian tissues. Additional, endocrine agents with more ill-defined mechanisms, such as progestogens, androgens, and corticosteroids, can also cause endocrine responses. In patients with oestrogen receptor-positive advanced breast cancer, endocrine treatments in general achieve a response rate of between 20 and 40%, according to the type of therapy and prior exposure to endocrine treatment. Predictors of response to hormone therapy include a previous response to endocrine treatment, the site of metastases, coexpression of progesterone receptor, and the age of the patient. The median response duration to endocrine therapy in advanced disease is about 8–14 months and for some patients response duration can last several years. In patients with early stage oestrogen receptor-positive breast cancer, adjuvant endocrine therapy given for 5 years after primary surgery delays local and distal relapse and prolongs survival. It also substantially reduces the incidence of contralateral breast cancer in patients with primary breast cancers, and similarly will reduce the incidence of breast cancer in healthy women by about 50%. As such, endocrine therapy can be used as chemoprevention of breast cancer. Overall, the development of relatively low toxicity endocrine treatments for advanced and for operable breast cancer has had a substantial impact on the management of this disease, and the types of treatment will be reviewed in this chapter.

Prognostic Role of Hedgehog-GLI1 Signaling Pathway in Aggressive and Metastatic Breast Cancers

2020 ◽  
Vol 21 (1) ◽  
pp. 33-43 ◽  
Author(s):  
Prasuja Rokkam ◽  
Shailender Gugalavath ◽  
Deepak Kakara Gift Kumar ◽  
Rahul Kumar Vempati ◽  
Rama Rao Malla
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Neural Development ◽  
Splice Variants ◽  
Metastatic Breast ◽  
Basic Function ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Aberrant Expression ◽  
Cellular Processes

Glioma-associated oncogene homolog 1 (GLI1) is reported as an amplified gene in human glioblastoma cells. It is a krupple like transcription factor, belonging to the zinc finger family. The basic function of GLI1 is normal neural development at various stages of human. The GLI1 gene was first mapped on the chromosome sub-bands 12q13.3-14.1. Further, single nucleotide polymorphism is mostly observed in translating a region of 5’ and 3’- UTR of GLI1 gene in addition to two post-transcriptional splice variants, GLIΔN and tGLI. Additionally, it also regulates a plethora of gene which mediates crucial cellular processes like proliferation, differentiation, oncogenesis, EMT, and metastasis. It also regulates tumor tolerance, chemoresistance, and radioresistance. Aberrant expression of GLI1 predicts the poor survival of breast cancer patients. GLI1 is an essential mediator of the SHH signaling pathway regulating self-renewal of stem cells, angiogenesis, and expression of FOXS1, CYR61. GLI1 mediated HH pathway can induce apoptosis. Hence, GLI1 can be a future diagnostic, prognostic marker, and as well as a potent target of therapeutics in breast cancer.

scholarly journals Impact of Nuclear Oestrogen Receptor Beta Expression in Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy

2019 ◽  
Vol 79 (10) ◽  
pp. 1110-1117
Author(s):  
Florian Heitz ◽  
Sherko Kümmel ◽  
Bianca Lederer ◽  
Christine Solbach ◽  
Knut Engels ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Hormone Receptor ◽  
Oestrogen Receptor ◽  
Multivariate Analyses ◽  
Complete Response ◽  
Breast Cancer Patients ◽  
Hormone Receptor Positive ◽  
The Impact ◽  
Receptor Beta

Abstract Introduction Oestrogen receptor beta (ER-β) is abundantly expressed in breast cancer (BC), but its impact on neoadjuvant chemotherapy outcome is unknown. Patients and Methods Patients treated in the neoadjuvant GeparTrio trial with available tissue for immunohistochemical analyses were included. Nuclear ER-β expression was correlated with clinico-pathologic characteristics. The impact of its expression on pathological complete response (pCR [ypT0/ypN0]) and survival was determined. Results Samples of 570 patients were available. Low nuclear ER-β expression (IRS < 9) was observed in 48.4% of hormone receptor positive and 58.6% of hormone receptor negative tumours. Low nuclear ER-β expression was associated with higher pCR rates compared to high nuclear ER-β expression (16.1% vs. 4.7%, p = 0.026). Low ER-β expression was no independent predictor of pCR in multivariate analyses. Disease-free and overall survival were not statistically different between patients with high and low nuclear ER-β expression. Triple-negative BCs showed low nuclear ER-β expression in 57.7%, and pCR rates were 27.1% and 0% (p = 0.23) in low and high ER-β expressing tumours, respectively. Conclusion Low ER-β expression is associated with improved pCR rates in univariate analyses. However multivariate analyses and survival analyses do not indicate an impact of ER-β on survival in patients undergoing neoadjuvant chemotherapy. Further examination of ER-β as predictor for endocrine therapy might be of value.

Adjuvant Endocrine Therapy for Women With Hormone Receptor–Positive Breast Cancer: ASCO Clinical Practice Guideline Focused Update

2019 ◽  
Vol 37 (5) ◽  
pp. 423-438 ◽  
Author(s):  
Harold J. Burstein ◽  
Christina Lacchetti ◽  
Holly Anderson ◽  
Thomas A. Buchholz ◽  
Nancy E. Davidson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Practice ◽  
Endocrine Therapy ◽  
Clinical Practice Guideline ◽  
Practice Guideline ◽  
Cancer Recurrence ◽  
Endocrine Treatment ◽  
Breast Cancers ◽  
Node Negative ◽  
Positive Breast Cancer

Purpose To update the ASCO clinical practice guideline on adjuvant endocrine therapy based on emerging data about the optimal duration of aromatase inhibitor (AI) treatment. Methods ASCO conducted a systematic review of randomized clinical trials from 2012 to 2018. Guideline recommendations were based on the Panel’s review of the evidence from six trials. Results The six included studies of AI treatment beyond 5 years of therapy demonstrated that extension of AI treatment was not associated with an overall survival advantage but was significantly associated with lower risks of breast cancer recurrence and contralateral breast cancer compared with placebo. Bone-related toxic effects were more common with extended AI treatment. Recommendations The Panel recommends that women with node-positive breast cancer receive extended therapy, including an AI, for up to a total of 10 years of adjuvant endocrine treatment. Many women with node-negative breast cancer should consider extended therapy for up to a total of 10 years of adjuvant endocrine treatment based on considerations of recurrence risk using established prognostic factors. The Panel noted that the benefits in absolute risk of reduction were modest and that, for lower-risk node-negative or limited node-positive cancers, an individualized approach to treatment duration that is based on considerations of risk reduction and tolerability was appropriate. A substantial portion of the benefit for extended adjuvant AI therapy was derived from prevention of second breast cancers. Shared decision making between clinicians and patients is appropriate for decisions about extended adjuvant endocrine treatment, including discussions about the absolute benefits in the reduction of breast cancer recurrence, the prevention of second breast cancers, and the impact of adverse effects of treatment. Additional information can be found at www.asco.org/breast-cancer-guidelines .

Late relapse associated with CEP 17 polysomic breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 20011-20011
Author(s):  
L. J. Theobald ◽  
S. Dobin ◽  
S. Beeran ◽  
D. Miltenburg ◽  
H. Rajab ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Amplification ◽  
Tumor Size ◽  
Nodal Status ◽  
Gene Copy ◽  
Categorical Variables ◽  
Late Relapse ◽  
Study Cohort ◽  
Breast Cancers ◽  
Clinicopathologic Factor

20011 Background: The clinicopathologic features associated with chromosome enumeration probe 17 (CEP 17) polysomy by fluorescence in situ hybridization (FISH) are not well defined. CEP 17 polysomy is frequently encountered in assessing Her-2neu amplification, which has become an important adjuvant therapeutic target. One mechanism to increase Her-2neu gene copy is polysomy. In this analysis the prognostic and predictive factors associated with CEP 17 polysomy are compared to similar factors in Her-2neu gene amplification. Methods: All cases of Her-2neu gene amplification and CEP 17 polysomic breast cancers from 2000 to present were abstracted. The polysomy group was defined as at least 3 gene copies and was further subdivided into two groups; 3–4 copies and ≥ 5 copies. This resulted in 193 cases of invasive breast cancer, which became the study cohort. Polysomic status and her-2neu gene amplification was compared to age, estrogen receptor (ER), progesterone receptor (PR), grade, tumor size, cell type, mitotic rate, nodal status, number of positive nodes and relapse. Descriptive statistics were used for categorical variables. The χ2 test was used to compare each clinicopathologic factor. Results: Both the ER and PR status was significantly different in the 3 groups. For the Her-2neu amplified, the polysomic 3–4, and the polysomic ≥ 5, the ER positive status was 53%, 67% and 81%, respectively (p = .012). Histologic grade, tumor size and nodal status were not significantly different between groups. Lobular pathology was present in 15% of the polysomy ≥ 5 group, 8% of the polysomy 3–4 group and 1.7% of the amplified group and this difference was significant (p = .03). Relapse disease status was significantly more frequent in the polysomy ≥ 5 group (18.5%) compared to the amplified group (2.6%) (p = .007). Within the relapsed group the median time to relapse was 4 years for the amplified patients versus 12 years and 10 years for the polysomic patients. Conclusion: The incidence of CEP 17 polysomy varies in the literature from 10–50% depending on definitions. Our study is unique in that we divided the polysomic group into 3–4 copies which can be complicated by proliferative activity versus ≥ 5 copies. A significant association between relapse and polysomic breast cancer is described in our dataset. No significant financial relationships to disclose.

Breast cancers with stem cell-like features delineate endocrine responsiveness

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10517-10517
Author(s):  
A. Rody ◽  
T. Karn ◽  
C. Solbach ◽  
R. Gaetje ◽  
R. Diallo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Lymph Node ◽  
Survival Rates ◽  
Disease Recurrence ◽  
Normal Breast ◽  
Endocrine Treatment ◽  
Breast Cancers ◽  
Er Positive ◽  
Er Status

10517 Background: Endocrine responsiveness is one of the most important characteristics of breast cancer. The negative association between expression of the estrogen receptor (ER) and proliferation detected in normal breast is frequently lost in breast cancers leading to receptor independent growth and poor patients’ prognosis. Methods: Microarray analysis of 171 breast cancer samples allowed the discrimination of a KIT+ tumor group by using a set of genes coregulated with the “stem cell factor” receptor KIT. Validation was performed on three independent datasets encompassing 637 samples. Furthermore the response to endocrine treatment only was analyzed in a dataset of 700 patients. Results: KIT+ tumors are transcriptionally related to proposed mammary stem cells. Two types of KIT+ tumors were identified which are characterized by their positive and negative ER status, respectively. The inverse link of ER expression and proliferation is perfectly conserved within the KIT+ tumor groups, while it is uncoupled among half of the KIT-Low ER positive tumors. Those “uncoupled” ER positive tumors with altered ER response are characterized by a prognosis inferior to the ER negative cancers despite an apparent positive ER status (hazard ratio for disease recurrence, 2.07; 95% CI 1.53–2.81; P<0.001). Moreover, the 5 and 10 year survival rates of lymph node negative “uncoupled” tumors are even worse than those of lymph node positive “normal” ER positive cancers. While all ER positive patients seem to profit from endocrine treatment the relative benefit was reduced in uncoupled tumors (21.2 % vs. 31.7 %). Conclusions: The classification of breast cancers according to this biologically based model identified clinical relevant tumor groups whose further characterization will have important implications. Moreover, since the ability to recognize malfunctions in ER pathways largely depends on an appropriate reference system, the KIT+ tumors could allow a dissection of estrogen responsiveness giving crucial insights for prediction of response to endocrine therapy. No significant financial relationships to disclose.

Claudin 1, 3, 4, and 7 expression in triple-negative breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1070-1070
Author(s):  
Beom Seok Ko ◽  
Hee Jeong Kim ◽  
Jong Han Yu ◽  
jong Won Lee ◽  
Byung Ho Sohn ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Triple Negative Breast Cancer ◽  
Poor Prognosis ◽  
Triple Negative ◽  
Disease Free Survival ◽  
Endocrine Treatment ◽  
Lymph Node Status ◽  
High Recurrence Rate ◽  
Breast Cancers

1070 Background: Triple negative breast cancer (TNBC) often grows rapidly and has poor prognosis, with a high recurrence rate. Because conventional endocrine treatment and HER2 targeted therapy for TNBC is invalid, chemotherapy is the only systemic treatment for TNBC. It is known that several subtypes within the TNBC show different responses to chemotherapy, depending on the subtypes. Recently, a claudin (CLDN) low breast cancer has been identified, exhibiting low expressions of CLDNs 1, 3, 4 and 7. CLDNs are transmembrane proteins that seal tight junctions and are critical for maintaining cell-to-cell adhesion in epithelial cell sheets. However, their role in cancer progression remains largely unexplored. Methods: Surgically removed, formalin-fixed, paraffin-embedded breast cancers from 341 TNBC patients were analyzed to identify CLDN expression.They underwent wide local excision or mastectomy between March, 2004 and December, 2007 at the breast surgery unit of Asan Medical Central Hospital. Results: In our tumor series, we found 45.0% (153/339) of high expressing cases for CLDN1, 57.0% (192/337) for CLDN3, 57.6% (194/337) for CLDN4 and 44.0% (149/339) for CLDN7. Overall, we found 20.5% (70/341) of cases were within the low CLDN expression group and 79.5% (271/341) of tumors were within the high expression group of CLDN1, 3, 4 ,7. Although the high CLDN expression group was significantly associated with positive lymph node status and higher stage, there were no significant differences between CLDN low and high groups in disease free survival (p=0.477) or overall survival (p=0.253). Conclusions: CLDN high tumors are associated with poor prognosis features, but they are not an independent prognostic factor in TNBC patients. However, the mechanisms underlying the different roles of CLDNs in tumorigenesis are largely unclear. Studying the associations of these CLDNs with the TNBC subgroup of breast cancers might provide us with potential diagnostic biomarkers or therapeutic targets for cancer cells.

Mammostrat as an immunohistochemical multigene assay for prediction of early relapse risk in the TEAM pathology study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 516-516
Author(s):  
John M. S. Bartlett ◽  
Kenneth J. Bloom ◽  
Tammy Robson ◽  
Thomas J. Lawton ◽  
Cornelis J. H. Van De Velde ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Endocrine Therapy ◽  
Disease Free Survival ◽  
Postmenopausal Breast Cancer ◽  
Nodal Status ◽  
Endocrine Treatment ◽  
Breast Cancer Patients ◽  
Additional Information ◽  
Er Positive

516 Background: Some postmenopausal patients with hormone sensitive early breast cancer remain at high risk of relapse despite endocrine therapy, and might benefit additionally from adjuvant chemotherapy. The challenge is to prospectively identify such patients. The Mammostrat test uses five immunohistochemical markers to stratify patients regarding recurrence risk, and may inform treatment decisions. We tested the efficacy of this panel in the TEAM trial. Methods: Pathology blocks from 4598 TEAM patients were collected and TMAs constructed. The cohort was 47% node positive and 36% were also treated with adjuvant chemotherapy. Triplicate 0.6mm2 TMA cores were stained and positivity for p53, HTF9C, CEACAM5, NDRG1, SLC7A5 assessed. Cases were assigned a Mammostrat risk score, and distant relapse free (DRFS) and disease free survival (DFS) analysed. Results: In multivariate regression analyses, corrected for conventional clinicopathological markers, Mammostrat provided significant additional information on DRFS after endocrine therapy in ER positive node negative patients (N=1226) not receiving chemotherapy (p=0.004). Further analyses in all patients not exposed to chemotherapy, irrespective of nodal status (N=2559) and in the entire cohort (N=3837) showed Mammostrat scores provide additional information on DRFS in these groups (p=0.001 and p<0.0001 respectively; multivariate analyses). No differences were seen between the two endocrine treatment regimens. Conclusions: The Mammostrat score predicts DRFS for both exemestane and tamoxifen-exemestane treated patients irrespective of nodal status and chemotherapy. The ability of this test to provide additional outcome data following treatment provides further evidence for its’ utility in risk stratification of ER positive postmenopausal breast cancer patients.

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