Pure Invasive Ductal Carcinoma Research Articles

Abstract PO2-01-12: Preoperative cryoablation in 52 Her2- Luminal invasive ductal carcinomas ≤ 2cm. Analysis of the tumor specimen

Abstract Objective: 1st: Assess the presence of residual infiltrating component in the surgical specimen of patients with Luminal Her2- tumors ≤ 2cm and ultrasound-negative axilla, following ultrasound-guided cryoablation. 2nd: Demonstrate that preoperative seed placement prior to cryoablation does not interfere with tumor cell elimination by freezing. Methods: Between April 2021 and April 2023, we performed preoperative cryoablation on 52 patients aged 53 to 79 years (mean 64) with 52 unifocal invasive ductal carcinomas (IDC) measuring 4 to 20 mm (mean 10), low grade (24 G1, 28 G2), 31 Luminal A and 21 B, Ki67 between 3 and 30% (mean 13). On ultrasound, all IDCs were visible and axilla-negative. 26 of them (50%) were referred from the screening program of the Community of Madrid. The tumor-to-skin surface distance ranged from 2 to 18 mm (mean 9 mm). All patients underwent mammography-tomosynthesis, staging, and biopsy under ultrasound guidance. The minimum time elapsed until surgery was 6 days, and the maximum was 78 days (mean 22). All patients underwent mammography-tomosynthesis, staging, and biopsy under ultrasound guidance. MRI was performed to rule out extensive intraductal component in 17 out of 20 patients with associated intraductal carcinoma (IDC) in the diagnostic biopsy. Preoperative marking with ferromagnetic seed placement was performed in all cases prior to cryoablation, using a single dose of anesthesia and through the same skin access. We used the ICEfx Galil Boston Scientific cryoablation system with 17G or 14G needles, applying the standard triple-phase protocol: freezing-passive thawing-freezing for approximately 40 minutes. The correct placement of the seed was subsequently confirmed by mammography. Results: There were no significant complications in any case. Out of 52 low-risk unifocal IDCs: -32 were pure IDCs (without associated intraductal component in diagnostic biopsy): no residual IDC was identified in the tumor specimen. -20 were mixed IDCs (with associated IDC in the diagnostic biopsy): *In 4 cases, residual IDC was found in the surgical specimen, with some foci of IDC remaining at the periphery of the post-cryoablation necrosis. *In 8 patients, foci of IDC were detected distant from the cryoablation zone. The pathologist determined that all samples had tumor-free margins. Conclusions: Cryoablation is effective in 100% of cases for pure infiltrating tumors ≤ 2cm. The presence of scattered IDC nests away from the cryoablation zone or at the margin of fat necrosis does not indicate technique failure, as all surgical specimens were determined to have tumor-free margins by the pathologist. For mixed infiltrating tumors, the ice ball should broadly cover the tumor size estimated by ultrasound and MRI. Standard adjuvant treatment will equalize the risk of recurrence with conventional lumpectomy. Table 1: 52 cases IDC unifocal ≤2cm Table 2: IDC Pure ≤2cm. Table 3: IDC mixed: IDC+DCIs ≤2cm Analysis of surgical specimen Citation Format: Maria José Roca Navarro, Pilar Zamora, Ylenia Navarro Monforte, Diego Garrido Alonso, Vicenta Córdoba Chicote, Teresa Diaz de Bustamante Durban, José María Oliver Goldaracena, Laura Yebenes Gregorio, Covadonga Marti, Jose Ignacio Sanchez-Mendez, Elisa Moreno, Laura Frías Aldeguer, Adolfo Loayza Galindo, Alberto Berjón García, Marcos Melendez Gisper, Carmen Martín Hervás, Lara Miralles, Cristina Escabias del Pozo, Younes Abadi, Elisa York Pineda, Gonzalo Garzón Moll, David Hardisson Hernáez, Alicia Hernández Gutiérrez, César Casado Sánchez, Virginia Martínez Marín, Shirin Zarbakhsh, Joaquin Gomez Ramirez. Preoperative cryoablation in 52 Her2- Luminal invasive ductal carcinomas ≤ 2cm. Analysis of the tumor specimen [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 PO2-01-12.

Prediction of coexisting invasive carcinoma on ductal carcinoma in situ (DCIS) lesions by mass spectrometry imaging.

Due to limited biopsy samples, ~20% of DCIS lesions confirmed by biopsy are upgraded to invasive ductal carcinoma (IDC) upon surgical resection. Avoiding underestimation of IDC when diagnosing DCIS has become an urgent challenge in an era discouraging overtreatment of DCIS. In this study, the metabolic profiles of 284 fresh frozen breast samples, including tumor tissues and adjacent benign tissues (ABTs) and distant surrounding tissues (DSTs), were analyzed using desorption electrospray ionization-mass spectrometry (DESI-MS) imaging. Metabolomics analysis using DESI-MS data revealed significant differences in metabolite levels, including small-molecule antioxidants, long-chain polyunsaturated fatty acids (PUFAs) and phospholipids between pure DCIS and IDC. However, the metabolic profile in DCIS with invasive carcinoma components clearly shifts to be closer to adjacent IDC components. For instance, DCIS with invasive carcinoma components showed lower levels of antioxidants and higher levels of free fatty acids compared to pure DCIS. Furthermore, the accumulation of long-chain PUFAs and the phosphatidylinositols (PIs) containing PUFA residues may also be associated with the progression of DCIS. These distinctive metabolic characteristics may offer valuable indications for investigating the malignant potential of DCIS. By combining DESI-MS data with machine learning (ML) methods, various breast lesions were discriminated. Importantly, the pure DCIS components were successfully distinguished from the DCIS components in samples with invasion in postoperative specimens by a Lasso prediction model, achieving an AUC value of 0.851. In addition, pixel-level prediction based on DESI-MS data enabled automatic visualization of tissue properties across whole tissue sections. Summarily, DESI-MS imaging on histopathological sections can provide abundant metabolic information about breast lesions. By analyzing the spatial metabolic characteristics in tissue sections, this technology has the potential to facilitate accurate diagnosis and individualized treatment of DCIS by inferring the presence of IDC components surrounding DCIS lesions. © 2023 The Pathological Society of Great Britain and Ireland.

Abstract P4-03-11: Population-based survival outcomes of pure vs mixed invasive lobular breast carcinoma in Ontario, Canada

Abstract Purpose: We aim to determine incidence and survival rates of pure vs mixed invasive lobular breast carcinoma between 1990 and 2020 in the province of Ontario, Canada. We further evaluated patient and tumour factors that predict survival for invasive lobular carcinoma (ILC). Methods: Using population-based administrative healthcare datasets at Institute of Clinical Evaluative Sciences (ICES) Ontario, we calculated the crude 5-year incidence rates of pure ILC versus invasive ductal carcinoma (IDC) versus mixed ILC-IDC in the province of Ontario, Canada between 1990 and 2020. Kaplan-Meier survival curves were generated to determine the 5-, 10-, 15- and 20-year survival for ILC (and mixed ILC-IDC) as compared with IDC. Survival curves were compared using the log-rank test and stratified by stage. Using a multivariable Cox proportional hazards regression analysis, we identified patient (e.g. demographic, geographic, socioeconomic) and tumour (grade, stage, receptor subtype) factors that predicted survival for patients with ILC. Statistical analysis was performed using SAS® and P values < 0.05 were considered statistically significant. Results: We identified 18,551 (8%) pure ILC, 10,234 (4%) mixed ILC-IDC and 192,371 (81%) IDC cases. The crude incidence of pure ILC increased from 55.7 per 100,000 in 1990 to 80.2 per 100,000 in 2020. The crude incidence of mixed ILC-IDC peaked in the mid-2000s at 48.6 per 100,000 and subsequently declined to 32.1 per 100,000 in 2020. There was a significant difference in overall survival between the three breast cancer subtypes. Over a 30-year follow-up period (mean 9.3 +/- 7.3 years), overall survival of mixed ILC-IDC mirrors the survival of pure IDC, while women with pure ILC have inferior survival compared with IDC beginning after 10 years of follow-up (P < .001). The 20-year overall survival was 40% for ILC and 50% for IDC and mixed ILC-IDC. Older age > 55 years (vs. 50-54 years, P < .0001), lowest neighborhood income quintile (HR 1.1, P = .038), geographic location within Ontario (P < .01) and increasing Elixhauser Comorbidity Index score (P < .0001) predicted worse overall survival for ILC patients. Conversely, the increasing number of mammograms received in the five years prior to diagnosis predicted better overall survival (P < .0001). When stratified by cancer stage, the worse survival in ILC (compared with IDC and mixed ILC-IDC) was only observed for stage III patients (P = .01). Stage III and IV disease, grade 3 histology and ER/PR negativity predicted worse survival (P < .01). Conclusion: The crude incidence of ILC is increasing over time. Over a 30-year follow-up period (mean 9.3 +/- 7.3 years), ILC had worse overall survival compared with IDC and mixed ILC-IDC, particular stage III patients. Patient demographic and tumour factors predict overall survival in ILC. While treatment paradigms for ILC mirror that for IDC, our data demonstrates worse overall survival for ILC and a need for more research and treatments focused on improving long-term survival for ILC patients. Citation Format: David Lim, Vasily Giannakeas, Steven Narod, Kelly Metcalfe. Population-based survival outcomes of pure vs mixed invasive lobular breast carcinoma in Ontario, Canada [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-03-11.

Abstract P5-06-02: A gene expression meta-analysis identifies microenvironment differences in cellular composition and cell-cell interactions associated with breast cancer invasion

Abstract Background: The invasion of malignant cells into surrounding stroma is the histological hallmark differentiating invasive ductal carcinoma (IDC) from ductal carcinoma in situ (DCIS). The associated variations in the cellular composition and interactions in the tumor microenvironment, and how those mediate invasion are poorly understood. Systematic analyses of gene expression differences between DCIS and IDC are rare, confounded by cellular heterogeneity, and limited to few cases unable to distinguish stromal from epithelial contributions or compare pure DCIS from those synchronous with IDC. To address these problems we have assembled multiple datasets from publicly available gene expression studies of microdissected DCIS and IDC samples. Methods: The transcriptome from 192 regions microdissected from 140 cases was assembled from 5 published studies and included DCIS (83 epithelial, 22 stromal) and IDC (67 epithelial, 20 stromal) cases. Differences in infiltration of 10 immune cell types were measured using expression signatures. Expression subtypes were determined from the PAM50 signatures of epithelial regions using the genefu package. Gene Set Enrichment Analysis (GSEA) was performed using the gene sets in the Hallmark and Reactome collections. Cell-cell interactions between stromal and epithelial regions were measured using the co-expression of 1175 curated pairs of ligand-receptor genes and compared between DCIS and IDC using a permutation test. The corresponding interacting cell types were identified using RNA sequencing of 5444 single nuclei extracted from fine needle aspirates of two excised DCIS specimens. Results: Of the measured immune cell types, B cells showed a progressive depletion from normal to DCIS to IDC stroma. Pure IDC regions were significantly less likely to be the Luminal A subtype compared to synchronous IDC/DCIS and pure DCIS (p=0.0008). IFN signaling was higher in IDC epithelium suggesting possible differences in immune visibility between these two diseases. Higher calcium and glutamate signaling is observed in the DCIS stroma compared to IDC, calcium signaling has been implicated as both essential to normal breast function and as a positive effector of IDC proliferation. The expression-based measurement of stromal-epithelial interactions identified 99 and 115 ligand-receptor interactions enriched in DCIS and IDC, respectively (FDR<0.1). To precisely identify the corresponding interacting cell types, the expression profile of cells within the DCIS microenvironment was determined using single-nucleus RNA sequencing from two DCIS patients. The analysis identified 9 cell types, including luminal, basal, macrophage, adipocyte and endothelial, and 54% of the candidate cell-cell interactions could be mapped to at least one cell type pair. Based on these cell type mappings, interactions between luminal cells and fibroblasts were gained in IDC while those involving the vascular endothelium were lost, including interactions between CD24 and P-selectin, an interaction involved in leukocyte recruitment. Increased macrophage autocrine interactions were identified in both IDC stroma and epithelium through urokinase-urokinase receptor gene co-expression, an interaction previously associated with a transition to the M2 phenotype. Conclusions: The meta-analysis combined with novel computational methods, improves our ability to characterize the micro-environment of DCIS specimens, typically hard to study. Changes in cellular dynamics involving both immune and non-immune cell types suggest that mechanisms other than direct immune escape accompany progression. Citation Format: Adam Officer, Andre Dempsey, Farnaz Hasteh, Michal Slyper, Asa Segerstolpe, Joanna Klughammer, Judit Jane-Valbuena, Orit Rozenblatt-Rosen, Lyndsay Murrow, Zev Gartner, Aviv Regev, Christina Yau, Pablo Tamayo, Olivier Harismendy. A gene expression meta-analysis identifies microenvironment differences in cellular composition and cell-cell interactions associated with breast cancer invasion [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-06-02.

Contrast-Enhanced Mammographic Features of In Situ and Invasive Ductal Carcinoma Manifesting Microcalcifications Only: Help to Predict Underestimation?

Simple SummaryMammography frequently detects the early breast cancers manifesting microcalcifications only. By means of mammographically guided vacuum-assisted core needle biopsy, noninvasive ductal carcinoma in situ (DCIS) is often diagnosed. Unfortunately, invasive components are occasionally embedded within the noninvasive cancer bed, which will alter the preoperative planning. Whether or not to perform single-step sentinel lymph node sampling is an area of controversy. In order to minimize the overtreatment or undertreatment, we retrospectively reviewed the enhanced features of DCIS and invasive ductal carcinomas (IDCs) on contrast-enhanced spectral mammograms (CESMs). The CESM is a modern technique enabling the provision of conventional mammograms and contrast-enhanced images. The results of our study revealed low DCIS upgrade of the unenhanced DCIS. Otherwise, DCIS tended to appear as nonmass and pure ground glass enhancements, and IDC tended to appear as mass and unpurified solid enhancement. The enhanced features allow distinguishing DCIS and IDC.Background: The contrast-enhanced mammographic features of ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) manifesting microcalcifications only on mammograms were evaluated to determine whether they could predict IDC underestimation. Methods: We reviewed patients who underwent mammography-guided biopsy on suspicious breast microcalcifications only and received contrast-enhanced spectral mammography (CESM) within 2 weeks before the biopsy. Those patients who were proven to have cancers (DCIS or IDC) by biopsy and subsequently had surgical treatment in our hospital were included for analysis. The presence or absence, size, morphology and texture of enhancement on contrast-enhanced spectral mammography were reviewed by consensus of two radiologists. Results: A total of 49 patients were included for analysis. Forty patients (81.6%) showed enhancement, including 18 (45%) DCIS and 22 (55%) IDC patients. All nine unenhanced cancers were pure DCIS. Pure DCIS showed 72.22% nonmass enhancement and 83.33% pure ground glass enhancement. IDC showed more mass (72.2% vs. 27.8%) and solid enhancements (83.33% vs. 16.67%). The cancer and texture of enhancement were significantly different between pure DCIS and IDC, with moderate diagnostic performance for the former (p-value < 0.01, AUC = 0.66, sensitivity = 93%, specificity = 39%) and the latter (p-value < 0.01, AUC = 0.74, sensitivity = 65%, specificity = 83%). Otherwise, pure DCIS showed a significant difference in enhanced texture compared with upgraded IDC and IDC (p = 0.0226 and 0.0018, respectively). Conclusions: Nonmass and pure ground glass enhancements were closely related to pure DCIS, and cases showing mass and unpurified solid enhancements should be suspected as IDC. Unenhanced DCIS with microcalcifications only has a low DCIS upgrade rate. The CESM-enhanced features could feasibly predict IDC underestimation.

Abstract PO-059: The genomic landscape of the in situ to invasive ductal breast carcinoma transition shaped by the immune system

Abstract Background: The transition from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) is an evolutionary bottleneck where progression occurs only in 30% of patients. Whilst the genetic drivers of this transition remain poorly understood, we have previously shown that immune escape is a key event. In this study, we profile the evolutionary trajectory of matched pure DCIS and IDC in the context of the immune microenvironment. Methods: We have evaluated changes in copy number profiles, mutational profiles, expression and neoantigen load in 6 cases of matched pure DCIS and IDC using exome and RNA sequencing. We have integrated this information with topologic assessment of H&amp;E images and cyclic immunofluorescence. Results: We provide evidence for an evolutionary bottleneck during DCIS to IDC in matched patient samples, showing that copy number aberrations are early events, but low overlap in mutational profiles. Variation in immune composition and spatial orientation can arise as early as in DCIS and are subtype specific. Tumor-specific copy number changes including loss of MHC-I presentation machinery or changes at cytokine rich loci specifically in ER− tumors could contribute to a more immunosuppressive environment in IDC. Oncogenic hotspot mutations can present as neoantigens yet are paradoxically conserved during the DCIS-to-IDC transition. We suggest these mutations have a secondary immune-modulatory function or may be present in normal tissue, escaping immune surveillance as early as in DCIS. Conclusions: We show both genomic and microenvironmental differences in matched pure DCIS and recurrent IDC, highlighting that progression is shaped by both tumor and immune system at this evolutionary bottleneck. Citation Format: Anne Trinh, Carlos R. Gil Del Alcazar, Sachet A. Shukla, Koei Chin, Young Hwan Chen, Guillaume Thibault, Jennifer Eng, Bojana Jovanovic, C. Marcelo Aldaz, So Yeon Park, Joon Jong, Catherine Wu, Joe Gray, Kornelia Polyak. The genomic landscape of the in situ to invasive ductal breast carcinoma transition shaped by the immune system [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-059.

Metastatic behavior of mixed invasive ductal lobular carcinoma (mIDC/ILC).

1085 Background: Mixed invasive ductal lobular carcinoma (mIDC/ILC) is a poorly described subtype of invasive breast cancer, characterized by its composition of both ductal and lobular histopathology. It is unclear if individual or both components drive metastasis. Literature is sparse regarding sites of metastatic spread of this elusive subtype of invasive breast cancer. Methods: Cohorts of patients with mIDC/ILC, invasive ductal carcinoma (IDC), and invasive lobular carcinoma (ILC) were identified from the UPMC Network Cancer Registry. Among these, 46 patients with mIDC/ILC, 1,131 patients with IDC, and 145 patients with ILC seen at UPMC Magee Women’s Hospital from 1990 – 2017 were found to have developed distant metastasis during the course of their disease. The metastatic pattern of spread was compared between the cohorts. Formalin-fixed, paraffin-embedded patient samples from the metastatic sites of a portion of the mIDC/ILC cases (n = 19) was acquired and evaluated by H&amp;E staining. Results: Patients with IDC were more likely than patients with ILC to have metastasis to the liver (p = 0.001) and lung (p &lt; 0.001), and less likely to have metastasis to the peritoneum (p &lt; 0.001). Patients with mIDC/ILC were more likely than patients with IDC to have peritoneal metastasis (p = 0.01), similar to patients with ILC. Compared to patients with ILC, patients with mIDC/ILC were more likely to have liver metastasis (p = 0.001), similar to patients with IDC. Evaluation of the metastatic lesions originating from mIDC/ILC displayed a spectrum of histopathology including mixed histology (n = 3), pure IDC (n = 3), pure ILC (n = 5), and indeterminate lesions with features of both IDC and ILC (n = 6). Two cases were uninterpretable due to significant crush artifact. Metastatic mIDC/ILC lesions with retained mIDC/ILC histology were found in vertebral, pleural, and skin tissues. Metastatic mIDC/ILC lesions with IDC histology were found in a cerebellar, liver, and chest wall lesion; whereas, those with ILC histology were found in bowel, omental fat, ovary, bone, and sacrum. Indeterminate histology metastatic lesions were found at liver, chest wall, cerebellar, and bone sites. Conclusions: mIDC/ILC metastasizes to a range of distant sites with a higher preference to the liver and peritoneum as compared to ILC and IDC, respectively. Metastatic lesions arising from mIDC/ILC tumors showed a spectrum of histologies, including mIDC/ILC, IDC, ILC and indeterminate lesions with features of both IDC and ILC. Ongoing genomics studies will provide further insight into development of metastases from mIDC/ILC tumors.

Potential biomarkers of ductal carcinoma in situ progression

BackgroundDuctal carcinoma in situ is a non-obligate precursor of invasive breast carcinoma and presents a potential risk of over or undertreatment. Finding molecular biomarkers of disease progression could allow for more adequate patient treatment. We aimed to identify potential biomarkers that can predict invasiveness risk.MethodsIn this epithelial cell-based study archival formalin-fixed paraffin-embedded blocks from six patients diagnosed with invasive lesions (pure invasive ductal carcinoma), six with in-situ lesions (pure ductal carcinoma in situ), six with synchronous lesions (invasive ductal carcinoma with an in-situ component) and three non-neoplastic breast epithelium tissues were analyzed by gene expression profiling of 770 genes, using the nCounter® PanCancer Pathways panel of NanoString Technologies.ResultsThe results showed that in comparison with non-neoplastic tissue the pure ductal carcinoma in situ was one with the most altered gene expression profile. Comparing pure ductal carcinoma in situ and in-situ component six differentially expressed genes were found, three of them (FGF2, GAS1, and SFRP1), play a role in cell invasiveness. Importantly, these genes were also differentially expressed between invasive and noninvasive groups and were negatively regulated in later stages of carcinogenesis.ConclusionsWe propose these three genes (FGF2, GAS1, and SFRP1) as potential biomarkers of ductal carcinoma in situ progression, suggesting that their downregulation may be involved in the transition of stationary to migrating invasive epithelial cells.

Is there a difference in FDG PET findings of invasive ductal carcinoma of the breast with and without coexisting DCIS?

Objective(s):Studies have reported that invasive ductal carcinoma (IDC) with coexisting ductal carcinoma in situ (DCIS) show lower metastatic potential and recurrence and better overall survival than pure IDC. In this study, we assessed F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) images of patients with newly diagnosed IDC to determine if there is any difference in PET findings in IDC-DCIS and pure IDC cases.Methods:FDG PET/CT images of patients with newly diagnosed IDC of the breast who subsequently underwent breast surgery and had histopathology result in our records were further evaluated. Tumor grade, pathological staging, and presence of DCIS were noted from the histopathology results. Standardized uptake value (SUV) of the primary tumor (SUVmax and SULmax), other hypermetabolic foci in the breast, and ipsilateral normal breast were measured. Presence of axillary and distant metastases was noted. Results:Fifty seven (57) patients with IDC were included. Coexisting DCIS was present in 44 (IDC-DCIS) and not present in 13 (pure IDC) cases. Per histopathology, the primary tumor was unifocal in 33 IDC-DCIS (75%) and 12 pure IDC (92.3%) cases, and multifocal in 11 IDC-DCIS cases (25%), and 1 pure IDC case (7.7%). FDG uptake was multifocal in 20 IDC-DCIS cases (45.5%) and 1 pure IDC case (7.7%), and unifocal in 24 IDC-DCIS (54.5%), and 12 pure IDC (92.3%) cases. There was no significant difference in patient age, size of the primary tumor, SUVmax and SULmax of the primary tumor and SUVmax of the normal breast in IDC-DCIS and pure IDC cases (p>0.05). Pathology showed axillary metastasis in all 13 pure IDC (100%), and 27 IDC-DCIS (61.4%) cases. PET showed axillary uptake in 25 IDC-DCIS (56.8%), and 8 pure IDC (61.5%) cases, and abnormal/questionable distant uptake in 12 IDC-DCIS cases and 1 pure IDC case.Conclusion:In our preliminary findings, multifocal breast FDG uptake and multifocal tumor appear to be more common in IDC-DCIS than pure IDC. There is no significant difference in SUV and size of the primary tumor in IDC-DCIS and pure IDC cases. Axillary metastases appear to be more common in pure IDC than IDC-DCIS cases.

Overall survival is improved when DCIS accompanies invasive breast cancer

Invasive ductal carcinoma (IDC) often presents alone or with a co-existing ductal carcinoma in situ component (IDC + DCIS). Studies have suggested that pure IDC may exhibit different biological behavior than IDC + DCIS, but whether this translates to a difference in outcomes is unclear. Here, utilizing the National Cancer Database we identified 494,801 stage I-III breast cancer patients diagnosed with either IDC alone or IDC + DCIS. We found that IDC + DCIS was associated with significantly better overall survival (OS) compared to IDC alone (5-year OS, 89.3% vs. 85.5%, p < 0.001), and this finding persisted on multivariable Cox modeling adjusting for demographic, clinical, and treatment-related variables. The significantly superior OS observed for IDC + DCIS was limited to patients with invasive tumor size < 4 cm or with node negative disease. A greater improvement in OS was observed for tumors containing ≥25% DCIS component. We also found IDC + DCIS to be associated with lower T/N stage, low/intermediate grade, ER/PR positivity, and receipt of mastectomy. Thus, the presence of a DCIS component in patients with IDC is associated with favorable clinical characteristics and independently predicts improved OS. IDC + DCIS could be a useful prognostic factor for patients with breast cancer, particularly if treatment de-escalation is being considered for small or node negative tumors.

Invasive ductal carcinoma with coexisting ductal carcinoma in situ (IDC/DCIS) versus pure invasive ductal carcinoma (IDC): a comparison of clinicopathological characteristics, molecular subtypes, and clinical outcomes.

Ductal carcinoma in situ (DCIS) is widely recognized as the precursor of invasive ductal carcinoma (IDC). We aimed to analyze the clinicopathological characteristics and clinical outcomes of coexisting DCIS component in IDC and its clinical significance according to molecular subtypes. Data from 3001 patients with IDC (79.4%) and IDC/DCIS (20.6%) who underwent surgery from January 2009 to June 2016 were retrospectively assessed. The clinical outcomes of IDC with coexistent DCIS in different molecular subtypes were evaluated. IDC/DCIS patients were more likely to be younger (P < 0.001), had low tumor grade (P = 0.001), had less lymph node involvement (P = 0.038) and received more mastectomy (P = 0.002) than IDC patients. In the comparison of molecular subtype prevalence, IDC/DCIS patients were more frequently presented with luminal B/HER2 positive (12.5% vs 11.0%, P < 0.001) and HER2 positive subtypes (20.9% vs 9.8%, P < 0.001). The 5-year disease-free survival (DFS, 90.9% vs 87.5%, P = 0.021) and 5-year overall survival (OS 96.1% vs 94.0%, P = 0.018) were significantly improved in IDC/DCIS patients compared to IDC patients. In multivariate analysis, the presence of coexisting DCIS (P = 0.048), tumor size (P < 0.001), lymph node status (P < 0.001), lymphovascular invasion (P = 0.007) and molecular subtypes (P < 0.001) were independent prognostic factors for DFS. Furthermore, coexistence of DCIS component in IDC significantly improved DFS in HER2 positive (94.8% vs 78.5%, P = 0.003), but had no association in luminal and triple negative subtypes. IDC with coexisting DCIS was associated with improved prognosis. Patients with IDC/DCIS presented with more HER2 positive expression and might improve DFS in HER2 positive breast cancer.

Outcomes of Breast Cancer (Invasive Lobular and Ductal Carcinoma) Treated with Boost Intraoperative Electron Radiotherapy Versus Conventional External Beam Radiotherapy

Background: Breast conserving surgery (BCS) and its following radiotherapy is an accepted therapeutic method for patients with invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC). Objectives: The aim of this study was to investigate the effect of intraoperative electron radiotherapy on women with breast cancer (invasive lobular and ductal carcinoma). Methods: Between August 2013 and September 2017, 968 patients, who were referred to Cancer Research Center, Shahid Beheshti University of Medical Sciences with invasive breast cancer, were treated with breast-conserving surgery and radiotherapy. Of those, 426 patients received a tumor bed boost with intraoperative electron radiotherapy (IOERT) during lumpectomy (58 patients with pure invasive lobular carcinoma, 239 patients with pure invasive ductal carcinoma, and 129 patients with other diagnoses). 542 patients received a tumor bed boost with conventional external beam radiotherapy post lumpectomy (24 patients with pure invasive lobular carcinoma, 418 patients with pure invasive ductal carcinoma, and 100 patients with other diagnoses). The patients were followed up to 49 months. A comprehensive list of clinical and pathologic features was evaluated for all patients. We retrospectively analyzed outcomes of breast cancer treated with boost intraoperative electron radiotherapy (pure ILC and IDC groups) and in other group treated with boost conventional external beam radiotherapy (pure ILC group). Results: None of the ILC patients had recurrence in the two groups. The four-year survival rate for ILC patients was 100%, but in the IDC group the survival rate was 97%. Survival analyses showed patients with IDC had a higher risk of ipsilateral breast tumor recurrence (IBTR) and metastasis. Conclusions: Overall, the rates of IBTR and metastasis in the ILC boost IOERT group were significantly low. This finding suggests that IOERT technique deployment in ILC had no inferiority compared with the control group.

Abstract P4-13-01: Oncoplastic breast conservations – The Scottish Audit: Surgical techniques, oncological outcomes, complication rates and variations in practice across the country based on the analysis of 589 patients

Abstract Introduction: current evidence for oncoplastic breast conservation (OBC) is based on single institutional series. We studied the outcomes of OBC practice in Scotland and compare individual breast units. Methods: a predefined database of patients treated with OBC was completed retrospectively in 11 breast units in Scotland. Patients were treated with OBC from 2005 onwards were included. For statistical calculations Chi-test, ANOVA and Pearson correlation analysis were used. Results: Altogether 589 patients were included. Median age was 56 years [21-86]. Patients were diagnosed between September 2005 and March 2017. Number of patients treated with OBC per unit ranged between 4 and 145. High volume units were doing a mean of 19.3 OBCs per year [17.3 – 26.5] vs. low volume units doing 11.1 OBCs per year [7 .7– 14.4] (p=0.012). 23 different oncoplastic surgical techniques were applied. Range of oncoplastic techniques used was associated with case-loads: high volume units used a wider range (8 – 14 different techniques) compared to low volume units (3 – 6) (p=0.004). Volume displacement was done in 515 patients (91.3%), volume replacement in 49 patients (8.7%). OBC was carried out as a joint operation between a breast and a plastic surgeon in 66.3% (389 patients). Immediate contralateral symmetrisation rate was significantly higher when the procedure was carried out as a joint operation (70.7% vs. not joint operations: 29.8%; p&amp;lt;0.001). Incomplete excision rate was 10.4% (60 of 578). Incomplete excision was significantly higher after invasive lobular carcinoma (18.9%; 10 of 43; p=0.0292). After neoadjuvant chemotherapy incomplete excision rate was significantly lower (3%; 2 of 66 vs. no neoadjuvant chemotherapy: 11%; 35 of 319; p=0.031). Neodjuvant systemic treatment rate was 28.6% (142 of 496 patients). Of those 68 patients received neoadjuvant chemotherapy (13.7%) and 74 patients had neoadjuvant hormonal treatment (14.9%). Neoadjuvant systemic treatment rate varied amongst the units from 9.7% to 57.2% for patients with invasive carcinoma. 259 patients diagnosed with (non)invasive carcinoma had a median follow-up time of 5 years [35-124]. Of these 7 patients (2.7%) developed isolated local recurrence. 5-year local recurrence rate after DCIS was higher than after pure invasive ductal carcinoma (DCIS: 8.3%; 3 of 36 vs. ductal: 1.6%; 3 of 181; p=0.02567). 5-year disease-free survival of these patients was 91.7%, overall survival was 93.8%, and cancer-specific survival was 96.1%. 145 of 510 patients developed complications, which is 28.4% overall complication rate. 71 patients had major complications (13.9%) and 74 patients had minor complications (14.5%). Overall complication rate was significantly lower after neoadjuvant chemotherapy (15.9%; 11 of 69) compared to patients who did not receive neoadjuvant chemotherapy (27.9%; 127 of 455 patients) (p=0.035). Conclusion: this national audit demonstrated similar outcomes overall compared to relevant published data. Units should be urged to build stronger collaboration in order to reduce variability in OBC practices. None of the authors have conflict of interest to declare. Citation Format: Romics L, Macaskill J, Fernandez T, Morrow E, Simpson L, Pitsinis V, Barber M, Tovey S, Masannat Y, Young O, Mansell J, Stallard S, Doughty J, Dixon M. Oncoplastic breast conservations – The Scottish Audit: Surgical techniques, oncological outcomes, complication rates and variations in practice across the country based on the analysis of 589 patients [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 P4-13-01.

MiR-106b-5p, miR-17-5p to predict recurrence and progression in breast DCIS model based on TGFβ paradox.

e23019 Background: Ductal carcinoma in situ (DCIS) is a well-known precursor of invasive ductal carcinoma (IDC). Part of patients show disease recurrence as DCIS or IDC after local treatment, but there are no established markers for prediction of recurrence. Methods: Authors analyzed 30 patients diagnosed as pure DCIS, recurrent DCIS, and IDC progressed in DCIS background. miRNA was extracted from archival tissue, and hierarchical clustering of miRNA microarray was performed. We selected highly expressed miR-17-5p and miR-106b-5p as marker for recurrence of DCIS. Two miRNAs were transfected to MCF-12 and MCF-7 cell line. Cell proliferation assay and Western blot analysis was performed for analyzing the interaction between cell proliferation and TGFβ downstream pathway. Results: miR-106b-5p single and combined miR-106b-5p and miR-17-5p transfected MCF-12 cell line showed increased proliferation index compared to un-transfected cell line. In MCF-7, miR-106b and miR-17-5p transfected cell line showed inferior proliferation index compared to un-transfected cell line. Western blot analysis showed minimal increased expression of SMAD4, phosphorylated SMAD2 (pSMAD2) in miR-106b-5p and miR-17-5p transfected MCF-12 cell line. However, decreased expression of TGFBR2 and no interval change of SMAD4 and pSMAD2 was detected in miR-106b-5p and miR-17-5p transfected MCF-7 cell line. Conclusions: miR-106-5p, miR-17-5p showed increased expression in recurrent DCIS or IDC based on miRNA hierarchical microarray. miRNA transfected MCF-12 cell line showed increased proliferation index and activated TGFβ downstream pathway. miRNA transfection might have made normal cell line to pre-cancerous cell line and TGFβ pathway might have influenced to promote tumor proliferation, based on TGFβ paradox hypothesis.

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.

Abstract P3-17-10: The impact of the presence of ductal carcinoma in situ in patients with invasive ductal carcinoma

Abstract Background: Ductal carcinoma in situ (DCIS) is considered to be a precancerous lesion that shares many genetic similarities with invasive ductal carcinoma (IDC). However, it remains unclear how DCIS might develop into IDC and whether the coexistence of DCIS has any clinical significance.There is limited data on whether coexisting DCIS in patients with IDC (IDC-DCIS) has any impact on patients' clinical presentation, tumor characteristics, prognosis and treatment selection. We aim to investigate differences in patients with pure IDC versus patients with IDC-DCIS. Methods: We reviewed clinicopathologic data from the Breast Molecular Epidemiological Resource (BMER) database, which is a prospectively maintained breast cancer database from the University of Iowa. Missing information was supplemented by Iowa Cancer Registry database. Patients with a diagnosis of pure IDC and IDC-DCIS from 2009 to 2014 who underwent surgical resection of their breast cancer were included. We excluded patients with stage IV disease at diagnosis and those who underwent neoadjuvant therapy. Patients who had more than one tumor were only analyzed once using parameters of the largest tumor. Patient and tumor characteristics and treatment selection were compared between the IDC and IDC-DCIS groups. Student's t test was used for continuous variables and chi squared test for categorical variables. Results: We observed that women with IDC-DCIS (n=226) had higher incidence of Her-2 positive cancers than those with pure IDC (n=95) (p=0.04). The IDC-DCIS group was more likely to be ER + and PR +, though these differences were not statistically significant. Another distinguishing characteristic between the two groups was that the IDC group contained more current smokers than the IDC-DCIS group (18.9% vs 10.6%, p&amp;lt;0.01). Patients with IDC-DCIS were more likely, than patients with pure IDC, to be under-staged based on clinical information. Clinical stage distribution in IDC-DCIS group was: 4% stage 0, 61.9% stage I, 28.3% stage II and 5.8% stage III. In contrast, the percentages of pathologic stage I, II and III were 54.5%, 35.4% and 10.2%, respectively (p=0.002). Similar analysis for patients with pure IDC showed no significant overall change from clinical to pathologic stage. Patients with IDC-DCIS tended to have higher total mastectomy rates than patients with IDC (37.2% vs 31.6%, p=0.34). Management of patients in either group were not significantly different in terms of radiation, chemotherapy, or hormonal therapy. There were 4 deaths (4.2%) in the IDC group and 12 deaths (5.3%) in the IDC-DCIS group (p=0.68). Conclusions: Our study showed that active smoking may be a risk factor for the development of IDC without pre-existing DCIS. Patients with IDC-DCIS had higher rates of Her-2 positivity and significant differences between clinical and pathologic stages. Management and survival of both groups were similar. Citation Format: Xu L, Monga V, Thomas A, Leone JP. The impact of the presence of ductal carcinoma in situ in patients with invasive ductal carcinoma [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 P3-17-10.

Abstract P6-09-18: Predictive factors of pathologic complete response to neoadjuvant chemotherapy in patients with Luminal HER2(-) local advanced breast cancer using the DMET microarray

Abstract Introduction Patients with similar local advanced breast cancer (LABC) could respond different to neoadjuvant chemotherapy (NC). Luminal HER2(-) tumors have pathologic complete response (pCR) by 5-7%. Ki67, tumor grade and hormonal receptors, could be helpful but not enough to choice between NC vs. initial surgery. Response to drugs depends on enzymes involved in absorption, distribution, metabolism and elimination (ADME); the drug-metabolizing enzyme and transporter platform (DMET), could identify 1936 single nucleotide polymorphism (SNP) from 225 genes involved in ADME proccess. Objective To identify predictive factors to pCR in patients with Luminal HER2(-) LABC underwent NC, to distinguish wish patients could have a real benefit from NC. Material and Methods This is a prospective nested case control study (1:4) with LABC patients, pure invasive ductal carcinoma Luminal HER2(-) subtypes, and sequential NC (anthracyclines and taxanes). Cases were defined as patients with pCR (Residual Cancer Burden=0), and controls those without pCR. SNPs were evaluated from DNA of leucocytes using DMET microarrays by Affymetrix. Bivariate analyses were used as appropriate. Microarrays were processed by the DMET analyzer console. OR and 95%CI were used to test association between pCR and variables with a non-conditional logistic regression analysis; p value ≤0.05 was considered statistically significant (two-sided). Results From 2005 to 2014, of 3762 treated patients, 287 women met inclusion criteria. We included 117 patients, 21 cases and 96 controls. Patients with pCR were 5 years younger than controls (45.4 vs 49.4), have more grade-3 tumors, (66.7 vs 22.3%), more Luminal B subtypes (90.5 vs 64.6%), lower expression of estrogen receptor (60 vs 80%) and higher Ki67 expression (65 vs 12%), all with p≤0.05. No differences in toxicity existed between groups. In an initial screening procedure, 13 SNPs were identified, but only 4 SNPs (4 genes) are known to participate in ADME of antineoplastic agents. All pCR cases did not have the C/C allelic variant in the rs2072671 SNP (CDA gene); while in rs1883322 SNP (PPARD gene) all had T/T variant SNPs identified in DMET microarray known to participate with antineoplastic agentsGENESNPAllelic variantpCR, n=21No pCR, n=96pDPYDrs17376848T/T13 (61.9%)83 (86.4%)0.007 C/T8 (38.1%)11 (11.4%) CDArs2072671A/A6 (28.5%)51 (53.1%)0.013 A/C15 (71.4%)36 (37.5%) C/C09 (9.3%) PPARDrs1883322T/T21 (100%)69 (71.8%)0.022 C/T022 (22.9%) C/C05 (5.2%) GSTM3rs7483A/A7 (33.3%)20 (20.8%)0.024 A/G13 (61.9%)43 (44.7%) G/G1 (4.7%)33 (34.3%) pCR= pathologic complete response After logistic regression analysis, pCR predictive factors were the presence of grade-3 tumors OR=6.66 (95%CI=1.67-26.56), Ki67 ≥14% OR=15.45 (95%CI=1.71–138.86), premenopausal status OR=6.540 (95%CI=1.50–28.38) and A/A or A/G allele in rs7483 SNP (GSTM3 gene) OR=19.16 (95%CI=1.97–185.93). Conclusions Genetic variability encoded in the DMET-chip, could be helpful as a predictive factor of pCR in patients with Luminal HER2(-) LABC, but only in combination with other factors such as grade-3 tumors, elevated Ki67, and premenopausal status. Citation Format: Ruvalcaba-Limon E, Rodriguez-Cuevas S, Hidalgo-Miranda A, Villa-Romero A, Bautista-Piña V, Rebollar-Vega R, Fernandez-Lopez JC, Morales-Vasquez F. Predictive factors of pathologic complete response to neoadjuvant chemotherapy in patients with Luminal HER2(-) local advanced breast cancer using the DMET microarray [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 P6-09-18.

149PD - Prognostic impact of proliferation for resected early stage breast cancer according to histology: Cut-off analysis of Ki67 in 859 patients with pure invasive lobular and ductal breast carcinoma (ILC/IDC)

While the prognostic impact of Ki67 has been extensively investigated in IDC, despite the absence of standardized cut-off, its role in ILC has not been fully validated. Thus, the aim of this analysis was to investigate the prognostic potential of Ki67 in a multi-center series of patients (pts) affected by early stage pure ILC comparing with IDC. Clinicalpathological data of consecutive pts affected by pure ILC and IDC, referring to 2 institutions, were correlated with overall survival and disease-free survival (OS/DFS) using a Cox model. The maximally selected Log-Rank statistics (MSLRS) analysis was applied to the Ki67 continuous variable to estimate the appropriate cut-off according to histology. Data from 457 ILC and 402 IDC pts were gathered (median age 61/59 years [yrs]). At a median follow-up of 75 months, 10-yrs OS and DFS for ILC and IDC were 81.7%/83.4%, and 71.4%/76.2%, respectively. The MSLRS analysis identified 4% and 18% as optimal Ki67 cut-offs for OS for ILC and IDC, respectively. At the multivariate analysis Ki67, Performance Status (PS), nodal status (N), and TNM-tumor-size (T-size) were independent predictors for OS in ILC pts. Ki67 highly replicated at the internal cross-validation analysis. For IDC pts, PS, age, estrogen receptor expression and T-size were independent predictors for OS. With regard to DFS, the MSLRS analysis identified 4% and 14% as optimal KI67 cut-offs for ILC and IDC, respectively. PS and N were independent predictors for ILC, while PS, age, grading and T-size were predictors for IDC. Log-rank analysis is shown in the table:Tabled 1HistotypeKi675-yrs OS (%)10-yrs OS (%)Log-RankILC≤ 4%96.989.9p = 0.008> 4%90.177.2IDC≤ 18%97.495.8p = 0.002> 18%93.662.65-yrs DFS (%)10-yrs DFS (%)ILC≤ 4%88.279.4p = 0.03> 4%81.169.2IDC≤ 14%96.087.0p = 0.002> 14%89.261.8 Open table in a new tab Despite the retrospective and exploratory nature of the study, the prognostic relevance of Ki67 (as well as its optimal cut-off) seems to significantly differ according to histology. In particular, a very low cut-off of Ki67 (4%) may significantly discriminate the prognosis of pts with ILC.

Comparison of clinical and pathological characteristics between screen-detected and self-detected breast cancers: a Hong Kong study

Breast cancer is the leading cause of death of Hong Kong women with increasing incidence. This study aimed to determine any prognostic differences between screen-detected and self-detected cases of breast cancer in a cohort of Hong Kong patients. This was a case series with internal comparison carried out in a private hospital in Hong Kong. Approximately 3000 cases of Chinese patients diagnosed with ductal carcinoma in situ or invasive breast cancer were reviewed. The screen-detected group showed better pathological characteristics than the self-detected group. Number of lymph nodes involved, invasive tumour size, and tumour grade were more favourable in the screen-detected group. There was also a lower proportion of patients with pure invasive ductal carcinoma and mastectomy in the screen-detected group. This study provides indirect evidence that women in the local population may gain clinical benefit from regular breast cancer screening. The findings need to be validated in a representative population of Hong Kong women.

Breast cancer risk factor associations differ for pure versus invasive carcinoma with an in situ component in case-control and case-case analyses.

Invasive ductal carcinoma (IDC) is diagnosed with or without a ductal carcinoma in situ (DCIS) component. Previous analyses have found significant differences in tumor characteristics between pure IDC lacking DCIS and mixed IDC with DCIS. We will test our hypothesis that pure IDC represents a form of breast cancer with etiology and risk factors distinct from mixed IDC/DCIS. We compared reproductive risk factors for breast cancer risk, as well as family and smoking history between 831 women with mixed IDC/DCIS (n = 650) or pure IDC (n = 181), and 1,620 controls, in the context of the Women's Circle of Health Study (WCHS), a case-control study of breast cancer in African-American and European-American women. Data on reproductive and lifestyle factors were collected during interviews, and tumor characteristics were abstracted from pathology reports. Case-control and case-case analyses were conducted using unconditional logistic regression. Most risk factors were similarly associated with pure IDC and mixed IDC/DCIS. However, among postmenopausal women, risk of pure IDC was lower in women with body mass index (BMI) 25 to <30 [odds ratio (OR) 0.66; 95 % confidence interval (CI) 0.35-1.23] and BMI ≥ 30 (OR 0.33; 95 % CI 0.18-0.67) compared to women with BMI < 25, with no associations with mixed IDC/DCIS. In case-case analyses, women who breastfed up to 12 months (OR 0.55; 95 % CI 0.32-0.94) or longer (OR 0.47; 95 % CI 0.26-0.87) showed decreased odds of pure IDC than mixed IDC/DCIS compared to those who did not breastfeed. Associations with some breast cancer risk factors differed between mixed IDC/DCIS and pure IDC, potentially suggesting differential developmental pathways. These findings, if confirmed in a larger study, will provide a better understanding of the developmental patterns of breast cancer and the influence of modifiable risk factors, which in turn could lead to better preventive measures for pure IDC, which have worse disease prognosis compared to mixed IDC/DCIS.