Invasive Micropapillary Carcinoma Research Articles

Abstract PO3-08-05: Prognostic value of multigene test to the patients with Hormone receptor-positive, HER2-negative breast cancer based on special histologic subtypes

Abstract Background: Special histologic subtypes of breast cancer, including mucinous and tubular, account for 25% of all invasive breast cancers. Multigene tests (MGT) play a crucial role in guiding adjuvant chemotherapy and predicting prognosis for the patients with Hormone receptor-positive HER2-negative breast cancer. This research aims to examine the results of multigene tests for special histologic subtype patients and review the prognosis of each group. Methods: A retrospective analysis was conducted on data from 133 patients with special histologic subtypes of breast cancer who underwent surgery at Severance Hospital between November 2013 and December 2022. Each patient underwent one type of MGT, including Oncotype Dx, MammaPrint, or EndoPredict. Patients were grouped in two groups according to histologic types, based on WHO classification. Favorable types consist of type A mucinous carcinoma, pure tubular carcinoma, invasive solid papillary carcinoma, encapsulated papillary carcinoma with invasion, invasive cribriform carcinoma, secretory carcinoma, and invasive carcinoma with apocrine differentiation. Unfavorable types included type B mucinous carcinoma, mucinous carcinoma with micropapillary feature or neuroendocrine differentiation, mixed IDC, ILC or invasive micropapillary carcinoma, mixed invasive solid papillary carcinoma, mixed invasive papillary carcinoma, and mixed invasive cribriform carcinoma with IDC. Results: Patients with favorable types accounted for 42.86% (57 patients), while patients with unfavorable types accounted for 57.14% (76 patients). Patients with unfavorable histologic subtypes of breast cancer tended to have a higher incidence of high-risk results in MGT, as well as a greater prevalence of multiple (multifocal, multicentric) cancer and higher histologic grade. In multivariate analysis using logistic regression, unfavorable types showed a significantly high ratio of having high risk on MGT compared to the favorable type (OR = 4.327, 95% CI 1.210 – 15.475, p-value = 0.024). Moreover, overall survival in unfavorable histologic types showed a statistically significant difference between high-risk and low-risk in Kaplan-Meier survival analysis (p-value = 0.001). Conclusions: Unfavorable subtypes have shown a significantly higher-risk result of MGT, and patients with unfavorable types of breast cancer and high-risk MGT results have exhibited the worst prognosis. Consequently, we can suggest that MGT can be used as a prognosis evaluation tool for certain special subtypes of breast cancer and further utilized to aid in treatment decisions. Citation Format: Seung Hye Yang, Jee Hyun Ahn, Suk Jun Lee, Jee Ye Kim, Hyung Seok Park, Seung Il Kim, Byeong Woo Park, Seho Park. Prognostic value of multigene test to the patients with Hormone receptor-positive, HER2-negative breast cancer based on special histologic subtypes [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-08-05.

Abstract PO2-28-11: How to improve margins in breast cancer surgery: a

Abstract Objective: Intraoperative specimen mammography (ISM) is a diffuse technique that allows surgeons to check specimens immediately after lumpectomy, instead of intraoperative frozen sections, definitely abandoned. in Italy and Europe, because it is regarded as too expensive and time-consuming examination. Although the specimen is slightly compressed, the radiological image can be distorted by tissue overlap, and this may affect the evaluation of tumor borders, resulting in extension of the lumpectomy. As ISM may be less precise due to inadequate compression, a vacuum effect was applied to the specimen to increase the precision of margin detection. Study design: This study was conducted at St. Anna Hospital Breast Unit, Turin, Italy. Women who underwent lumpectomy for cancer were eligible for inclusion. BCS resection was performed with a free margin, and the surgical specimen was imaged immediately by SSM and evaluated by an expert radiologist and surgeon.Inclusion criteria were: breast cancer detected by a screening test, and treatment with surgical lumpectomy. Both standard ISM (sISM) and vacuum ISM (vISM) were performed. A dedicated breast surgeon at the study institution performed both surgery and radiological scans, and their interpretation. A dedicated radiologist reviewed all of the images. ISM was performed by a digital specimen mammography system (Faxitron, Bioptics Inc., Tucson, AZ, USA) in the operating room. Specimen registration and ISM analysis took 3 min. sISM (two orthogonal projections) was performed. Specimens were sealed in plastic bags in the vacuum apparatus (TissueSAFE Milestone Medical, Sorisole, Italy); this process took a few seconds. 152 specimens obtained after lumpectomy from 1 April 2021 to 31 April 2022 were scanned. sISM (two orthogonal projections) was performed. Next, the specimen was placed in a vacuum bag, and vISM was performed. Additional tissue was removed if the surgeon considered that excision was inadequate. Finally, the specimen was sent for definitive histopathological analysis, which is the gold standard for the assessment of surgical margins. Intraoperative histological margin assessment was not performed. The sISM and vISM images and final histopathology reports were compared. A first experience on a limited number of patients to demonstrate feasibility of the technique, is reported in table 1 and 2. Results: For sISM, specificity was 43,85% [95 % confidence interval (CI) 35.96-51.73], sensitivity was 40.91% (95 % CI 33.09-48.73), positive predictive value (PPV) 10.98% (95 % CI 6.01-15.95) and negative predictive value (NPV) 81.43% (95 % CI 75.25-87.61). For vISM, specificity 92,31% (95 % CI 88,07-96.54), sensitivity 72.73% (95 % CI 65.65-79.81), PPV 61.54% (95 % CI 53.80-69.27) and NPV 95.24% (95 % CI 91.85-98.62). Conclusion: ISM is a valid, safe and quicker alternative to intraoperative histopathological study, but has been reported to be limited due to less compression than standard SSM. Consequently, ISM may result in a high percentage of false-positive results, meaning unnecessary wider resections that lead to increased operative times and worse aesthetic results. A vacuum effect was performed on the specimen to increase the precision of margin detection. vISM images seem to be easier to interpret than sISM images (Figs. 1–3) as they are characterized by a vacuum-created radiolucent rim that better defines the tumor margins. These data suggest that the vacuum technique is feasible, cost-saving and yields results that are similar to those from frozen sections but without the limitations, such as prolonged operating time, high variability in sensitivity due to pathologists abilities, risk of compromising the histology, and unreliability for small lumps and ductal carcinoma in situ. Keywords: Breast cancer; Intraoperative mammography; Lumpectomy; Specimen mammography; Vacuum intraoperative mammography. Table 1. Clinical Data IC, invasive cancer; DCIS ductal carcinoma in situ; ADH, atypical ductal hyperplasia; ILC, invasive lobular cancer; B3, lesions of uncertain malignant potential; IMPC, invasive micropapillary carcinoma; NST, no special type; sISM, standard intraoperative specimen mammography; vISM, vacuum intraoperative specimen mammography. ª Margin: 0, involved; 1, free Table 2. Figure 1 - 2 - 3 Standard intraoperative specimen mammography (left) and vacuum intraoperative specimen mammography (right). Citation Format: Maria Grazia Baù, Vincenzo Marra, Alessandra Surace, Donatella Tota, Maria Piera Mano, Aurelia Mondino, Alessandro Bottero, Elisabetta Robba. How to improve margins in breast cancer surgery: a [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-28-11.

Log odds of positive lymph nodes (LODDS)-based novel nomogram for survival estimation in patients with invasive micropapillary carcinoma of the breast

BackgroundInvasive micropapillary carcinoma (IMPC) of the breast is known for its high propensity for lymph node (LN) invasion. Inadequate LN dissection may compromise the precision of prognostic assessments. This study introduces a log odds of positive lymph nodes (LODDS) method to address this issue and develops a novel LODDS-based nomogram to provide accurate prognostic information.MethodsThe study analyzed data from 1,901 patients with breast IMPC from the Surveillance, Epidemiology, and End Results database. It assessed the relationships between LODDS and the number of excised LN (eLN), positive LN (pLN), and the pLN ratio (pLNR), identifying an optimal threshold value using a restricted cubic spline method. Predictive factors were identified by the Cox least absolute shrinkage and selection operator (Cox-LASSO) regression and validated through multivariate Cox regression to construct a nomogram. The model's accuracy, discrimination, and utility were assessed. The study also explored the consequences of excluding LODDS from the nomogram and compared its effectiveness with the tumor-node-metastasis (TNM) staging system.ResultsLODDS improved N status classification by identifying heterogeneity in patients with pLN ratios of 0% (pLN =0) or 100% (pLN =eLN) and setting -1.08 as the ideal cutoff. Five independent prognostic factors for breast cancer-specific survival (BCSS) were identified: tumor size, N status, LODDS, progesterone receptor status, and histological grade. The LODDS-based nomogram achieved a strong concordance index of 0.802 (95% CI: 0.741-0.863), surpassing both the version without LODDS and the conventional TNM staging in all tests.ConclusionsFor breast IMPC, LODDS served as an independent prognostic factor, its effectiveness unaffected by the anatomical LN count, enhancing the accuracy of N staging. The LODDS-based nomogram showed promise in offering more personalized prognostic information.

Non-primary solid malignancies of breast in needle core biopsy: a clinicopathological analysis of 23 cases

Objective: To investigate the accurate diagnosis and differential diagnosis of non-primary solid malignant tumors in breast needle core biopsy. Methods: Twenty-three cases of breast, axilla or neck lymph nodes pathologically diagnosed as non-primary solid malignant tumors were collected at the First Affiliated Hospital of Nanjing Medical University, Nanjing, China from January 2013 to March 2023. The differential diagnoses and diagnostic features were analyzed, based on combining clinical data, histology, and expression characteristics of biomarkers. Results: All patients were female, with age ranging from 29 to 75 years (average 56 years). The average time from the diagnosis of primary tumor to the current diagnosis was 21 months (0 to 204 months).The primary sites included the ovary (9 cases), the lung (5 cases), the gastrointestinal tract (4 cases), the pancreas, intrahepatic bile duct, thyroid gland, nasal cavity and forearm skin (1 case each). No carcinoma in situ was found in any of the cases. The morphological differences were significant among the tumors, but similar to the primary tumors. The tumors of neuroendocrine and female reproductive tract had great morphological and immunophenotypic overlaps with breast cancer. Metastatic lung cancer cells showed obvious atypia and tumor giant cells. The morphology and immunophenotype of metastatic serous carcinoma of female reproductive system might resemble invasive micropapillary carcinoma of the breast. Metastatic adenocarcinoma of the gastrointestinal tract often had features of mucous secretion. Metastatic neuroendocrine tumors were bland in appearance and morphologically similar to solid papillary carcinoma of breast, but negative for ER. TRPS1 was mostly negative (18/23) and variably positive in ovarian (4/9) and intrahepatic bile duct (1/1) tumors. Conclusions: The diagnosis of breast needle core biopsy specimen should be combined with clinical history, imaging study, and careful examination of histological features, such as presence of in situ component, morphological similarity between the primary and metastatic tumors, and using appropriate markers to differentiate the primary from metastatic tumors.

Correlation Analysis of Digital Mammography, Ultrasonography, and Pathologic Features in Pure Invasive Micropapillary Carcinoma of the Breast (PIMPC).

This study determined the digital mammography and ultrasonography imaging features of pure invasive micropapillary carcinoma of the breast (PIMPC) and the correlation with pathologic features. Nineteen patients diagnosed with PIMPC at Yantaishan Hospital from October 2015 to February 2022 were included in the study group. Forty patients with breast masses diagnosed as nonspecific invasive ductal carcinoma of the breast (NIDC) from July to December 2021 were included in the control group. Digital mammography and ultrasonography features were compared between the two groups. Patients with PIMPC had a younger age profile compared to patients with NIDC (P=0.017). Moreover, PIMPC masses were smaller than NIDC masses (P=0.040). Imaging features analysis revealed significant differences in age groups (<45 years: χ²=5.971, P=0.044) and the presence of spiculations or the crab claw sign (χ²=8.583, P=0.004) between patients with PIMPC and NIDC. However, there were no statistically significant differences in the presence of calcifications, blood flow grading, pathologic molecular subtypes between the study and control groups. The Ki-67 proliferative index (χ²=1.052, P=0.389), vascular invasion (χ²=2.263, P=0.197), and lymph node metastasis (χ²=1.968, P=0.386) showed no significant differences between PIMPC and NIDC patients. PIMPC imaging features show specificity, such as tiny breast masses, spiculated edges, or crab claw-like patterns, and malignant signs appeared when the lesion was <2 cm in diameter. PIMPC mainly occurs in middle-aged women 45-59 y of age. Patients with PIMPC and NIDC of the breast are frequently associated with lymph node metastases and greater than one-half of the cases (74%) were shown to have a Ki-67 index >30%, suggesting a significant risk of recurrence and metastasis. Early therapeutic care for these patients is crucial. These results warrant further validation with additional samples from several centers due to the limited single-center sample size in the current study.

279 (PB-095) Poster - Reassessment of HER2 Status in Invasive Micropapillary Carcinoma of the Breast - Recommendations for Improvement of 2023 ASCO/CAP Guideline on HER2 Testing

279 (PB-095) Poster - Reassessment of HER2 Status in Invasive Micropapillary Carcinoma of the Breast - Recommendations for Improvement of 2023 ASCO/CAP Guideline on HER2 Testing

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.

INVASIVE MICROPAPILLARY BREAST CARCINOMA DISCOVERED DURING THE INVESTIGATION OF ACUTE RESPIRATORY DISTRESS IN A POSTPARTUM WOMAN: A CASE REPORT

Invasive micropapillary carcinoma of the breast is a rare histological entity among breast cancers, representing 2 to 3% of breast carcinomas. Its clinical and radiological presentation is similar to other carcinoma entities. Diagnosis is primarily histological but remains challenging and dependent on the operator. It is an aggressive tumor with both local and distant extension (lymphatic, cutaneous, etc.). In this study, we present a case of invasive micropapillary carcinoma of the breast discovered during acute respiratory distress due to serous extension (pleural effusion). Through this case, we will discuss the various clinical, radiological, therapeutic, and particularly histological aspects of this rare type of carcinoma.

Comprehensive genomic evaluation of advanced and recurrent breast cancer patients for tailored precision treatments

AimThe aim of this study was to investigate genetic alterations within breast cancer in the setting of recurrent or de novo stage IV disease.Patients and methods: This study included 22 patients with recurrent breast cancer (n = 19) and inoperable de novo stage IV breast cancer (n = 3). For next generation sequencing, FoundationOneCDx (F1CDx) (Foundation Medicine Inc., Cambridge, MA, USA) was performed in 21 patients and FoundationOneLiquid CDx was performed in 1 patient.ResultsMedian age was 62.9 years (range, 33.4–82.1). Pathological diagnoses of specimens included invasive ductal carcinoma (n = 19), invasive lobular carcinoma (n = 2), and invasive micropapillary carcinoma (n = 1). F1CDx detected a median of 4.5 variants (range, 1–11). The most commonly altered gene were PIK3CA (n = 9), followed by TP53 (n = 7), MYC (n = 4), PTEN (n = 3), and CDH1 (n = 3). For hormone receptor-positive patients with PIK3CA mutations, hormonal treatment plus a phosphoinositide 3-kinase inhibitor was recommended as the treatment of choice. Patients in the hormone receptor-negative and no human epidermal growth factor receptor 2 expression group had significantly higher tumor mutational burden than patients in the hormone receptor-positive group. A BRCA2 reversion mutation was revealed by F1CDx in a patient with a deleterious germline BRCA2 mutation during poly ADP ribose polymerase inhibitor treatment.ConclusionGuidance on tailored precision therapy with consideration of genomic mutations was possible for some patients with information provided by F1CDx. Clinicians should consider using F1CDx at turning points in the course of the disease.

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.

Construction and validation of a nomogram for predicting the prognosis of patients with lymph node-positive invasive micropapillary carcinoma of the breast: based on SEER database and external validation cohort

BackgroundInvasive micropapillary carcinoma (IMPC) of the breast is a rare subtype of breast cancer with high incidence of aggressive clinical behavior, lymph node metastasis (LNM) and poor prognosis. In the present study, using the Surveillance, Epidemiology, and End Results (SEER) database, we analyzed the clinicopathological characteristics and prognostic factors of IMPC with LNM, and constructed a prognostic nomogram.MethodsWe retrospectively analyzed data for 487 breast IMPC patients with LNM in the SEER database from January 2010 to December 2015, and randomly divided these patients into a training cohort (70%) and an internal validation cohort (30%) for the construction and internal validation of the nomogram, respectively. In addition, 248 patients diagnosed with IMPC and LNM at the Fourth Hospital of Hebei Medical University from January 2010 to December 2019 were collected as an external validation cohort. Lasso regression, along with Cox regression, was used to screen risk factors. Further more, the discrimination, calibration, and clinical utility of the nomogram were assessed based on the consistency index (C-index), time-dependent receiver operating characteristic (ROC), calibration curve, and decision curve analysis (DCA).ResultsIn summary, we identified six variables including molecular subtype of breast cancer, first malignant primary indicator, tumor grade, AJCC stage, radiotherapy and chemotherapy were independent prognostic factors in predicting the prognosis of IMPC patients with LNM (P &amp;lt; 0.05). Based on these factors, a nomogram was constructed for predicting 3- and 5-year overall survival (OS) of patients. The nomogram achieved a C-index of 0.789 (95%CI: 0.759-0.819) in the training cohort, 0.775 (95%CI: 0.731-0.819) in the internal validation cohort, and 0.788 (95%CI: 0.756-0.820) in the external validation cohort. According to the calculated patient risk score, the patients were divided into a high-risk group and a low-risk group, which showed a significant difference in the survival prognosis of the two groups (P&amp;lt;0.0001). The time-dependent ROC curves, calibration curves and DCA curves proved the superiority of the nomogram.ConclusionsWe have successfully constructed a nomogram that could predict 3- and 5-year OS of IMPC patients with LNM and may assist clinicians in decision-making and personalized treatment planning.

Radiological characteristics of invasive micropapillary carcinoma of the breast

To analyse the various imaging features of invasive micropapillary carcinoma (IMPC), a distinct variant of breast cancer, by mammography, ultrasound, and contrast-enhanced mammography. This study included 68 female patients with histopathologically proven invasive micropapillary carcinoma who underwent mammography, ultrasound, and contrast-enhanced mammography examinations. The findings encountered by each imaging tool were analysed using the Breast Imaging Reporting and Data System (BI-RADS) lexicon. In this retrospective study, 64.7% of cases were of the pure form of IMPC. Most of the cases showed an aggressive clinical course, with lymphovascular invasion noted in 76.5% of cases, while 60.3% of cases showed associated pathological lymphadenopathy. The N3 stage was reported in 25% of cases. On analysing the mammographic and ultrasound imaging findings, a significant association between irregular shape and a non-circumscribed margin with IMPC was found. Associated calcification was noted in 47% of cases. Pathological enhancement of moderate or marked conspicuity was noted in cases that underwent contrast-enhanced mammography, with the most commonly encountered finding being enhancing irregular and non-circumscribed masses. The mammographic and ultrasound imaging features of IMPC are indistinguishable from other aggressive types of breast cancer. At contrast-enhanced mammography examination, pathological enhancement of moderate to marked conspicuity was shown in all cases. The observed strong association of IMPC with lymphovascular invasion and lymph node metastasis with higher nodal stage in this study mandate meticulous sonographic examination of the axilla, as well as the infra, and supraclavicular regions if pathological axillary lymphadenopathy was noted.

Nomogram predicting overall prognosis for invasive micropapillary carcinoma of the breast: a SEER-based population study

ObjectivesThe prognosis of invasive micropapillary carcinoma (IMPC) of the breast is determined by many clinicopathological factors. This study aims to identify prognostic factors and develop reliable nomogram to predict the...

Authentication of a survival nomogram for non-invasive micropapillary breast cancer.

We aimed at establishing a nomogram to accurately predict the overall survival (OS) of non-metastatic invasive micropapillary breast carcinoma (IMPC). In the training cohort, data from 429 patients with non-metastatic IMPC were obtained through the Surveillance, Epidemiology, and End Results (SEER) database. Other 102 patients were enrolled at the Xijing Hospital as validation cohort. Independent risk factors affecting OS were ascertained using univariate and multivariate Cox regression. A nomogram was established to predict OS at 3, 5 and 8 years. The concordance index (C-index), the area under a receiver operating characteristic (ROC) curve and calibration curves were utilized to assess calibration, discrimination and predictive accuracy. Finally, the nomogram was utilized to stratify the risk. The OS between groups was compared through Kaplan-Meier survival curves. The multivariate analyses revealed that race (p = 0.047), surgery (p = 0.003), positive lymph nodes (p = 0.027), T stage (p = 0.045) and estrogen receptors (p = 0.019) were independent prognostic risk factors. The C-index was 0.766 (95% CI, 0.682-0.850) in the training cohort and 0.694 (95% CI, 0.527-0.861) in the validation cohort. Furthermore, the predicted OS was consistent with actual observation. The AUCs for OS at 3, 5 and 8 years were 0.786 (95% CI: 0.656-0.916), 0.791 (95% CI: 0.669-0.912), and 0.774 (95% CI: 0.688-0.860) in the training cohort, respectively. The area under the curves (AUCs) for OS at 3, 5 and 8 years were 0.653 (95% CI: 0.498-0.808), 0.683 (95% CI: 0.546-0.820), and 0.716 (95% CI: 0.595-0.836) in the validation cohort, respectively. The Kaplan-Meier survival curves revealed a significant different OS between groups in both cohorts (p<0.001). Our novel prognostic nomogram for non-metastatic IMPC patients achieved a good level of accuracy in both cohorts and could be used to optimize the treatment based on the individual risk factors.

Metabolome Sequencing Reveals that Protein Arginine-N-Methyltransferase 1 Promotes the Progression of Invasive Micropapillary Carcinoma of the Breast and Predicts a Poor Prognosis

Invasive micropapillary carcinoma (IMPC) of the breast is a special histopathologic type of cancer with a high recurrence rate and the biological features of invasion and metastasis. Previous spatial transcriptome studies indicated extensive metabolic reprogramming in IMPC, which contributes to tumor cell heterogeneity. However, the impact of metabolome alterations on IMPC biological behavior is unclear. Herein, endogenous metabolite-targeted metabolomic analysis was done on frozen tumor tissue samples from 25 patients with breast IMPC and 34 patients with invasive ductal carcinoma not otherwise specified (IDC-NOS) by liquid chromatography-mass spectrometry. An IMPC-like state, which is an intermediate transitional morphologic phenotype between IMPC and IDC-NOS, was observed. The metabolic type of IMPC and IDC-NOS was related to breast cancer molecular type. Arginine methylation modification and 4-hydroxy-phenylpyruvate metabolic changes play a major role in the metabolic reprogramming of IMPC. High protein arginine-N-methyltransferase (PRMT) 1 expression was an independent factor related to the poor prognosis of patients with IMPC in terms of disease-free survival. PRMT1 promoted H4R3me2a, which induced tumor cell proliferation via cell cycle regulation and facilitated tumor cell metastasis via the tumor necrosis factor signaling pathway. This study identified the metabolic type-related features and intermediate transition morphology of IMPC. The identification of potential targets of PRMT1 has the potential to provide a basis for the precise diagnosis and treatment of breast IMPC.

A web-based novel model for predicting prognostic value in patients with invasive micropapillary carcinoma in breast cancer: a real-world data retrospective cohort study.

Invasive micropapillary carcinoma (IMPC) accounts for less than 2% of all invasive breast cancers and usually associates with poor survival, so we investigated the prognostic factors for IMPC using a large population-based database and designed a web-based novel model. Clinicopathological prognostic factors were evaluated using the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate Cox regression analysis was performed to evaluate the prognostic value of variables on the overall survival. A web-based nomogram was finally constructed to predict the survival probability. The model was validated in an external dataset. A web-based model, combined with age, radiation, clinical stage, and hormone receptor (HR) immunochemistry status four prognostic factors, was constructed. The C-index (0.714, 95% CI 0.683-0.741), calibration curves, and decision curves showed that this model was superior in prediction. By determining the cut-off values, high-risk group and low-risk group were divided. The Kaplan-Meier survival curves showed that these two groups had significantly different survival rates (P < 0.0001). The result of C-index, calibration curves, and Kaplan-Meier survival curves were consistent in the validation cohort. The novel nomogram with four risk factors resulted in accurate prognostic prediction for IMPC.

Molecular Pathology of Micropapillary Carcinomas: Is Characteristic Morphology Related to Molecular Mechanisms?

Micropapillary carcinoma is an entity defined histologically in many organs. It is associated with lymph node metastasis and poor prognosis. The main mechanism for its histopathologic appearance is reverse polarization. Although the studies on this subject are limited, carcinomas with micropapillary morphology observed in different organs are examined by immunohistochemical and molecular methods. Differences are shown in these tumors compared with conventional carcinomas regarding the rate of somatic mutations, mRNA and miRNA expressions, and protein expression levels. TP53, PIK3CA, TERT, KRAS, EGFR, MYC, FGFR1, BRAF, AKT1, HER2/ERBB2, CCND1, and APC mutations, which genes frequently detected in solid tumors, have also been detected in invasive micropapillary carcinoma (IMPC) in various organs. 6q chromosome loss, DNAH9, FOXO3, SEC. 63, and FMN2 gene mutations associated with cell polarity or cell structure and skeleton have also been detected in IMPCs. Among the proteins that affect cell polarity, RAC1, placoglobin, as well as CLDNs, LIN7A, ZEB1, CLDN1, DLG1, CDH1 (E-cadherin), OCLN, AFDN/AF6, ZEB1, SNAI2, ITGA1 (integrin alpha 1), ITGB1 (integrin beta 1), RHOA, Jagged-1 (JAG1) mRNAs differentially express between IMPC and conventional carcinomas. Prediction of prognosis and targeted therapy may benefit from the understanding of molecular mechanisms of micropapillary morphology. This review describes the molecular pathologic mechanisms underlying the micropapillary changes of cancers in various organs in a cell polarity-related dimension.

Nomograms for predicting overall survival and cancer-specific survival in patients with invasive micropapillary carcinoma: Based on the SEER database

BackgroundInvasive micropapillary carcinoma (IMPC) is a rare subtype of breast cancer that lacks a prognostic prediction model. Its treatment and prognostic factors remain controversial. Our study aimed to develop nomograms to predict overall survival (OS) and cancer-specific survival (CSS) in IMPC patients. MethodsA total of 2149 patients confirmed to have IMPC between 2003 and 2018 were selected from the Surveillance, Epidemiology and End Results (SEER) database. They were divided into training and validation cohorts. Univariate and multivariate Cox regression analyses were used to identify significant independent prognostic factors. The nomograms were used to predict 3- and 5-year OS and CSS. The training and validation cohorts were used to verify the nomograms internally and externally. The predictive capability of the nomograms was evaluated by the consistency index (C-index), calibration curve, receiver operating characteristic (ROC) curve and decision curve analysis (DCA) curve. ResultsIn the study, 2149 IMPC patients were randomized to a training group (n = 1611) and a validation group (n = 538). Age, T stage, N stage, ER, radiotherapy, and surgery were identified as independent prognostic factors for OS and CSS. These variables were selected to construct nomograms for IMPC. The C-index (0.768 for OS and 0.811 for CSS) and the time-dependent AUC (>0.7) indicated satisfactory discriminative ability of the nomograms. Additionally, DCA showed that the nomograms had higher clinical value than traditional TNM tumor staging. ConclusionsThe models can accurately predict the prognosis of IMPC patients and can aid in providing individualized treatment for patients.

Pathological features and immune microenvironment in HER-2 intratumoral heterogeneous breast cancers

Objective: To observe the clinical pathology features, and immune microenvironment of HER-2 intratumoral heterogeneity breast cancer. Methods: Thirty cases of HER-2 intratumoral heterogeneous breast cancer were retrospectively analyzed in Tianjin Medical University Cancer Institute and Hospital from November 2017 to June 2020. HER-2 expression was detected by immunohistochemistry and verified by dual color silver-enhanced in-situ hybridization (D-SISH). HER-2 intratumoral positive and negative regions were divided. The pathological characteristics, subtype, and the level of tumor infiltrating lymphocytes (TILs) and the expression of programmed cell death-ligand 1 (PD-L1) were evaluated respectively. Results: The proportion of HER-2 positive cells of the breast cancer ranged from 10% to 90%. The pathological type was mainly invasive non-special typecarcinoma. Six cases presented different pathological types between HER-2 positive and negative regions. The HER-2-positive areas included 2 cases of carcinoma with apocrine differentiation, and the negative areas included 2 cases of invasive micropapillary carcinoma, 1 case of invasive papillary carcinoma, and 1 case of carcinoma with apocrine differentiation. In HER-2 positive regions, 17 cases were Luminal B and 13 cases were HER-2 overexpressed types. There were 22 cases of Luminal B and 8 cases of triple negative tumors in the HER-2 negative areas. The levels of TILs in HER-2 positive and negative areas accounted for 53.3% (16/30) and 26.7% (8/30), respectively, with a statistically significant difference (P=0.035). The positive expression of PD-L1 in HER-2 positive area and HER-2 negative area were 6 cases and 9 cases, respectively. Among 8 cases with HER-2 negative regions containing triple negative components, 4 cases were positive for PD-L1 expression. Conclusions: In the case of HER-2 intratumoral heterogeneity, it is necessary to pay attention to both HER-2 positive and negative regions, and evaluate subtype separately as far as possible. For HER-2 intratumoral heterogeneous breast cancer containing triple negative components, the treatment mode can be optimized by refining the intratumoral expression of PD-L1.

Transformation of breast micropapillary ductal carcinoma in situ into invasive micropapillary carcinoma after recurrence in chest wall: report of a case

乳腺导管内癌是一种常见的乳腺原位癌，因肿瘤未突破基底膜，手术切除通常有效，少部分复发，极少部分以浸润癌复发。本文报道1例微乳头型乳腺导管内癌，乳腺改良根治术和内分泌治疗4年后出现同侧胸壁浸润性微乳头状癌复发，再次行化疗+放疗+内分泌治疗后随访3年无异常。本文回顾其临床病理资料并复习相关文献，以提高对该病的认识，并探讨可能的治疗方案。.