Invasive Micropapillary Carcinoma Patients Research Articles

Clinicopathological characteristics and prognostic factors in invasive micropapillary carcinoma of the breast.

Invasive micropapillary carcinoma (IMPC) treatment only relies on the standard treatment of nonspecific invasive breast cancer (NSIBC), and it remains controversial whether the survival of patients improves. Therefore, this study aimed to analyze the clinicopathological features of IMPC and to investigate the factors affecting its prognosis. This retrospective cohort study included 104 IMPC patients who met the study's inclusion criteria out of a total of 4,532 patients with invasive breast cancer between January 2015 and December 2019. A contemporaneous cohort of 230 patients with non-specific invasive breast cancer (NSIBC) who underwent surgery was identified and matched using propensity scores. The survival rate for patients with IMPC ranged from 1.12% to 7.03%. Statistically significant differences were observed in the proportion of endocrine treatment, lymphatic invasion, estrogen receptor (ER)-positive rate, molecular subtypes, molecular typing, and 5-year loco-regional recurrence-free survival (LRRFS) between the two cohorts (p < 0.05). The univariate analysis showed that T stage, N stage, lymphatic invasion, vascular invasion, ER-positive rate, and progesterone receptor (PR)-negative rate were all prognosis risk factors (p < 0.05) for IMPC. Furthermore, the multivariate analysis indicated that lymphatic invasion and N stage were independent prognostic factors (p < 0.05). The incidence of micropapillary IMPC, among other pathological subtypes, is steadily increasing. ER-positive and PR-positive rates, as well as luminal subtypes, are frequent, with a concurrent increase in the 5-year locoregional recurrence rate. It would be interesting to compare the effect following these therapeutic modifications in larger cohorts in future studies.

Association of molecular subtypes and treatment with survival in invasive micropapillary breast cancer: an analysis of the Surveillance, Epidemiology, and End Results database.

This study aims to examine the features, treatments, and survival of invasive micropapillary carcinoma (IMPC) according to different molecular subtypes. In this cohort study, data between 2010 and 2018 were retrospectively reviewed from the Surveillance, Epidemiology, and End Results database. Molecular subtypes were categorized into four varieties: hormone receptor (HR)+/HER2- (Luminal A), HR+/HER2+ (Luminal B), HR-/HER2- [triple-negative (TN)], and HR-/HER2+ (HER2 enriched). In this study, 1,180 IMPC patients were included, with 99 patients (8.39%) of the 1,180 patients having an overall mortality, and 53 patients (53.54%) of the 99 patients having a breast cancer-specific mortality. The follow-up duration was 40.00 (18.50, 61.00) months. TN molecular subtype was associated with worse OS and BCSS in IMPC patients. Treatment of chemotherapy, radiation, and combination therapy were associated with better survival in HR+/HER2+ molecular subtype and HR+/HER2- molecular subtype. However, in HR-/HER2- molecular subtype, treatment of chemotherapy was associated with a poor BCSS, and treatment of radiation was not associated with OS and BCSS. Surgery treatment was not associated with survival in HR+/HER2+ molecular subtype and HR+/HER2- molecular subtype. However, surgery treatment of mastectomy was associated with better OS in HR-/HER2- molecular subtype (P < 0.05). The prognosis of IMPC was significantly influenced by different molecular subtypes. Chemotherapy and radiotherapy are beneficial in HR+/HER2+ and HR+/HER2- patients. However, they should be used with caution in HR-/HER2- (TN) patients.

PRMT3 regulates the progression of invasive micropapillary carcinoma of the breast.

Invasive micropapillary carcinoma (IMPC) is a special histopathological subtype of breast cancer. Clinically, IMPC exhibits a higher incidence of lymphovascular invasion and lymph node metastasis compared with that of invasive ductal carcinoma (IDC), the most common type. However, the metabolic characteristics and related mechanisms underlying malignant IMPC biological behaviors are unknown. We performed large-scale targeted metabolomics analysis on resected tumors obtained from chemotherapy-naïve IMPC (n=25) and IDC (n=26) patients to investigate metabolic alterations, and we integrated mass spectrometry analysis, RNA sequencing, and ChIP-sequencing data to elucidate the potential molecular mechanisms. The metabolomics revealed distinct metabolic profiles between IMPC and IDC. For IMPC patients, the metabolomic profile was characterized by significantly high levels of arginine methylation marks, and protein arginine methyltransferase 3 (PRMT3) was identified as a critical regulator that catalyzed the formation of these arginine methylation marks. Notably, overexpression of PRMT3 was an independent risk factor for poor IMPC prognosis. Furthermore, we demonstrated that PRMT3 was a key regulator of breast cancer cell proliferation and metastasis both in vitro and in vivo, and treatment with a preclinical PRMT3 inhibitor decreased the xenograft tumorigenic capacity. Mechanistically, PRMT3 regulated the endoplasmic reticulum (ER) stress signaling pathway by facilitating histone H4 arginine 3 asymmetric dimethylation (H4R3me2a), which may endow breast cancer cells with great proliferative and metastatic capacity. Our findings highlight PRMT3 importance in regulating the malignant biological behavior of IMPC and suggest that small-molecule inhibitors of PRMT3 activity might be promising breast cancer treatments.

Development and validation of nomograms to predict survival in patients with invasive micropapillary carcinoma of the breast

ObjectivesThe present study aimed to develop and validate nomograms to predict the survival of patients with breast invasive micropapillary carcinoma (IMPC) to aid objective decision-making.DesignPrognostic factors were identified using Cox...

A prognostic nomogram based on risk assessment for invasive micropapillary carcinoma of the breast after surgery.

Invasive micropapillary carcinoma (IMPC) is one of the rare subtypes of breast cancer. This study aimed to explore a predictive nomogram model for IMPC prognosis. A total of 1855 IMPC patients diagnosed after surgery between 2004 and 2014 were identified from the Surveillance, Epidemiology and End Results (SEER) database to build and validate nomogram. A nomogram was created based on univariate and multivariate Cox proportional hazards regression analysis. Receiver operating characteristic (ROC) curves were used to demonstrate the accuracy of the prognostic model. Decision curve analysis (DCA) was performed to evaluate the safety of the model in the range of clinical applications, while calibration curves were used to validate the prediction consistency. Cox regression analysis indicated that age ≥62 at diagnosis, negative ER status, and tumor stage were considered adverse independent factors for overall survival (OS), while patients who were married, white or of other races, received chemotherapy or radiotherapy, had a better postoperative prognosis. The nomogram accurately predicted OS with high internal and external validation consistency index (C index) (0.756 and 0.742, respectively). The areas under the ROC curve (AUCs) of the training group were 0.787, 0.774 and 0.764 for 3, 5 and 10 years, respectively, while those of the validation group were 0.756, 0.766 and 0.762, respectively. The results of both DCA and calibration curves demonstrated the good performance of the model. A nomogram for IMPC of the breast patients after surgery was developed to estimate 3, 5 and 10 years-OS based on independent risk factors. This model has good accuracy and consistency in predicting prognosis and has clinical application value.

Nomogram for predicting overall survival in patients with invasive micropapillary carcinoma after breast-conserving surgery: Apopulation-based analysis.

Due to the loss of prediction of overall survival (OS) for patients with invasive micropapillary carcinoma (IMPC) after breast-conserving surgery (BCS), this study aimed to construct a nomogram for predicting OS in IMPC patients after BCS. In total, 481 eligible cases staged 0-III IMPC from 2000 to 2016 were retrieved from the SEER database. A nomogram was built based on the variables selected by LASSO regression to predict the 3-year and 5-year probabilities of OS. A total of 336 patients were randomly assigned to the training cohort and 145 cases in the validation cohort. The LASSO regression revealed that six variables (age at diagnosis, AJCC stage, marital status, ER status, PR status, and chemotherapy) were predictive variables of OS, and then a nomogram model and an easy-to-use online tool were constructed. The C-indices 0.771 in the training cohort and 0.715 in the validation cohort suggested the robustness of the model. The AUC values for 3-year and 5-year OS in the training cohort were 0.782, 0.790, and 0.674, and 0.682 in the validation cohort, respectively. Based on the cutoff values of 147.23 and 222.44 scores calculated by X-tile analysis, participants in the low-risk group (≤147.23 scores) had a more favorable OS in comparison with those in the medium (>147.23, but <222.44 scores)- and high-risk groups (≥222.44 scores). By risk stratification, this model is expected to provide a precise and personalized prediction of the cumulative risk and guide treatment decision-making in improving OS strategies for IMPC patients.

Prediction of lymph node metastasis in patients with breast invasive micropapillary carcinoma based on machine learning and SHapley Additive exPlanations framework.

Background and purpose: Machine learning (ML) is applied for outcome prediction and treatment support. This study aims to develop different ML models to predict risk of axillary lymph node metastasis (LNM) in breast invasive micropapillary carcinoma (IMPC) and to explore the risk factors of LNM.MethodsFrom the Surveillance, Epidemiology, and End Results (SEER) database and the records of our hospital, a total of 1547 patients diagnosed with breast IMPC were incorporated in this study. The ML model is built and the external validation is carried out. SHapley Additive exPlanations (SHAP) framework was applied to explain the optimal model; multivariable analysis was performed with logistic regression (LR); and nomograms were constructed according to the results of LR analysis.ResultsAge and tumor size were correlated with LNM in both cohorts. The luminal subtype is the most common in patients, with the tumor size <=20mm. Compared to other models, Xgboost was the best ML model with the biggest AUC of 0.813 (95% CI: 0.7994 - 0.8262) and the smallest Brier score of 0.186 (95% CI: 0.799-0.826). SHAP plots demonstrated that tumor size was the most vital risk factor for LNM. In both training and test sets, Xgboost had better AUC (0.761 vs 0.745; 0.813 vs 0.775; respectively), and it also achieved a smaller Brier score (0.202 vs 0.204; 0.186 vs 0.191; 0.220 vs 0.221; respectively) than the nomogram model based on LR in those three different sets. After adjusting for five most influential variables (tumor size, age, ER, HER-2, and PR), prediction score based on the Xgboost model was still correlated with LNM (adjusted OR:2.73, 95% CI: 1.30-5.71, P=0.008).ConclusionsThe Xgboost model outperforms the traditional LR-based nomogram model in predicting the LNM of IMPC patients. Combined with SHAP, it can more intuitively reflect the influence of different variables on the LNM. The tumor size was the most important risk factor of LNM for breast IMPC patients. The prediction score obtained by the Xgboost model could be a good indicator for LNM.

Clinicopathological Features and Prognosis of Invasive Micropapillary Carcinoma Compared to Invasive Ductal Carcinoma-NOS: Worse or Better?

To evaluate whether there are differences in invasive micropapillary carcinoma (IMPC) and invasive ductal carcinoma-NOS (IDC-NOS) according to the clinicopathological features and prognosis including molecular subtypes. Descriptive study. Department of Pathology, University of Health Sciences, Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey, from 2003 to 2016. Operated breast cancer cases (58 IMPC + 326 IDC-NOS), with long-term follow-up findings (cases followed up until 2020), were reviewed. The cases, whose other component was only IDC-NOS, were included in the mixed IMPC group. The clinical features, including clinical presentation, treatments, and follow-up information were obtained from the patient clinical database. The IMPC cases included in the study were re-examined, and micropapillary tumour components were confirmed based on the criteria set by the World Health Organisation (WHO). The clinicopathological findings, recurrence, and survival data of both groups were compared. In addition, IDC-NOS was divided into the molecular subgroups and compared with IMPC cases in terms of 5-year overall survival (OS). There was no significant difference between the two groups for the distribution of molecular subtypes. There was a statistically significant difference among the nuclear grade, tumour size, nodal status, lymphovascular, and perineural invasion. In the first 5-year period, the OS rate for IDC-NOS and IMPC was 90.8% and 86.2% (p<0.05). The 5-year OS rate of luminal A, luminal B, HER2, triple negative (TN), and IMPC patients was 97.6%, 91.3%, 90%, 70%, and 86.2%, respectively (p<0.05). The OS rate in patients with TN and IMPC was similar which was found significantly lower than the other groups (luminal A, luminal B, and HER2). The median OS was 51.3 months and 53.9 months for the patients with TN and IMPC, respectively (p<0.001). This difference disappeared in the 10th and 15th years of follow-up. The majority of the deaths in IMPC occurred within the first 5 years. The 5-year OS rates were similar in the TN and IMPC patients. The survival pattern of IMPC is parallel with TN, Therefore, clinical, therapeutic, and prognostic evaluation in IMPC can be done like TN. Invasive ductal carcinoma, Invasive micropapillary carcinoma, Survival.

Evaluation of Lymph Node Metastasis in Invasive Micropapillary Breast Carcinoma and Other Its Related Variables

Background: The rate of lymph node metastasis in patients with invasive micropapillary carcinoma (IMPC) could be considered a critical prognostic factor whose measurement may enhance therapeutic outcomes in these patients. Objectives: The current study aims at determining the rate of lymph node involvement in IMPC patients and comparing it with that of invasive ductal carcinoma, not otherwise specified (IDC-NOS) patients. Methods: In this case-control study, a total of 124 participated, including 61 patients with IMPC and 63 patients with IDC-NOS. The rate of lymph node metastasis and its possible connection with the patient's age, tumor size, grade and focality, lymphovascular invasion, and proportion of micropapillary component were determined in patients with IMPC and compared to that of IDC-NOS patients. Results: Lymph node involvement was detected in 80.3% of patients with IMPC, which is significantly higher compared to patients with IDC-NOS. No significant correlation was found between lymph node metastasis and the patients’ age, tumor size, and focality in both IMPC and IDC-NOS groups. Furthermore, no significant relationship was observed between lymph node metastasis and tumor grade in IMPC, while metastasis to lymph nodes was directly correlated with higher tumor grades of NOS type. Moreover, in both types of cancer, lymph node metastasis was significantly associated with lymphovascular invasion. In patients with IMPC, no statistically significant relevance was observed between lymph node metastasis and the percentage of micropapillary components. Conclusions: According to the results of this study, patients with IMPC had a significantly higher rate of lymph node involvement compared to IDC-NOS. Hence, the rate of lymph node involvement could be used as a prognostic factor in these patients.

Spatial transcriptomics reveals gene expression characteristics in invasive micropapillary carcinoma of the breast

Invasive micropapillary carcinoma (IMPC) is a special histological subtype of breast cancer, featured with extremely high rates of lymphovascular invasion and lymph node metastasis. Based on a previous series of studies, our team proposed the hypothesis of “clustered metastasis of IMPC tumor cells”. However, the transcriptomics characteristics underlying its metastasis are unknown, especially in spatial transcriptomics (ST). In this paper, we perform ST sequencing on four freshly frozen IMPC samples. We draw the transcriptomic maps of IMPC for the first time and reveal its extensive heterogeneity, associated with metabolic reprogramming. We also find that IMPC subpopulations with abnormal metabolism are arranged in different spatial areas, and higher levels of lipid metabolism are observed in all IMPC hierarchical clusters. Moreover, we find that the stromal regions show varieties of gene expression programs, and this difference depends on their distance from IMPC regions. Furthermore, a total of seven IMPC hierarchical clusters of four samples share a common higher expression level of the SREBF1 gene. Immunohistochemistry results further show that high SREBF1 protein expression is associated with lymph node metastasis and poor survival in IMPC patients. Together, these findings provide a valuable resource for exploring the inter- and intra-tumoral heterogeneity of IMPC and identify a new marker, SREBF1, which may facilitate accurate diagnosis and treatment of this disease.

Abstract P4-08-14: Invasive micropapillary carcinoma had no difference in prognosis compared with invasive ductal carcinoma: A propensity-matched analysis

Abstract Background: Invasive micropapillary carcinoma (IMPC) is a rare histopathological variant of breast carcinoma and usually performs poor clinical characteristics, such as high tendency of lymph nodes metastases. But whether it has worse prognosis than invasive ductal carcinoma (IDC) is still controversial nowadays. We conducted this retrospective study to figure out the prognostic difference between IMPC and IDC, then guide therapy of IMPC ultimately. Methods: In this study, we analyzed 327 cases of IMPC patients and 4979 cases of IDC who underwent primary resection in our institution during 2008 to 2012. By using propensity score matching, two groups were matched at a ratio of 1:1 by age, tumor size, nodal status, hormone and HER2 status to demonstrate the difference of prognosis assessed by Kaplan-Meier estimates and Cox regression analysis. Result: After a mean follow-up of 52 months, we established the IMPC group and figured out 324 IDC patients from the control group by propensity score matching (3 IMPC patients were canceled because of data missing). The result of survival analysis indicated that women diagnosed with IMPC had no significant reduced overall survival (OS) (p = 0.752) and disease-free survival (DFS) (p = 0.578) compared with women with IDC. Multivariate Cox regression analysis revealed that IMPC was not found as an independent prognostic factor for DFS (hazard ratio [HR] = 0.858; 95% confidential interval [CI], 0.419-1.757) or OS (HR = 0.720; 95%CI, 0.353-1.469). Conclusion: The consequence of survival analysis manifested that there was no statistically significant difference between 2 groups, and elucidated proactive or radical clinical therapy was unnecessary. Citation Format: Hao S, Zhao Y-Y, Peng J-J, Yang W-T, Ren F, Yu K-D, Shao Z-M. Invasive micropapillary carcinoma had no difference in prognosis compared with invasive ductal carcinoma: A propensity-matched analysis [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-08-14.

Invasive micropapillary carcinoma of the breast had no difference in prognosis compared with invasive ductal carcinoma: a propensity-matched analysis

Invasive micropapillary carcinoma (IMPC) is a rare histopathological variant of breast carcinoma that is usually associated with poor clinical characteristics. Whether IMPC has worse prognosis than invasive ductal carcinoma (IDC) is controversial. This retrospective study examined the prognostic difference between IMPC and IDC. We analysed 327 cases of IMPC patients and 4979 IDC cases who underwent primary resection in our institution between 2008 and 2012. Using propensity score matching, the two groups were matched at 1:1 by age, tumour size, nodal status, hormone status, and HER2 status. Differences in prognosis were assessed by Kaplan-Meier estimates and Cox regression analysis. We established the IMPC group and identified 324 IDC patients by propensity score matching. The survival analysis indicated that IMPC patients had no significant reduced overall survival (p = 0.752) or disease-free survival (p = 0.578) compared with IDC patients. Multivariate Cox regression analysis revealed that IMPC was not an independent prognostic factor for disease-free survival (hazard ratio [HR] = 0.944; 95% confidential interval [CI], 0.601–1.481) or overall survival (HR = 0.727; 95% CI, 0.358–1.478). Survival analysis demonstrated no statistically significant difference between IMPC and IDC, indicating that proactive or radical clinical therapy is unnecessary.

Abstract P6-09-06: The impact of molecular status on survival outcomes for invasive micropapillary carcinoma of the breast: An analysis from the National cancer data base

Abstract Purpose/Objectives: Invasive micropapillary carcinoma (IMPC) is an uncommon variant of breast cancer, accounting for &amp;lt;2% of all cases. Previous studies demonstrated that this subtype often presents with hormone receptor (HR) positive disease, resulting in survival outcomes similar to invasive ductal carcinoma. However, many of these studies were conducted prior to the availability of HER2 testing. In this study, we aim to determine the impact of molecular marker status (including HER2 status) on survival outcomes of invasive micropapillary carcinoma. Materials/Methods: The National Cancer Data Base (NCDB) was used to retrieve patients with biopsy-proven IMPC diagnosed from 2007-2012. Only patients with known estrogen receptor (ER) status, progesterone receptor (PR) status and HER2 status were included in the analysis. Cox multivariate regression was used to determine prognostic factors. Results: Overall, 865 patients met inclusion criteria. The median follow-up was 2.5 years. Out of all patients, 651 (75.3%) had HR+, HER2 negative disease, 128 (14.8%) had HR+, HER2+ disease, 41 (4.7%) had HR negative, HER2+ disease, and 45 (5.2%) had triple negative disease. Patients with triple negative disease were more likely to have poorly differentiated/undifferentiated histology (66.7%), lymphovascular invasion (73.3%), stage 3 disease (37.8%), undergone mastectomy (68.9%), and positive surgical margins (15.6%). On Cox multivariate regression, those with triple negative disease had worse overall survival (hazard ratio 7.28, P&amp;lt;0.001). Other prognostic factors associated with worse overall survival included African American descent (hazard ratio 2.24, P=0.018), comorbidity score of 1 (hazard ratio 2.50, P=0.011), comorbidity score ≥2 (hazard ratio 3.27, P=0.06), and ≥3 positive lymph nodes (hazard ratio 3.23, P=0.007). Conclusions: Similar to invasive ductal carcinoma, triple negative disease in invasive micropapillary carcinoma results in worse survival outcomes. This is the largest and first study to characterize molecular status (including HER2 status) in IMPC patients, as well as its impact on survival outcomes. Citation Format: Lewis GD, Xing Y, Patel T, Schwartz M, Rodriguez AA, Chen AC, Farach A, Hatch SS, Butler EB, Chang JC, Teh BS. The impact of molecular status on survival outcomes for invasive micropapillary carcinoma of the breast: An analysis from the National cancer data base [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-09-06.

Overexpression of β1 integrin contributes to polarity reversal and a poor prognosis of breast invasive micropapillary carcinoma.

Invasive micropapillary carcinoma (IMPC) of the breast is a highly aggressive breast cancer. Polarity reversal exemplified by cluster growth is hypothesized to contribute to the invasiveness and metastasis of IMPC. In this study, we demonstrate that levels of β1 integrin and Rac1 expression were greater in breast IMPC than in invasive breast carcinoma of no specific type and paraneoplastic benign breast tissue. We show that silencing β1 integrin expression using the β1 integrin inhibitor AIIB2 partially restored polarity in IMPC primary cell clusters and downregulated Rac1. Thus, overexpression of β1 integrin upregulates Rac1. Univariate analysis showed that overexpression of β1 integrin and Rac1 was associated with breast cancer cell polarity reversal, lymph node metastasis, and poor disease-free survival in IMPC patients. Multivariate analysis revealed that polarity reversal was an independent predictor of poor disease-free survival. These findings indicate that overexpression of β1 integrin and the resultant upregulation of Rac1 contribute to polarity reversal and metastasis of breast IMPC, and that β1 integrin and Rac1 could be potential prognostic biomarkers and targets for treatment of breast IMPC.

Amplification and overexpression of PSCA at 8q24 in invasive micropapillary carcinoma of breast.

Invasive micropapillary carcinoma (IMPC) of the breast has distinct histological features and molecular genetic profiles. Gains/amplifications of 8q24 are found associated with IMPC. Although the prostate stem cell antigen (PSCA) gene is located at chromosome8q24, and found over-expressed in prior studies, its prognostic values and biological significance in IMPC have not been well studied. Fluorescence in situ hybridization (FISH) was used to assess the frequencies of PSCA copy number gains in IMPC, invasive ductal carcinoma of no special type (IDC-NST), and invasive lobular carcinoma (ILC) samples. The protein expression levels of PSCA were examined in 56 IMPC, 72 IDC-NST, and 56 ILC samples using immunohistochemical analysis. PSCA gene amplification was detected in 45.2% (14/31) of the IMPC, 28.1% (9/32) of the IDC-NST, and none (0/25) of the ILC. PSCA protein expression was observed in 58.9% (33/56), 40.3% (29/72), and 3.6% (2/56) of IMPC, IDC-NST, and ILC samples, respectively. The concordantrateof the immunohistochemistry andFISHdata was 85.2%. PSCA gene amplification highly correlated with its protein overexpression (rs=0.687, P<0.001), suggesting that gene amplification is an important mechanism involved in PSCA overexpression. Our univariate analysis showed that the patients with PSCA-positive IMPC had a decreased disease-free survival (DFS) compared to PSCA-negative IMPC patients (P=0.003). Our multivariate analysis confirmed the worse DFS in PSCA-positive IMPC patients (P=0.022). Our results indicate that PSCA may be an attractive target in the 8q24 amplicon and that it may serve as a molecular marker of metastasis and recurrence in IMPC. The differential expression of PSCA may be associated with cell adhesion. Detection of PSCA protein and gene amplification may help manage and predict the prognosis of IMPC patients.

Loss of ARID1A expression is associated with poor prognosis in invasive micropapillary carcinomas of the breast: A clinicopathologic and immunohistochemical study with long-term survival analysis.

Invasive micropapillary carcinoma (IMPC) of the breast is a highly aggressive and a rare subtype of breast cancer. In this study, we aimed to investigate differences between pure and mixed IMPCs of the breast in terms of clinicopathologic features, and also to analyze the significance of expressions of ARID1A and bcl-2 regarding prognosis. Sixty-nine of IMPCs consisting of 21 pure and 48 mixed type diagnosed at Pathology Department of Istanbul Medical Faculty between 2000 and 2011, who had complete follow-up data, were collected to analyze ARID1A and bcl-2 expressions immunohistochemically with prognosis. The median follow-up period was 94months. No significant difference was found between pure and mixed type IMPC, as well as in luminal subgroups in terms of prognostic and clinicopatologic features. ARID1A and human epidermal growth factor receptor-2 (Her-2) status were found to be independent prognostic factors of both overall survival (OS) (HR=6.1, 95% CI 1.4-26.6, P=.02; HR=15.9, 95% CI 3.5-71.5, P<.0001, respectively) and disease free survival (DFS) (HR=4, 95% CI 1.1-14.9, P=.04; HR=7.2, 95% CI 2-25.4, P=.002, respectively) in multivariate analysis using Cox regression. The loss of ARID1A expression was significantly related with 10year-OS (P=.001) and 10year-DFS (P=.05). Statistically significant effect of ARID1A expression was also stated on DFS and OS in Luminal B group (P=.05 and P=.001 respectively). Pure and mixed type IMPCs are similar in terms of clinicopathologic and prognostic features. The loss of ARID1A expression and Her-2 positivity have significant adverse effect clinical outcomes of IMPC patients.

Clinicopathologic study of invasive micropapillary carcinoma of the breast.

Invasive micropapillary carcinoma (IMPC) is a rare subtype of breast carcinoma. It is presumed to be more aggressive than invasive ductal carcinoma (IDC), though it is uncertain whether the prognoses of IMPC and IDC differ. In this retrospective study, we compared the clinicopathologic characteristics and survival between 170 female patients with IMPC (pure or mixed with IDC) and 728 with pure IDC. The IMPC patients had higher clinical stages and histologic grades, higher incidences of lymphovascular invasion and axillary lymph node extracapsular extension, and a higher degree of lymph node involvement than IDC patients. Moreover, IMPC was associated with increases in estrogen receptor (ER) and progesterone receptor (PR) positivity and HER-2 overexpression. Although locoregional recurrence-free survival (LRRFS) and recurrence-free survival (RFS) were poorer in IMPC patients than IDC patients, overall survival and distant metastasis survival did not differ between the two groups. Multivariate analysis revealed that IMPC was an independent prognostic factor for LRRFS in breast cancer, and IMPC patients had poorer clinicopathologic characteristics and poorer RFS and LRRFS than IDC patients. We therefore suggest that to improve treatment decisions, patients with breast carcinoma be tested for the presence of this specific subtype.

Loss of Leucine Zipper Putative Tumor Suppressor 1 (LZTS1) Expression Contributes to Lymph Node Metastasis of Breast Invasive Micropapillary Carcinoma

Breast invasive micropapillary carcinoma (IMPC) is a rare subtype of breast cancer with a high potential of lymph node metastasis, aggressive clinical behavior, and poor disease-free or overall survival. Expression of leucine zipper putative tumor suppressor 1 (LZTS1) was frequently lost or reduced in breast cancer tissues. This study investigated the expression of LZTS1 protein in breast IMPC tissues using immunohistochemistry. In addition, somatic LZTS1 mutations and promoter methylation were assessed to determine an association with clinicopathological data from IMPC patients. LZTS1 protein was downregulated in 62 (62 %) of 100 IMPC tissue samples and was significantly associated with lymph node metastasis (P < 0.05). A LZTS1 exon mutation occurred in one of the 53 IMPC cases analyzed, whereas a LZTS1 intron mutation occurred in 26 of 53 cases. Moreover, LZTS1 promoter was frequently methylated in IMPC samples and was associated with reduced LZTS1 expression levels in IMPC tissues. These data demonstrated that the loss of LZTS1 expression was associated with lymph node metastasis in patients with IMPC, and LZTS1 promoter methylation could be responsible for the loss of LZTS1 expression.

Clinico-pathological features and prognosis of invasive micropapillary carcinoma compared to invasive ductal carcinoma: a population-based study from China.

BackgroundInvasive micropapillary carcinoma (IMPC) of the breast is a rare subtype of breast cancer that is associated with a high incidence of regional lymph node metastases and a poor clinical outcome. However, the clinico-pathological features and prognostic factors of IMPC are not well understood.Patients and MethodsA total of 188 IMPC cases and 1,289 invasive ductal carcinoma (IDC) cases were included. The clinical features, breast cancer-specific survival (BCSS) and recurrence/metastasis-free survival (RFS) of the patients were compared between these two groups.ResultsThe IMPC patients exhibited more features of aggressive carcinoma than the IDC patients, including larger tumor size, higher tumor stage, a greater proportion of nodal involvement and an increased incidence of lymphovascular invasion. Patients with IMPC had lower 5-year BCSS and RFS rates (75.9% and 67.1%, respectively) than patients with IDC (89.5% and 84.5%, respectively). Compared to IDC patients, the patients with IMPC had a significantly higher percentage of stage III breast cancer (51.3% versus 21.7%). In a stage-matched Kaplan-Meier analysis, the patients with stage III IMPC had lower 5-year BCSS and RFS rates than patients with stage III IDC (BCSS, P = 0.004; RFS, P = 0.034). A multivariate analysis revealed that TNM stage was an independent prognostic factor for patients with IMPC. The proportion of cancers with a luminal-like subtype was significantly higher in IMPC than in IDC (P<0.001). However, after matching by molecular subtype, the patients with IMPC had significantly worse clinical outcomes than patients with IDC.ConclusionsIn Chinese women, IMPCs displayed more aggressive behaviors than IDCs, resulting in poorer clinical outcomes for patients with IMPC, regardless of a favorable molecular subtype. Our findings illustrate that the poorer survival of patients with IMPC might be due to an increased incidence and aggressiveness of tumors in TNM stage III.

Abstract P6-07-11: Is the prognosis of lymphotropic invasive micropapillary carcinoma worse than invasive ductal carcinoma?: A population-based study of 645 patients

Abstract Purpose: Invasive micropapillary carcinoma (IMPC) is an uncommon distinct variant of breast carcinoma and is associated with an increased risk for regional lymph node metastases. Therefore, IMPC is considered to have an unfavorable prognosis when compared to invasive ductal carcinoma (IDC). The prognostic factors for IMPC are not well characterized due to the relative scarcity of cases reported in the literature. Methods: We analyzed the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database to evaluate prognostic factors of a population of 645 breast IMPC patients and 300,060 breast IDC patients reported between 2001 and 2008. Using univariate and multivariate analyses, hazard ratios (HR) were calculated for disease-specific (DSS) and overall survival (OS) for these patients using parameters such as patient age at diagnosis, histological grade, ER status, PR status, tumor size, and degree of lymph node positivity. Subset analysis of high grade, lymph node-positive patients was performed to compare DSS and OS between IMPC and IDC. Results: The 5-year DSS and OS for IMPC patients were 92.1% and 84.6% compared to 5-year DSS and OS of 88.5% and 80.2% for IDC patients. At presentation, TNM staging of IMPC cases was similar to IDC except for a higher percentage of LN metastases (52.4% in IMPC vs. 34.7% in IDC). Of those with known estrogen receptor (ER) status, 84.2% of IMPC cases were ER-positive, which was associated with better DSS (Hazard Ratio (HR) 0.36, p &amp;lt; 0.002) and OS (HR 0.62, p = 0.072). Patients with four or more positive lymph nodes had worse DSS (HR 7.1, p &amp;lt; 0.0001) and OS (HR 3.2, p &amp;lt; 0.0001) than node-negative patients, but those with one to three positive lymph nodes had similar DSS (HR 1.04, p = 0.96) and OS (HR 0.99, p = 0.97) as node-negative patients. In the subset of patients with high grade, node-positive breast carcinoma, patients with micropapillary histology had better DSS (p &amp;lt; 0.03) and a trend towards better OS (p = 0.12) than high grade, node-positive invasive ductal carcinoma. This subset of IMPC patients also had a higher percentage of ER-positive tumors (77%) compared to IDC patients (56%). Conclusions: While IMPC has a high propensity for lymph node metastasis, it has a disease-specific and overall prognosis that compares favorably to IDC. The higher percentage of hormone-receptor positivity may account for this survival advantage, even in high grade, node-positive disease. Therefore, estrogen-receptor-negativity or having four or more positive lymph nodes at presentation may potentially serve as prognostic markers for IMPC patients. In this study population, patients with one to three positive lymph nodes have DSS and OS similar to node-negative patients. Additional clinical studies are warranted to further investigate this observation. This is the largest study of IMPC to date, and these findings help our understanding of this uncommon histological variant of breast cancer. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-07-11.