Scarff-Bloom-Richardson Research Articles

A study of CD10 positivity of stromal cells in core needle biopsy specimen of breast cancer patients and its relation with histological grade and lymphovascular invasion.

In core needle biopsy (CNB) often the histological grade of invasive breast carcinoma is under-estimated due to heterogeneity of epithelial component. Stroma is relatively homogenous throughout the tumor and strong CD10 stromal positivity is proposed to be associated with high tumor grade. The aim of this work was to study the expression of CD10 in stromal cells of invasive carcinoma of breast, no specific type (NST) in CNB specimens, and analyze its association with final histological grade and lymphovascular invasion (LVI). A total of 50 cases of invasive carcinoma of breast, NST were studied for 18 months. CNB specimens were graded according to modified Scarff-Bloom-Richardson (SBR) system and CD10 positivity was assessed in stromal cells. Mastectomy specimens were also similarly graded. Relation of stromal CD10 positivity with histological grading and LVI was studied. Associations between the variables were studied by Chi-square test. A value of P < 0.05 was considered to be statistically significant. On CNB 46% patients had a grade 2 tumor, followed by 30% grade 3 and 24% grade 1 tumor. Strong CD10 positivity was seen in 40% cases, 32% showed weak positivity and 28% were negative for CD10 in stromal cells in CNB specimen. On evaluation of mastectomy specimen 48% of the patients had a grade 2 tumor, followed by 40% grade 3 tumor and 12% grade 1 tumor. Strong CD10 positivity was found to be significantly associated with final grade 3 tumor (P < 0.001) and LVI (P = 0.005). There was underestimation of histological grade on CNB, while strong stromal CD10 positivity in CNB was significantly associated with final grade 3 tumor and LVI.

Bioinformatics analysis of prognostic value of PITX1 gene in breast cancer.

Background: Paired-like homeodomain transcription factor 1 (PITX1) participates in miscellaneous biological processes including cell growth, development, progression and invasion in various malignant tumors. However, the analysis of the association between PITX1 expression and the survival in breast cancer remains unclear. Methods: Clinical prognostic parameters and survival data related to PITX1 in breast cancer patients were performed using the bioinformatic analysis including Oncomine, Bc-GenExMiner v4.3, PrognoScan and UCSC Xena. Results: We found that PITX1 gene expression was significantly higher in different histological classification of breast cancer. The Scarff–Bloom–Richardson (SBR) grade, Nottingham prognostic index (NPI), estrogen receptor (ER) negative, epidermal growth factor receptor-2 (HER2) positive, lymph node positive, triple-negative status and basal-like status were positively correlated with PITX1 level, except for patients’ age and the progesterone receptor (PR) status. We have found that the increased PITX1 expression correlated with worse relapse-free survival, disease specific survival and overall survival. PITX1 was positively correlated with metastatic relapse-free survival and distant metastasis-free survival. We also confirmed positive correlation between PITX1 and the nucleotide-binding oligomerization domain 2 (NOD2). Conclusion: The lower expression of PITX1 was associated with better clinical prognostic parameters and clinical survival in breast cancer according to the bioinformatic analysis.

Evaluation of the prognostic significance of CDK6 in breast cancer

Cyclin-dependent kinase (CDK) gene family is an important cell cycle progression regulator, which may function as a tumor suppressor. We performed a systematic onco-informatics analysis to investigate the prognostic value of CDK6 in breast cancer. CDK6 expression was evaluated using the Oncomine and UALCAN database. The relevance between CDK6 level and clinical parameters and survival data in breast cancer was analyzed using the bc-GenExMiner, and Kaplan–meier plotter databases. The methylation status and heat map of CDK6 were analyzed by utilizing the UCSC Xena and UALCAN. It was identified that CDK6 was under-expressed in different subtypes of breast cancer. Estrogen receptor (ER) and progesterone receptor (PR) were negatively correlated with CDK6 expression. On the other hand, nottingham prognostic index (NPI), human epidermal growth factor receptor-2 (HER-2) status, basal-like status, scarff–bloom–richardson (SBR) grade, and triple-negative status were positively correlated with CDK6 level in breast cancer samples with respect to normal tissues. Besides, a positive correlation between CDK6 and pronecroptosis E3 ubiquitin ligase (PELI1) gene expression was confirmed. Our study revealed that CDK6 might be used as a biomarker for breast cancer prognosis with PELI1. However, more comprehensive experimental data are needed to clarify the value of CDK6 in breast cancer.

Cell division cycle proteinising prognostic biomarker of breast cancer.

Cell division cycle protein (CDC20) has been observed to be expressed higher in various kinds of human cancers and was associated with poor prognosis. However, studies on role of CDC20 in breast cancer are seldom reported till now, most of which are not systematic and conclusive. The present study was performed to analyze the expression pattern, potential function, and distinct prognostic effect of CDC20 in breast cancer using several online databases including Oncomine, bc-GenExMiner, PrognoScan, and UCSC Xena. To verify the results from databases, we compared the mRNA CDC20 expression in breast cancer tissues and adjacent normal tissues of patients by real-time PCR. We found that CDC20 was expressed higher in different types of breast cancer, comparing with normal tissues. Moreover, the patients with a more advanced stage of breast cancer tended to express higher level CDC20. CDC20 was expressed higher in breast cancer tissues than normal tissues from patients in our hospital, consistent with the results from databases. Estrogen receptor (ER) and progesterone receptor (PR) status were negatively correlated with CDC20 level. Conversely, Scarff–Bloom–Richardson (SBR) grade, Nottingham prognostic index (NPI), epidermal growth factor receptor-2 (HER-2) status, basal-like status, and triple-negative status were positively related to CDC20 expression in breast cancer patients with respect to normal individuals. Higher CDC20 expression correlated with worse survival. Finally, a positive correlation between CDC20 and Targeting protein for Xenopus kinesin-like protein 2 (TPX2) expression was revealed. CDC20 could be considered as a potential predictive indicator for prognosis of breast cancer with co-expressed TPX2 gene.

Identification of prognostic significance of BIRC5 in breast cancer using integrative bioinformatics analysis.

Aims: Baculoviral inhibitor of apoptosis repeat containing 5 (BIRC5) plays vital roles in carcinogenesis by influencing cell division and proliferation and by inhibiting apoptosis. However, the prognostic significance of BIRC5 remains unclear in breast cancer.Methods: BIRC5 expression and methylation status were evaluated using the Oncomine and The Cancer Genome Atlas (TCGA) databases. The relevance between BIRC5 and different clinicopathological features as well as survival information was analyzed using the bc-GenExMiner database and Kaplan–Meier Plotter. BIRC5–drug interaction network was obtained using the Comparative Toxicogenomics Database.Results: Based on the results from databases and own hospital data, BIRC5 was higher expressed in different breast cancer subtypes compared with the matched normal individuals. Hormone receptors were negatively correlated with BIRC5 expression, whereas the Scarff–Bloom–Richardson (SBR) grade, Nottingham Prognostic Index (NPI), human epidermal growth factor receptor-2 (HER-2) status, basal-like status, and triple-negative status were positively related to BIRC5 level in breast cancer samples with respect to normal tissues. High BIRC5 expression was responsible for shorter relapse-free survival, worse overall survival, reduced distant metastasis free survival, and increased risk of metastatic relapse event. BIRC5–drug interaction network indicated that several common drugs could modulate BIRC5 expression. Furthermore, a positive correlation between BIRC5 andcell-division cycle protein 20 (CDC20) gene was confirmed.Conclusion: BIRC5 may be adopted as a promising predictive marker and potential therapeutic target in breast cancer. Further large-scale studies are needed to more precisely confirm the value of BIRC5 in treatment of breast cancer.

Bioinformatics analysis of prognostic significance of COL10A1 in breast cancer.

Background: Collagen type X alpha 1 (COL10A1) is overexpressed in diverse tumors and displays vital roles in tumorigenesis. However, the prognostic value of COL10A1 in breast cancer remains unclear.Methods: The expression of COL10A1 was analyzed by the Oncomine database and UALCAN cancer database. The relationship between COL10A1 expression level and clinical indicators including prognostic data in breast cancer were analyzed by the Kaplan–Meier Plotter, PrognoScan, and Breast Cancer Gene-Expression Miner (bc-GenExMiner) databases.Results: COL10A1 was up-regulated in different subtypes of breast cancer. Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2) status and nodal status were positively correlated with COL10A1 expression. Conversely, age, the Scarff–Bloom–Richardson (SBR) grade, basal-like status, and triple-negative status were negatively related to COL10A1 level in breast cancer samples compared with normal tissues. Patients with increased COL10A1 expression level showed worse overall survival (OS), relapse-free survival (RFS), distant metastasis-free survival (DMFS) and disease-free survival (DFS). COL10A1 was positively correlated with metastatic relapse-free survival. GSEA analysis revealed that enrichment of TGF-β signaling pathway. 15-leucine-rich repeat containing membrane protein (LRRC15) is a correlated gene of COL10A1.Conclusion: Bioinformatics analysis revealed that COL10A1 might be considered as a predictive biomarker for prognosis of breast cancer. Further experiments and clinical trials are essential to elucidate the value of COL10A1 in breast cancer treatment.

Expression of human epidermal growth factor receptor 2/neu in breast carcinoma: Experience from a tertiary care center in Tamil Nadu, India

Background and Aim: Women diagnosed with the foremost common cancer are the breast carcinoma. Human epidermal growth factor receptor 2 (HER2)/neu status has become an important part of immunohistochemical evaluation of breast carcinoma. Hence, the main aim of our study was to correlate the HER2/neu expression in breast carcinoma patients with certain clinicopathological parameters to ensure the better prognosis of the disease. Materials and Methods: The present study included 56 breast carcinoma patients. The surgically dissected breast carcinoma specimens were subjected to immunohistochemistry staining and were evaluated for certain clinicopathological prognostic parameters that included tumor size, Nottingham modification of the Scarff Bloom-Richardson (NSBR) grading, necrosis, lymph vascular invasion, fibrosis, stromal reaction, and lymph node metastasis. Statistical analysis by the Chi-square and Student's t-test was performed. Results: Most patients belonged to the postmenopausal age group (62.5%). Only 19 (33.9%) out of 56 patients showed positive for HER2/neu expression with maximum HER2/neu expression noted in the 40–60 years' (44.83%) age group. A greater proportion of cases (66.07%) had tumor size ranging from 2 to 5 cm with a majority of HER2/neu-positive (40.5%) cases among them. Majority of patients (96.24%) were of infiltrating ductal carcinoma. With respect to NSBR grading, 50% patients in Grade 3 showed positive HER2/neu expression (P = 0.048). It was also observed that 17 patients showed positive HER2/neu expression at the varying stages of lymph node metastasis (P = 0.022). Conclusion: The evaluation of HER2/neu expression indicates it to be a stronger prediction of poor prognosis due to its association with prognostic parameters.

Expression and prognostic analyses of early growth response proteins (EGRs) in human breast carcinoma based on database analysis.

BackgroundEarly growth response proteins (EGRs), as a transcriptional regulatory family, are involved in the process of cell growth, differentiation, apoptosis, and even carcinogenesis. However, the role of EGRs in tumors, their expression levels, and their prognostic value remain unclear.MethodsUsing the Oncomine database, Kaplan–Meier Plotter, bcGenExMiner v4.2, cBioPortal, and other tools, the association between the survival data of breast carcinoma (BC) patients and transcriptional levels of four EGRs was investigated.ResultsAccording to the Oncomine database, in comparison to normal tissues, the expression level of EGR2/3 mRNA in BC tissues was decreased, but there was no difference in the expression level of EGR4 mRNA. On the basis of the Scarff-Bloom-Richardson (SBR) grading system, the downregulated expression level of EGR1/2/3 and upregulated expression level of EGR4 were correlated with an increased histological differentiation level, with significant differences (p < 0.05). Kaplan–Meier curves suggest that a reduction in EGR2/3 mRNA expression is related to recurrence-free survival (RFS) in BC patients. In addition, the mRNA expression level of EGR1/2/3 was related to metastatic relapse-free survival (MRFS) in BC patients with metastatic recurrence (p < 0.05).ConclusionEGR1/2/3 can be utilized as an important factor for evaluating prognosis and may be relevant to diagnosis. EGR4 may play a role in the occurrence and development of BC. The specific function and mechanism of EGRs in BC deserve further study.

Characterization of Kelch domain-containing protein 7B in breast tumours and breast cancer cell lines.

Adenocarcinomas exhibit great heterogeneity, with many genetic and epigenetic alterations. The Kelch domain-containing protein 7B (KLHDC7B) has recently been identified as epigenetically modified and upregulated in breast cancer. The potential reversibility of epigenetic states offers exciting possibilities for novel cancer diagnostics and drugs. However, to properly evaluate specific inhibitors, the role of KLHDC7B in the development and progression of breast cancer should be established. With that objective in mind, the present study investigated a series of human breast tumours and correlated their clinicopathology, according to the Elston-Ellis modification of the Scarff-Bloom-Richardson (SBR) grading system, with KLHDC7B mRNA expression, analysed using quantitative PCR (qPCR). The results revealed that KLHDC7B was significantly upregulated in grade 3 tumours, and that KLHDC7B expression varied according to the tumour grade and the individual, being downregulated in well-differentiated and moderately-differentiated tumours (grade 1–2) and upregulated in poorly-differentiated tumours (grade 3). Immunohistochemical staining revealed that ductal tumours and tumours with a higher percentage of Ki67 positive cells showed the highest levels of KLHDC7B. Receptor expression, HER, p53 status, presence of metastasis, and vascular invasion showed no association with KLHDC7B expression. Previous studies have proposed KLHDC7B as an epigenetic marker of breast cancer. We propose that KLHDC7B should be used as a marker for poorly-differentiated tumours only; use of KLHDC7B without considering tumour grade could lead to an inaccurate diagnosis. Finally, we suggest the appropriate breast cancer cell lines to use to determine the functions of KLHDC7B. KLHDC7B expression was tested in the non-tumour cell line MCF-10A and in the breast cancer cell lines MCF-7, MDA-MB-231 and MDA-MB-468, using qPCR and western blotting. The results revealed that all tested cancer cell lines overexpressed KLHDC7B mRNA, but MDA-MB-468 exhibited a much lower level of protein expression relative to mRNA. Although the breast cancer cell lines used may be appropriate for studying KLHDC7B epigenetic status, MDA-MB-468 should be excluded from functional experiments.

Five miRNAs-mediated PIEZO2 downregulation, accompanied with activation of Hedgehog signaling pathway, predicts poor prognosis of breast cancer.

Roles of Piezo-type mechanosensitive ion channel component 2 (PIEZO2) in cancer remain largely unknown. Herein, we explored PIEZO2 expression, prognosis and underlying mechanisms in cancer. Breast was selected as the candidate as its relatively higher expression level of PIEZO2 than other human tissues. Next, we identified a decreased expression of PIEZO2 in breast cancer compared with normal controls, and found that PIEZO2 expression positively correlated with estrogen receptor (ER) and progesterone receptor (PR) status but negatively correlated with human epidermal growth factor receptor 2 (HER2) status, Nottingham Prognostic Index (NPI) score, Scarff-Bloom-Richardson (SBR) grade, basal-like and triple-negative status. Subsequent analysis revealed that high expression of PIEZO2 had a favorable prognosis in breast cancer. 182 miRNAs were predicted to target PIEZO2. Among these miRNAs, five miRNAs (miR-130b-3p, miR-196a-5p, miR-301a-3p, miR-421 and miR-454-3p) possess the greatest potential in targeting PIEZO2. 109 co-expressed genes of PIEZO2 were identified. Pathway enrichment analysis showed that these genes were enriched in Hedgehog signaling pathway, including Cell adhesion molecule-related/downregulated by oncogenes (CDON). CDON expression was decreased in breast cancer and downregulation of CDON indicated a poor prognosis. Altogether, these findings suggest that decreased expression of PIEZO2 may be utilized as a prognostic biomarker of breast cancer.

Bioinformatics analysis revealing prognostic significance of RRM2 gene in breast cancer.

Background: Ribonucleotide reductase M2 subunit (RRM2) plays vital roles in many cellular processes such as cell proliferation, invasiveness, migration, angiogenesis, senescence, and tumorigenesis. However, the prognostic significance of RRM2 gene in breast cancer remains to be investigated. Methods: RRM2 expression was initially evaluated using the Oncomine database. The relevance between RRM2 level and clinical parameters as well as survival data in breast cancer was analyzed using the Kaplan–Meier Plotter, PrognoScan, and Breast Cancer Gene-Expression Miner (bc-GenExMiner) databases. Results: RRM2 was overexpressed in different subtypes of breast cancer patients. Estrogen receptor (ER) and progesterone receptor (PR) were negatively correlated with RRM2 expression. Conversely, the Scarff–Bloom–Richardson (SBR) grade, Nottingham prognostic index (NPI), human epidermal growth factor receptor-2 (HER-2) status, nodal status, basal-like status, and triple-negative status were positively related to RRM2 level in breast cancer samples with respect to normal tissues. Patients with increased RRM2 showed worse overall survival, relapse-free survival, distant metastasis-free survival, disease-specific survival, and disease-free survival. RRM2 also exerted positive effect on metastatic relapse event. Besides, a positive correlation between RRM2 and KIF11 genes was confirmed. Conclusion: Bioinformatics analysis revealed that RRM2 might be used as a predictive biomarker for prognosis of breast cancer. Further studies are needed to more precisely elucidate the value of RRM2 in evaluating breast cancer prognosis.

Molecular Profile of Breast Cancer in Women at Pointe Noire (Congo Brazzavile)

Objective: To determine molecular profile of breast cancer in Pointe Noire. Patients and Methods: We conducted a cross-sectional study covering the period of January 2018 to September 2019, one (1) year and nine (09) months in the General Hospital of Pointe-Noire. 48 records of patients who were diagnosed with breast cancer with or not immunohistochemistry results at Loandjili General hospital. The variables studied were: Age; the family breast cancer history; tumor localization, histological type, estrogen receptors status, progesterone receptors status; HER2 receptors expression, and molecular profile. The comparison of the qualitative variables was made by the chi2 test and the comparison of the quantitative variables was made by the student test (t-test). The p-values were calculated with the data comparison program that uses chi2 tests (Pearson and Fischer) and t-test. Results were statistically significant for P˂0.05. Results: The average age was 45.7 years with extremes of 22 and 79 years. Two women had a history of breast cancer. Breast cancer was more located in right in 46 % of cases. Ductal invasive carcinoma was the most represented histologic type in 73 %. The histopronostic grade II of Scarff bloom Richardson (SBR) was the most represented in 47.5% of cases. 65% of the estrogen receptors were negative. Negative progesterone receptors were the most represented in 53% of cases. Negative expression of the HER2 were the most represented in 62 % of cases. The molecular profile Luminal A were the le most represented molecular profile accounted for 45. In our study, we noted a prevalence of the age group of 40 to 49 years of 25% of which 15% of Luminal A was also observed. There was not relationship between age and molecur profile (P˃ 0.05). A relationship was noted between molecular profile and histological grade (p ˂0.05). Conclusion: Breast cancer is a real public health problem worldwide. It is the first cancer and the leading cause of cancer death in women worldwide. In Pointe Noire the molecular profile is dominated by Luminal A. This study is important and help to the best therapeutic choice of breast cancer.

Impact of breast cancer prognostic factors on the response to controlled ovarian stimulation patients undergoing fertility preservation

The objective is to know if breast cancer (BC) prognostic factors influence ovarian function and response to controlled ovarian stimulation (COS) in patients seeking fertility preservation (FP)? A total of 151 BC patients undergoing COS for FP were prospectively included between November 2013 and December 2016. COS was initiated regardless of the phase of the cycle, with or without letrozole supplementation. Matured oocytes and/or embryos obtained were vitrified. COS characteristics and outcomes were analyzed in all women BC prognostic factors considered in the present study were Scarff-Bloom-Richardson (SBR) SBRIII grade, Ki 67> 20%, HER2 overexpression and "triple negative” tumor. Univariate and multivariate analysis were performed to determine their impact on ovarian reserve markers (serum Anti-Müllerian Hormone (AMH) and antral follicle count (AFC)) as well as on ovarian response to exogenous FSH. Less than 8 mature oocytes vitrified, maturation rate under 70% or Follicle Output RaTe (FORT) under 35% were considered as poor COS outcomes A total of 154 COS cycles were performed and analyzed in BC patients 33.4±4.1 years of age were analyzed. Mean AMH and AFC were 3.2±4.5 ng/mL and 20.2±14.3 follicles, respectively. HER2 overexpression was observed in 18.9% and 34.7% of tumors expressed estrogen or progesterone receptors. Triple negative status characterized 25% of tumors. BRCA1/2 mutation was found in 22.4% of patients. A mean of 9.2 ± 7.4 mature oocytes were cryopreserved per cycle. After multivariate analysis, only serum AMH levels, AFC and smoking status were significantly associated with the number of mature oocytes obtained following COS. BC prognostic factors did not appear to have a significant influence on ovarian reserve markers, number of retrieved oocytes, maturity rate or on ovarian response to exogenous FSH assessed by FORT index, defined as the ratio of the number of pre-ovulatory follicle (16-22 mm) count on the triggering day X100 to the antral follicle (3-8 mm) count at baseline BC prognostic factors probably have no or low impact on ovarian function in terms of ovarian reserve and response to COS. Further analysis, in particular after oocyte thawing will be needed to clarify a possible impact egg quality.

To Evaluate the Applicability of Parameters of Cytological Grading Systems on Aspirates of Breast Carcinoma.

Background:Fine-needle aspiration cytology (FNAC) is still an important first line diagnostic procedure in developing countries. FNAC of breast lesions is quite specific and sensitive investigation and the results are comparable to histopathology.Aim:To evaluate applicability of parameters of different cytological grading (CG) systems, for aspirates of breast cancers, and its correlation with histopathology grading parameters.Materials and Methods:A cross-sectional observational study was carried out on 30 female patients with ductal carcinoma breast, diagnosed on FNAC and subsequently confirmed histopathologically. The cytological smears were graded using six different cytological parameters/criteria described by Robinson et al. (Robinson grading system) and modified Scarff-Bloom-Richardson (SBR) grading system considering three parameters. The results of cytological grade (CG) were compared with parameters of gold standard modified SBR histological grading (HG) system.Results:Important influential cytological parameters to predict final RBS cytological score came out to be chromatin, nucleoli, nuclear size, cell uniformity, and cell dissociation with statistically significant P value (0.0001) except for mitotic count. The important influential predictor of final SBR histological score is nuclear pleomorphism.Conclusion:SBR HG has good correlation with both RBS and SBR CG systems. The cytological nuclear grade provides important prognostic information which is very sensitive and equally specific hence should be done in breast aspirates and is now replaced by Core Needle biopsy. In developing country like India FNAC of breast aspirates still holds diagnostic value in the classification of breast lesions as compared to core guided image biopsy.

Anatomo-Clinical Case: Coexistence of Tuberculosis with Axillary Lymph Node Metastasis in Breast Carcinoma

Introduction: The coexistence of tuberculosis with axillary lymph node metastasis in breast carcinoma is uncommon. Observation: We report a case of a patient aged 59 years presenting a painless nodule in the right breast for one year. The scan and mammography revealed a long-axis node of 3 × 2 × 1 cm in the upper outer quadrant of the right breast ranked stage IV by the American College of Radiology (ACR), associated with a set of axillary lymph nodes and the largest one measuring 15 × 15 × 20 millimeters (mm). The breast biopsy helped diagnose a Scarff Bloom Richardson (SBR) grade II non-specific invasive carcinoma, modified by Ellis and Elston. A right mastectomy associated with a lymph node dissection was performed. We noticed a not well defined and whitish 5 mm tumor mass associated with 16 lymph nodes removed. The histological examination confirmed the diagnosis of SBR grade II non-specific invasive carcinoma with invasion of 7 lymph nodes (N+ = 7/16). In 3 metastatic lymph nodes, there were epithelioid and gigantocellular granulomas with full central necrosis. The Ziehl Neelsen staining had highlighted acid-fast bacilli. The tumor was oestrogen and progesteron receptor, without an overexpression of the oncoprotein human epidermal growth factor receptor 2 (HER2), which corresponds to a 0 score and the Ki 67 proliferation index assessed at 10%. The patient was given an anti-tuberculosis treatment combining Rifampicin (H), Isoniazid (I), Pyrazinamid (Z), Ethambutol (E) over 2 months and secondly a combination of Rifampicin and Isoniazid over 4 months (2RHZE/4 RH). The anti-tumor chemotherapy used a protocol combining 3 FAC60+ 3 Docetaxel (F = Fluorouracil®; A = Adriblastin®, C = Cyclophosphamid). Conclusion: This coexistence is uncommon, of incidental discovery and necessitates a multidisciplinary care.

Inflammatory Breast Cancer Outcomes in a Contemporary Series.

Evidence on the management of inflammatory breast cancer (IBC) is limited. This study investigated factors influencing IBC treatment outcomes such as event-free survival (EFS) and overall survival (OS). Data were collected from 173 patients with stage III non-IBC and 17 patients with IBC diagnosed at the Keck Medical Center and Los Angeles County and University of Southern California (LAC+USC) Medical Center. Cox proportional hazard regression evaluated associations between variables significant for EFS and OS. On multivariate analysis, negative estrogen receptor (ER)status [hazard ratio (HR)=1.88, 95% confidence interval (CI)=1.11-3.18, p<0.06) and lack of postoperative radiation treatment (HR=2.07, 95% CI=1.03-4.15, p<0.04) were significant for poorer EFS. High Scarff-Bloom-Richardson (SBR) score (HR=2.24, 95% CI=0.79-6.36, p<0.13) and lack of postoperative radiation treatment to the breast (HR=4.39, 95% CI=0.39-49.55, p<0.23) were associated with lower rates of OS. The diagnosis of IBC has a significantly worse prognosis. Receipt of post-mastectomy radiation therapy was a significant predictor of better EFS and OS.

Optimal duration of adjuvant chemotherapy for high-risk node-negative (N–) breast cancer patients: 6-year results of the prospective randomised multicentre phase III UNICANCER-PACS 05 trial (UCBG-0106)

PurposeOptimal duration of adjuvant chemotherapy in the treatment of early-stage breast cancer remained to be investigated rigorously for the standard regimens in widespread use in North America (doxorubicin/cyclophosphamide, AC) and Europe (5-fluorouracil/epirubicin/cyclophosphamide, FEC). Whether six cycles of FEC 100 present an advantage, or not, compared with only four cycles was tested directly in a phase III prospective multicentre trial. Patients and methodsBetween 2002 and 2006, 1515 women between 18 and 65°years of age, with node negative N(−) high-risk early-stage breast cancer, were included in the study following breast surgery and axillary lymph node dissection or procedure by sentinel node technique. Inclusion in the study required tumour size T ≥ 1 cm and at least one of the high-risk factors: T > 2 cm, negative oestrogen receptor/progesterone receptor (ER– and PR–), Scarff-Bloom-Richardson (SBR) grade II or III and age ≤ 35°years. Patients were randomly assigned to either six FEC 100 (Arm A) or four FEC 100 (Arm B). The trial was powered to detect an absolute difference ≥6% in disease-free survival (DFS) at 5°years. ResultsAt 6.1°years median follow-up, with 91 (12%) events recorded in Arm A versus 106 (14%) in Arm B, no statistically significant risk increase was associated with four versus six FEC 100: DFS (hazard ratio (HR) = 1.18; CI 95% [0.89–1.56], P = .24) and overall survival (OS) (HR = 1.39; CI 95% [0.91–2.13], P = .12). ConclusionDifferences in chemotherapy duration did not induce notably different outcomes in our cohort of high-risk patients. Clinical trial registry numberNCT00055679, Agence National de Sécurité du Médicament (ANSM) – France.

Overexpression of p53 protein is a marker of poor prognosis in Mexican women with breast cancer.

Breast cancer (BC) is a disease with different clinical, histological and molecular characteristics, frequently presenting mutated tumour-suppressing genes and oncogenes. P53 is a known tumour suppressor that is often mutated in BC; several mutations in p53 inhibit its role as a transcriptional repressor of several oncogenes. Topoisomerase2α (TOP2α) is a gene target of p53, and it is also a known target for anthracyclines. The aim of the present study, was to analyse the genetic alterations of p53 and TOP2α genes and their levels of protein expression, as well as their association with survival in Mexican women with BC. A total of 102biopsies were collected (tumour and adjacent tissues) from patients with BC. To identify point mutations and deletions in the p53 gene, the Sanger sequencing method was carried out. Deletions or amplifications for TOP2α gene were determined using quantitative polymerase chain reaction (qPCR). In addition, the expression of the TOP2α and p53 proteins was evaluated by western blotting. Furthermore, p53 protein expression was analysed by proximity ligation assay (PLA)-qPCR. Only 28.5% of the patients were found to have triple-negative breast cancer (TNBC); the average age at the time of diagnosis of these patients was 50years, and Scarff-Bloom-Richardson (SBR) histological gradeIII (p=0.0089). No differences in point mutations or deletions in p53, and deletions or amplifications as well as protein expression level of TOP2α were observed between patients with TNBC and non-TNBC patients. However, patients with TNBC showed p53 protein overexpression as determined by PLA-qPCR and western blotting (p<0.0001). Furthermore, we found an association between TOP2α amplification and overexpression of its protein in patients with TNBC (p<0.0001). Concerning p53, overexpression resulted in a lower survival in patients with BC.

Benefit of adjuvant chemotherapy with or without trastuzumab in pT1ab node-negative human epidermal growth factor receptor 2-positive breast carcinomas: results of a national multi-institutional study.

Benefit of adjuvant trastuzumab-based chemotherapy for node-positive and/or >1cm human epidermal growth factor receptor 2-positive (HER2+) breast carcinomas has been clearly demonstrated in randomized clinical trials. Yet, evidence that adjuvant chemotherapy with or without trastuzumab is effective in pT1abN0 HER2+ tumors is still limited. The primary objective of this study was to investigate the impact of adjuvant chemotherapy±trastuzumab on outcome in this subpopulation. A total of 356 cases of pT1abN0M0 HER2+breast cancers were retrospectively identified from a large cohort of 22,334 patients, including 1248 HER2+ patients who underwent primary surgery at 17 French centers, between December 1994 and January 2014. The primary end point was disease-free survival (DFS). A multivariate Cox model was built, including adjuvant chemotherapy, tumor size, hormone receptor status, and Scarff Bloom Richardson (SBR) grade. A total of 138 cases (39%) were treated with trastuzumab-based chemotherapy, 29 (8%) with chemotherapy alone, and 189 (53%) received neither trastuzumab nor chemotherapy. Adjuvant chemotherapy±trastuzumab was associated with a significant DFS benefit (3-year 99 vs. 90%, and 5-year 96 vs. 84%, Hazard ratio, HR 0.26 [0.10-0.67]; p=0.003, logrank test) which was maintained in multivariate analysis (HR 0.19 [0.07-0.52]; p=0.001). Metastasis-free survival was also increased (HR0.25 [0.07-0.86]; p=0.018, logrank test) at 3-year (99 vs. 95%) and 5-year (98 vs. 89%) censoring. Exploratory subgroup analysis found DFS benefit to be significant in hormone receptor-negative, hormone receptor-positive, and pT1b tumors, but not in pT1a tumors. Adjuvant chemotherapy±trastuzumab is associated with a significantly reduced risk of recurrence in subcentimeter node-negative HER2+ breast cancers. Most of the benefit may be driven by pT1b tumors.

A Prognostic Model for Patients with Triple-Negative Breast Cancer: Importance of the Modified Nottingham Prognostic Index and Age.

PurposeConsidering the distinctive biology of triple-negative breast cancer (TNBC), this study aimed to identify TNBC-specific prognostic factors and determine the prognostic value of the Nottingham Prognostic Index (NPI) and its variant indices.MethodsA total of 233 patients with newly diagnosed stage I to III TNBC from 2003 to 2012 were reviewed. We retrospectively analyzed the patients' demographics, clinicopathologic parameters, treatment, and survival outcomes. The NPI was calculated as follows: tumor size (cm)×0.2+node status+Scarff-Bloom-Richardson (SBR) grade. The modified NPI (MNPI) was obtained by adding the modified SBR grade rather than the SBR grade.ResultsThe median follow-up was 67.8 months. Five-year disease-free survival (DFS) and overall survival (OS) were 81.4% and 89.9%, respectively. Multivariate analyses showed that the MNPI was the most significant and common prognostic factor of DFS (p=0.001) and OS (p=0.019). Young age (≤35 years) was also correlated with poor DFS (p=0.006). A recursive partitioning for establishing the prognostic model for DFS was performed based on the results of multivariate analysis. Patients with a low MNPI (≤6.5) were stratified into the low-risk group (p<0.001), and patients with a high MNPI (>6.5) were subdivided into the intermediate (>35 years) and high-risk (≤35 years) groups. Age was not a prognostic factor in patients with a low MNPI, whereas in patients with a high MNPI, it was the second key factor in subdividing patients according to prognosis (p=0.023).ConclusionThe MNPI could be used to stratify patients with stage I to III TNBC according to prognosis. It was the most important prognosticator for both DFS and OS. The prognostic significance of young age for DFS differed by MNPI.