Cases Of Invasive Breast Carcinoma Research Articles

A Cross-Sectional Study of Tumor Budding in Correlation with Clinicopathological Parameters in Invasive Breast Carcinoma

Introduction: Breast carcinoma is the largest cause of mortality from cancer among women in India. Tumor budding is usually defined as isolated single cancer cells or clusters of up to four cancer cells located at the invasive tumor front. Tumor budding is associated with poor clinicopathological characteristics, such as Tumor size, tumor differentiation, lymph node invasion, lymphatic or vascular invasion etc. Aim: To study tumor budding and its association with known clinicopathological parameters and hormone receptor status in invasive breast carcinoma. Methods : A Cross-sectional study was conducted after approval from the ethics committee. The duration of study was 1.5 years (Jan 2022- June 2023). Results: A total of fifty cases of invasive breast carcinomas were included in this study. 70% (35cases) were >50yrs of age, 65% (33cases) were of T2 (tumor size) category. 82%(41cases) of Invasive duct carcinoma, No specific type, 12% (6 cases) of mixed carcinomas followed by three cases, one is invasive lobular carcinoma(6%), others are high grade papillary duct carcinoma(6%) and mucinous carcinoma (6%). 76%(38cases) showed presence of lymphovascular invasion, 74%(37cases) showed absence of necrosis, 54%(27 cases) are categorized as grade 2. High grade tumor budding was seen in 54% (27 cases). Conclusion: The following variables had a significant association with the tumor budding in present study: Tumor size, TNM staging, treatment status, lymphovascular invasion showing a p-value of <0.05. ER positive tumors are also associated with high grade tumor budding. Keywords: Breast Carcinoma, Clinicopathological Variables, Lymphovascular Invasion, Tumor Budding

Breast fat grafting and cancer: a systematic review of the science behind enhancements and concerns.

Autologous fat transfer (AFT) is gaining popularity in breast surgery, offering a natural-looking and minimally invasive approach for augmentation, reconstruction, and contouring. However, concerns about its impact on breast cancer necessitate an understanding of the interplay between transplanted adipose-derived stem cells (ADSCs) and the breast tissue microenvironment. Renowned for regeneration, ADSCs raise questions about their role in cancer promotion. This systematic review delves into the complex relationship between AFT and breast cancer, exploring how ADSCs may influence development, growth, and metastasis. A systematic search of electronic databases, including PubMed, Embase, and BVS was conducted to identify relevant studies. The search strategy employed a combination of keywords, including "breast augmentation", "fat grafting", "breast enhancement", "mammoplasty", "cancer", "neoplasm" and related terms. Two reviewers independently screened titles and abstracts. Full-text articles were then retrieved for further evaluation based on their potential contribution to the review objectives. Two hundred and forty records were identified. Among these, 104 duplicates were removed, resulting in 136 reports available for title and abstract screening. Subsequently, 54 papers were deemed potentially eligible for inclusion, and all reports were retrieved. In vitro studies reveal ADSCs dual role in breast cancer, influencing proliferation, migration, and drug resistance through complex signaling pathways. Animal studies highlight distinct ADSC subpopulations impacting tumor growth via direct interactions and extracellular vesicle cargo. In vivo, ADSC-enriched fat grafting is generally safe, showing no increased cancer recurrence risk compared to other methods. Notably, cases of invasive breast carcinoma warrant special attention. ADSC-enriched fat grafts exhibit potential benefits in graft retention and survival rates. Despite promising evidence, further studies are needed to comprehensively understand the intricate relationship between ADSCs and breast cancer for optimized clinical applications and potential therapeutic innovations.

Cytoplasmic Expression of p16 Is Associated with Carcinoma Breast: It Is Not an Artifact.

p16 has different roles in the nuclear and cytoplasmic locations. The nuclear localization of the p16 protein explains its role in cell cycle regulation. Cytoplasmic expression was considered an artifact in the initial years, but there is evidence to prove that cytoplasmic localization is real and that p16 has different roles in the nuclear and cytoplasmic locations. We aimed to study the immunoexpression of p16 protein in the nuclear and cytoplasmic locations of the epithelial and stromal compartments of fibroadenoma, invasive breast carcinoma, and a select number of phyllodes tumors. The study included a total of 107 patients, comprising 51 cases of invasive breast carcinoma, 51 cases of fibroadenoma, 4 cases of benign phyllodes tumors, and 1 case of lobular carcinoma in situ (LCIS). The p16 immunohistochemistry was evaluated for nuclear and cytoplasmic localization in the epithelial and stromal compartments of the tumors. Of the 51 fibroadenoma cases, 23 showed strong nuclear p16 epithelial expression, but no case showed cytoplasmic expression. In 19/51 cases, stromal cells also showed strong p16 nuclear expression. Moderate stromal p16 expression was observed in 3 out of 4 cases of benign phyllodes. Out of the 51 cases of invasive carcinoma, 31 showed moderate to strong nuclear p16 immunopositivity, while 27 cases exhibited cytoplasmic p16 expression. We found a statistically significant correlation between moderate to strong nuclear p16 immunoexpression and the molecular subtype of breast carcinoma. The cytoplasmic localization of p16 immunohistochemistry is not seen in epithelial components of fibroadenoma, while it is seen frequently in breast carcinoma. Nuclear p16 expression has a statistically significant correlation with molecular subtypes of breast carcinoma.

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

[This retracts the article DOI: 10.1155/2022/3158956.].

Concordance between cytological and histopathological grading in invasive breast carcinoma – A cross sectional study

Invasive Breast carcinoma means that the cancer has spread beyond the ducts/lobules into the surrounding tissue. The present 2 year study was carried out at a tertiary care hospital to find the concordance between cytological and histopathological grading in invasive breast carcinoma. It included all the 100 cases of invasive breast carcinoma diagnosed on histopathology during this period with available cytology reports. Concordance of Robinson's cytological grading system was calculated in each grade with respect to histological grading. All cases evaluated for presence of metastasis to axillary lymph nodes. We found Concordance rate between cytological and histological grade as 76%. The coefficient of correlation between cytological grade and histological grade was 0.83 and P value was <0.001 which indicated a strong correlation and significant association between the cytological and histological grade. High degree of concordance is seen between cytological and histopathological grading system. Preoperative grading using FNAC helps in determining neo adjuvant chemotherapy as well as prognosis. This grading should be included in cytology reports on a regular basis because it correlates well with histological grade.

PRAME expression and its prognostic significance in invasive breast carcinoma

ObjectivesPRAME (PReferentially expressed Antigen in MElanoma) is a carcinoma testis antigen expressed in numerous tumour types. The aim of this study was to assess PRAME expression in different surrogate subtypes of breast carcinoma and its correlation with other prognostic factors. Material and methodsA total of 220 cases of invasive breast carcinoma were selected and categorized according to ER, PgR, HER2 status, and Ki67 proliferation index in luminal A like, luminal B HER2+ like, luminal B HER2- negative like, HER2 positive like and triple-negative or basal-like. All cases were examined for PRAME expression by immunohistochemistry (IHC). ResultsA PRAME-high profile was detected in 53 (24,1 %) of all examined breast carcinoma samples. A significantly higher expression of PRAME was detected in HER2-positive carcinomas (50 %) and TN breast carcinomas (40,54 %) compared to ER-positive (luminal-like) subtype of breast carcinomas (3,38 % luminal A and 15,38 % luminal B). Percentage of PRAME positive tumour cells showed positive correlation with tumor size, Ki67 proliferation index, HER2 status, nuclear grade, TILs and presence of metastasis, and negative correlation with ER status and disease-free survival (DFS). ConclusionOur study showed that HER2 positive and TN breast carcinomas more commonly express PRAME than ER positive carcinomas and that PRAME expression shows positive correlation with certain prognostic factors, however PRAME wasn't revealed as an independent prognostic factor in our study. The importance of PRAME expression in breast carcinoma lies in its potential use as an immunotherapeutic target, particularly in patients with limited therapeutic options.

Subtyping of Breast Carcinoma According to ER/PR and HER2/neu Expression: A Cross-Sectional Study from Southern Part of Assam, India

Introduction: Globally, breast carcinoma is the most prevalent and lethal form of cancer in women. Breast cancer is no longer considered a single disease but a complex heterogeneous disease with multiple genetic and epigenetic alterations. The prognosis and management of the disease depend on histological stage, type, grade, tumour size, lymph node status, and the status of hormonal receptors like ER, PR, and Her2/ neu. Recently, more attention has been given to the molecular classification of breast cancer. Aim: To analyse and compare the clinicopathological characteristics of invasive breast cancer in the four breast carcinoma subtypes defined by the immunohistochemical expression of Estrogen Receptor (ER), Progesterone Receptor (PR), and Human Epidermal Growth Factor Receptor 2 (Her2/neu). Materials and Methods: The cross-sectional study was conducted on 64 primary invasive breast carcinoma cases diagnosed on mastectomy specimens between February 1, 2018, and July 30, 2022, in the Department of Pathology at the histopathology section of Silchar Medical College and Hospital, Silchar, Assam, India. Age and tumour characteristics (morphology, grade, stage, and size) and nodal disease status were included in the data for analysis. Immunohistochemical markers were analysed on the sections of these diagnosed cases. IBM Statistical Packages for Social Sciences (SPSS) software was used for data analysis. Qualitative data was presented as frequency and percentage, while quantitative data was presented as mean ±{Standard Deviation (SD)}. The Chi- square test was used to determine the statistical significance of hormonal receptors with the various clinicopathological features. A p-value of <0.05 was considered statistically significant. Results: In present study of 64 cases of invasive breast carcinoma, the mean age of patients was 51.95±12.72 years. Subtyping was performed based on hormonal receptors. Authors found that the Luminal A variety 33 (51.6%) was the most common hormonal subtype in present study, followed by the basal subtype 24 (37.5%). The Luminal A subtype was found to be predominant among others. The majority of the patients (59.4%) had stage-I tumours, and Ductal type carcinoma was the most common (57.8%). Histologically, most of the tumours were poorly differentiated (28, 43.8%), and most were sized ≤2 cm (41, 64.1%). Lymph nodes were not palpable in most of the patients (43, 67.2%). Subtype comparison with respect to age, stage, histological grade, type, size, and nodal status revealed statistically significant outcomes (p-value of <0.05). Conclusion: Classification based on Immunohistochemistry (IHC) provides prognostic and therapeutic information that cannot be obtained from either ER/PR or Her2/Neu status alone. The present study provides the incidence of different molecular subtypes in the southern region of Assam, and comparison among them with statistical correlation offers improved and crucial treatment guidance. IHC classification as a clinical tool for ER/PR and Her2/Neu testing is widely accessible, reasonably priced, based on immunophenotype/biologic phenotype categorisation of breast cancer, and is prognostic as well as partly predictive and needs to be practiced invariably.

Study of tumor budding and its association with clinicopathological parameters in breast carcinoma.

Tumor budding is a phenomenon in which the tumor cells detach from the main mass and are present at the invasive front. The present study was conducted to study tumor budding in invasive breast carcinoma and to correlate it with clinicopathological parameters and molecular subtypes. The study was conducted over a period of 1 year, and tumor budding was studied as a single or group of cells at the invasive front of breast carcinoma counted in a high-power field (40×). The grading was statistically correlated with tumor size, grade, lymph node status, lymphovascular invasion, pathological TNM staging, molecular subtype, and survival of patients. A total of 50 cases of invasive breast carcinoma were included, out of which 66% (n=33) showed high-grade tumor budding, which was statistically significantly higher in grade 2 invasive ductal carcinoma (p<0.05). High tumor budding was associated with lymphovascular invasion, lymph node metastasis, and a high Ki-67 proliferative index. All cases showing low-grade budding were alive until 6 months of diagnosis, but there was no statistically significant association between stage and budding. Tumor buds are significantly higher in grade 2 invasive ductal carcinoma with lymphovascular invasion, lymph node metastasis, and a high Ki-67 proliferative index. Immunohistochemistry may prove helpful in distinguishing tumor buds from their mimickers. Further studies with extended follow-up are recommended to predict tumor budding as a prognostic marker in breast carcinoma, which may play an important role in cancer therapy.

Prognostic significance of alpha-2-macrglobulin and low-density lipoprotein receptor-related protein-1 in various cancers.

Cancer is the leading cause of death worldwide. The World Health Organization (WHO) estimates that 10 million fatalities occurred in 2023. Breast cancer (BC) ranked first among malignancies with 2.26 million cases, lung cancer (LC) second with 2.21 million cases, and colon and rectum cancers (CC, CRC) third with 1.93 million cases. These results highlight the importance of investigating novel cancer prognoses and anti-cancer markers. In this study, we investigated the potential effects of alpha-2 macroglobulin and its receptor, LRP1, on the outcomes of breast, lung, and colorectal malignancies. Immunohistochemical staining was used to analyze the expression patterns of A2M and LRP1 in 545 cases of invasive ductal breast carcinoma (IDC) and 51 cases of mastopathies/fibrocystic breast disease (FBD); 256 cases of non-small cell lung carcinomas (NSCLCs) and 45 cases of non-malignant lung tissue (NMLT); and 108 cases of CRC and 25 cases of non-malignant colorectal tissue (NMCT). A2M and LRP1 expression levels were also investigated in breast (MCF-7, BT-474, SK-BR-3, T47D, MDA-MB-231, and MDA-MB-231/BO2), lung (NCI-H1703, NCI-H522, and A549), and colon (LS 180, Caco-2, HT-29, and LoVo) cancer cell lines. Based on our findings, A2M and LRP1 exhibited various expression patterns in the examined malignancies, which were related to one another. Additionally, the stroma of lung and colorectal cancer has increased levels of A2M/LRP1 areas, which explains the significance of the stroma in the development and maintenance of tumor homeostasis. A2M expression was shown to be downregulated in all types of malignancies under study and was positively linked with an increase in cell line aggressiveness. Although more invasive cells had higher levels of A2M expression, an IHC analysis showed the opposite results. This might be because exogenous alpha-2-macroglobulin is present, which has an inhibitory effect on several cancerous enzymes and receptor-dependent signaling pathways. Additionally, siRNA-induced suppression of the transcripts for A2M and LRPP1 revealed their connection, which provides fresh information on the function of the LRP1 receptor in A2M recurrence in cancer. Further studies on different forms of cancer may corroborate the fact that both A2M and LRP1 have high potential as innovative therapeutic agents.

HER2 amplification in cases with low HER2 expression by immunohistochemistry (IHC): A Single Institutional Experience

Abstract Introduction/Objective HER2 testing in invasive breast carcinoma (IBC) is the standard of care to determine patient eligibility for HER2 directed therapy with trasuzumab. Initial testing of tissue by HER2 immunohistochemistry (IHC) can be positive, negative, or equivocal. In equivocal cases as well as negative cases in our institution HER2 FISH is also performed. According to ASCO/CAP guidelines a subset of equivocal and negative IHC cases are considered HER2 positive if they meet criteria for increased HER2/CEP17 ratio and HER2 copy number by FISH, allowing more patients to be treated with HER2 directed therapies. HER2 grouping per ASCO is as follows; Group 1: HER2 copy number ≥4 signals/cell, Group 2: &amp;lt;4.0 signals/cell, Group 3: ≥6 signals/cell, Group 4: HER2 copy number ≥4 and &amp;lt;6 signals/cell, Group 5: HER2 copy number &amp;lt;4 signals/cell Methods/Case Report All cases of IBC resection with HER2 IHC and FISH results from Jan 2018-Dec 2021 were included in this study. All cases positive for HER2 by IHC alone (3+ staining) were excluded. The ASCO/CAP 2018 guidelines for HER2 testing in breast cancer were used to evaluate HER2 positivity by FISH and the relation to IHC scores Results (if a Case Study enter NA) A total of 2630 IBC cases with both HER2 IHC and FISH testing were included. Of these, 131 (5.0%) were in FISH group 1, 17 (0.7%) in group 2, 11 (0.4%) in group 3, 161 (6.1%) in group 4, and 2310 (87.8%) in group 5. A total of 142 (5.4%) cases that were HER2 equivocal or negative by IHC were HER2 positive by FISH. Specifically, 0.3% of cases with an IHC score of 0, 1.4% with a score of 1+, and 14.6% of cases with a score of 2+ were positive by FISH. Of the 14.6% IHC 2+ cases that were FISH positive 13.3% were in FISH group 1 (115 cases) and 1.3% (11 cases) in FISH group 3. Of FISH positive cases 1.4% had an IHC score of 0, 9.9% had an IHC score of 1 and 88.7% had a score of 2 Conclusion At our institution 14.6% of IBC with equivocal HER2 staining on IHC, 1.4% of cases with negative (1+) staining and 0.3% of cases with negative (0) were HER2 FISH positive. Since HER2 FISH is not reflexively performed on cases HER2 negative by IHC, this additional 1.7% will qualify for HER2 targeted therapy Interpretation of low HER2 expression by IHC by traditional IHC assay may miss a small percentage of cases eligible for HER2 directed therapy. Accurate interpretation of HER2 low by IHC is critical as recent clinical trials have shown that low HER2 expression with IHC scores of 1+ or 2+ without gene amplification by FISH could benefit from Trastuzumab Deruxtecan

Comparing Heat-Induced Antigen Retrieval Methods for ER Expression in Invasive Breast Carcinoma

In the realm of cancer diagnosis and treatment, immuno-histochemical staining has become a pivotal tool for discerning molecular markers within tissue samples. Objective: To comprehensively compare different heat-induced antigen retrieval methods for evaluating estrogen receptor (ER) expression in female invasive breast carcinoma of no special type. Methods: A cross-sectional design was employed utilizing 250 formalin-fixed paraffin-embedded (FFPE) tissue samples from confirmed cases of invasive breast carcinoma. The study was conducted within Histopathology Department in CMH Peshawar. The study spanned from January 6, 2022 to June 30, 2023. Three heat-induced antigen retrieval methods were evaluated: conventional microwave-based retrieval, pressure cooking retrieval, and water bath heating. ER expression was assessed through immune-histo-chemical staining, and scores were analyzed using descriptive statistics and ANOVA. A post hoc Tukey's Honestly Significant Difference (HSD) test was conducted to identify which specific retrieval methods exhibited significant differences in ER expression scores. Results: The pressure-cooking retrieval method exhibited significantly higher mean ER expression scores (7.52) compared to the conventional microwave-based (6.87) and water bath heating methods (6.65). Post hoc analysis confirmed the substantial differences. Standard deviations and interquartile ranges were consistent with each method. Conclusions: The study underscores the pivotal role of retrieval techniques in accurate ER expression assessment in female invasive breast carcinoma of no special type. The pressure cooking method emerges as a potent enhancer of ER expression, advocating for standardized protocols to ensure consistent diagnostic outcomes and informed therapeutic decisions. Despite limitations, this research contributes to the refinement of patient care in the management of invasive breast carcinoma.

The Relationship between Body Mass Index (BMI) and Clinical Pathological Profile of Invasive Breast Carcinoma Patients in the Department of Anatomic Pathology FKUI/RSCM from 2019 to 2022

Background&#x0D; Breast cancer is the most prevalent malignancy among women and is the second largest contributor to cancer-related deaths globally. Women with a high body mass index (BMI) are at a greater risk of developing breast cancer and an increased risk of lymph node metastasis. This retrospective study aimed to determine the relationship between BMI and the clinical pathological profile of invasive breast carcinoma (IBC) patients.&#x0D; Method&#x0D; This study was conducted from 2019 to 2022. Data were collected through the archives of the Department of Anatomic Pathology FKUI/RSCM (Faculty of Medicine, University of Indonesia/Cipto Mangunkusumo Hospital). Clinical pathological data were collected. The histological type, grade, lymphovascular invasion, and lymph node metastasis of the tumors were re-evaluated. The chi-square hypothesis test was used to determine the relationship between BMI and clinical pathological profile. The results were considered statistically significant with a p &lt;0.05.&#x0D; Result&#x0D; A total of 151 cases of IBC with lymph node dissection from 2019 to 2022 were included in this study, all of which were female, with the majority being &gt;50 years old (55%). The most common tumor size and histological type were T2 (39,7%) and invasive ductal carcinoma NST (74,8%), 49% of cases were grade 3 tumors. Most IBC cases had an obese BMI (49%), 63.1% with lymph node metastasis had an overweight-obese BMI. Statistical analysis was performed between BMI and lymph node metastasis status, and p-value=0.025 was obtained. The relationship between tumor size and lymphovascular invasion with lymph node metastasis was also found to be statistically significant, as indicated by a p-value of 0.000.&#x0D; Conclusion&#x0D; Cases with lymph node metastasis had the highest rate of overweight-obesity, and a significant relationship was found between BMI and lymph node metastasis status. A significant relationship was also found between tumor size and lymphovascular invasion with lymph node metastasis.

Trichorhinophalangeal syndrome type 1 (TRPS1) expression in male breast carcinoma

Currently, there is a paucity of highly specific and sensitive markers to identify breast carcinoma in male patients. Immunohistochemical stains commonly used for unmasking primary breast carcinomas include estrogen receptor (ER) and GATA3. However, these markers are commonly expressed in carcinomas originating from other organ systems and can be reduced in breast carcinomas with higher histologic grades. Androgen receptor (AR) may be used to highlight primary male breast cancer, but this marker can also be expressed in other carcinomas. We evaluated TRPS1, a highly sensitive and specific marker for female breast carcinoma, in cases of male breast carcinoma. Through an institutional database search, we identified 72 cases of primary invasive breast carcinoma in male patients. Among ER/progesterone receptor (PR)-positive cancers, 97% showed intermediate or high positivity for both TRPS1 and GATA3. Among HER2-positive cancers, 100% showed intermediate or high positivity for TRPS1 and GATA3. One case of triple-negative breast cancer was collected, showing high positivity for TRPS1 and negativity for GATA3. AR staining was non-specific and heterogeneous: 76% showed high positivity, but the remaining 24% showed low or intermediate positivity. Additionally, among 29 cases of metastatic carcinoma to male breast tissue, 93% were negative for TRPS1, and the remaining 2 cases (7%), which were carcinomas from salivary gland primary tumors, were intermediate positive. TRPS1 is a sensitive and specific marker in the unmasking of male primary invasive breast carcinoma across different subtypes. Additionally, TRPS1 is not expressed in metastatic carcinomas of multiple primaries, with the exception of salivary gland primaries.

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.

Tumour budding in invasive breast carcinoma and its correlation with histopathological prognostic parameters and hormone receptor status.

Tumor Budding (TB) is emerging as an important sensitive indicator of aggressiveness over traditional histopathological variables such as lymph node metastasis and lymphovascular invasion because TB at the invasive front was postulated as the first step of invasion and metastasis. But the role of TB in breast carcinoma is not yet standardized. This study aims to assess the prognostic significance of TB in breast carcinoma. To study and grade TB in invasive breast carcinoma and correlate it with known histopathological prognostic markers and hormone receptor status. In this ambispective study, 51 cases of invasive breast carcinoma undergoing radical surgery were studied from September 2017 to September 2021. Tumor buds were defined as a single or cluster of up to four tumor cells at the invasive front of the tumor and were counted by using IHC Pancytokeratin in 200X and graded into a three-tier grading system. The correlation between TB with established histopathological parameters and hormone receptor status was studied. A Chi-square test was used and a P value < 0.05 was considered significant. TB was seen in all cases of invasive breast carcinoma. Grade 1 TB was seen in 37.26% (19/51) of cases and Grade 2 TB and Grade 3 TB in 31.37% (16/51) of cases each. There was a lack of significant correlation between TB with histologic grade, lymph node status, and HER2 neu. Correlation between TB with Estrogen receptor (ER), Progesterone receptor (PR), and American Joint Committee on Cancer (AJCC) Prognostic stage group was noted but it was not statistically significant. Although several studies have confirmed the prognostic value of TB in breast carcinoma, they had used several different methods of assessment. So, there is a need for a standardized method for the assessment of TB in breast carcinoma. Further standardization of TB may add its value as a prognostic factor.

Using Deep Learning to Predict Final HER2 Status in Invasive Breast Cancers That are Equivocal (2+) by Immunohistochemistry.

Invasive breast carcinomas are routinely tested for HER2 using immunohistochemistry (IHC), with reflex in situ hybridization (ISH) for those scored as equivocal (2+). ISH testing is expensive, time-consuming, and not universally available. In this study, we trained a deep learning algorithm to directly predict HER2 gene amplification status from HER2 2+ IHC slides. Data included 115 consecutive cases of invasive breast carcinoma scored as 2+ by IHC that had follow-up HER2 ISH testing. An external validation data set was created from 36 HER2 IHC slides prepared at an outside institution. All internal IHC slides were digitized and divided into training (80%), and test (20%) sets with 5-fold cross-validation. Small patches (256×256 pixels) were randomly extracted and used to train convolutional neural networks with EfficientNet B0 architecture using a transfer learning approach. Predictions for slides in the test set were made on individual patches, and these predictions were aggregated to generate an overall prediction for each slide. This resulted in a receiver operating characteristic area under the curve of 0.83 with an overall accuracy of 79% (sensitivity=0.70, specificity=0.82). Analysis of external validation slides resulted in a receiver operating characteristic area under the curve of 0.79 with an overall accuracy of 81% (sensitivity=0.50, specificity=0.82). Although the sensitivity and specificity are not high enough to negate the need for reflexive ISH testing entirely, this approach may be useful for triaging cases more likely to be HER2 positive and initiating treatment planning in centers where HER2 ISH testing is not readily available.

The presence of retraction clefts correlates with lymphovascular invasion and lymph node metastasis and predicts poor outcome: Analysis of 2497 breast cancer patients

Some invasive breast carcinomas are surrounded by a clear space that separate the tumor cells from the adjacent stroma, similar to invasive micropapillary carcinoma (IMPC), but lack the thin strands of connective tissue that separate the cells and characteristic “inside-out” growth pattern of IMPC on immunohistochemical stain for EMA. We consider the presence of the retraction clefts a common phenomenon that may present as a precursor stage of IMPC (PSIMPC). In this study, a total of 2497 cases of invasive breast carcinomas were prospectively collected. Among 2497 cases of breast cancer, 949 (38.0 %) cases were PSIMPC, 200 (8.0 %) cases were IMPC and 1348 (54.0 %) cases were IBC-NST. LVI was seen in128 of 200 (64 %) IMPC and 364 of 948 (38.0 %) PSIMPC, in contrast to 246 of 1341 (18 %) IBC-NST (P < 0.001). Lymph node metastasis was seen in 147 of 200 (73.4 %) IMPC and 551 of 949 (58 %) PSIMPC, in contrast to 563 of 1345 (42 %) IBC-NST (P < 0.001). The 5-year disease-free survival (DFS) and overall survival (OS) of PSIMPC were 76.8 % and 87.6 %, compared to 63.2 % and 85.9 % in IMPC, 86.2 % and 93.7 % in IBC-NST. PSIMPC demonstrated a more favorable DFS and OS compared to IMPC, but worse DFS and OS compared to IBC-NST. Cox and logistic regression analysis showed that PSIMPC was an independent predictor of DFS and OS. Our findings suggest that the presence of retraction clefts is a precursor state of IMPC, exhibiting IMPC-like features, such as higher incidence of lymphovascular invasion, lymph node metastasis and more aggressive clinical behavior.

Differences of Clinicopathological Features between Metaplastic Breast Carcinoma and Nonspecific Invasive Breast Carcinoma and Prognostic Profile of Metaplastic Breast Carcinoma.

Introduction Metaplastic breast carcinoma is a rare special type of breast cancer, which has distinguished clinical characteristics. We aimed to evaluate the clinicopathological features of metaplastic breast carcinoma compared with nonspecific invasive breast carcinoma and study the prognosis of metaplastic breast carcinoma. Methods We reviewed metaplastic breast carcinoma cases (n = 37) from January 2000 to December 2021 and nonspecific invasive breast carcinoma cases (n = 433) from January 2019 to December 2020 extracted from our institution retrospectively. The following variables were recorded, including the patients' general information, complications, T stage, expression of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, Ki-67, molecular subtyping, lymph node status, skin or chest wall involvement, vessel carcinoma embolus, therapy modality (surgical treatments, chemotherapy, and radiotherapy), and survival. Results Patients with metaplastic breast carcinoma had more advanced disease than patients with nonspecific invasive breast carcinoma (T stage: P=0.0011). A greater proportion of metaplastic breast carcinoma presented with triple-negative breast cancer than nonspecific invasive breast carcinoma (79.41% vs. 12.47%, P ≤ 0.001). Our study showed that the skin or chest wall invasion was more frequent in metaplastic breast carcinoma patients (11.76% vs. 1.62%, P=0.005). The 5-year survival rate for metaplastic breast carcinoma patients was 57.66% (95% CI: 0.3195∼0.7667). No local recurrence was observed while distant metastasis occurred in 33.33% of patients with metaplastic breast carcinoma. Death due to disease occurred in 24.24% of patients with metaplastic breast carcinoma. Conclusion The majority of metaplastic breast carcinoma patients had more advanced disease and triple-negative disease than nonspecific invasive breast carcinoma patients. Also, metaplastic breast carcinoma patients had frequent skin or chest wall invasion and a high rate of distant metastasis and mortality.

Quantitative classification of invasive and noninvasive breast cancer using dynamic magnetic resonance imaging of the mammary gland.

ObjectivesBreast cancers are classified as invasive or noninvasive based on histopathological findings. Although time-intensity curve (TIC) analysis using magnetic resonance imaging (MRI) can differentiate benign from malignant disease, its diagnostic ability to quantitatively distinguish between invasive and noninvasive breast cancers has not been determined. In this study, we evaluated the ability of TIC analysis of dynamic MRI data (MRI-TIC) to distinguish between invasive and noninvasive breast cancers.Material and MethodsWe collected and analyzed data for 429 cases of epithelial invasive and noninvasive breast carcinomas. TIC features were extracted in washout areas suggestive of malignancy.ResultsThe graph determining the positive diagnosis rate for invasive and noninvasive cases revealed that the cut-off θi/ni value was 21.6° (invasive: θw > 21.6°, noninvasive: θw ≤ 21.6°). Tissues were classified as invasive or noninvasive using this cut-off value, and each result was compared with the histopathological diagnosis. Using this method, the accuracy of tissue classification by MRI-TIC was 88.6% (380/429), which was higher than that using ultrasound (73.4%, 315/429).ConclusionMRI-TIC is effective for the classification of invasive vs. noninvasive breast cancer.

Crosstalk Between Programmed Death Ligand 1, Ki-67 Labelling Index, and Tumor-Infiltrating Lymphocytes in Invasive Breast Cancer and Clinicopathological Correlations in a Tertiary Care Center in Western India.

Background & Objective:Breast cancer is the leading cancer among Indian women and accounts for about 25% of all cancer cases worldwide. The present study aimed to assess Programmed Death Ligand-1 (PD-L1) expression in tumoral cells and tumor-infiltrating lymphocytes (TILs) and evaluate their correlations with the Ki-67 labelling index in invasive breast carcinomas (IBC). Methods:This descriptive observational study was conducted during 2016-2018 and included all diagnosed cases of IBC. The relationships between PD-L1 expression, TILs, hormone receptors, Ki-67, and clinicopathological parameters were studied in IBC. Statistical analysis was performed by SPSS version 23.Results:Out of 114 evaluated cases, 33.33% (N=38) showed PD-L1+ expression in tumor cells and 47.37% (N=54) had PD-L1+ expression in TILs. A high Ki-67 index was observed in 96 cases. Moreover, 49 patients were estrogen receptor (ER)- and 65 were ER+. We observed that 22 of 49 ER- and 49 of 65 ER+ subjects showed PD-L1+ expression, respectively. Conclusion: Our results showed a significant relationship between PD-L1 expression in tumoral cells and TILs, as well as between Ki-67 and TILs. In addition, an inverse correlation was noted between PD-L1 expression and ER. The PD-L1 expression in tumors and TILs and correlation with high Ki-67 may prove the importance of PD-L1 in targeted chemotherapy. An inverse relationship between PD-L1 and ER expression in tumoral cells suggests scope for immunotherapy in ER- IBC. However, further research with more cases is required.