Cases Of Ductal Carcinoma Research Articles

The study of mutations of CDK4 and TP53 genes in selected breast lesions

Lesions are abnormal changes in tissue. The theories behind tumorigenesis can be genetic epigenetic, immune surveillance and monoclonal hypothesis, which led to genetic changes. The genetic change can be the inactivation of tumor suppressor genes or the activation of oncogenes in the cell cycle. This study investigated the presence of gene mutation in CDK4 and TP53 genes in breast lesions. Ten (10) formalin fixed paraffin embedded tissue block, which includes 5 cases of fibroadenoma and 5 cases of invasive ductal carcinoma from the pathological archives were used. The nuclei amplification technique was carried out on the formalin fixed paraffin embedded tissue blocks. DNA extraction involves lysing the cells and solubilizing DNA, which is followed by chemical or enzymatic methods to remove macromolecules, lipids, RNA or proteins. Thereafter, the DNA is amplified using reagents and heated (denaturing) and cooling (annealing) steps. PCR requires free nucleotide (dNTPs), template DNA to amplify and unique single-stranded DNA primers that bind upstream (5') and downstream (3') of the DNA region of the tissue blocks. The integrity of the DNA is assessed by loading approximately 100 ng per sample on a 1.5% agarose gel and the sizes of PCR products were estimated by comparison with the mobility of a 100bp molecular weight ladder that was run alongside the samples in the gel. However, the amplified fragment was purified to remove PCR reagents and thereafter it was sequenced. The sequence of single nucleotide polymorphism of each gene was analyzed, and the results were reported. In mutation was more in both genes compared to the sequence of FA and IDC. From this study, both genes showed segments of mutation which were either SNPs or functional mutation. It showed that both genes were modified from a proto-oncogene to an oncogene and the protein it produces is an oncoprotein and as such it favours the alteration of both genes led to cell proliferation. The data generated from this research has highlighted the importance of carrying out further studies in assessing both genes to understand their involvement in the etiology of carcinogenesis which will help in clinical information about breast cancer. In line with the findings, there is an urgent need to understand carcinogenesis which may serve in early diagnosis and understanding of breast conditions and further help prevent or delay the onset of chronic complications and reduce morbidity and mortality rates to improve and assure the health of individuals.

Abstract P2-14-20: Comparison of robot-assisted nipple sparing mastectomy with conventional nipple sparing mastectomy: a single-center experience

Abstract Purpose: Robot-assisted nipple-sparing mastectomy (RANSM) improves cosmetic outcomes compared to conventional nipple-sparing mastectomy (CNSM) since RANSM is performed with minimal incisions. However, there are few studies on the feasibility and surgical outcome of RANSM. The aim of this study was to compare the surgical outcomes of RANSM and CNSM in breast cancer patients. Method: A retrospective observational study was conducted at our institution between January 2021 and December 2021. A total of 54 patients diagnosed with breast malignancy that underwent either a robotic-assisted or conventional nipple-sparing mastectomy were included. The demographics of the patient’s sex, age, body mass index (BMI), breast weight, and preoperative diagnosis were investigated. The surgical method, operation time (including docking time and console time in the case of robotic surgery), postoperative complications, length of hospital stay, pain score, and adjuvant therapy were analyzed. Result: A total of 57 breasts in 54 female patients were included in the study: 36 invasive ductal carcinoma patients, 11 ductal carcinoma cases, 6 invasive lobular carcinoma, 2 mucinous carcinoma, one solid papillary carcinoma and one lobular carcinoma in situ. A median age of 49(27-66), mean BMI of 22 (18.89-26.28), and mean breast weight was 246 g (120-305g). The mean operation time was 122 minutes (robotic 140 vs. conventional 118), and the average docking time was five minutes and console time 60 minutes in the robot-assisted surgery. There was only one postoperative complication in the robot group and ten cases in the conventional group. The mean hospital stay was 12.6 days (RANSM 10.75 vs. CNSM 12.92), and the average pain score was 3.53 (RANSM 3.50 vs. CNSM 3.54). None needed adjuvant therapy in the robot group. In the conventional surgical group, four patients underwent adjuvant radiotherapy and sixteen patients underwent chemotherapy including six neoadjuvant cases. Conclusion: Our results showed that RANSM had advantages of shorter hospitalization and lower pain scores although it had slightly longer operation time and could not applicable in relatively large breasts. In the near future, RANSM may be considered as the surgery of choice over CNSM in breast cancer patients. Citation Format: Ji Young You, Haemin Lee, Eun-Shin Lee, Seung Pil Jung. Comparison of robot-assisted nipple sparing mastectomy with conventional nipple sparing mastectomy: a single-center experience. [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 P2-14-20.

Expression analysis of novel long non-coding RNAs for invasive ductal and invasive lobular breast carcinoma cases

AimLong non-coding RNAs (LncRNAs) serve as important regulatory molecules of gene expression and protein functionality at multiple biological levels, and their deregulation plays a key role in tumorigenesis including in breast cancer metastasis. Therefore, in this study, we aim to compare the expression of novel lncRNAs in the landscape of invasive ductal carcinoma (IDC) and invasive lobular (ILC) carcinoma of breast. Main MethodsWe have designed an in-silico approach to find the lncRNAs that regulate the breast cancer. Then, we used the clinical samples to carry out the verification of our in silico finding. In the present study, the tissues of breast cancer were deparaffinized. RNA was extracted by the TRIzole method. After synthesizing cDNA from the extracted RNA, expression levels of lncRNAs were analyzed by qPCR using primers specifically designed and validated for the targeted lncRNAs. In this study, breast biopsy materials from 41 female patients with IDC and 10 female patients with ILC were examined histopathological and expression changes of candidate lncRNAs were investigated in line with the findings. The results were analyzed using IBM SPSS Statistics 25 version. ResultsThe mean age of the cases was 53.78 ± 14.96. The minimum age was 29, while the maximum age was 87. While 27 of the cases were pre-menopausal, 24 cases were post-menopausal. The number of hormone receptor-positive cases was found to be 40, 35, and 27 for ER, PR, and cerb2/neu, respectively. While the expressions of LINC00501, LINC00578, LINC01209, LINC02015, LINC02584, ABCC5-AS1, PEX5L-AS2, SHANK2-AS3 and SOX2-OT showed significant differences (p < 0.05), the expressions of LINC01206, LINC01994, SHANK2-AS1, and TPRG1-AS2 showed no significant differences (p > 0.05). In addition, it was determined that the regulation of all lncRNAs could be able to involve in the development of cancer such as the NOTCH1, NFKB, and estrogen receptor signalings. ConclusionAs a result, it was thought that the discovery of novel lncRNAs might be an important player in the diagnosis, prognosis and therapeutic development of breast cancer.

New Staging System and Prognostic Model for Malignant Phyllodes Tumor Patients without Distant Metastasis: A Development and Validation Study

To build a new staging system and new prognostic models for MPTB. We performed a comprehensive analysis of the data from the SEER database. We discussed the characteristics of MPTB by comparing 1085 MPTB cases with 382,718 invasive ductal carcinoma cases. We established a new stage- and age-stratification system for MPTB patients. Furthermore, we built two prognostic models for MPTB patients. The validity of these models was confirmed through multifaceted and multidata verification. Our study provided a staging system and prognostic models for MPTB patients, which can not only help to predict patient outcomes, but also enhance the understanding of the prognostic factors associated with MPTB.

Expression of RBMS3 in Breast Cancer Progression.

The aim of the study was to evaluate the localization and intensity of RNA-binding motif single-stranded-interacting protein 3 (RBMS3) expression in clinical material using immunohistochemical (IHC) reactions in cases of ductal breast cancer (in vivo), and to determine the level of RBMS3 expression at both the protein and mRNA levels in breast cancer cell lines (in vitro). Moreover, the data obtained in the in vivo and in vitro studies were correlated with the clinicopathological profiles of the patients. Material for the IHC studies comprised 490 invasive ductal carcinoma (IDC) cases and 26 mastopathy tissues. Western blot and RT-qPCR were performed on four breast cancer cell lines (MCF-7, BT-474, SK-BR-3 and MDA-MB-231) and the HME1-hTERT (Me16C) normal immortalized breast epithelial cell line (control). The Kaplan-Meier plotter tool was employed to analyze the predictive value of overall survival of RBMS3 expression at the mRNA level. Cytoplasmatic RBMS3 IHC expression was observed in breast cancer cells and stromal cells. The statistical analysis revealed a significantly decreased RBMS3 expression in the cancer specimens when compared with the mastopathy tissues (p < 0.001). An increased expression of RBMS3 was corelated with HER2(+) cancer specimens (p < 0.05) and ER(-) cancer specimens (p < 0.05). In addition, a statistically significant higher expression of RBMS3 was observed in cancer stromal cells in comparison to the control and cancer cells (p < 0.0001). The statistical analysis demonstrated a significantly higher expression of RBMS3 mRNA in the SK-BR-3 cell line compared with all other cell lines (p < 0.05). A positive correlation was revealed between the expression of RBMS3, at both the mRNA and protein levels, and longer overall survival. The differences in the expression of RBMS3 in cancer cells (both in vivo and in vitro) and the stroma of breast cancer with regard to the molecular status of the tumor may indicate that RBMS3 could be a potential novel target for the development of personalized methods of treatment. RBMS3 can be an indicator of longer overall survival for potential use in breast cancer diagnostic process.

The Role of Artificial Intelligence in Accurate Interpretation of HER2 Immunohistochemical Scores 0 and 1+ in Breast Cancer

The new human epidermal growth factor receptor (HER)2-targeting antibody-drug conjugate offers the opportunity to treat patients with HER2-low breast cancer. Distinguishing HER2 immunohistochemical (IHC) scores of 0 and 1+ is not only critical but also challenging owing to HER2 heterogeneity and variability of observers. In this study, we aimed to increase the interpretation accuracy and consistency of HER2 IHC 0 and 1+ evaluation through assistance from an artificial intelligence (AI) algorithm. In addition, we examined the value of our AI algorithm in evaluating HER2 IHC scores in tumors with heterogeneity. AI-assisted interpretation consisted of AI algorithms and an augmenting reality module with a microscope. Fifteen pathologists (5 junior, 5 midlevel, and 5 senior) participated in this multi-institutional 2-round ring study that included 246 infiltrating duct carcinoma cases that were not otherwise specified. In round 1, pathologists analyzed 246 HER2 IHC slides by microscope without AI assistance. After a 2-week washout period, the pathologists read the same slides with AI algorithm assistance and rendered the definitive results by adjusting to the AI algorithm. The accuracy of interpretation accuracy with AI assistance (0.93 vs 0.80), thereby the evaluation precision of HER2 0 and the recall of HER2 1+. In addition, the AI algorithm improved the total consistency (intraclass correlation coefficient = 0.542-0.812), especially in HER2 1+ cases. In cases with heterogeneity, accuracy improved significantly (0.68 to 0.89) and to a similar level as in cases without heterogeneity (accuracy, 0.97). Both accuracy and consistency improved more for junior pathologists than those for the midlevel and senior pathologists. To the best of our knowledge, this is the first study to show that the accuracy and consistency of HER2 IHC 0 and 1+ evaluation and the accuracy of HER2 IHC evaluation in breast cancers with heterogeneity can be significantly improved using AI-assisted interpretation.

Clustered Microcysts Detected on Breast US in Asymptomatic Women.

To investigate the incidence, outcomes, and imaging characteristics of clustered microcysts detected on breast US in asymptomatic women, and suggest appropriate management guidelines. We identified and reviewed the lesions recorded as "clustered microcysts" on breast US performed in asymptomatic women between August 2014 and December 2019. The final diagnosis was based on pathology and imaging follow-up results for at least 12 months. The incidence was 1.5% and 100 patients with 117 lesions were included. Among 117 lesions, 3 (2.6%), 2 (1.7%), and 112 (95.7%) were malignant, high-risk benign, and benign lesions, respectively. The malignant lesions included two cases of ductal carcinoma in situ and one invasive ductal carcinoma. Two of them were assessed as category 4, showing mammographic suspicious microcalcifications and internal vascularity on Doppler US. The remainder was a false negative case and showed echo pattern change on the 12-month follow-up US. The incidence of clustered microcysts on breast US in asymptomatic women was 1.5% and malignancy rate was 2.6% (3 of 117). Knowledge of outcomes and imaging features of benign and malignant clustered microcysts may be helpful for radiologists, thereby aiding categorization and management recommendations.

A case of invasive ductal carcinoma with multiple osteoclast-like giant cells in fine needle aspiration cytology specimen

背景：破骨細胞様巨細胞（osteoclast-like giant cell：OGC）の出現を伴う乳癌は 0.5～1.2%とまれである．われわれは，細胞診検体に多数の OGC が出現した浸潤性乳管癌の 1 例を経験したので報告する．

Accessory Breast Cancer: A Case Series

Accessory breast tissue (ABT) is ectopic breast tissue that occurs due to the failure of the embryonic mammary ridge to resolve during fetal breast development. This can occur anywhere along the milk line, with the axilla being the most common area of occurrence. Due to its pathophysiologic similarity with normal breast tissue, it is also susceptible to developing malignancies [1]. Primary accessory breast cancer accounts for 0.3-0.6% of all breast cancers [1]. The axillary area is the most commonly reported area of accessory breast carcinoma, accounting for 58% of reported ectopic cases [2]. Other reported areas include the parasternal line (18.5%), the subclavicular area (8.6%), the submammary region (8.6%), and the vulvar region (4%) [2]. Given the rarity of primary accessory axillary breast carcinoma, presentation and diagnosis can be challenging. Clinicians ought to be aware of this variance to ensure prompt management. Imaging plays an essential role in diagnosis. Treatment involves a multidisciplinary approach, including surgery, systemic therapy and radiation therapy as dictated by tumor biology and the stage of the disease. Here we report two cases of invasive ductal carcinomas arising in axillary accessory breast tissue.

Prognosis and effectiveness of chemotherapy for medullary breast carcinoma.

We aimed to determine the prognosis and potential benefit of postoperative chemotherapy according to subtype of medullary breast carcinoma (MedBC), a very rare invasive breast cancer. A cohort of 1518 female patients with unilateral MedBC and 284,544 invasive ductal carcinoma (IDC) cases were enrolled from the Japanese Breast Cancer Registry. Prognosis of MedBC was compared to IDC among patients with estrogen receptor (ER)-negative and HER2-negative subtype (553 exact-matched patients) and ER-positive and HER2-negative subtype (163 MedBC and 489 IDC patients via Cox regression). Disease free-survival (DFS) and overall survival (OS) were compared between propensity score-matched adjuvant chemotherapy users and non-users with ER-negative and HER2-negative MedBC. Among ER-negative and HER2-negative subtype patients, DFS (hazard ratio (HR) 0.45; 95% confidence interval (95% CI), 0.30-0.68; log-rank P < 0.001) and OS (HR 0.51; 95% CI 0.32-0.83; log-rank P = 0.004) were significantly better in MedBC than IDC. Patients treated with postoperative chemotherapy showed better DFS (HR 0.27; 95% CI 0.09-0.80; log-rank P = 0.02) and OS (HR 0.27; 95% CI 0.09-0.80; log-rank P = 0.02) compared to those without. For the ER-positive and HER2-negative subtype, the point estimate for HR for DFS was 0.60 (95% CI 0.24-1.22) while that for OS was 0.98 (95% CI 0.46-1.84) for MedBC. In ER-negative and HER2-negative MedBC, the risk of recurrence and death was significantly lower than that of IDC, about half. Postoperative chemotherapy reduced recurrence and mortality. ER-positive and HER2-negative MedBC may have a lower risk of recurrence compared to IDC.

S3718 A Rare Case of Invasive Ductal Carcinoma of the Breast With Metastases to the Stomach

Introduction: The most common type of breast cancer is invasive ductal carcinoma (IDC) followed by invasive lobular carcinoma (ILC). Both histologic subtypes have the potential to metastasize to distant sites, but each demonstrates different metastatic tendencies. IDC metastasizes more often to the bone, lung, and liver, while ILC metastasizes more frequently to the peritoneum and gastrointestinal tract. Gastric metastases are a rare occurrence and are predominately seen in patients with ILC. Here, we present an unusual case of IDC of the breast with metastases to the stomach. Case Description/Methods: A 77-year-old female with a history of estrogen and progesterone receptor negative, HER2 positive IDC of the breast with metastases to the liver, brain, and lung on palliative chemotherapy presented to our hospital with one month of abdominal pain and melena. On evaluation, the patient was hemodynamically stable with an abdominal exam revealing moderate tenderness in the epigastric region. Lab tests showed acute normocytic anemia with a hemoglobin 8.2 g/dl. The patient underwent esophagogastroduodenoscopy demonstrating a 1.5 cm ulcer at the gastric cardia with surrounding erythema and friable tissue. Pathology from gastric ulcer biopsy showed poorly differentiated adenocarcinoma in the deeper aspect of the lamina propria with immunohistochemistry positive for GATA-3, BRST-2, E-cadherin and HER2 consistent with metastatic breast IDC. The patient was discharged to home with oral pantoprazole and iron supplements. She was later seen in oncology clinic with labs showing improvement in her anemia and palliative chemotherapy was resumed. (Figure) Discussion: Gastric metastases are an infrequent discovery. When detected, the most common primary source is breast cancer and more often the ILC histologic subtype. Our patient’s breast cancer initially followed the typical pattern of IDC with metastases to the liver, brain, and lung. Her disease then progressed to involve the stomach, which is rarely seen in HER2 positive IDC. Gastric metastases may present as a single ulcerative lesion on endoscopy, which may be difficult to differentiate from primary gastric cancer as seen in this case. The immunohistochemistry of our patient’s gastric ulcer biopsy revealed positive biomarkers for metastatic IDC thereby confirming the diagnosis. Physicians should consider the possibility of metastasis to the stomach in patients with breast cancer presenting with symptoms of a gastric ulcer even in those with the IDC histologic subtype.Figure 1.: [A] H and E shows gastric mucosa with expansion of the lamina propria by malignant cells (10x). [B] The malignant cells are positive for GATA-3 immunostain which supports metastasis from patient’s known breast primary (10x). [C] 1.5 cm ulcer at the gastric cardia with surrounding erythema and friable tissue.

Transcription factor SOX3 upregulated pro-apoptotic genes expression in human breast cancer.

Sex-determining region Y-box 3 (SOX3) protein, a SOX transcriptions factors group, has been identified as a key regulator in several diseases, including cancer. Downregulation of transcriptions factors in invasive ductal carcinoma (IDC) can interfere in neoplasia development, increasing its aggressiveness. We investigated SOX3 protein expression and its correlation with apoptosis in the MDA-MB-231 cell line, as SOX3 and Pro-Caspase-3 immunoexpression in paraffin-embedded invasive ductal carcinoma tissue samples from patients (n = 27). Breast cancer cell line MDA-MD-231 transfected with pEF1-SOX3 + and pEF1-Empty vector followed by cytotoxicity assay (MTT), Annexin-V FITC PI for apoptosis percentage assessment by flow cytometry, qPCR for apoptotic-related gene expression, immunofluorescence, and immunohistochemistry to SOX3 immunolocalization in culture cells, and paraffin-embedded invasive ductal carcinoma tissue samples. Apoptotic rate was higher in cells transfected with pEF1-SOX3 + (56%) than controls (10%). MDA-MB-231 transfected with pEF1-SOX3 + presented upregulation of pro-apoptotic mRNA from CASP3, CASP8, CASP9, and BAX genes, contrasting with downregulation antiapoptotic mRNA from BCL2, compared to non-transfected cells and cells transfected with pEF1-empty vector (p < 0.005). SOX3 protein nuclear expression was detected in 14% (4/27 cases) of ductal carcinoma cases, and pro-Caspase-3 expression was positive in 50% of the cases. Data suggest that SOX3 transcription factor upregulates apoptosis in breast cancer cell line MDA-MB-231, and has a down nuclear expression in ductal carcinoma cases, and need to be investigated as a tumor suppressor protein, and its loss of expression and non-nuclear action turn the cells resistant to apoptosis. Further studies are necessary to understand how SOX3 protein regulates the promoter regions of genes involved in apoptosis.

Correlation of Tumor Budding With Known Clinicopathological, Histomorphological and Hormonal Receptor Status in Patients With Invasive Breast Carcinoma.

Introduction: Tumor blossoming may be a predictive indicatorfor a variety of cancers. At the invasive origin of the tumor, cells get detached from the original tumor mass. Aims & objectives: Studying breast cancer tumor budding, as well as its link to other prognostic indicators, such as clinicopathological features and hormone receptor status, will be the focus of this study. Materials & methods: Over six years, 110 cases of invasive breast cancer were examined. Ten high-power fields were used to analyze H&E-stained slices for tumor sprouting. It was determined that the tumor buds were divided into low and high grades. Tumor budding and other prognostic factors were compared using the chi-square test. It was considered significant if the p-value was less than or equal to 0.05. Results:There were 110 cases of invasive ductal carcinoma, which accounts for more than half of the total cases (88.18%). A total of 144 tumors were present, of which 74 displayed strong budding and 36 displayed poor budding. A correlation between tumor budding and tumor size, lymph node metastasis, and tumor stage is statistically significant (P = 0.0099). Conclusion: Tumor budding in breast cancer is an easily visible in microscopy, novel prognostic indicator. A new prognostic element may be added to the reporting process.

Spatial interplay of tissue hypoxia and T-cell regulation in ductal carcinoma in situ

Hypoxia promotes aggressive tumor phenotypes and mediates the recruitment of suppressive T cells in invasive breast carcinomas. We investigated the role of hypoxia in relation to T-cell regulation in ductal carcinoma in situ (DCIS). We designed a deep learning system tailored for the tissue architecture complexity of DCIS, and compared pure DCIS cases with the synchronous DCIS and invasive components within invasive ductal carcinoma cases. Single-cell classification was applied in tandem with a new method for DCIS ductal segmentation in dual-stained CA9 and FOXP3, whole-tumor section digital pathology images. Pure DCIS typically has an intermediate level of colocalization of FOXP3+ and CA9+ cells, but in invasive carcinoma cases, the FOXP3+ (T-regulatory) cells may have relocated from the DCIS and into the invasive parts of the tumor, leading to high levels of colocalization in the invasive parts but low levels in the synchronous DCIS component. This may be due to invasive, hypoxic tumors evolving to recruit T-regulatory cells in order to evade immune predation. Our data support the notion that hypoxia promotes immune tolerance through recruitment of T-regulatory cells, and furthermore indicate a spatial pattern of relocalization of T-regulatory cells from DCIS to hypoxic tumor cells. Spatial colocalization of hypoxic and T-regulatory cells may be a key event and useful marker of DCIS progression.

Simultaneous Contralateral Autologous Breast Augmentation during Unilateral Breast Reconstruction Utilizing Deep Inferior Epigastric Flaps.

Background:It is predicted that 281,550 new cases of invasive breast cancer and 49,290 new cases of ductal carcinoma in situ will be diagnosed this year. In this study, we will detail our experience with simultaneous contralateral autologous breast augmentation during unilateral breast reconstruction utilizing bilateral deep inferior epigastric perforator (DIEP) flaps.Methods:A retrospective analysis of patients who underwent simultaneous contralateral autologous breast augmentation during unilateral breast reconstruction utilizing bilateral DIEP flaps by the senior surgeons at Beaumont Health Systems, Royal Oak, was conducted. Demographic data, operative details, complications, medical comorbidities, and patient outcomes were retrospectively analyzed.Results:Seven patients who met the inclusion criteria were identified. One patient underwent immediate reconstruction with DIEP flaps, one patient had a history of lumpectomy and underwent delayed partial breast reconstruction, three patients had delayed unilateral DIEP breast reconstruction with contralateral breast augmentation, and two patients had previous augmentations that were revised. All patients examined in this review tolerated the procedures well and had clinically viable flaps along with superior aesthetic outcomes.Conclusions:This technique can be applied to various clinical conditions, including immediate breast reconstruction, delayed breast reconstruction, and salvage for failed implant-based reconstruction, leading to optimal patient outcomes and satisfaction. Unilateral breast reconstruction with simultaneous contralateral autologous breast augmentation utilizing bilateral DIEP flaps is a surgical technique that more plastic surgeons should utilize.

The value of immunohistochemical expression of Ki-67 and CD34 in differentiating ductal carcinoma in situ from ductal carcinoma in situ-like invasive breast cancer

Objective: To investigate the expression of Ki-67 and CD34 in the differential diagnosis of ductal carcinoma in situ (DCIS) and DCIS-like invasive breast cancer (DLIBC). Methods: A total of 100 cases of DCIS and 150 cases of DLIBC diagnosed pathologically in Yantai Yuhuangding Hospital from January 2019 to March 2022 were collected. The expression of p63, CK5/6, Ki-67 and CD34 in both groups were detected by immunohistochemical (IHC) staining and evaluated. Results: The 100 cases of DCIS included 11 cases of low-grade DCIS, 28 cases of intermediate-grade DCIS and 61 cases of high-grade DCIS. IHC staining of p63 and CK5/6 showed the myoepithelial cells around cancerous duct were complete or partial absence. Ki-67 expression showed two patterns: high expression in the basal layers and scattered expression within the tumor. Most cases showed mainly high basal expression (77/100, 77%), and the proportion of this pattern was significantly different between low grade and high grade DCIS (P<0.05). All cases showed complete CD34 expression surrounding the cancerous duct with different proportion (vascular necklace) suggested small vessels proliferation. The 150 cases of DLIBC included 142 cases of invasive ductal carcinoma (IDC) (three cases of basal-like breast cancer was included), two cases of secretory carcinoma, three cases of solid papillary carcinoma, two cases of adenoid cystic carcinoma and one case of acinar cell carcinoma. Among 142 cases of IDC, 13 cases were grade Ⅰ, 77 were grade Ⅱ and 52 were grade Ⅲ. IHC staining of p63 showed complete absence of myoepithelium. CK5/6 was negative in most cases and only positively expressed within the tumor in 3 cases of basal-like breast cancer. Ki-67 indicated a scattered expression pattern within the tumor. In most cases, CD34 immunostaining showed scattered positive blood vessels within the tumor while only two cases showed incomplete expression of CD34 around the tumor (2/150, 1.3%). The different expression patterns of Ki-67 and CD34 in DCIS and DLIBC was statistically significant (P<0.05). Conclusions: The different expression patterns of Ki-67 and CD34 are helpful to distinguish DLIBC from DCIS. The appearance of "vascular necklace" with CD34 and the high expression of Ki-67 around the cancerous duct highly support the diagnosis of DCIS, and the scattered expression pattern of CD34 supports DLIBC.

Expression of NUCB2/NESF-1 in Breast Cancer Cells.

Recently, the expression of NUCB2/NESF-1 has been linked to tumor development. We report NUCB2/NESF-1 expression and its relation to clinicopathological parameters in breast cancer cells. Immunohistochemical reactions were conducted on 446 cases of invasive ductal carcinoma (IDC) and 36 cases of mastopathy. The expression of NUCB2/NESF-1 was also examined at the mRNA and protein levels in breast cancer cell lines. A statistically significant higher level of NUCB2/NESF-1 in IDC cells was noted compared to that in mastopathy samples. The level of NUCB2 expression in the cytoplasm of IDC cells decreased with the increasing degree of tumor malignancy (G). Higher NUCB2 expression was found in tumors with estrogen receptor (ER)-positive and progesterone receptor (PR)-positive phenotypes compared to that in estrogen-receptor-negative and progesterone-receptor-negative cases. Moreover, a higher expression was shown in ER(+) and PR(+) MCF-7 and T47D cell lines compared to that in triple-negative MDA-MB-468 and normal human breast epithelial cells. The analysis of the five-year survival rate indicated that a positive NUCB2/NESF-1 expression in tumor cells was also associated with longer patient survival. The study results suggest that NUCB2/NESF1 may play an important role in malignant transformation and may be a positive prognostic factor in IDC.

Synchronous breast cancer and non-Hodgkin lymphoma: A case report.

IntroductionAmong women, breast cancer (BC) is the most prevalent type of cancer and the top cause of cancer deaths. Although non-Hodgkin lymphoma (NHL) is the most prevalent hematological cancer, it is rarely reported synchronous with BC. Moreover, which malignancy appears first can rarely be explained because they are usually detected incidentally while diagnosing and treating other malignancies. This paper reports a case of invasive ductal carcinoma (IDC) concomitant with NHL.Presentation of caseA 35-year-old woman presented with simultaneous IDC in the left breast and NHL in a lymph node in the neck. The patient underwent a modified radical mastectomy for stage IIIA IDC and received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy for stage I NHL.Clinical discussionTreating BC and NHL remains challenging due to their significantly different management, the lack of guidelines for treating BC and lymphoma simultaneously, and uncertainty about whether synchronous tumors should be treated separately as distinct clinical entities or as one disease with treatment covering both. Therefore, the best approach continues to be focusing on the most biologically aggressive malignancies.ConclusionThe enlargement of lymph nodes not in the lymphatic drainage of the primary tumor should be suspected of indicating multiple primary malignancies until proven otherwise. For patients with luminal-B BC, NHL chemotherapy can involve receiving the R-CHOP regimen, including doxorubicin and cyclophosphamide, which can help to mitigate BC.

Clinicopathological Features of 166 Cases of Invasive Ductal Breast Carcinoma and Effect of Primary Tumor Location on Prognosis after Modified Radical Mastectomy.

Objective To investigate the clinicopathological features of 166 cases of invasive ductal carcinoma (IDC) of the breast and to analyze the effect of the location of the primary tumor on the prognosis of modified radical mastectomy. Materials and Methods The clinical data of 166 patients with IDC who underwent modified radical mastectomy in our hospital from May 2015 to May 2017 were retrospectively analyzed. The clinicopathological features of IDC patients were recorded. Univariate analysis and the multivariate logistic regression model were used to analyze the relationship between the location of the primary tumor and the prognosis of IDC patients after modified radical surgery. The effect of primary tumor location on the prognosis of modified radical resection was used with Survival curve analysis. Results Among the patients in the central region, 13.33% had tumors >5 cm in diameter, which was higher than those in the other four groups. Among the patients in the upper inner quadrant, 59.38% received hormone therapy after operation, which was higher than those in the other four groups (P < 0.05). There were no significant differences in age, menopause, histological grading, molecular typing, lymph node metastasis, vascular invasion, radiation therapy, and chemotherapy among different groups (P > 0.05). Univariate analysis showed that molecular typing, lymph node metastasis, vascular invasion, and location of the primary tumor were all related to the prognosis of IDC patients after modified radical surgery, and the differences were statistically significant (P < 0.05). Logistic regression analysis showed that molecular typing, lymph node metastasis, vascular invasion, and primary tumor location were all independent influencing factors for prognosis of IDC patients after modified radical surgery (P < 0.05). As of 31 May 2021, there were 11 patients with recurrence and metastasis and 20 patients with death. The median survival time in the outer upper quadrant group was 80 months, which was higher than that in the outer lower quadrant group by 72 months, the median survival time in the central region group by 71 months, the median survival time in the inner upper quadrant group by 67 months, and the median survival time in the inner lower quadrant group by 61 months. The log-rank test showed all P < 0.001. Conclusion Patients with primary tumors located in the central area have larger tumor diameters. Patients located in the central area, upper inner quadrant, and lower inner quadrant are more likely to have lymphatic metastasis, have a more serious condition, and have a shorter prognosis survival time. Unluminal type, multiple lymph node metastases, vascular invasion, and the location of the primary tumor in the inner quadrant are all independent risk factors for prognosis in patients after modified radical surgery for IDC.

Abstract 43: Predictive biomarkers of recurrence may not be useful for deescalating treatment of breast ductal carcinoma in situ due to de novo ipsilateral breast carcinoma development

Abstract Introduction: Up to 25% of cases of ductal carcinoma in situ (DCIS) recur, and half of these recur as invasive breast cancer (IBC). There is no biomarker to predict which DCIS cases will recur but it has been suggested that a biomarker would allow de-escalation of the current paradigm of treating most patients with surgery and/or radiotherapy. However, we hypothesize that not all recurrences are genetically similar to the primary DCIS (i.e. non-clonal) and therefore arise de novo. To test this we assembled a large recurrence cohort to explore the clonal relatedness of primary-recurrence tumor pairs prior to proposing a predictive biomarker (Gorringe et al Mod Pathol 2015). Method: We microdissected and extracted DNA from 65 pairs of primary DCIS and recurrences. Half of these recurrences were IBC. We analyzed 21 pairs by targeted sequencing or low-coverage whole-genome sequencing (LCWGS, 2x depth) and 44 pairs with Whole Exome Sequencing (WES, average depth 95x). We similarly analyzed a set of non-recurrent DCIS cases (n=29) treated with wide local excision and with a minimum of 7 years follow-up. No matched normal samples were available. Several approaches were utilized to investigate clonal relatedness using copy number alterations and mutations (when detected), including the Clonality package (Mauguen et al Biometrics 2018), manual breakpoint inspection (Bollet et al JNCI 2008), and clonality indexes (Schultheis et al JNCI 2016). Phylogenetic analyses were carried out by MEDICC2 (Petkovic et al bioRxiv 2021) on WES samples. Results: 62% of cases were clonal (40/65), 28% were non-clonal. There were 7/65 that were equivocal, although further validation will be performed. There was no significant difference in clonal relatedness whether the recurrence was IBC or DCIS. IBC recurrent cases showed a significantly higher ploidy than the DCIS recurrences. The final phylogenetic analysis with MEDICC2 will be presented, which will take into account any subclonal whole-genome doubling events. Furthermore, clonal primary DCIS showed a significantly higher number of TP53 mutations compared to non-recurrent and non-clonal primaries (p&amp;lt;0.001, Fisher Exact test) and a higher level of copy number events overall. Conclusion: Detailed molecular analysis of a large cohort of matched DCIS primary and their recurrences using high sequencing resolution showed a substantial proportion of recurrences were not genetically related to the primary DCIS. Our observations raise the question of whether a tumor intrinsic biomarker alone would be sufficient to predict DCIS recurrences. Citation Format: Tanjina Kader, Sakshi Mahale, Magnus Zethoven, Hugo Saunders, Dorothea Lesche, David Byrne, Siqi Lai, Lauren Tjoeka, Claire Candido, Maree Pechlevanis, Olivia Craig, Jia-Min Pang, Lisa Devereux, Shona Hendry, Eloise House, Sureshni Jayasinghe, Michael Toss, Islam M. Miligy, Emad Rakha, Stephen Fox, Bruce Mann, Ian Campbell, Kylie Gorringe. Predictive biomarkers of recurrence may not be useful for deescalating treatment of breast ductal carcinoma in situ due to de novo ipsilateral breast carcinoma development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 43.