Infiltrating Ductal Carcinoma Patients Research Articles

Risk factors of diabetes and cancer-specific mortalities in patients with infiltrating ductal carcinoma of the breast: a population-based study.

Breast cancer is considered one of the most common neoplasms worldwide. Diabetes (DM) increases mortality among postmenopausal patients with breast cancer. Our study aims to identify the risk factors of DM-specific mortality and infiltrating ductal carcinoma (IDC) mortality in patients with IDC of the breast. Data of IDC patients were obtained from the Surveillance, Epidemiology, and End Results database from 1975 to 2016. Independent variables included age, race, marital status, the primary site of IDC, breast subtype, the disease stage, grade, chemotherapy, radiation, and surgery. Kaplan-Meier, Cox and Binary regression tests were used to analyze the data using SPSS software. A total of 673 533 IDC patients were analyzed. Of them, 4224 died due to DM and 116 822 died due to IDC. Factors that increase the risk of overall, IDC-specific, and DM-specific mortalities include older age, black race, widowed, uninsured, regional and distant stages, grade II and III, and no treatment with chemotherapy or radiotherapy or surgery. Additionally, the IDC mortality increased with separated status, all primary sites, all breast subtypes, and stage IV. In patients with IDC, controlling DM besides cancer is recommended to reduce the mortality risk. Old, black, widowed, uninsured, regional and distant stages, grade II and III, and no treatment are common risk factors for DM- and IDC-mortality.

Prognostic factors and adjuvant systemic therapy for patients with HER2-positive T1N0 breast cancer: evidence from a real-world study with long-term follow-up.

The optimal adjuvant systemic treatment and potential prognostic factors for patients with T1N0 HER2-positive breast cancer are still unclear. We conducted a real-world study in this relatively low-risk population to identify the clinical-pathological factors of potential prognostic value and to compare the efficacy of different adjuvant strategies. We included patients with HER2-positive T1N0 breast cancer of infiltrating ductal carcinoma (IDC) histology treated at the Cancer Hospital, Chinese Academy of Medical Sciences from April 2010 to April 2017. We performed Cox multivariate analysis to identify the potential prognostic factors for invasive disease-free survival (IDFS). We also compared survival outcomes of (1) patients treated with adjuvant chemotherapy alone, or chemotherapy plus trastuzumab, or observation; (2) patients receiving adjuvant anthracycline-based and non-anthracycline regimens, both combined with trastuzumab. Inverse probability of treatment weighting (IPTW) propensity score was used to reduce selection bias. Overall, 692 consecutive patients were included, with a median follow-up of 78.0months for IDFS. Age ≤ 40, T1c, ER + PR + , and adjuvant trastuzumab were identified as independent prognostic factors. For adjuvant treatment, compared with observation and chemotherapy alone, chemotherapy plus trastuzumab could significantly benefit patients (HR = 2.70, P = 0.034; HR = 3.95, P < 0.001). Meanwhile, compared with observation, chemotherapy alone did not significantly benefit patients (HR = 1.37, P = 0.424). For the comparison of anthracycline-based versus non-anthracycline regimens when combined with trastuzumab, patients in both groups had similar IDFS (HR = 1.74, P = 0.242). HER2-positive T1N0 IDC patients could benefit from adjuvant chemotherapy plus trastuzumab. Age ≤ 40, T1c, ER + PR + , and adjuvant trastuzumab are independent prognostic factors for this population.

Using Machine Learning Methods to Predict Bone Metastases in Breast Infiltrating Ductal Carcinoma Patients.

Breast cancer (BC) was the most common malignant tumor in women, and breast infiltrating ductal carcinoma (IDC) accounted for about 80% of all BC cases. BC patients who had bone metastases (BM) were more likely to have poor prognosis and bad quality of life, and earlier attention to patients at a high risk of BM was important. This study aimed to develop a predictive model based on machine learning to predict risk of BM in patients with IDC. Six different machine learning algorithms, including Logistic regression (LR), Naive Bayes classifiers (NBC), Decision tree (DT), Random Forest (RF), Gradient Boosting Machine (GBM), and Extreme gradient boosting (XGB), were used to build prediction models. The XGB model offered the best predictive performance among these 6 models in internal and external validation sets (AUC: 0.888, accuracy: 0.803, sensitivity: 0.801, and specificity: 0.837). Finally, an XGB model-based web predictor was developed to predict risk of BM in IDC patients, which may help physicians make personalized clinical decisions and treatment plans for IDC patients.

Clinical Characteristics and Survival Outcomes of Infiltrating Lobular Carcinoma: A Retrospective Study of 365 Cases in China.

PurposeThe objective of this study was to compare the demographic characteristics, clinicopathological factors and survival outcomes between infiltrating lobular carcinoma (ILC) and infiltrating ductal carcinoma (IDC) using our single-center database.MethodsSeventeen thousand two hundred and three breast cancer patients were treated at Fudan University Shanghai Cancer Center (FUSCC) from January 2000 to December 2017. We identified 365 cases with ILC and 16,838 cases with IDC. The Pearson chi-square test was used to compare tumor characteristics, and the Kaplan–Meier methods were used to perform the survival analysis.ResultsILC had some distinctive characteristics from IDC such as older age (ranged from 61 to 80: ILC 26.8% vs IDC 19.9%, P < 0.001; over 80: ILC 1.6% vs IDC 0.8%, P < 0.001), larger tumor size (ranged from 2 to 5: ILC 45.2% vs IDC 37.1%, P = 0.011), much more hormone receptor expression (ILC 92.9% vs IDC 73.0%, P < 0.001), extremely less HER-2 expression (ILC 7.1% vs IDC 25.9%, P < 0.001). The overall survival and disease-free survival of ILC were worse than IDC (5-year OS, ILC 93.6% vs IDC 94.5%, P < 0.001; 5-year DFS, ILC 88.5% vs IDC 91.6%, P = 0.008). It was worth noting that the ILC patients had a worse overall survival than IDC patients after our propensity score matching study (P = 0.037). The univariate analysis concluded that positive HR (hormone receptor), high expression of Ki-67 and higher pathologic tumor stage were poor prognostic markers of ILC. Multivariate analysis demonstrated that tumor stage was a poor prognostic marker after adjustment for the effects of the above three factors. The most common primary site of metastasis was bone, but the proportion in the ILC group was much higher than that in the IDC group (56.25% vs 36.40%, P = 0.003).ConclusionCompared with IDC, ILC survived worse and was more prone to bone metastasis. Therefore, a comprehensive understanding of ILC and specific treatments are needed for further research.

The clinical features and prognosis of patients with mucinous breast carcinoma compared with those with infiltrating ductal carcinoma: a population-based study

BackgroundAt present, the characteristics of mucinous breast carcinoma (MBC) and the factors affecting its prognosis are controversial. We compared the clinical features of MBC with those of infiltrating ductal carcinoma (IDC) and summarized the relevant prognostic factors.MethodsThe Surveillance, Epidemiology, and End Results (SEER) database includes information on 10,593 patients diagnosed with MBC between 2004 and 2016. Chi-square tests and analyses were used to analyze differences in variables between the MBC and IDC groups. Univariate and multivariate Cox proportional hazards models were used to assess the relative impacts of risk factors on cancer-specific survival (CSS) in patients. Kaplan-Meier survival curves were constructed to assess cancer-specific mortality and were compared using the log-rank test.ResultsFrom 2004 to 2016, 10,593 people were diagnosed with MBC, and 402,797 were diagnosed with IDC. Patients with MBC had significantly higher 5−/10-year CSS rates (96.4%/93.4%) than those with IDC (89%/83.8%). Compared with IDC patients, MBC patients had less lymph node metastasis, an earlier stage, a higher rate of hormone receptor positivity and a lower expression rate of HER2. Univariate and multivariate analyses showed that age ≥ 60 years old (HR = 1.574, 95%CI: 1.238–2.001, P < 0.001), singled status (HR = 1.676, 95%CI: 1.330–2.112, P < 0.001) and advanced TNM/SEER stage were independent prognostic risk factors for MBC. In addition, positive estrogen receptor (HR = 0.577, 95%CI: 0.334–0.997, P = 0.049), positive progesterone receptor (HR = 0.740, 95%CI: 0.552–0.992, P = 0.044), surgical treatment (HR = 0.395, 95%CI: 0.288–0.542, P < 0.001) and radiotherapy (HR = 0.589, 95%CI: 0.459–0.756, P < 0.001) were identified as protective factors.ConclusionCompared with IDC, MBC has a better prognosis. For patients with MBC, we identified prognostic factors that can help clinicians better assess patient outcomes and guide individualized treatment.

The overexpression of DNA repair genes in invasive ductal and lobular breast carcinomas: Insights on individual variations and precision medicine.

In the era of precision medicine, analyzing the transcriptomic profile of patients is essential to tailor the appropriate therapy. In this study, we explored transcriptional differences between two invasive breast cancer subtypes; infiltrating ductal carcinoma (IDC) and lobular carcinoma (LC) using RNA-Seq data deposited in the TCGA-BRCA project. We revealed 3854 differentially expressed genes between normal ductal tissues and IDC. In addition, IDC to LC comparison resulted in 663 differentially expressed genes. We then focused on DNA repair genes because of their known effects on patients’ response to therapy and resistance. We here report that 36 DNA repair genes are overexpressed in a significant number of both IDC and LC patients’ samples. Despite the upregulation in a significant number of samples, we observed a noticeable variation in the expression levels of the repair genes across patients of the same cancer subtype. The same trend is valid for the expression of miRNAs, where remarkable variations between patients’ samples of the same cancer subtype are also observed. These individual variations could lie behind the differential response of patients to treatment. The future of cancer diagnostics and therapy will inevitably depend on high-throughput genomic and transcriptomic data analysis. However, we propose that performing analysis on individual patients rather than a big set of patients’ samples will be necessary to ensure that the best treatment is determined, and therapy resistance is reduced.

Clinical characteristics and overall survival prognostic nomogram for invasive cribriform carcinoma of breast: a SEER population-based analysis

BackgroundThe prognositc factors in patient with invasive cribriform carcinoma (ICC) of breast is still remain controversal. The study aims to establish a nomogram to predict the survival outcomes in patients with ICC based on the Surveillance, Epidemiology and End Results (SEER) database.MethodsWe retrieved SEER database for clinical data about patients including ICC and infiltrating ductal carcinoma (IDC) from 2004 to 2015. Kaplan-Meier survival was used to compare the difference survival outcomes between ICC and IDC. ICC patients were randomly allocated to training cohort and validation cohort. A nomogram was built to predict individual patient’s 3-year and 5-year survival status for ICC. The established TMN model and the newly established nomogram was further evaluated by the concordance index (C-index) and the decision curve analysis (DCA).ResultsComparing the baseline clinical data between IDC and ICC, a significant of smaller tumor mass, less infiltrated lymph nodes, lower metastases rate, better tumor differentiation degree, higher proportion of estrogen receptor (ER) and progesterone receptor (PR) positive and lower rate of chemotherapy and radiotherapy was found in ICC. Age at diagnosis, marriage status, tumor location, T stage, M stage, ER status, surgery were independent significant prognostic factors for the overall survival (OS). A significantly higher C-index was found in nomogram compared with established TNM model in validation cohort.ConclusionsThe prognosis of ICC patients is better than that of IDC patients. The nomogram is recommended for future patient with ICC to survival analysis.

Breast cancer biobank from a single institutional cohort in an urban setting in india: Tumor characteristics and survival outcomes

A breast cancer biobank with retrospectively collected patient data and FFPE tissue samples was established in 2018 at Prashanti Cancer Care Mission, Pune, India. It runs a cancer care clinic with support from a single surgeon's breast cancer practice. The clinical data and tissue sample collection is undertaken with appropriate patient consent following ethical approval and guidelines. The biobank holds clinical history, diagnostic reports, treatment and follow-up information along with FFPE tumor tissue specimens, adjacent normal and, in few cases, contralateral normal breast tissue. Detailed family history and germline mutational profiles of eligible and consenting patients and their relatives are also deposited in the biobank. Here, we report the first audit of the biobank. A total number of 994 patients with breast disease have deposited consented clinical records in the biobank. The majority of the records (80%, n=799) are of patients with infiltrating ductal carcinoma (IDC). Of 799 IDC patients, 434 (55%) have deposited tumor tissue in the biobank with consent. In addition, germline mutation profiles of 84 patients and their family members are deposited. Follow-up information is available for 85% of the 434 IDC patients with an average follow-up of 3 years. The biobank has aided the initiation of translational research at our center in collaboration with eminent institutes like IISER Pune and SJRI Bangalore to evaluate profiles of breast cancer in an Indian cohort. The biobank will be a valuable resource to the breast cancer research community, especially to understand South Asian profiles of breast cancer.

Different prognosis by subtype in the early mucinous breast cancer: a SEER population-based analysis.

BackgroundOur study aims to investigate the clinicopathological characteristics and survival outcomes of mucinous breast cancer (MBC), and explore the effect of histology type on the breast cancer-specific survival (BCSS) by different subtypes.Methodswe identified 7,083 patients who were diagnosed with MBC and 248,751 with infiltrating ductal carcinoma (IDC) by using the Surveillance, Epidemiology and End Results (SEER) database. The propensity score matching was used to match baseline characteristics among MBC and IDC, and multivariable cox proportional hazards models were used to analyze the relationship between histology type stratified by subtype and BCSS.ResultsMBC patients were associated with a fewer nodal involvement, lower grade, earlier stage, more estrogen receptor (ER) or progesterone receptor (PR) positive, and more favorable prognosis compared to the overall IDC population. After 1:1 matching of MBC with IDC by other factors, we found that MBC patients presented better prognosis than the Matched IDC for BCSS. Analysis among ER+PR+ subgroup revealed that MBC patients was significantly better than that Matched IDC patients for BCSS (HR =0.78, 95% CI, 0.63–0.96). However, the survival analysis in the ER+PR− or ER−PR− subgroups suggested that no significant difference was seen between MBC patients and matched IDC patients for BCSS.ConclusionsOur findings support that MBC seems to be an independent factor for the better prognosis for breast cancer patients with ER+PR+ breast cancer but not in those with ER+PR− or ER−PR− disease.

Subgroups of parotid gland infiltrating ductal carcinoma benefit from postoperative radiotherapy: a population-based study.

To analyze the prognostic factors and the impact of postoperative radiotherapy (PORT) in parotid gland infiltrating ductal carcinoma (IDC). 252 patients diagnosed with parotid gland IDC were identified from the SEER database. Kaplan-Meier and Cox regression analysis was performed to evaluate the prognostic factors. Propensity score matching was applied then. Multivariate analysis showed old age and chemotherapy were independent risk factors in parotid gland IDC. Subgroup analysis demonstrated that overall survival (OS) rate of the PORT group was significantly superior to that of the no radiotherapy group in the T3-4 subgroup (p=0.049), N1 subgroup (p=0.019) and Tumor, Node, Metastasis (TNM) III subgroup (p=0.025). PORT improved survival of parotid gland IDC patients within T3-4, N1 and TNM III subgroups.

HER2-Positive Lobular Versus Ductal Carcinoma of the Breast: Pattern of First Recurrence and Molecular Insights

BackgroundInfiltrating lobular carcinoma (ILC) represents about 10% of breast cancer and rarely shows overexpression of human epidermal growth factor receptor 2 (HER2). We compared biological and clinical characteristics of HER2-positive ILC versus HER2-positive infiltrating ductal carcinoma (IDC). Patients and MethodsWe retrospectively analyzed the data of 328 patients with HER2-positive pure ductal or lobular breast carcinoma, comparing clinical and biological data at diagnosis as well as outcome between the 2 histologies. A gene-mutation analysis was performed in a subset of patients. ResultsTwo hundred ninety-one patients (88.7%) had IDC and 37 patients (11.3%) ILC. ILC resulted more frequently in multicenter (24.3% vs. 6.5%, P < .0001) and node-positive (54.1% vs. 45%, P = .013) disease of lower proliferative activity (Mib1 < 20%: 51.4% vs. 22.3%, P < .0001) and lower histologic grade (grade 3: 32.4% vs. 57.4%, P = .038). Disease recurred in 57 patients (17.4%) and involved the bone in 40% of ILC patients (vs. 17% of IDC patients) and the viscera in 30% of ILC patients (vs. 59.6% of IDC patients). No difference in the recurrence rate between the 2 histologies was observed in patients treated with adjuvant trastuzumab (12.5% of ILC patients and 8.3% of IDC patients). Exploratory molecular analysis revealed a higher frequency of mutations in ILC, with more cases of multiple mutations. ConclusionHER2-positive ILC shows different biological behavior than IDC, with a possible higher mutation load. Despite lower proliferation activity and estrogen receptor expression in ILC breast cancer, trastuzumab is clearly an effective therapy for this histologic subtype.

Distribution and Clinical Utility of the 21-gene Recurrence Score in Pure Mucinous Breast Cancer Patients: a case-control study.

The 21-gene recurrence score (RS) is increasingly being used for patients with early stage, hormone receptor-positive, Her-2-negative breast cancer. However, these results are largely from populations with infiltrating ductal carcinoma (IDC). The clinical value of RS testing in mucinous carcinoma has not been well investigated. Pure mucinous breast cancer (PMBC) and paired pure IDC patients who underwent 21-gene RS were retrospectively reviewed and matched with tumor stage and molecular subtype. Clinic-pathological factors, treatment strategies, and RS distribution were compared between the PMBC and IDC patients. A total of 35 PMBC and 70 IDC patients were included. We found that RS was lower in the PMBC as compared with the IDC group: 21.26 vs. 24.40 (P=0.037). Regarding RS categories, PMBC patients had a relatively lower percentage of high RS patients than the IDC group: 8.57% vs. 22.86% (P = 0.048). Multivariate analysis showed that histologic type was an independent factor predicting RS distribution: IDC patients were associated with a higher RS as compared with PMBC patients (OR: 1.27, 95% CI: 1.03-2.13; P=0.014). Among genes in 21-gene RS testing, HER2, STMY3, STK15, and BAG1 were significantly different between the PMBC and IDC groups (P < 0.05). Two patients (5.71%) in the PMBC group, both with high RS, were recommended to receive adjuvant chemotherapy, much lower than patients with IDC (57.14%, P < 0.001). In multivariate analysis, histologic type of IDC was an independent factor for chemotherapy recommendation (OR = 22.00, 95% CI: 4.89-98.97, P<0.001). With a medium follow-up time of 24 months, one IDC patient had ipsilateral axillary lymph nodes recurrence and one PMBC patient had contralateral breast cancer. In conclusion, PMBC patients, mostly classified with low or intermediate RS category, were associated with lower RS as compared with IDC patients. PMBC and IDC had different genes expression patterns. Patients with high RS in the PMBC group might be recommended to receive adjuvant chemotherapy, which deserves further clinical evaluation.

Abstract P6-09-29: Clinicopathological characteristics and survival outcomes in invasive papillary carcinoma of the breast: A population-based study

Abstract Background Invasive papillary carcinoma (IPC) is defined as having papillary architecture in &amp;gt;90% of the invasive component. The overall incidence of IPC is low, accounting for less than 1-2% of all newly diagnosed cases of invasive breast cancer. Limited data are available that contribute to a comprehensive summarization of the clinicopathological characteristics and prognostic factors that are associated with IPC. We aimed to determine the clinicopathological characteristics and prognostic factors of IPC in a large population and help physicians to acquire a better understanding of the disease and make better informed therapeutic decisions. Methods We identified 233,171 female patients in the Surveillance, Epidemiology, and End Results (SEER) database who had IPC (n = 524) or infiltrating ductal carcinoma (IDC) (n = 232,647). The demographics and tumour and treatment characteristics of IPC were compared to those of IDC. A Cox proportional hazards model was used to investigate the effects of baseline characteristics on disease-specific survival (DSS). We performed a 1:1 (IPC: IDC) matched case-control analysis using the propensity score-matching method. A forest plot of hazard ratios (HRs) that was used to illustrate the exploratory subgroup analyses. Results Generally, IPCs occurred in older women (≥50 years old) and presented with smaller sizes, lower grades, higher rates of oestrogen receptor (ER) and progesterone receptor (PR) positivity, and reduced lymph node (LN) involvement and were less likely to be treated with mastectomy than patients with IDC. The five-year DSS rates were significantly better in IPC than in IDC (97.5% vs. 93%, respectively; P &amp;lt; 0.001). In the multivariate analysis, patients with IPC showed a DSS that was similar to that of IDC (HR = 0.556, 95% confidence interval 0.289–1.070, P = 0.079). No significant difference was observed in DSS between matched IPC and IDC groups (P = 0.085). Subgroup analyses suggested that differences in outcomes may be partially explained by differences in tumour grade, LN status, and ER and PR status between the 2 groups. Most IPCs are ER-positive tumours. When the analysis was limited to 178,755 ER-positive IPC and IDC patients (457 IPCs and 178,298 IDCs), similar results were observed. Conclusions This study is currently the largest analysis of IPC. We investigated a large cohort of patients with IPC and found that this rare tumour type presents unique clinicopathological characteristics and is associated with a higher rate of breast-conserving surgery and favourable prognoses than are observed in the overall IDC population. However, this advantage was diminished after we adjusted for demographic and clinicopathological factors. Therefore, patients diagnosed with this rare variant should be made aware that its biological features are not as favourable as once thought. Therapeutic decisions should not be made based solely on this rare entity and evidence-based treatment guidelines should be strictly followed. Improving our understanding of the clinical and biological features of IPC may lead to more individualized and tailored therapies for breast cancer patients. Citation Format: Zheng Y-Z, Hu X, Shao Z-M. Clinicopathological characteristics and survival outcomes in invasive papillary carcinoma of the breast: A population-based study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-09-29.

Apparent diffusion coefficient value of diffusion-weighted imaging for differential diagnosis of ductal carcinoma in situ and infiltrating ductal carcinoma

The present meta-analysis investigated the clinical value of apparent diffusion coefficient (ADC) values in diffusion-weighted imaging (DWI) for differential diagnosis of ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDC). Electronic databases searches were employed to identify relevant scientific literature, and the search results were screened to selected high-quality studies for this meta-analysis. Methodological quality of the enrolled studies was evaluated by quality evaluation of diagnostic accuracy studies (QUADAS). Summary odds ratios (ORs) and its corresponding 95% confidence interval (95% CI) were calculated for DCIS versus IDC category of ADC value using Z test. Our meta-analysis contained a combined total of 1,097 subjects (928 patients with IDC and 169 patients with DCIS) from 9 relevant high-quality cohort studies. Pooled ORs demonstrated that ADC value in IDC patients was significantly lower than DCIS patients. Subgroup analysis stratified by ethnicity indicated a higher ADC value in DCIS patients compared to IDC, in Asian population, but not in Caucasians. Magnetic resonance imaging (MRI) machine type-stratified analysis revealed that the ADC value of DWI obtained from both non- General Electric Company (GE) 1.5T and GE 1.5T machines were highly reliable in the differential diagnosis of DCIS and IDC. Our meta-analysis provides evidence that ADC values in DWI accurately conveys the differences in tumor architecture between IDC and DCIS, which has high clinical value in differentiatal diagnosis of IDC and DCIS. This may lead to improved BC prediction and treatment.

Survival outcomes of metaplastic breast cancer patients: results from a US population-based analysis.

Metaplastic breast cancer (MBC) is a rare histologic subtype needing further characterization. The aim of our study was to compare MBC to infiltrating ductal carcinoma (IDC) of the breast and to identify demographic, clinicopathologic, treatment, and survival differences. MBC and IDC patients were identified using the Surveillance, Epidemiology, and End Results (SEER) public-use data set. Disease-specific survival (DSS) differences were compared using the Kaplan-Meier method and log-rank tests. Univariate and multivariate Cox proportional hazard models were used to assess factors prognostic for DSS. To control for hormone receptor status, a subsequent planned analysis was completed for receptor-negative MBC and IDC. Lastly, a matched case-control analysis was conducted to minimize potential bias due to baseline demographic, clinical, and pathologic differences. The SEER data set included 1,011 MBC and 253,818 IDC patients diagnosed from 2001 to 2010. MBC patients had larger, higher grade tumors, had less frequent axillary nodal involvement, and were more likely to be treated with mastectomy. Five-year DSS rates were significantly worse for patients with MBC than for IDC patients (78 vs. 93 %, p < 0.0001) and for patients with receptor-negative MBC than receptor-negative IDC (77 vs. 85 %, p < 0.0001). The findings were confirmed on matched analysis. Prognostic factors identified on multivariate analyses included age, MBC histology, tumor grade, T stage, and axillary lymph node involvement. MBC patients have shorter DSS than IDC patients. Improved clinical and biological understanding of MBC may result in more effective therapy and better cancer outcomes.

Genome-wide analysis of loss of heterozygosity in breast infiltrating ductal carcinoma distant normal tissue highlights arm specific enrichment and expansion across tumor stages.

Studies have shown concurrent loss of heterozygosity (LOH) in breast infiltrating ductal carcinoma (IDC) and adjacent or distant normal tissue. However, the overall extent of LOH in normal tissue and their significance to tumorigenesis remain unknown, as existing studies are largely based on selected microsatellite markers. Here we present the first autosome-wide study of LOH in IDC and distant normal tissue using informative loci deduced from SNP array-based and sequencing-based techniques. We show a consistently high LOH concurrence rate in IDC (mean = 24%) and distant normal tissue (m = 54%), suggesting for most patients (31/33) histologically normal tissue contains genomic instability that can be a potential marker of increased IDC risk. Concurrent LOH is more frequent in fragile site related genes like WWOX (9/31), NTRK2 (10/31), and FHIT (7/31) than traditional genetic markers like BRCA1 (0/23), BRCA2 (2/29) and TP53 (1/13). Analysis at arm level shows distant normal tissue has low level but non-random enrichment of LOH (topped by 8p and 16q) significantly correlated with matched IDC (Pearson r = 0.66, p = 3.5E-6) (topped by 8p, 11q, 13q, 16q, 17p, and 17q). The arm-specific LOH enrichment was independently observed in tumor samples from 548 IDC patients when stratified by tumor size based T stages. Fine LOH structure from sequencing data indicates LOH in low order tissues non-randomly overlap (∼67%) with LOH that usually has longer tract length (the length of genomic region affected by LOH) in high order tissues. The consistent observations from multiple datasets suggest progressive LOH in the development of IDC potentially through arm-specific pile up effect with discernible signature in normal tissue. Our finding also suggests that LOH detected in IDC by comparing to paired adjacent or distant normal tissue are more likely underestimated.

Differential occurrence of S100A7 in breast cancer tissues: A proteomic‐based investigation

The present study reports for the first time a large-scale proteomic screening of the occurrence, subcellular localization and relative quantification of the S100A7 protein among a group of 100 patients, clinically grouped for the diagnosis of infiltrating ductal carcinoma (IDC). To this purpose, the methods of differential proteomics, Western blotting, and immunohistochemistry were used. The identity of two isoforms of the protein was assessed by mass spectrometry and immunologically confirmed. Moreover, we proved by immunocytochemical applications the exclusive localization of the protein within the neoplastic cells. The correlation of S100A7 expression levels with the collective profile of cancer patients' proteomics predicted functional interactions, distinct for the two isoforms. The S100A7b isoform was significantly correlated with specific protein clusters (calcium binding, signaling and cell motion, heat shock and folding) and intercrossing pathways (antioxidant, metabolic and apoptotic pathways), while the more acidic isoform was correlated with a narrow number of proteins mainly unrelated to the b isoform. This study is the first proteomic-based report on S100A7 in a large series of IDC patients. The correlation with in silico data may significantly contribute the knowledge of possible pathways for S100A7, providing novel insights into the mechanism of action of this protein. We suggest that each S100A7 isoform is involved in critical phases of the breast cancer growth and progression, probably through interaction with different partner proteins.

Tumor characteristics and the clinical outcome of invasive lobular carcinoma compared to infiltrating ductal carcinoma in a Chinese population

BackgroundWe sought to compare the baseline demographics, standard pathologic factors and long-term clinical outcomes between ILC and infiltrating ductal carcinoma (IDC) using a large database.MethodsClinicopathologic features, overall survival (OS), and recurrence/metastasis-free survival (RFS) were compared between 2,202 patients with IDC and 215 patients with ILC.ResultsILC was significantly more likely to be associated with a favorable phenotype, but the incidence of contralateral breast cancer was higher for ILC patients than for IDC patients (8.4% vs. 3.9%; P =0.001). The frequencies of recurrence/metastasis (P = 0.980) and death (P = 0.064) were similar among patients with IDC and patients with ILC after adjustment for tumor size and nodal status. The median follow-up was 42.8 months.ConclusionsChinese women with ILCs do not have better clinical outcomes than their counterparts with IDC. Management decisions should be based on individual patient and tumor biologic characteristics, and not on lobular histology.

Overexpression of a novel cell cycle regulator ecdysoneless in breast cancer: a marker of poor prognosis in HER2/neu-overexpressing breast cancer patients

Uncontrolled proliferation is one of the hallmarks of breast cancer. We have previously identified the human Ecd protein (human ortholog of Drosophila Ecdysoneless, hereafter called Ecd) as a novel promoter of mammalian cell cycle progression, a function related to its ability to remove the repressive effects of Rb-family tumor suppressors on E2F transcription factors. Given the frequent dysregulation of cell cycle regulatory components in human cancer, we used immunohistochemistry of paraffin-embedded tissues to examine Ecd expression in normal breast tissue versus tissues representing increasing breast cancer progression. Initial studies of a smaller cohort without outcomes information showed that Ecd expression was barely detectable in normal breast tissue and in hyperplasia of breast, but high levels of Ecd were detected in benign breast hyperplasia, ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDCs) of the breast. In this cohort of 104 IDC patients, Ecd expression levels showed a positive correlation with higher grade (P = 0.04). Further analyses of Ecd expression using a larger, independent cohort (954) confirmed these results, with a strong positive correlation of elevated Ecd expression with higher histological grade (P = 0.013), mitotic index (P = 0.032), and Nottingham Prognostic Index score (P = 0.014). Ecd expression was positively associated with HER2/neu (P = 0.002) overexpression, a known marker of poor prognosis in breast cancer. Significantly, increased Ecd expression showed a strong positive association with shorter breast cancer specific survival (BCSS) (P = 0.008) and disease-free survival (DFS) (P = 0.003) in HER2/neu overexpressing patients. Taken together, our results reveal Ecd as a novel marker for breast cancer progression and show that levels of Ecd expression predict poorer survival in Her2/neu overexpressing breast cancer patients.Electronic supplementary materialThe online version of this article (doi:10.1007/s10549-011-1946-8) contains supplementary material, which is available to authorized users.

P4-09-34: Luminal Infiltrating Lobular Carcinoma of the Breast: Clinical and Prognostic Features.

Abstract Background Infiltrating lobular carcinoma (ILC) and infiltrating ductal carcinoma (IDC) are the two most common histologic types of invasive breast cancer. Previous studies have demonstrated distinctive clinical and biologic characteristics, however some features of ILC are yet uncertain like the relationship with the particular subtypes according to the gene expression profile. The purpose of our study is to analyze how the patients with ILC differ from IDC regarding of percentage of luminal subtype, the tumor factors, treatment and patterns of recurrence. Patients and Methods We assessed 1190 breast cancer patients treated at the Hospital Universitario 12 de Octubre between 1995 and 2006 categorized as having ILC or IDC pure types. Results: One thousand one hundred ninety tumors were included, being ILC 223 patients (18, 7%), IDC 967 patients (81, 3%) and 200 patients (10%) were luminal HER2+. The current analysis is limited to the 990 patients classified as luminal HER2−. Median age was 59, 2 years for ILC and 58, 8 for IDC, with no significant differences among the groups. Compared to IDC, ILC showed a larger tumor size (≥T3: 15, 2% vs. 4, 8%, ***p&amp;lt;0.01), lesser nodal involvement (35% vs 42, 7% p 0.048) and lower Ki67 expression (62, 6% vs. 52, 2% p=0.01). The proportion of luminal A subtype was greater in ILC (56, 3% vs. 46, 7% p=0.01). Mastectomy was more frequently performed for ILC (61, 2 % vs. 47, 7%, p=0.01). Regarding systemic therapy, 127(62,4%) ILC patients and 450 (57, 2%) IDC patients received adjuvant chemotherapy (QT). That was anthracycline-based in most cases (47, 2% for ILC and 46,4% for IDC). Adjuvant hormonal treatment was prescribed equally among both groups (196, 96% ILC and 739, 94% IDC), being the most commonly used drug ***tamoxifen. With a median follow-up of 94 months, 45 ILC patients (22%) and 159(20, 2%) IDC relapsed. No differences were observed in DFS (p=0, 81) or OS (p=0, 47). The most frequent metastatic site was bone (33% for ILC and 40, 8% for IDC), followed by local relapses (17, 7% for ILC vs. 17% for IDC) and liver (15, 5% for ILC vs. 15, 7% for IDC). ILC was associated with an increased incidence of peritoneal/mesenteric metastases (8 pts 17, 7% vs. 1pts 0,6% ***p&amp;lt;0.01) and a lower incidence of lung relapses (8, 8% vs. 19, 4 % pts p&amp;lt;0.05). Conclusion: Luminal HER2− Infiltrating lobular carcinoma carries distinct clinicopathological features. In our study, ILC had similar prognosis as IDC. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-09-34.