scholarly journals Gene Expression Profile Analysis of T1 and T2 Breast Cancer Reveals Different Activation Pathways

ISRN Oncology ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Margit L. H. Riis ◽  
Xi Zhao ◽  
Fateme Kaveh ◽  
Hilde S. Vollan ◽  
Anne-Jorunn Nesbakken ◽  
...  

Breast cancers today are of predominantly T1 (0.1≥2.0 cm) or T2 (>2≤5 cm) categories due to early diagnosis. Molecular profiling using microarrays has led to the notion of breast cancer as a heterogeneous disease both clinically and molecularly. Given the prognostic power and clinical use of tumor size, the purpose of this study was to search for molecular signatures characterizing clinical T1 and T2. In total 46 samples were included in the discovery dataset. After adjusting for hormone receptor status, lymph node status, grade, and tumor subclass 441 genes were differently expressed between T1 and T2 tumors. Focal adhesion and extracellular matrix receptor interaction were upregulated in the smaller tumors while p38MAPK signaling and immune-related pathways were more dominant in the larger tumors. The T-size signature was then tested on a validation set of 947 breast tumor samples. Using the T-size expression signatures instead of tumor size leads to a significant difference in risk for distant metastases (P<0.001). If further confirmed, this molecular signature can be used to select patients with tumor category T1 who may need more aggressive treatment and patients with tumor category T2 who may have less benefit from it.

1999 ◽  
Vol 45 (11) ◽  
pp. 1998-2004 ◽  
Author(s):  
Christian Murr ◽  
Anton Bergant ◽  
Martin Widschwendter ◽  
Kurt Heim ◽  
Hans Schröcksnadel ◽  
...  

Abstract Background: Neopterin, produced by human monocytes/macrophages upon stimulation by interferon-γ, is a sensitive marker for monitoring Th1-cell immune response in humans. In malignant diseases, the frequency of increases in neopterin in the serum and urine of patients depends on tumor stage and type. Methods: In a retrospective study comprising 129 females with breast cancer, urinary neopterin/creatinine ratios were measured at the time of diagnosis. Tumor characteristics were determined concomitantly. Results: Urinary neopterin was increased in 18% of the patients. It did not correlate with tumor size or lymph node status, but it was influenced by the presence of distant metastases (P &lt;0.05) and by tumor differentiation (P = 0.01). When product-limit estimates were calculated after follow-up for up to 13 years (median follow-up, 56 months), the presence of distant metastases (P &lt;0.001), neopterin (P &lt;0.001), tumor size (P = 0.001), and lymph node status (P &lt;0.01) were significant predictors of survival. By multivariate analysis, a combination of the variables presence of distant metastases (P &lt;0.001), neopterin (P &lt;0.01), and lymph node status (P &lt;0.05) was found to jointly predict survival. In lymph node-negative patients without distant metastases, the relative risk of death associated with increased neopterin concentrations was 2.5 compared with patients with neopterin concentrations within the reference interval. Conclusion: Urinary neopterin provides additional prognostic information in patients with breast cancer.


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.


2011 ◽  
Vol 29 (19) ◽  
pp. 2628-2634 ◽  
Author(s):  
Leonel F. Hernandez-Aya ◽  
Mariana Chavez-MacGregor ◽  
Xiudong Lei ◽  
Funda Meric-Bernstam ◽  
Thomas A. Buchholz ◽  
...  

Purpose To evaluate the clinical outcomes and relationship between tumor size, lymph node status, and prognosis in a large cohort of patients with confirmed triple receptor–negative breast cancer (TNBC). Patients and Methods We reviewed 1,711 patients with TNBC diagnosed between 1980 and 2009. Patients were categorized by tumor size and nodal status. Kaplan-Meier product limit method was used to calculate overall survival (OS) and relapse-free survival (RFS). A Sidak adjustment was used for multiple group comparisons. Cox proportional hazards models were fit to determine the association of tumor size and nodal status with survival outcomes after adjustment for other patient and disease characteristics. Results Median age was 48 years (range, 21 to 87 years). At a median follow-up of 53 months (range, 0.7 to 317 months), there were 614 deaths and 747 recurrences. The 5-year OS was 80% for node-negative patients (N0), 65% for one to three positive lymph nodes (N1), 48% for four to nine positive lymph nodes (N2), and 44% for ≥ 10 positive lymph nodes (N3; P < .0001). The 5-year RFS rates were 67% for N0, 52% for N1, 36% for N2, and 33% for N3 (P < .0001). Pairwise comparison by nodal status showed that when comparing N0 with node-positive disease, there was a significant difference in OS and RFS (P < .001 all comparisons). However, when comparing N1 with N2 and N3 disease regardless of tumor size, there were no significant differences in OS or RFS. Conclusion In patients with TNBC, once there is evidence of lymph node metastasis, the prognosis may not be affected by the number of positive lymph nodes.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e17516-e17516
Author(s):  
Carling Ursem ◽  
Gretchen Genevieve Kimmick ◽  
Roger T. Anderson ◽  
Wenke Hwang ◽  
Fabian Camacho

e17516 Background: Disparities are known to exist in breast cancer outcomes by age and socioeconomic status (SES), but there is little data regarding these disparities in the elderly. We studied older women in North Carolina (NC) using insurance status as an indicator of SES. Methods: From the 1999-2002 NC Central Cancer Registry, we identified women age ≥65 years presenting with nonmetastatic breast cancer, having surgery within 60 days of diagnosis, no neoadjuvant therapy, and insured by Medicare only (M) or dual Medicaid/Medicare (dMM). Chi-square tests followed by Tukey Style Multiple Comparison of Proportions were used to compare baseline characteristics and treatment received. Multivariate analyses including age, race, Charlson comorbidity, tumor size, lymph node status (LN), ER/PR status, HER2 status, and relevant treatment components, were used to determine predictors of use of chemotherapy. Results: The study population, n=3088 with mean age 75 (SD 6.69) years, included 560 dMM and 2528 M insured women. In dMM, tumors were larger (23.5 mm vs 18.5 mm, p<0.001), more likely poorly differentiated (p=0.04), and node positive (p=0.004). dMM were significantly less likely to have breast conserving surgery (vs mastectomy, p<0.001), radiation therapy after surgery (<0.001), adjuvant chemotherapy (0.007), and adjuvant endocrine therapy (<0.001). Significant predictors of receipt of adjuvant chemotherapy were: for dMM, white race (OR 0.22, 95% CI 0.06-0.78), positive LN (vs negative LN; 6.00, 1.44-25.02); for M, age 65-69 (vs 75+; 7.43, 3.64-15.18), age 70-74 (vs 75+; 4.93, 95% CI 2.38-10.22), larger tumor size (1.73, 1.09-2.74), positive LN (9.25, 4.80-17.83), and ER/PR negative (4.98, 2.29-10.85). Conclusions: Breast cancers in low SES, older patients are higher grade, larger, and more advanced, yet they less often receive adjuvant chemotherapy. Future work should focus on interventions to increase receipt of standard of care treatment among this population.


2004 ◽  
Vol 22 (13) ◽  
pp. 2567-2575 ◽  
Author(s):  
Mousumi Banerjee ◽  
Julie George ◽  
Eun Young Song ◽  
Anuradha Roy ◽  
William Hryniuk

Purpose To define prognostic groups for recurrence-free survival in breast cancer, assess relative effects of prognostic factors, and examine the influence of treatment variations on recurrence-free survival in patients with similar prognostic-factor profiles. Patients and Methods We analyzed 1,055 patients diagnosed with stage I-III breast cancer between 1990 and 1996. Variables studied included socioeconomic factors, tumor characteristics, concurrent medical conditions, and treatment. The primary end point was recurrence-free survival (RFS). Multivariable analyses were performed using recursive partitioning and Cox proportional hazards regression. Results The most significant difference in prognosis was between patients with fewer than four and those with at least four positive nodes (P < .0001). Four distinct prognostic groups (5-year RFS, 97%, 78%, 58%, and 27%) were developed, defined by the number of positive nodes, tumor size, progesterone receptor (PR) status, differentiation, race, and marital status. Patients with fewer than four positive nodes and tumor ≤ 2 cm, PR positive, and well or moderately differentiated had the best prognosis. RFS in this group was unaffected by type of adjuvant therapy (P = .38). Patients with at least four positive nodes and PR-negative tumors had the worst prognosis, and those treated with tamoxifen plus chemotherapy had the best outcome in this group (P = .0001). Among patients in the two intermediate-risk groups, those treated with tamoxifen or a combination of tamoxifen and chemotherapy had the best outcome. Conclusion Lymph node status, PR status, tumor size, differentiation, race, and marital status are valuable for prognostication in breast cancer. The prognostic groups derived can provide guidance for clinical trial design, patient management, and future treatment policy.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21060-21060
Author(s):  
D. Rayson ◽  
M. Abdolell ◽  
J. Payne ◽  
T. J. Foley ◽  
T. Younis ◽  
...  

21060 Background: Assessment of interval breast cancers and screening compliance are important parameters in the assessment of any comprehensive breast screening program. Clinical-pathologic examination of interval cancers may also be helpful in understanding differences between screen-detected and interval disease. The Nova Scotia Breast Screening Program (NSBSP) was founded in 1991 and, as of Jan 2007, 86,071 women aged 50–69 have entered the program, with 255,350 screening examinations completed. Methods: The Mammography Information System and Diagnostic Reporting System databases were used to identify all interval (diagnosed after a negative screen and before the recommended next screen) and non-compliant (diagnosed after a negative screen and after the recommended next screen) invasive breast cancer diagnoses. Unpaired t-tests were used to compare age at diagnosis, detection time and tumor size and the Chi- square test was used to compare the odds ratio of nodal involvement between interval and non-compliant cases. Results: A total of 1,189 screen-detected, 309 interval and 260 non-compliant invasive breast cancers were diagnosed amongst program participants aged 50–69 over this time period. Mean values (standard deviation, SD) for interval vs. non-compliant cases were; age at diagnosis 58.8 (SD=5.6) vs. 59.6 (SD=5.9) years (p=0.113); time to detection from last screen 363.9 (SD=187.6) vs. 1296 (SD=868.4) days (p<0.0001); tumor size 15.9 (SD=15.0) vs. 14.6 (SD=14.7) mms. (p=0.342). The incidence of nodal involvement in interval vs. non-compliant breast cancers was 32% and 23.5% respectively resulting in an odds ratio of 1.54, p=0.023. Conclusions: Interval and non-compliant breast cancers made up a significant proportion of all invasive cancers diagnosed amongst program participants. The finding of more cases having involved nodes at diagnosis despite no significant difference in mean age at diagnosis or tumor size suggests that interval disease may have a more aggressive phenotype. Data on tumor grade, lymphovascular invasion, hormone receptor status and HER2/neu over-expression are being collected. No significant financial relationships to disclose.


2021 ◽  
Vol 108 (Supplement_5) ◽  
Author(s):  
L J Sui ◽  
A Sanders ◽  
W G Jiang ◽  
L Ye

Abstract Introduction Role of Bone morphogenetic protein 8A (BMP8A) and BMP receptors (BMPRs) in the tumourigenesis and progression of breast cancer remains elusive. Present study aims to investigate the expression of BMP8A and related BMPRs in breast cancer and their clinical implication. Method Expression of BMP8A and BMPRs was analysed using the RNA sequencing data of the TCGA breast cancer cohort. Findings were further validated in a meta gene array dataset (E-MDTA6703, n = 2302). STRING dataset was applied to explore the predicted receptors of BMP8A. Clinical relevance of deregulated BMP8A and BMPRs in breast cancer was assessed using both ANOVA and Kaplan-Meier tests. Correlation with markers of proliferation and invasion was evaluated using Spearman test. Result Analysis of datasets revealed that BMP8A and BMPR1B were highly expressed in breast cancer while ACVRL1, ACVR1, BMPR1A, ACVR1C, TGFBR2, TGFBR3, BMPR2 and ACVR2A were lower-expressed compared with normal controls. Expressions of BMPR1B, BMPR1A, BMPR2, ACVR2A and ACVR2B were highly correlated with BMP8A in the breast cancers. Overall survival in the group with higher BMP8A expression was shorter(median= 122.3 months), P = 0.012 compared with lower-expressed group(median = 215.2 months). No significant difference was observed in BMP8A and BMPRs in tumours according to their staging and lymph node involvement. Positive correlations were found between BMP8A and tumour proliferation, EMT, angiogenic markers. Conclusion BMP8A is increased in breast cancer and correlates with poor prognosis. The highly correlated BMPRs might be involved in the signal transduction of BMP8A to co-regulate BMP responsive genes and cellular functions which is yet to be investigated. Take-home Message BMP8A is increased in breast cancer and correlates with poor prognosis.


Author(s):  
C. Divyapriya ◽  
Aarthi Kannan ◽  
Vijayashree Raghavan

Introduction: Tumor infiltrating lymphocytes (TILs) are widely considered a key sign of the immune interaction between host and tumor, and potentially prognostic biomarkers of good or bad outcome in various cancers, including invasive breast cancer (IBC). Aim and Objectives: To correlate the expression of CD4, CD8 T-lymphocytes in invasive carcinoma breast with established markers of prognosis like tumour size, grade, lymph node status and molecular subtypes mainly ER, PR, Her 2Neu, Ki67 status, mainly the triple negative breast cancers(TNBC). Methodology: 58 Invasive breast carcinoma proven tissue blocks were subjected to immunohistochemistry and morphometric analysis for positive CD4, CD8 T-lymphocytes were done. Results:  Triple negative breast cancer subtype shows high TILs than other pathologic subtypes. Tumor interface CD8+ cells very well correlated with the pathological higher nodal stage. Majority CD4, CD8 positive cells were populated more towards the stromal and interface of the tumor microenvironment rather thatintratumoral. Conclusion: CD4+ and CD8+ counts may be a valuable independent prognostic tool in predicting the outcome in invasive breast cancer.


2021 ◽  
Author(s):  
Juliana Fernandes ◽  
Beatriz Machado ◽  
Cassio Cardoso-Filho ◽  
Juliana Nativio ◽  
Cesar Cabello ◽  
...  

Abstract Background This study aims to assess breast cancer survival rates after one decade of mammography in a large urban area of Brazil. Methods It is a population-based retrospective cohort of women with breast cancer in Campinas, São Paulo, from 2010 to 2014. Age, vital status and stage were accessed through the cancer and mortality registry, and patients records. Statistics used Kaplan-Meier, log-rank and Cox's regression. Results Out of the 2,715 cases, 665 deaths (24.5%) were confirmed until early 2020. The mean age at diagnosis was 58.6 years. Women 50-69 years were 48.0%, and stage I the most frequent (25.0%). The overall mean survival was 8.4 years (8.2-8.5). The 5-year survival (5yOS) for overall, 40-49, 50-59, 60-69, 70-79 years was respectively 80.5%, 87.7%, 83.7%, 83.8% and 75.5%. The 5yOS for stages 0, I, II, III and IV was 95.2%, 92.6%, 89.4%, 71.1% and 47.1%. There was no significant difference in survival in stage I or II (p=0.058). Compared to women 50-59 years, death's risk was 2.3 times higher for women 70-79 years and 26% lower for women 40-49 years. Concerning stage I, the risk of death was 1.5, 4.1 and 8.6 times higher, and 34% lower, respectively, for stage II, III, IV and 0. Conclusions In Brazil, breast cancers are currently diagnosed in the early stages, although advanced cases persist. Survival rates may reflect improvements in screening, early detection and treatment. The results can reflect the current status of other regions or countries with similar health care conditions.


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