scholarly journals Pre-Menopausal Women With Breast Cancers Having High AR/ER Ratios in the Context of Higher Circulating Testosterone Tend to Have Poorer Outcomes

2021 ◽  
Vol 12 ◽  
Author(s):  
Savitha Rajarajan ◽  
Aruna Korlimarla ◽  
Annie Alexander ◽  
C. E. Anupama ◽  
Rakesh Ramesh ◽  
...  
Keyword(s):  
Prognostic Significance ◽  
Disease Free Survival ◽  
High Ratio ◽  
Total Testosterone ◽  
Breast Cancers ◽  
Serum Samples ◽  
Transcript Levels ◽  
Menopausal Women ◽  
Er Positive ◽  
Hormonal Milieu

PurposeWomen with breast tumors with higher expression of AR are in general known to have better survival outcomes while a high AR/ER ratio is associated with poor outcomes in hormone receptor positive breast cancers mostly in post menopausal women. We have evaluated the AR/ER ratio in the context of circulating androgens specifically in patients younger than 50 years most of whom are pre-menopausal and hence have a high estrogenic hormonal milieu.MethodsTumor samples from patients 50 years or younger at first diagnosis were chosen from a larger cohort of 270 patients with median follow-up of 72 months. Expression levels of ER and AR proteins were detected by immunohistochemistry (IHC) and the transcript levels by quantitative PCR. Ciculating levels of total testosterone were estimated from serum samples. A ratio of AR/ER was derived using the transcript levels, and tumors were dichotomized into high and low ratio groups based on the third quartile value. Survival and the prognostic significance of the ratio was compared between the low and high ratio groups in all tumors and also within ER positive tumors. Results were further validated in external datasets (TCGA and METABRIC).ResultsEighty-eight (32%) patients were ≤50 years, with 22 having high AR/ER ratio calculated using the transcript levels. Circulating levels of total testosterone were higher in women whose tumors had a high AR/ER ratio (p = 0.02). Tumors with high AR/ER ratio had significantly poorer disease-free survival than those with low AR/ER ratio [HR-2.6 (95% CI-1.02–6.59) p = 0.04]. Evaluation of tumors with high AR/ER ratio within ER positive tumors alone reconfirmed the prognostic relevance of the high AR/ER ratio with a significant hazard ratio of 4.6 (95% CI-1.35–15.37, p = 0.01). Similar trends were observed in the TCGA and METABRIC dataset.ConclusionOur data in pre-menopausal women with breast cancer suggest that it is not merely the presence or absence of AR expression but the relative activity of ER, as well as the hormonal milieu of the patient that determine clinical outcomes, indicating that both context and interactions ultimately influence tumor behavior.

Active c-Src has prognostic and therapeutic value in ER-negative breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10063-10063
Author(s):  
A. Arnaout ◽  
L. Yang ◽  
C. Holloway ◽  
N. Steven ◽  
P. Sun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Significance ◽  
Immunohistochemical Analysis ◽  
Tissue Microarrays ◽  
Distant Recurrence ◽  
Breast Cancers ◽  
Nonreceptor Tyrosine Kinase ◽  
Human Breast Carcinomas ◽  
Er Positive ◽  
Er Status

10063 Background: Approximately 33% of newly diagnosed breast cancers lack ER and these tend to have a worse prognosis as compared to ER-positive breast cancers. Therapeutic options are limited as they are not responsive to antihormonal therapy and often develop resistance to chemotherapies. We have recently shown that activation of the nonreceptor tyrosine kinase protein c-Src leads to the accelerated ER degradation in ER-negative breast cancers. This study performs an immunohistochemical analysis of activated c-Src in a large cohort of primary human breast carcinomas to a) assess its prognostic significance and b) correlate its relationship to the ER status of breast cancers. Methods: A total of 916 patients with breast cancer diagnosed between 1987 and 1997 had clinicopathological data and paraffin-embedded tumor tissues for the study. Tissue microarrays were constructed. A four point scoring system based on immunostaining intensity was used to grade the levels of active phosphorylated c-Src. Grading was done by one pathologist. Statistical analysis was used to assess the prognostic significance of activated c-Src and its relationship to other prognostic variables. Results: Median follow-up was 7.31 years. Active c-Src grade was inversely correlated with ER status (p=0.004) and predicted for treatment with chemotherapy (p=0.002) and lack of treatment with Tamoxifen (p=0.007). Patients with greater levels of c-Src tended to be younger (p=0.004) and had higher Bloom Richardson scores for their tumors (p=0.004). Higher levels of c-Src also predicted for for shorter timing to distant recurrence (p=0.01) and shorter timing to death (p=0.04). There was a trend towards a shorter timing to regional recurrence with higher levels of c-Src but the relationship was not statistically significant (p=0.08). Conclusion: This study supports the hypothesis that the presence of active, phosphorylated c-Src contributes to the development of ER-negative status in breast cancers. The presence of c-Src also is associated with other poor prognostic factors and contributes to a worse prognostic outcome. This study suggests that c-Src inhibitors may be a novel therapeutic strategy for the treatment of ER-negative breast cancers. No significant financial relationships to disclose.

Significance of chromosome 17 polysomy in breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e12002-e12002
Author(s):  
Robert W. Galamaga ◽  
Rachel Mariani ◽  
Imad Almanaseer ◽  
Jacob D. Bitran
Keyword(s):  
Breast Cancer ◽  
Survival Data ◽  
Copy Number ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Chromosome 17 ◽  
Gene Copy ◽  
Breast Cancers ◽  
Her 2 ◽  
Disease Free

e12002 Background: Human epidermal growth factor receptor 2 (HER-2) overexpression occurs in up to 30% of breast cancers and has been associated with poor clinical outcomes that have improved with advances in HER-2 directed therapy. The HER-2 gene resides on the long arm of chromosome 17 and amplification is typically assessed via immunohistochemistry or fluorescence in situ hybridization (FISH); HER-2 is interpreted as amplified, non-amplified, or equivocal. The effect and clinical impact of chromosome 17 polysomy in specimens interpreted as HER-2 non-amplified has not been well-established in breast cancer patients. This subgroup may represent a unique set of patients who may benefit from HER-2 directed therapy given the increase in HER-2 gene copy number. If tumors with polysomy 17 share biologic similarities with those positive for HER-2 amplification this may significantly influence the approach to treating these patients. In a single institution study we reviewed all breast cancer cases diagnosed in 2008 which were reported as HER-2 equivocal or non-amplified via FISH and with chromosome 17 polysomy in order to extrapolate disease-free and overall survival data within this subset. Methods: HER-2 expression via FISH from patients diagnosed with breast cancer in 2008 was reviewed. In those patients with equivocal or non-amplified HER-2 expression we selected those with chromosome 17 polysomy defined as a chromosome 17 centromere copy number of > 3 per tumor cell. A total of 9 patients were identified. Results: The median age was 74 (36-88). Median tumor size was 1.6 cm (0.7-4.9) and 8 patients (88%) had both estrogen and progesterone positive tumors. Stage distribution was as follows: stage IA: 4 (44%); stage IIA: 2 (22%); stage IIB: 2 (22%) and stage IIIA: 1 (11%). The actuarial 3 year disease free survival was 67%. Conclusions: Breast cancers with equivocal or non-amplified HER-2 expression with chromosome 17 polysomy represent a unique subset of tumors with a biology that is not well-understood. Previously published studies have yielded conflicting results regarding the prognostic significance of this genotype. Our study reflects a three year survival of 67% which suggests that these patients represent an aggressive subset.

scholarly journals The Role of Redox-Regulating Enzymes in Inoperable Breast Cancers Treated with Neoadjuvant Chemotherapy

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Nelli Roininen ◽  
Kirsi-Maria Haapasaari ◽  
Peeter Karihtala
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Nodal Metastasis ◽  
State Regulation ◽  
Lower Amount ◽  
Related Factor ◽  
Breast Cancers ◽  
Breast Cancer Patients

Although validated predictive factors for breast cancer chemoresistance are scarce, there is emerging evidence that the induction of certain redox-regulating enzymes may contribute to a poor chemotherapy effect. We investigated the possible association between chemoresistance and cellular redox state regulation in patients undergoing neoadjuvant chemotherapy (NACT) for breast cancer. In total, 53 women with primarily inoperable or inflammatory breast cancer who were treated with NACT were included in the study. Pre-NACT core needle biopsies and postoperative tumor samples were immunohistochemically stained for nuclear factor erythroid 2-related factor 2 (Nrf2), Kelch-like ECH-associated protein 1 (Keap1), thioredoxin (Trx), and peroxiredoxin I (Prx I). The expression of all studied markers increased during NACT. Higher pre-NACT nuclear Prx I expression predicted smaller size of a resected tumor (p=0.00052; r=−0.550), and higher pre-NACT cytoplasmic Prx I expression predicted a lower amount of evacuated nodal metastasis (p=0.0024; r=−0.472). Pre-NACT nuclear Trx expression and pre-NACT nuclear Keap1 expression had only a minor prognostic significance as separate factors, but when they were combined, low expression for both antibodies before NACT predicted dismal disease-free survival (log-rank p=0.0030). Our results suggest that redox-regulating enzymes may serve as potential prognostic factors in primarily inoperable breast cancer patients.

scholarly journals High Poly(ADP-Ribose) Polymerase Expression Does Relate to Poor Survival in Solid Cancers: A Systematic Review and Meta-Analysis

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5594
Author(s):  
Nishant Thakur ◽  
Kwangil Yim ◽  
Jamshid Abdul-Ghafar ◽  
Kyung Jin Seo ◽  
Yosep Chong
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Tumour Size ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Breast Cancers ◽  
Brca1 And Brca2 ◽  
Ki 67 ◽  
Free Survival ◽  
Liver Cancers

Poly (ADP-ribose) polymerase (PARP) is a DNA damage repair protein, and its inhibitors have shown promising results in clinical trials. The prognostic significance of PARP is inconsistent in studies of various cancers. In the present study, we conducted a systematic review and meta-analysis to reveal the prognostic and clinicopathological significance of PARP expression in multiple solid cancers. We searched the MEDLINE, EMBASE, and Cochrane databases for relevant research articles published from 2005 to 2021. The pooled hazard ratio (HR) with confidence interval (CI) was calculated to investigate the relationship between PARP expression and survival in multiple solid cancers. In total, 10,667 patients from 31 studies were included. A significant association was found between higher PARP expression and overall survival (OS) (HR = 1.54, 95% CI = 1.34–1.76, p < 0.001), disease-free survival (DFS) (HR = 1.15, 95% CI = 1.10–1.21, p < 0.001), and progression-free survival (PFS) (HR = 1.05, 95% CI = 1.03–1.08, p < 0.001). Subgroup analyses showed that PARP overexpression was significantly related to poor OS in patients with breast cancers (HR = 1.38, 95% CI = 1.28–1.49, p < 0.001), ovary cancers (HR = 1.21, 95% CI = 1.10–1.33, p = 0.001), lung cancers (HR = 2.11, 95% CI = 1.29–3.45, p = 0.003), and liver cancers (HR = 3.29, 95% CI = 1.94–5.58, p < 0.001). Regarding ethnicity, Asian people have almost twice their worst survival rate compared to Caucasians. The pooled odds ratio analysis showed a significant relationship between higher PARP expression and larger tumour size, poor tumour differentiation, lymph node metastasis, distant metastasis, higher TNM stage and lymphovascular invasion, and positive immunoreactivity for Ki-67, BRCA1, and BRCA2. In addition, nuclear expression assessed by the QS system using Abcam and Santa Cruz Biotechnology seems to be the most commonly used and reproducible IHC method for assessing PARP expression. This meta-analysis revealed that higher PARP expression was associated with a worse OS, DFS, and PFS in patients with solid cancers. Moreover, inhibition of this pathway through its specific inhibitors may extend the survival of patients with higher PARP expression.

Pathologic findings from the National Surgical Adjuvant Breast and Bowel Project: prognostic significance of erbB-2 protein overexpression in primary breast cancer.

1990 ◽  
Vol 8 (1) ◽  
pp. 103-112 ◽  
Author(s):  
S Paik ◽  
R Hazan ◽  
E R Fisher ◽  
R E Sass ◽  
B Fisher ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Nuclear Grade ◽  
Lymph Node Status ◽  
Breast Cancers ◽  
National Surgical Adjuvant Breast ◽  
Increased Risk ◽  
Bowel Project ◽  
Independent Variable

In order to investigate the prognostic significance of erbB-2 overexpression, immunohistochemical staining for the erbB-2 protein was performed on sections from paraffin blocks of 292 primary invasive breast cancers obtained from women enrolled in the National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol B-06. Positive reaction indicative of erbB-2 overexpression was observed on tumor cells in 62 (21%) samples. Women whose cancers were judged to have erbB-2 overexpression had a significantly worse overall survival (P = .0012) with twice the mortality rate of women without detectable erbB-2 expression. No statistically significant effect was evident for disease-free survival (P = .22). In multivariate analysis, detection of erbB-2 overexpression was the second most predictive independent variable for survival after nodal status. Overexpression of erbB-2 was more common among tumors of poor nuclear grade (29%) than those of good nuclear grade (12%). The association of erbB-2 overexpression with decreased survival was evident only among women with tumors of good nuclear grade. In this subgroup, erbB-2 overexpression was associated with an approximately fivefold increase in mortality rate (P = .00001). The combined predictive value of erbB-2 overexpression and nuclear grade was evident regardless of their lymph node status. These results provide evidence that detection of erbB-2 overexpression may be an independent prognostic variable for patient survival. Moreover, when combined with evaluation of nuclear grade, it may be possible to use immunostaining for erbB-2 protein to identify patients at increased risk from within a relatively low-risk group.

scholarly journals PD-L1 in Breast Cancers and its Prognostic Significance

2021 ◽  
Vol 11 (01) ◽  
pp. 40-43
Author(s):  
Sayher Kazmi ◽  
Sumayyah Shawana ◽  
Nighat Jamal
Keyword(s):  
Breast Cancer ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Tumour Cells ◽  
Breast Cancers ◽  
Free Survival ◽  
Disease Free ◽  
Treat Breast Cancer ◽  
Common Malignancy

Breast cancer is the most common malignancy in females globally. Various factors are responsible for its development which include both genetic and hormonal causes. An important discovery is the role of the PD-1/PD-L1 axis in the development of cancers. The PD-1-/PD-L1 pathway plays a part in allowing tumour cells escape from the hosts immune response and hence permits the proliferation of tumour cells. PD-L1 expression has been observed in various breast cancers at distinct levels such as in tissues and in blood. Different methods have been utilized for its detection including immunohistochemistry, RNA sequencing and ELISA, amongst others. The results have been conflicting regarding the expression of PD-L1 and the prognosis of breast cancer based on parameters such as overall survival and disease free survival. Different immunotherapies have also emerged as a new modality to treat breast cancer. This review intends to explore the prognostic significance of PD-L1 expression in breast cancers.

scholarly journals Breast Cancer Subtypes and Response to Docetaxel in Node-Positive Breast Cancer: Use of an Immunohistochemical Definition in the BCIRG 001 Trial

2009 ◽  
Vol 27 (8) ◽  
pp. 1168-1176 ◽  
Author(s):  
Judith Hugh ◽  
John Hanson ◽  
Maggie Chon U. Cheang ◽  
Torsten O. Nielsen ◽  
Charles M. Perou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Luminal A ◽  
Her2 Positive ◽  
Luminal B ◽  
Node Positive ◽  
Er Positive ◽  
Positive Breast Cancer

PurposeTo investigate the prognostic and predictive significance of subtyping node-positive early breast cancer by immunohistochemistry in a clinical trial of a docetaxel-containing regimen.MethodsPathologic data from a central laboratory were available for 1,350 patients (91%) from the BCIRG 001 trial of docetaxel, doxorubicin, and cyclophosphamide (TAC) versus fluorouracil, doxorubicin, and cyclophosphamide (FAC) for operable node-positive breast cancer. Patients were classified by tumor characteristics as (1) triple negative (estrogen receptor [ER]–negative, progesterone receptor [PR]–negative, HER2/neu [HER2]–negative), (2) HER2 (HER2-positive, ER-negative, PR-negative), (3) luminal B (ER-positive and/or PR-positive and either HER2-positive and/or Ki67high), and (4) luminal A (ER-positive and/or PR-positive and not HER2-positive or Ki67high), and assessed for prognostic significance and response to adjuvant chemotherapy.ResultsPatients were subdivided into triple negative (14.5%), HER2 (8.5%), luminal B (61.1%), and luminal A (15.9%). Three-year disease-free survival (DFS) rates (P values with luminal B as referent) were 67% (P < .0001), 68% (P = .0008), 82% (referent luminal B), and 91% (P = .0027), respectively, with hazard ratios of 2.22, 2.12, and 0.46. Improved 3-year DFS with TAC was found in the luminal B group (P = .025) and a combined ER-positive/HER2-negative group treated with tamoxifen (P = .041), with a marginal trend in the triple negatives (P = .051) and HER2 (P = .068) subtypes. No DFS advantage was seen in the luminal A population.ConclusionA simple immunopanel can divide breast cancers into biologic subtypes with strong prognostic effects. TAC significantly complements endocrine therapy in patients with luminal B subtype and, in the absence of targeted therapy, is effective in the triple-negative population.

Study the Relationship Between Estrogen Hormone and Calcium in Normal Females Before and After Menopause in Baghdad / Iraq

2018 ◽  
Vol 2 (1) ◽  
Author(s):  
Sameerah Mustafa ◽  
Asal Tawfeeq ◽  
Hadeel Hasan
Keyword(s):  
Oral Contraceptive ◽  
Healthy Controls ◽  
Serum Samples ◽  
Oral Contraceptive Pills ◽  
Contraceptive Pills ◽  
Menopausal Women ◽  
Before And After ◽  
Group A ◽  
Group B ◽  
Age Range

This study involved the collection of (90) samples of women serum which included (30) serum samples collected from women before menopause (reproductive women) in the age range of (22-43) years and were considered as (group A- control). While, (group B) included (30) serum samples collected from women using oral contraceptive pills between the ages of (22-43) years old. Whereas, another (30) serum samples were collected from women after menopause between the ages of (43-54) years and were considered as (group C). All of the collected serum samples were subjected to a number of serological and chemical tests for the measurement of (E2, HDL, LDL and Ca). Then, the obtained data were statistical analyzed and results showed a significant decrease (p˂ 0.05) in (E2 ,Ca and HDL) levels in menopausal women compared to that of the normal healthy controls. While, there were non-significant decrease (p> 0.05) in (E2, Ca and HDL) levels in women taking oral contraceptive when compared to the normal healthy controls. On the other hand, a significant increase (p˂ 0.05) was recorded in LDL level in menopausal women compared to that of the normal healthy controls whereas, no-significant increase (p˃ 0.05) in the LDL level in women taking oral contraceptives when compared to the control women.

Breast carcinoma in young females below the age of 35 years - histopathological and prognostic significance

1970 ◽  
Vol 2 (3) ◽  
pp. 198-202
Author(s):  
D Ghartimagar ◽  
A Ghosh ◽  
OP Talwar ◽  
R Narasimhan
Keyword(s):  
Breast Carcinoma ◽  
Young Women ◽  
Early Stage ◽  
Prognostic Significance ◽  
Age Group ◽  
Breast Cancers ◽  
Young Females ◽  
Younger Age ◽  
Grade 3 ◽  
Group Grade

Background: Breast cancers rarely occur in young women but are known to have more aggressive behaviors and poorer outcome. We here compare the significance of breast carcinoma in female below the age of 35 to the age over 35 whose specimens were submitted to Manipal teaching hospital, Pokhara. Materials and Methods: All cases of mastectomy with carcinoma from January 2000 to September 2011 were included in the study. Clinical and histopathological datas of all cases were reviewed and collated. Results: A total of 148 mastectomy specimens were received, among which, 23 cases (16%) were below 35 years; whereas 125 cases (84%) were above 35 years of age. In both groups, Stage II was the commonest stage but stage III was much more common in older group (33% versus 9%) and stage I was more common in younger age group (39% versus 27%). Bloom Richardson grading showed that in the older age group, grade 1 is the commonest grade (50%) while in the younger group; grade 3 is the commonest (39%). Patients were followed for a varying period of 6 months to 5 years. Two cases (2% of followed up cases) in older group and 3 cases (15% of followed up cases) in the younger group showed recurrence. Conclusion: Breast carcinoma in the patients younger than 35 years though presented at an early stage has higher grade tumor and poorer outcome. DOI: http://dx.doi.org/10.3126/jpn.v2i3.6021 JPN 2012; 2(3): 198-202

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