scholarly journals Association between Lymph Node Status and Expression Levels of Androgen Receptor, miR-185, miR-205, and miR-21 in Breast Cancer Subtypes

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Tatiana S. Kalinina ◽  
Vladislav V. Kononchuk ◽  
Alisa K. Yakovleva ◽  
Efim Y. Alekseenok ◽  
Sergey V. Sidorov ◽  
...  

Breast cancer is the most commonly diagnosed cancer among women. Difficulties in treating breast cancer are associated with the occurrence of metastases at early stages of disease, leading to its further progression. Recent studies have shown that changes in androgen receptor (AR) and microRNAs’ expressions are associated with mammary gland carcinogenesis, in particular, with the formation of metastases. Thus, to identify novel metastatic markers, we evaluated the expression levels of AR; miR-185 and miR-205, both of which have been confirmed to target AR; and miR-21, transcription of which is regulated by AR, in breast cancer samples (n=89). Here, we show that the molecular subtypes of breast cancer differ in the expression profiles of AR and AR-associated microRNAs. In addition, the expression of AR and these microRNAs may depend on the expression of PR, ER, and HER2 receptors. Our results show that the possibility of using AR and microRNAs as markers depends on the tumor subtype: a decrease in AR expression may be the marker for the presence of lymph node metastases in patients with HER2-positive subtypes of breast cancer, and disturbance of miR-205, miR-185, and miR-21 expressions may be the marker in patients with a luminal B HER2-positive subtype. Cases with metastases in this type of breast cancer are characterized by a higher level of miR-205 and a lower level of miR-185 and miR-21 in tumor tissues compared to nonmetastatic cases. A decrease in the miR-185 level is also associated with lymph node metastasis in luminal B HER2-negative breast cancer. Thus, the expression levels of AR, miR-185, miR-205, and miR-21 can serve as markers to predict cancer spread to the lymph node in luminal B- and HER2-positive subtypes of breast cancer.

2020 ◽  
Vol 7 (1) ◽  
pp. 30-35
Author(s):  
Nur E Jannatul Ferdous ◽  
Dabashish Patowary ◽  
Yeasmin Nahar ◽  
Mohammad Shafiul Islam ◽  
Suporna Saleh ◽  
...  

Background: Carcinoma of the breast is one of the most common cancer in women and it is the second cause of cancer deaths only to lung cancer. Recent attention has been directed singularly at molecular classifications of breast cancer. Molecular subtypes have different prognostic and therapeutic implications. Objective: The aim of this study was to assess the ER, PR, and HER-2/neu reactivity pattern in breast carcinomas and to correlate this reactivity pattern with stage tumor size and lymph node metastasis. Methodology: This is a prospective analytical observational study was conducted in the North East Cancer Hospital and Department of Pathology of North East Medical College, Sylhet, Bangladesh during a 42 months period from July 2015 to December 2018. Result: Among 67 Cases of primary invasive breast carcinoma only one case was male and 66 were female. In aspect of tumor size most of the patient presented with 2 to 5cm tumor, 47(70.2%) cases and (80.6%) presented with more than 2cm tumor size. In our study 38(56.7%) cases of breast cancer found ER positive, 38.8%(26 cases) PR positive and 22.4% (15 cases) HER2/neu positive, most common presentation of the disease was at stage llB(29 cases,45%), lymph node positivity 46(68.7%) cases and lymph node negative 21(31.3%) cases, 5(7.5%)cases. In aspect of molecular subtyping we found luminl A 29 (43.3%) cases Luminal B 11.9% (8 cases) basal like 22(32.8%) cases and HER-2/neu over expressed 8(11.9%) cases. Conclusion: Cancer screening and early detection program can improve our scenario. Journal of Current and Advance Medical Research 2020;7(1): 30-35


2018 ◽  
Vol 38 (2) ◽  
pp. 54 ◽  
Author(s):  
Jyh-Cherng Yu ◽  
Guo-Shiou Liao ◽  
Huan-Ming Hsu ◽  
Chi-Hong Chu ◽  
Zhi-Jie Hong ◽  
...  

2018 ◽  
Vol 11 (1) ◽  
pp. 177-191
Author(s):  
Nada A.S. Alwan ◽  
David Kerr ◽  
Dhafir Al-Okati ◽  
Fransesco Pezella ◽  
Furat N. Tawfeeq

Background:Breast cancer is the most common cancer in Iraq and the United Kingdom. While the disease is frequently diagnosed among middle-aged Iraqi women at advanced stages accounting for the second cause of cancer-related deaths, breast cancer often affects elderly British women yielding the highest survival of all registered malignancies in the UK.Objective:To compare the clinical and pathological profiles of breast cancer among Iraqi and British women; correlating age at diagnosis with the tumor characteristics, receptor-defined biomarkers and phenotype patterns.Methods:This comparative retrospective study included the clinical and pathological characteristics of (1,940) consecutive female patients who were diagnosed with invasive breast cancer from 2014 to 2016 in Iraq (Medical City Teaching Hospital, Baghdad: 635 cases) and UK (John Radcliffe, Oxford and Queen's, BHR University Hospitals: 1,305 cases). The studied parameters in both groups comprised the age of the patient at the time of diagnosis, breast cancer histologic type, grade, tumor size, lymph node status, clinical stage at presentation, Estrogen Receptor (ER), Progesterone Receptor (PR) and HER2 positive tumor contents and the receptor-defined breast cancer surrogate subtypes.Results:The Iraqi patients were significantly younger than their British counterparts and exhibited higher trend to present at advanced stages; reflected by larger size tumors and frequent lymph node involvement compared to the British (p<0.00001). They also had worse receptor-defined breast cancer subtypes manifested by higher rates of hormone receptor (ER/PR) negative, HER2 positive tumor contents, Triple Positive and Triple Negative phenotypes (p<0.00001). Excluding HER2 status, the significant differences in the clinical and tumor characteristics between the two populations persisted after adjusting for age among patients younger than 50 years.Conclusion:The remarkable differences in the clinical and tumor characteristics of breast cancer between the Iraqi and British patients suggest heterogeneity in the underlying biology of the tumor which is exacerbated in Iraq by the dilemma of delayed diagnosis. The significant ethnic disparities in breast cancer profiles recommend the prompt strengthening of the national cancer control plan in Iraq as a principal approach to the management of the disease.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 549-549
Author(s):  
Robert Konigsberg ◽  
Georg Pfeiler ◽  
Nicole Hammerschmid ◽  
Tatjana Klement ◽  
Christian Dittrich

549 Background: In 2011, the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer (bc) suggested the distinction between Luminal A and Luminal B subtypes. In Luminal A patients (pts) endocrine therapy seems to be sufficiently effective, whereas in Luminal B pts the additional application of chemotherapy should be considered. It is currently unknown, whether the risk stratification into Luminal A and B is comparably or more discriminatory than the established pathologic tumor size (pT) and lymph node (pN) status in pts ≥ 65 years. This analysis evaluates the discriminatory capacity of the new distinction between Luminal A and B and the established prognostic factors in bc pts ≥ 65 years treated with endocrine therapy only. Methods: Clinico-pathological data of 190 bc pts ≥ 65 years diagnosed between 1998 and 2004 were retrospectively analyzed. Pts were classified as Luminal A [ER (+) and/ or PR (+) and Her/2neu (-) and Ki-67 < 14%] or Luminal B [ER (+) and/ or PR (+) and Her2 (-) and Ki-67 ≥ 14%]. The Kaplan-Meier method was used to assess the progression-free survival (PFS) and overall survival (OS) estimates. Differences in survival between groups were tested for significance by the log-rank test. Results: Median age was 74 years (65–92 years) and median time of follow-up was 69 months (0–134 months). 68.9% and 31.1% pts had Luminal A and B subtypes, respectively. 73.3% and 26.7% of pts had pT1 and pT2 tumors, respectively. 79.7% and 20.3% of pts had pN0 and pN1 status, respectively. Overall, median PFS was 33 months. No significant difference regarding PFS could be detected between Luminal A and B pts, between pT1 and pT2 tumors and between pN0 and pN1 status (p=0.458; 0.172; 0.156), respectively. Overall, median OS was not reached. No significant difference regarding OS could be detected between Luminal A and B pts, between pT1 and pT2 tumors and between pN0 and pN1 status (p=0.328; 0.951; 0.976), respectively. Conclusions: In bc pts ≥ 65 years treated with endocrine therapy only, neither the recently consented dichotomization into Luminal A and B subtypes nor pathologic tumor size and lymph node status could be confirmed to be discriminative as propagated in the 2011 St. Gallen Consensus for the overall bc population.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6599-6599
Author(s):  
Andrew Cota Shaw ◽  
Hanna Kelly Sanoff ◽  
Mark E Smolkin

6599 Background: Many cancer centers routinely re-review outside pathologic specimens. We hypothesized re-review rarely changes patient treatment plans. Methods: Of 1495 patients seen at the University of Virginia with a diagnosis of breast cancer from 2006-2011, the 276 cases with both internal and outside pathology reports comprised the study cohort. Interobserver agreement (kappa coefficient, K) between internal and outside diagnoses were calculated for histopathology, lymph node, margin, ER/PR, and HER2 status. We then evaluated if the change would result in a change in therapy or surveillance per the National Comprehensive Cancer Network (NCCN) guidelines. The effect of region and teaching affiliation of outside institutions was explored. Results: For the 276 cases with re-reviewed pathology at UVA there was absolute agreement for ER/PR and surgical margins, and excellent agreement for lymph node, K= 0.93, and histopathology, K=0.93. Agreement was good for HER2, K=0.83. 3 cases were changed from HER2 positive to negative (2) or intermediate (1). Of 9 changes in histopathology, 2 had a major upgrade: 1 ADH to DCIS; 1 DCIS to carcinoma. 3 had a major downgrade: 2 from DCIS to ADH; 1 from carcinoma to DCIS. 2 cases changed from ALH to LCIS. Lymph node status was changed from positive to negative in one out of 31 reviewed cases. Treatment plan would have changed for all 13, 4.7% of all patients. Changes were made almost exclusively (11/13) if referred from a hospital with no or minor teaching affiliation, including all major histopathology changes and changes in lymph node and HER2 status. Conclusions: Interobserver agreement for breast pathology between pathologists at an NCI designated cancer center and outside institutions was good. However, 4.7% of women had discordant results that would lead to a change in their care. Changes were most common for noninvasive carcinoma and benign atypia. In order to best utilize resources, referral centers may want to consider limiting re-review to the pathology from centers with high risk for discordance.


2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 140-140 ◽  
Author(s):  
Hans-Christian Kolberg ◽  
Leyla Akpolat-Basci ◽  
Miltiades Stephanou ◽  
Carla Hannig ◽  
Cornelia Liedtke

140 Background: Most patients with HER2-positive receive chemotherapy and trastuzumab. Data from adjuvant trials have shown that the combination of docetaxel, carboplatin and weekly trastuzumab (TCH) is well tolerated and as effective as anthracycline containing regimes. Previous investigations on neoadjuvant treatment with TCH showed pCR-rates in the range of 40%, however, survival data have not yet been presented. Here we present 4.5-year follow-up data for a cohort of 51 patients treated with neoadjuvant TCH. Methods: We treated 51 patients with operable HER2-positive breast cancer with a neoadjuvant schedule of docetaxel (75 mg/m2) and carboplatin (AUC 6) q3w and trastuzumab (2(4)mg/kg) q1w. Lymph node involvement was verified by SLNB or core-cut-biopsy. Mean age at diagnosis was 55 years, 68.6% had ER positive tumors, 39.2% presented with grade 3 disease and 49% of patients were node-positive. Patients were monitored by ultrasound. After 6 cycles of chemotherapy all patients had surgery. Axillary dissection was performed in case of positive lymph node status prior to TCH. After surgery trastuzumab was continued q3w up to one year. Results: Side effects were mild, no grade III/IV toxicities occurred and no case of cardiomyopathia was observed. 21 (41.18%) patients achieved a pCR, 18 (72.0%) patients converted from cN+ to ypN0. Outcome data at a median follow-up of 53.6 months are as follows (see table). Conclusions: Outcome following neoadjuvant TCH as observed in our analysis compares well to outcome data observed in adjuvant trastuzumab trials such as HERA or BCIRG006. Particularly among patients with ER positive disease and those experiencing axillary conversion we observed an excellent outcome. Importantly, TCH was well tolerated in our cohort. Therefore our data support the use of TCH as neoadjuvant therapy regimen for patients with HER-positive breast cancer. [Table: see text]


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12010-e12010
Author(s):  
Marta Bonotto ◽  
Lorenzo Gerratana ◽  
Alessandro Bettini ◽  
Marika Cinausero ◽  
Debora Basile ◽  
...  

e12010 Background: The use of adjuvant chemotherapy (CT) in small luminal-like breast cancer (BC) is still heavily debated. International guidelines identify endocrine therapy as the backbone of adjuvant treatment for these patients (pts), while the addition of CT should be limited to high risk cases. The aim of this study was to evaluate the association between patient- or disease-related factors with the prescription of adjuvant CT. Methods: This retrospective study reviewed data from 559 consecutive pts with pT1 ( < 2 cm) luminal-like BC treated between 2004 and 2015 at the Department of Oncology of Udine (Italy). No restrictions were applied regarding lymph node status. The cut-off point of 1% was used to define ER and/or PgR positivity. Factors influencing the prescription of CT were investigated through uni- and multivariate logistic regression with odds ratio (OR) calculation. Prognosis was explored through Cox regression. Results: About thirty percent (173/559) of pts received adjuvant CT. By multivariate analysis, lymph node involvement was highly associated with CT prescription (OR 16.94, 95% CI 7.86-36.50, P < 0.001 for pN1; OR 3.92, 95% CI 1.45-10.58, P = 0.007 for pNmi). Tumor size drove towards the use of CT among pts with pT1c tumors (OR 12.87, 95% CI 1.49-110.88, P = 0.020) but not in pts with pT1b BC (OR 2.38, 95% CI 0.26-21.38, P = 0.437). In addition, a higher CT use was observed in pts with luminal B-like disease (OR 3.79, 95% CI 2.16-6.65, P < 0.001) or in presence of a Ki67 > 14% (OR 1.05, 95% CI 1.03-1.07, P < 0.001). On the contrary, pts with age > 60 years had a very low chance of receiving adjuvant CT (OR 0.09, 95% CI 0.04-0.20, P < 0.001). Notably, the use of CT was not associated with Disease Free Survival or Overall Survival (HR 1.3, 95% CI 0.77-2.17, P = 0.320; HR 1.05, 95% CI 0.56-2, P = 0.866; respectively). Conclusions: Nodal status, tumor size, disease sub-type, Ki67 expression and age are determinants of adjuvant CT prescription in pts with small luminal-like BC. Prospective studies are needed to identify which pts could safely avoid CT without influencing prognosis.


2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
S. Bonin ◽  
D. Pracella ◽  
R. Barbazza ◽  
I. Dotti ◽  
S. Boffo ◽  
...  

Lymph node metastatic involvement persists to be among the most important predictors of recurrence and survival in breast carcinoma (BC). This study is aimed at investigating possible gene expression differences in primary BC between patients with or without lymph node involvement at the time of diagnosis. In a retrospective study, we investigated the potential prognostic role of 9 candidate biomarkers at the mRNA level in a cohort of 305 breast cancer patients, 151 lymph node-negative (LN-) and 154 lymph node-positive (LN+) individuals. The analyzed genes belonged to the RAS pathway (RAF1, ERBB2, PIK3CB, AKT1, AKT2, and AKT3), RB pathway (RB1 and CDK2), and cellular differentiation (KRT8). Their expression profiles were investigated by RT-qPCR and were correlated to immunohistochemically based molecular subtypes and BC clinical and pathological features. The differential expression of several genes in the primary tumor tissue was related to the LN involvement. Some of those genes, including PIK3CB, RB1, and AKT3, were more expressed in LN- BC patients, while some others, notably ERBB2 and AKT1, in LN+ ones. Among the candidate biomarkers, the expression levels of AKT isoforms influenced also patients’ survival rates. In detail, higher expression levels of AKT1 and AKT2 negatively influenced overall patients’ survival, and in particular, AKT2 expression levels defined a group of luminal B BC patients with shorter cancer-specific survival. On the contrary, longer cancer-specific survival was recorded in luminal A BC patients with higher expression levels of AKT3. That finding was also confirmed by Cox multivariate analysis. The same AKT3 resulted to be a possible candidate predictive biomarker for Tamoxifen response. In conclusion, our study highlighted the complex regulation of the PI3K/AKT pathway in BC and its differences in BC patients with and without lymph node involvement.


2018 ◽  
Vol 26 (3) ◽  
pp. 154-161
Author(s):  
Linda Perron ◽  
Sue-Ling Chang ◽  
Jean-Marc Daigle ◽  
Nathalie Vandal ◽  
Isabelle Theberge ◽  
...  

Objective In mammography screening, interval cancers present a problem. The metric ‘screening sensitivity’ monitors both how well a programme detects cancers and avoids interval cancers. To our knowledge, the effect of breast cancer surrogate molecular subtypes on screening sensitivity has never been evaluated. We aimed to measure the 2-year screening sensitivity according to breast cancer subtypes. Methods We studied 734 women with an invasive breast cancer diagnosed between 2003 and 2007 after participating in one regional division of Quebec’s Mammography Screening Program. They represented 83% of all participating women with an invasive BC diagnosis in that region for that period. Tumours were categorized into ‘luminal A-like’, ‘luminal B-like’, ‘triple-negative’ and ‘HER2-positive’ subtypes. We used logistic regression and marginal standardization to estimate screening sensitivity, sensitivity ratios (SR) and sensitivity differences. We also assessed the mediating effect of grade. Results Adjusted 2-year screening sensitivity was 75.4% in luminal A-like, 66.1% in luminal B-like, 52.9% in triple-negative and 45.3% in HER2-positive, translating into sensitivity ratios of 0.88 (95% confidence interval [CI] = 0.78–0.98) for luminal B-like, 0.70 (CI = 0.56–0.88) for triple-negative and 0.60 (CI = 0.39–0.93) for HER2-positive, when compared with luminal A-like. Grade entirely mediated the subtype-sensitivity association for triple negative and mediated it partly for HER2-positive. Screening round (prevalent vs. incident) did not modify results. Conclusion There was substantial variation in screening sensitivity according to breast cancer subtypes. Aggressive phenotypes showed the lowest sensitivity, an effect that was mediated by grade. Tailoring screening according to women’s subtype risk factors might eventually lead to more efficient programs.


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