Poor Prognostic Factor In Breast Cancer Research Articles

Impact of young age at diagnosis on survival outcomes in patients with early breast cancer according to tumor subtype: Pooled analysis of 5 randomized clinical trials from the Mammella InterGruppo (MIG) and Gruppo Italiano Mammella (GIM).

523 Background: The incidence of breast cancer (BC) among young patients is increasing. Historically, young age itself has been recognised as a poor prognostic factor for BC. However, there is limited evidence regarding the impact of age at diagnosis and on survival outcomesaccording to tumor subtype. Methods: We collected individual patient (pt)-level data from newly diagnosed stage I to III BC pts participating in 5 randomized clinical trials conducted by Mammella InterGruppo (MIG) and Gruppo Italiano Mammella (GIM) study groups. Patients were categorized into the following age groups based on their age at BC diagnosis: ≤40, 41-50, 51-60, 61-70, >70 years (yr). Multivariable Cox proportional hazards models were used to assess the relationship between age and breast cancer–free interval (BCFI) and breast cancer specific survival (BCSS). Results: 8,338 pts with stage I to III BC were included in the study: 778 (9%) aged ≤40 years, 1629 (20%) 41-50 years, 2,595 (31%) 51-60 years, 2,435 (29%) 61-70 years, and 901 (11%) >70 years. Compared to older, young pts were more likely to have ductal tumors as histology, larger than 2 cm, with nodal involvement, G3 and triple negative or HER2 positive subtypes (p<0.001). With a median follow-up of 9.0 years (IQR 5.5-14.4), 2,161 BCFI and 927 BCSS events were observed in the overall population. Pts ≤40 years at diagnosis had greater risk of reporting BC event (adjusted hazard ratio (adjHR) for BCFI 1.27, 95% CI 0.93-1.74) compared to pts aged 51-60 years (reference group), while pts 41-50 years had a lower risk (adjHR 0.74, 95%CI 0.55-0.99). Pts aged ≤40 years presented some evidence of a lower risk of BCSS events (adjHR 0.80, 95%CI 0.50-1.26) compared to pts aged 51-60 years, while pts aged 41-50 years had the lowest risk (adjHR 0.50, 95%CI 0.32-0.78). There was evidence of interaction between age and tumor subtype, nodal status both for BCFI and BCSS. A significant increase in risk of BC events was observed among pts ≤40 years with hormone-receptor positive/HER2 negative tumors (HR 1.70 for BCFI) and among ≤40 years with node negative tumors (HR for BCFI 2.43). Conclusions: The prognostic significance of young age at diagnosis may vary depending on tumor subtypes and nodal status, indicating poorer outcomes for young pts with hormone-receptor positive/HER2 negative and node negative tumors.

Lateral interactions between CD276 and CD147 are essential for stemness in breast cancer: a novel insight from proximal proteome analysis

Oncogenic cell-surface membrane proteins contribute to the phenotypic and functional characteristics of cancer stem cells (CSCs). We employed a proximity-labeling proteomic approach to quantitatively analyze the cell-surface membrane proteins in close proximity to CD147 in CSCs. Furthermore, we compared CSCs to non-CSCs to identify CSC-specific cell-surface membrane proteins that are closely interact with CD147 and revealed that lateral interaction between CD147 and CD276 concealed within the lipid raft microdomain in CSCs, confers resistance to docetaxel, a commonly used chemotherapy agent for various cancer types, including metastatic breast cancer. Moreover, we investigated the clinical relevance of CD147 and CD276 co-expression in HER2+ breast cancer (BC) and triple-negative breast cancer patients who underwent chemotherapy. We observed poor disease-free survival and Overall survival rates in patients of CD147 and CD276 (p = 0.04 and 0.08, respectively). Subsequent immunohistochemical analysis in independent cohorts of HER2+ BC support for the association between co-expression of CD147 and CD276 and a poor response to chemotherapy. Collectively, our study suggests that the lateral interaction between CD147 and its proximal partners, such as CD276, may serve as a poor prognostic factor in BC and a predictive marker for the critical phenotypic determinant of BC stemness.

71P Impact of body mass index (BMI) on pathological complete response (pCR) and survival of breast cancer (BC) patients receiving neoadjuvant chemotherapy (NAC)

High BMI is generally considered a poor prognostic factor in BC. However, its association with pCR and survival after NAC is still controversial. The aim of this study was to evaluate the prognostic impact of BMI on clinical outcomes in BC patients undergoing NAC.

MRPL13 is a Prognostic Cancer Biomarker and Correlates with Immune Infiltrates in Breast Cancer.

ObjectiveTo study the expression of MRPL13 in breast cancer tissues using TCGA database, analyze the correlation between the expression and clinicopathological characteristics of patients, and explore the role of MRPL13 in the development of breast cancer (BC).MethodsThe BC mRNA data and clinical information were downloaded from TCGA database. The correlation between MRPL13 expression and clinicopathological parameters was analyzed. Cox regression multivariate analysis was used to explore the factors affecting the prognosis of BC patients. The UALCAN database was used to analyze the expression level of MRPL13 in BC and its relationship with clinical pathological factors. The GSEA method was used to predict the possible regulatory pathways of MRPL13. Immune responses of MRPL13 expression were analyzed using TISIDB and CIBERSORT. Additionally, GEPIA, K-M survival analysis and data from the HPA were used to validate the outcomes.ResultsThe expression of MRPL13 in BC tissues was significantly higher than normal counterparts, patients with low MRPL13 expression had a better survival prognosis, also indicated an independent prognostic factor. GSEA analysis showed that the regulation of cell migration, positive regulation of endothelial cell migration, and Notch signaling pathway were enriched in tissues with low expression of MRPL13. Additionally, depleting MRPL13 expression inhibited invasion in MCF-10A and MCF-7 cells. Furthermore, PCR showed that MRPL13 affected VEGFA and MMP gene expression. CIBERSORT analysis revealed that the amount of NK cells decreased when MRPL13 expression was high.ConclusionThe expression of MRPL13 mRNA is upregulated in BC tissues, and the expression level of MRPL13 is significantly related to the clinicopathological factors of patients. High MRPL13 expression is a poor prognostic factor for BC, and it can be used as a molecular marker for prognosis judgment and as a potential therapeutic target.

Prognostic value of aldehyde dehydrogenase 1 (ALDH1) in invasive breast carcinomas.

Aldehyde dehydrogenase 1 (ALDH1) has been identified as a marker of cancer stem cells in breast cancer (BC). Recent studies showed that ALDH1 expression is correlated with poor prognostic parameters and worse clinical outcome in BC. We evaluated ALDH1 expression by immunohistochemistry in a series of 217 invasive BCs and investigated the correlation between ALDH1 expression and clinicopathological parameters, molecular subtypes (luminal A, luminal B, human epidermal growth factor receptor 2 [HER2] type, and triple-negative BC [TNBC]), and patient survival. There was a significant association between ALDH1 expression and tumor grade (p < 0.001), i.e., the expression of ALDH1 was higher in high-grade tumors. ALDH1 expression was significantly associated with estrogen and progesterone receptor (ER and PR) negativity (p < 0.001) and HER2 positivity (p = 0.001). ALDH1 expression ratios were higher in HER2 type and TNBC. There was a statistically significant correlation between ALDH1 negativity and luminal A subtype (p < 0.001). The overall and disease free survival were shorter in ALDH1+ tumors, although without statistical significance. We confirm that ALDH1 is a potentially important, poor prognostic factor in BC, associated with high histological grade, ER/PR negativity and HER2 positivity. For more accurate results, ALDH1 expression should be evaluated in larger case series including various types/subtypes of BC.

Equivalent Survival With Mastectomy or Breast-conserving Surgery Plus Radiation in Young Women Aged < 40 Years With Early-Stage Breast Cancer: A National Registry-based Stage-by-Stage Comparison

BackgroundStudies have shown that young patients with early-stage breast cancer (BC) are increasingly undergoing mastectomy instead of breast-conserving therapy (BCT) consisting of lumpectomy and radiation. We examined the difference in outcomes in young women (aged < 40 years) who had undergone BCT versus mastectomy. Materials and MethodsThe Surveillance, Epidemiology, and End Results database was queried for women aged < 40 years with stage I or II invasive BC treated with surgery from 1998 to 2003. Breast cancer-specific survival (BCSS) and overall survival (OS) were evaluated using Kaplan-Meier survival analysis and the log-rank test between treatment types. ResultsOf the 7665 women, 3249 received BCT and 2627 underwent mastectomy without radiation. When separated by stage (I, IIA, and IIB), with a median follow-up duration of 111 months, the BCT and mastectomy-only groups showed no statistically significant differences in BCSS and OS. Overall, the age group of 35 to 39 years (66% of total) was associated with better 10-year BCSS (88%) and OS (86.1%) compared with the younger patients aged 20 to 34 years (34% of total). The latter group had a 10-year BCSS and OS of 84.1% and 82.3%, respectively (P < .001 for both BCSS and OS). However, when the patients of each age group were further subdivided by stage, the BCT group continued to show noninferior BCSS and OS compared with the mastectomy group in all subgroups. ConclusionThe results of our study suggest that although young age might be a poor prognostic factor for BC, no evidence has shown that these patients will have better outcomes after mastectomy than after BCT.

RETRACTED ARTICLE: Expression of microRNA-497 and its prognostic significance in human breast cancer

ObjectiveDysregulation of microRNAs (miRNAs) plays critical roles in tumor progression. The aim of this study was to investigate the clinicopathologic and prognostic significance of miR-497 expression in human breast cancer (BC).MethodsTaqman qRT-PCR assay was performed to detect the expression of microRNA (miR)-497 in 30 pairs of BC tissues and corresponding noncancerous breast tissues. Additionally, the expression of this miRNA was detected in another 128 BC tissues and its correlations with clinicopathologic features of patients were analyzed. Kaplan-Meier analyses were used to assess survival of patients. Univariate and multivariate analyses were performed using the Cox proportional hazards model to analyze the prognostic significance of miR-497 expression.ResultsOur data indicated that the relative level of miR-497 expression in BC tissues was significantly lower than that in corresponding noncancerous breast tissues (P = 0.0046). Of 128 BC patients, 74 (57.8%) were placed in the high-miR-497 group and 54 (42.2%) were placed in the low-miR-497 group. By statistical analyses, low miR-497 expression was observed to be closely correlated with higher differentiation grade, positive HER-2 expression, higher incidence of lymph node metastasis and advanced clinical stage. Moreover, patients with high miR-497 expression had better 5-year disease-free and overall survival compared with the low miR-497 group (P = 0.0124 and 0.0018, respectively). Univariate and multivariate analyses indicated that low miR-497 expression was an independent poor prognostic factor for BC patients.ConclusionsOur data provided the first evidence that downregulation of miR-497 was correlated with BC progression, and miR-497 might be a potential molecular biomarker for predicting the prognosis of patients.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2025828761093488

Prognosis related to Ki67 in early breast cancer.

e11085 Background: Breast cancer (BC) is the most common tumor in Mexican women. Ki67 is a nuclear antigen considered as a proliferation marker with potential prognostic significance in BC survival. Our objectives are determine the prognosis and correlation between Ki67 and prognostic factors in BC patients (pts). Methods: From January 2000 to December 2008, patients (pts) > 18 yrs old with invasive BC, I to IIB, ductal or lobular, treated with surgery were included. Pts with in situ or inflammatory BC or neoadjuvant chemotherapy were excluded. Age, tumor size, lymph node status, Ki-67, HER2, ER, PR, p53, angiogenesis, adjuvant therapy, recurrence and overall survival were registered. Pts were divided into four groups according to Ki67 levels: 1) Ki67 < 5%, 2) 6 to 20%, 3) 21 to 50%, and 4) > 51%. Descriptive statistical methods and X2, ANOVA tests were applied. Results: 132 pts analyzed. Groups 1 to 4 were integrated by 23 pts (17.4%), 49 (37.1%), 39 (29.5%) and 21 (15.9%); median age 49, 48, 51 and 48 yrs (p > 0.05), respectively. Conservative surgery 56.4%, 30.6%, 25.6% y 42.9%, respectively. In each group, adjuvant chemotherapy was indicated in 82.6%, 83.6%, 89.7% and 90.4%; radiation 47.8%, 36.7%, 43.5% and 42.8%; hormonal therapy 65.2%, 71.4%, 50.9% and 38%. Chemotherapy based in anthracyclines in 36.8%, 34.1%, 31.4% and 31.5%, anthracyclines and taxanes in 57.8%, 53.6%, 62.8% and 68.5%. Ki67 was associated to tumor size > 2 cm (p = 0.02), negative ER (p = 0.000), negative p53 (p= 0.048). A tendency was detected for relationship to negative PR (p = 0.06) and hypodiploid DNA (p = 0.071). We noted higher frequency of triple negative immunophenotype in the groups with greater expression of Ki67 (8.7%, 10.2%, 10.2% y 28.5%) (p > 0.05). In each group, median follow-up time was 49, 37, 41 y 48 mos, (p > 0.05). Recurrence was observed in 18 pts (13.6%), of them 0, 5, 7 y 6 in the groups 1 to 4, respectively. Systemic was more frequent than local recurrence (66.6% vs. 27.4%). Median time to recurrence was 27, 39 and 60 mos in the groups 2 to 4. There were 0, 2 (4%), 4 (10.2%) and 3 (14.2%) deaths in each group, median overall survival 49, 25.5, 38.5 y 36 mos, respectively. Conclusions: High cellular proliferation through Ki67 (> 51%) was related to poor prognostic factors in BC. No significant financial relationships to disclose.

Clinical outcome of breast cancer occurring after treatment for Hodgkin's lymphoma: case-control analysis

BackgroundTo evaluate diagnosis, management and outcome of breast cancer (BC) occurring after irradiation for Hodgkin's lymphoma (HL).Methods39 cases of BC in 28 HL survivors were retrospectively reviewed. 21 patients were included in a case-control analysis.ResultsThe median age at diagnosis of HL and BC was 25.3 and 45.3 years, respectively. The median interval to develop BC was 16.1 years. Eleven women (39.2%) had bilateral disease. Mode of detection of the index breast cancers was by mammographic screening in 17 patients (60.7%), palpable lump in 8 patients (28.6%), clinical examination in two patients (7.1%), and unknown in one patient (3.6%). Case-control analysis showed that histological features and prognosis of BC after HL were similar to those of primary BC, however, for BC after HL, mastectomy was the predominant surgery (P = .001) and adjuvant radiotherapy and anthracycline-based chemotherapy were less frequently used as compared to primary BC (P < .001 and .003, respectively).ConclusionThe previous history of HL does not appear to be a poor prognostic factor for BC occurring thereafter.

KI67 in breast cancer: Correlation between proliferation cellular and other prognostic factors

e22184 Background: Breast cancer (BC) is the most common tumor in Mexican women between 35 to 50 years old. KI67 is a nuclear antigen considered as a proliferation marker with potential prognostic significance in BC survival. Objective: To determine the correlation between KI67 and prognostic factors in BC patients (pts). Methods: Of 340 consecutive BC pts seen from January 2000 to September 2008, pts with invasive BC that have a complete IHC assay determination were analyzed (estrogen receptor [ER], progesterone receptor [PR], HER2, p53, KI67). KI67 was determined by monoclonal antibody MIB-1. Patients ´s clinical characteristics and tumor immunohistochemical factors were registered. Patients were divided into 4 groups according to KI67 levels: 1) KI67 &lt; 5%, 2) 6 to 20%, 3) 21 to 50% and 4) &gt; 51%. Descriptive statistical methods and X2, ANOVA tests were used. Results: 154 pts analyzed, mean age 53.5 ± 12 yrs, range 28 -83, median KI67: 25, (0 - 95%). Group 1: 22 pts (14.3%), Group 2: 52 (33.8%); group 3: 49 (31.8%), group 4: 31 pts (20.1%). Median KI67 by group: 5, 15, 30 70%. Among pts with KI67 &gt; 51% we observed: higher proportion of advanced stages (III-IV) [27.3%, 7.7%, 25.6%, 38.7% (p= 0.027)], positive lymph nodes (59%, 25%, 42.8% 70.9%, [p=0.003]), ER negative (27.3%, 5.8%, 28.4%, 51.7% [p= 0.000]), PR negative (36.4%, 26.9%, 22.5%, 61.3%; [p= 0.003]); P53 +ve (9.1%, 71.1%, 73.4%, 77.4%; [p= 0.028]), angiogenesis [&gt; 15 vessels × field] (31.8%, 21.1%, 24.5%, 54.5%; [p=0.006])), triple negative phenotype (4.5%; 3.8%, 10.2%, 41.9%; [p=0.000]). We do not observe correlation among KI67 status age, tumor size and HER2 (p &gt; 0.05). Conclusions: High cellular proliferation through KI 67 (&gt; 51%) was related to poor prognostic factors in BC. No significant financial relationships to disclose.