4,769 research outputs found

    Pretreatment prognostic value of dynamic contrast-enhanced magnetic resonance imaging vascular, texture, shape, and size parameters compared with traditional survival indicators obtained from locally advanced breast cancer patients

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    Objectives: The aim of this study was to determine if associations exist between pretreatment dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI)-based metrics (vascular kinetics, texture, shape, size) and survival intervals. Furthermore, the aim of this study was to compare the prognostic value of DCE-MRI parameters against traditional pretreatment survival indicators. Materials and Methods: A retrospective study was undertaken. Approval had previously been granted for the retrospective use of such data, and the need for informed consent was waived. Prognostic value of pretreatment DCE-MRI parameters and clinical data was assessed via Cox proportional hazards models. The variables retained by the final overall survival Cox proportional hazards model were utilized to stratify risk of death within 5 years. Results: One hundred twelve subjects were entered into the analysis. Regarding disease-free survival-negative estrogen receptor status, T3 or higher clinical tumor stage, large ( > 9.8 cm 3 ) MR tumor volume, higher 95th percentile ( > 79%) percentage enhancement, and reduced ( > 0.22) circularity represented the retained model variables. Similar results were noted for the overall survival with negative estrogen receptor status, T3 or higher clinical tumor stage, and large ( > 9.8 cm 3 ) MR tumor volume, again all been retained by the model in addition to higher ( > 0.71) 25th percentile area under the enhancement curve. Accuracy of risk stratification based on either traditional (59%) or DCEMRI (65%) survival indicators performed to a similar level. However, combined traditional and MR risk stratification resulted in the highest accuracy (86%). Conclusions: Multivariate survival analysis has revealed thatmodel-retained DCEMRI variables provide independent prognostic information complementing traditional survival indicators and as such could help to appropriately stratify treatment

    Neutrophil gelatinase-associated lipocalin (NGAL) predicts response to neoadjuvant chemotherapy and clinical outcome in primary human breast cancer

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    In our previous work we showed that NGAL, a protein involved in the regulation of proliferation and differentiation, is overexpressed in human breast cancer (BC) and predicts poor prognosis. In neoadjuvant chemotherapy (NACT) pathological complete response (pCR) is a predictor for outcome. The aim of this study was to evaluate NGAL as a predictor of response to NACT and to validate NGAL as a prognostic factor for clinical outcome in patients with primary BC. Immunohistochemistry was performed on tissue microarrays from 652 core biopsies from BC patients, who underwent NACT in the GeparTrio trial. NGAL expression and intensity was evaluated separately. NGAL was detected in 42.2% of the breast carcinomas in the cytoplasm. NGAL expression correlated with negative hormone receptor (HR) status, but not with other baseline parameters. NGAL expression did not correlate with pCR in the full population, however, NGAL expression and staining intensity were significantly associated with higher pCR rates in patients with positive HR status. In addition, strong NGAL expression correlated with higher pCR rates in node negative patients, patients with histological grade 1 or 2 tumors and a tumor size <40 mm. In univariate survival analysis, positive NGAL expression and strong staining intensity correlated with decreased disease-free survival (DFS) in the entire cohort and different subgroups, including HR positive patients. Similar correlations were found for intense staining and decreased overall survival (OS). In multivariate analysis, NGAL expression remained an independent prognostic factor for DFS. The results show that in low-risk subgroups, NGAL was found to be a predictive marker for pCR after NACT. Furthermore, NGAL could be validated as an independent prognostic factor for decreased DFS in primary human BC

    Neoadjuvant chemotherapy and trastuzumab versus neoadjuvant chemotherapy followed by post-operative trastuzumab for patients with HER2-positive breast cancer

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    Neoadjuvant chemotherapy plus trastuzumab (NCT) increases the rate of pathological complete response (pCR) and event-free survival (EFS) compared to neoadjuvant chemotherapy (NC) alone in women with HER2 positive breast cancer (BC). pCR in this setting is associated with improved EFS. Whether NCT preferentially improves EFS in comparison to NC followed by adjuvant trastuzumab initiated postoperatively (NCAT) has not been addressed. Using clinical data from women with HER2 positive BC treated at 7 European institutions between 2007 and 2010 we sought to investigate the impact on breast cancer outcomes of concomitant (NCT) versus sequential (NCAT) treatment in HER2 positive early BC. The unadjusted hazard ratio (HR) for event free survival with NCT compared with NCAT was 0.63 (95% CI 0.37–1.08; p = 0.091). Multivariable analysis revealed that treatment group, tumour size and ER status were significantly associated with EFS from diagnosis. In the whole group NCT was associated with a reduced risk of an event relative to NCAT, an effect that was confined to ER negative (HR: 0.25; 95% CI, 0.10–0.62; p = 0.003) as opposed to ER positive tumours (HR: 1.07; 95% CI, 0.46–2.52; p = 0.869). HER2 positive/ER negative BC treated with NC gain greatest survival benefit when trastuzumab is administered in both the neoadjuvant and adjuvant period rather than in the adjuvant period alone. These data support the early introduction of targeted combination therapy in HER2 positive/ER negative BC

    Neoadjuvant chemotherapy and trastuzumab versus neoadjuvant chemotherapy followed by post-operative trastuzumab for patients with HER2-positive breast cancer

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    Neoadjuvant chemotherapy plus trastuzumab (NCT) increases the rate of pathological complete response (pCR) and event-free survival (EFS) compared to neoadjuvant chemotherapy (NC) alone in women with HER2 positive breast cancer (BC). pCR in this setting is associated with improved EFS. Whether NCT preferentially improves EFS in comparison to NC followed by adjuvant trastuzumab initiated postoperatively (NCAT) has not been addressed. Using clinical data from women with HER2 positive BC treated at 7 European institutions between 2007 and 2010 we sought to investigate the impact on breast cancer outcomes of concomitant (NCT) versus sequential (NCAT) treatment in HER2 positive early BC. The unadjusted hazard ratio (HR) for event free survival with NCT compared with NCAT was 0.63 (95% CI 0.37–1.08; p = 0.091). Multivariable analysis revealed that treatment group, tumour size and ER status were significantly associated with EFS from diagnosis. In the whole group NCT was associated with a reduced risk of an event relative to NCAT, an effect that was confined to ER negative (HR: 0.25; 95% CI, 0.10–0.62; p = 0.003) as opposed to ER positive tumours (HR: 1.07; 95% CI, 0.46–2.52; p = 0.869). HER2 positive/ER negative BC treated with NC gain greatest survival benefit when trastuzumab is administered in both the neoadjuvant and adjuvant period rather than in the adjuvant period alone. These data support the early introduction of targeted combination therapy in HER2 positive/ER negative BC

    Treatment related morbidity in breast cancer patients

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    Background: Sentinel lymph node biopsy (SLNB) was introduced for staging of the axilla to reduce the number of unnecessary axillary lymph node dissections (ALND’s) and proved to be an accurate and safe procedure to predict metastatic disease in clinically negative axillary lymph nodes. SLNB was expected to have less treatment related morbidity in comparison to ALND. In a multicenter prospective cohort study, long term upper-limb morbidity, perceived disabilities in activities of daily life (ADL) and quality of life (QOL) were assessed before and six weeks, 12 month and 24 month after SLNB or ALND for breast cancer. - \ud Methods: 204 patients with stage I/II breast cancer, mean age 55.6 years (sd: 11.6) entered the study and 181 patients (89%) could be evaluated after two years. Sixty-six patients (32%) underwent SLNB only, and 138 (68%) underwent a level I-II ALND. Reliable and valid assessment instruments were used for assessment of upper limb morbidity, ADL and QOL. Assessment included evaluation of shoulder range of motion, muscle strength, grip strength, pain, upper/forearm circumference, shoulder disability and activities of daily life (ADL) and Quality of Live. - \ud Results: Considerable treatment related upper-limb morbidity was observed. Significant (p<0.05) changes between before and up till two years after surgery were found in almost all assessments of shoulder function, ADL and several QOL subscales. Patients in the ALND group showed significant more changes in range of motion (ROM), grip strength, arm volume, ADL and QOL physical- and role functioning, pain and sleeplessness and arm symptoms compared to the SLNB group. Upper limb morbidity and associated disabilities in ADL are at worse in the early stage (first months) after surgical treatment. Concerning arm edema; in the ALND group arm volume increased significantly at 1 and 2 years follow up. Concerning QOL, significantly differences in mean change over the two years comparing SLNB with ALND were found for physical and role functioning and also for symptom items such as pain, insomnia (sleeplessness) and arm symptoms in favor of the SLNB group. QOL in the SLNB group was just improving in the 2 years after treatment whereas in de ALND group only emotional functioning and future perspective improved. Multivariate linear regression analysis showed that radiation therapy on the axilla is besides ALND an important factor in the prediction of impaired shoulder ROM and arm edema. Radiation therapy on the breast had no influence on shoulder ROM. - \ud Conclusion: 1. Significant treatment related short-term, middle-term and long-term upper limb morbidity and perceived disabilities in ADL and long-term reduction of QOL exist in breast cancer patients. 2. In the assessment of changes in upper limb function, ADL and QOL, ALND is the most frequent found predictor of deterioration. Additional radiation therapy on the axilla predicts a further decrease in shoulder ROM and arm edema. 3. Long-term upper limb morbidity is significantly correlated with disabilities in ADL and worsening of QOL

    Comparative study of ER status in premenopausal and postmenopausal women with carcinoma breast

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    INTRODUCTION: Breast cancer, which is the most common malignancy in women, was found to have association with estrogen The discovery of the estrogen receptor produced vast changes in the management of cancer breast. It is an important prognostic marker. On treating patients with carcinoma of the breast we are often confronted with the dilemma of how to identify those patients who are most likely to benefit from hormonal treatment. Estrogen receptor rich tumors respond to hormone therapy more frequently than do estrogen receptor poor tumors. Estrogen receptor status is the most important indicator in predicting the response of advanced breast cancer to hormonal manipulation and possibly chemotherapy. AIM AND OBJECTIVES: The aim of this work is: 1. To study the pattern of Estrogen Receptor status in female patients with breast cancer. 2. To find out eventual correlation between Estrogen Receptor status and menstrual status. 3. To predict the value of Estrogen Receptor status in choosing patients for adjuvant hormonal treatment. MATERIALS AND METHODS: Government Rajaji Hospital is a tertiary care centre in Madurai, Tamilnadu. It has the privilege of having maximum number of outpatients in South Tamilnadu. Carcinoma breast is one of the common surgical problems presenting to our everyday outpatient department. Modified radical mastectomy is a common surgical procedure being performed in our operation theatres. The purpose of this study is to compare the “Estrogen Receptor Status” between premenopausal and post menopausal women with carcinoma breast. Duration of the study: from September 2010 to August 2012. SELECTION OF STUDY SUBJECTS: Genders eligible for study: Females only . Age eligible for study: Premenopausal: 30-40 years. Postmenopausal: > 50 years. INCLUSION CRITERIA: 1. All patients with carcinoma breast attending the out patient department of surgery at Government Rajaji Hospital, Madurai are included. The clinical finding should be in favour of carcinoma breast. The malignancy should be proved either by FNAC or Trucut biopsy – HPE report. 2. The patient should have a clearcut menstrual history with regular menstrual periods. EXCLUSION CRITERIA: 1. Patients with intake of exogenous estrogen exposure in the form of “Hormone Replacement Therapy” or prolonged intake of OCP. 2. Patients who had undergone hysterectomy previously ie. Surgical menopause. CONCLUSION: In this study 50 post mastectomy specimens were collected (25-premenopausal and 25-postmenopausal) and subjected to estrogen receptor assay by biochemical monoclonal antibody method. Estrogen receptor status was correlated with age and menstrual status. ‱ The frequency of ER positivity increase steadily with age. ‱ The concentration and proportion of ER positivity were higher in postmenopausal than in premenopausal patients. ‱ ER assay is recommended as a routine test in the management of breast cancer because of its help in predicting the response to hormonal therapy, in addition its an important prognostic factor

    Parity-related molecular signatures and breast cancer subtypes by estrogen receptor status

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    INTRODUCTION: Relationships of parity with breast cancer risk are complex. Parity is associated with decreased risk of postmenopausal hormone receptor–positive breast tumors, but may increase risk for basal-like breast cancers and early-onset tumors. Characterizing parity-related gene expression patterns in normal breast and breast tumor tissues may improve understanding of the biological mechanisms underlying this complex pattern of risk. METHODS: We developed a parity signature by analyzing microRNA microarray data from 130 reduction mammoplasty (RM) patients (54 nulliparous and 76 parous). This parity signature, together with published parity signatures, was evaluated in gene expression data from 150 paired tumors and adjacent benign breast tissues from the Polish Breast Cancer Study, both overall and by tumor estrogen receptor (ER) status. RESULTS: We identified 251 genes significantly upregulated by parity status in RM patients (parous versus nulliparous; false discovery rate = 0.008), including genes in immune, inflammation and wound response pathways. This parity signature was significantly enriched in normal and tumor tissues of parous breast cancer patients, specifically in ER-positive tumors. CONCLUSIONS: Our data corroborate epidemiologic data, suggesting that the etiology and pathogenesis of breast cancers vary by ER status, which may have implications for developing prevention strategies for these tumors

    Transcriptome-wide association study of breast cancer risk by estrogen-receptor status

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    Previous transcriptome-wide association studies (TWAS) have identified breast cancer risk genes by integrating data from expression quantitative loci and genome-wide association studies (GWAS), but analyses of breast cancer subtype-specific associations have been limited. In this study, we conducted a TWAS using gene expression data from GTEx and summary statistics from the hitherto largest GWAS meta-analysis conducted for breast cancer overall, and by estrogen receptor subtypes (ER+ and ER-). We further compared associations with ER+ and ER- subtypes, using a case-only TWAS approach. We also conducted multigene conditional analyses in regions with multiple TWAS associations. Two genes, STXBP4 and HIST2H2BA, were specifically associated with ER+ but not with ER- breast cancer. We further identified 30 TWAS-significant genes associated with overall breast cancer risk, including four that were not identified in previous studies. Conditional analyses identified single independent breast-cancer gene in three of six regions harboring multiple TWAS-significant genes. Our study provides new information on breast cancer genetics and biology, particularly about genomic differences between ER+ and ER- breast cancer.Peer reviewe
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