Search Results (77)

Pleomorphic invasive lobular carcinoma (PILC or PLC) is a malignant breast tumor considered a rare variant of invasive lobular carcinoma in women, characterized morphologically by marked nuclear pleomorphism, with cells resembling plasmacytoid, histiocytoid, or apocrine cells. One of its defining features is the loss of E-cadherin expression. Considering the biological similarities between species and the limited data available for female dogs, this study aimed to characterize PLC in canines, with an emphasis on its histopathological and immunophenotypic features and its potential applicability as a comparative model. Histopathological analysis of PLC was performed alongside immunohistochemical evaluation using HER2, estrogen receptors (ER), progesterone receptors (PR), E-cadherin, and Ki-67 (cell proliferation indexing) markers. All canine PLCs tested positive for PR, with the majority being negative for ER, and all were negative for HER2 and E-cadherin. In contrast, in women, all cases were positive for ER, most were positive for PR, and all were negative for HER2. The Luminal B molecular subtype was the most frequent in dogs, whereas Luminal A and Luminal B subtypes showed equal prevalence in women. These findings reveal shared and distinct immunophenotypic features between species. The similarities and differences observed emphasize the relevance of the canine model for comparative oncology. Furthermore, the use of spontaneous tumors in immunocompetent dogs in this study strengthens the translational potential of the findings, thereby reinforcing the use of the canine model in breast cancer research and supporting its role within the One Medicine concept. Full article

Background and Objectives: Although breast cancer is the most common type of cancer among women, bilateral breast cancer (BBC) remains exceedingly rare. BBC can present as either synchronous (SBBC) or metachronous (MBBC) disease. Data regarding the clinical characteristics of BBC are limited. In this study, we aimed to share our multicenter, retrospective experience on the clinicopathological and demographic features of SBBC and MBBC, their survival outcomes, and the factors influencing survival, in light of current knowledge. Material and Method: A total of 125 patients who were treated and followed between 2015 and 2024 across six different centers were included in the study. The patients were categorized into synchronous (SBBC) and metachronous (MBBC) groups. Their clinicopathological characteristics were analyzed, along with disease-free survival (DFS) and 5-year overall survival (OS) outcomes. Results: DFS was 5.7 years in the SBBC group and 5.6 years in the MBBC group (p = 0.95). The 5-year OS rate was 95.2% in the MBBC group and 80.7% in the SBBC group (p = 0.035). Hormone receptor negativity was identified as an independent risk factor for lower DFS in the overall patient cohort (HR: 0.55, 95% CI: 0.31–0.98, p = 0.04). Conclusion: Significant differences were found between the SBBC and MBBC groups in terms of hormone receptor status, presence of an invasive lobular carcinoma component, recurrence/metastasis status, and molecular subtype discordance between the two primary tumors. Although DFS did not significantly differ between the groups, the 5-year OS was significantly higher in the MBBC group. In multivariate regression analysis, hormone receptor negativity was identified as an independent risk factor for decreased DFS among all BBC patients. Our study is noteworthy for shedding light on the clinical features of BBC in the context of current knowledge and for its multicenter design. Full article

Background: The role of CDK4/6 inhibitors (CDK4/6i) has expanded from the treatment of advanced breast cancer to early-stage disease, as recent studies have demonstrated their therapeutic benefits. However, evidence regarding the safety of combining CDK4/6i with adjuvant radiation therapy (RT) in a curative setting remains limited. This study aims to present clinical experiences of pulmonary toxicity following the combined use of adjuvant RT and CDK4/6i. Case presentation: We report a case of an Asian female with left breast cancer who underwent a modified radical mastectomy followed by adjuvant chemotherapy, RT, endocrine therapy, and CDK4/6i (abemaciclib) treatment. Cancer therapy-induced grade 2 pneumonitis was impressed by clinical signs and image findings. A 57-year-old postmenopausal woman was diagnosed with left breast invasive lobular carcinoma, hormone receptor–positive, human epidermal growth factor receptor 2–negative (HR+/HER2−), K67 index of 5–10%, and classified as pT3N3aM0 (stage IIIC). She received adjuvant chemotherapy with FEC followed by docetaxel, endocrine therapy with letrozole, and adjuvant RT of 50.4 Gy in 28 fractions to the left chest wall and regional nodal irradiation. Abemaciclib was initiated after completing RT. Treatment-related pneumonitis developed five months after RT and abemaciclib use. Conclusions: In breast cancer patients receiving a combination of RT and CDK4/6i as curative adjuvant treatment, pulmonary toxicity is a concern and requires careful monitoring, particularly in Asian populations. Full article

The association between breast cancer and non-Hodgkin lymphoma of the spleen is extremely rare, with very few cases documented in the medical literature. We present the case of a 39-year-old woman in good health but with a family history of breast cancer, who, in 2017, developed invasive lobular carcinoma in her right breast, which was treated with mastectomy followed by hormonal therapy. In 2024, she presented with a suspicious right axillary mass, suspected of recurrence, which was confirmed by fine-needle aspiration biopsy. The patient received neoadjuvant chemotherapy, followed by axillary lymph node dissection and bilateral adnexectomy. CT and PET scans showed suspicious splenic lesions suggestive of metastases. Infectious and hematological tests were negative, leading to the decision to perform laparoscopic splenectomy. Histological examination revealed follicular B-cell non-Hodgkin lymphoma. The patient is now in good general condition and is on a biannual follow-up. The case highlights the diagnostic complexity of tumor recurrences and the need to consider alternative diagnoses other than metastasis in oncological patients. Full article

Background: In Saudi Arabia, breast cancer is the most common malignancy among women, significantly impacting cancer-related morbidity and mortality. The country’s unique demographics and rapid socioeconomic development contribute to distinct breast cancer patterns. Objective: To analyze demographic and pathological characteristics of breast cancer with an emphasis on associations between the Ki67 proliferation index, tumor stages, and molecular subtypes. Materials and Methods: An analytical cross-sectional study was conducted on 294 breast cancer patients from 2013 to 2019, recruited from the Comprehensive Cancer Center at King Fahad Medical City, Riyadh, Saudi Arabia. A one-way ANOVA and logistic regression were used to identify risk factors associated with elevated Ki67 levels. Significance was set at a 95% confidence level. Results: The mean age of patients was 51.58. Among them, 67% were overweight/obese, 21.1% were diabetic, and 17% were hypertensive. Approximately 28.9% of all tumors were classified as T3, 46.9% as Grade III, and 40% as Stage IV. Invasive ductal carcinomas (83.9%) were the most common. ER, PR, and HER2 expression were positive in 63.4%, 54.3%, and 34.9% of patients, respectively, with a high Ki67 index in 50.7%. As compared to Grade I cancer, grade II cancer increased the likelihood of elevated Ki67 by 41 times (p = 0.001), Grade III cancer by 7.43 times (p = 0.001), and Stage IV cancer by 2.26 times (p = 0.03). Conversely, invasive lobular carcinomas and other cancer types were significantly less likely to have high Ki67 levels (p < 0.05). Conclusions: Elevated Ki67 appeared to predict higher tumor grades and certain molecular subtypes cancer. Full article

Purpose: Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) are the most common breast cancer types. While they differ biologically and pathologically, their association with axillary lymph node (ALN) metastasis and survival remains unclear. This study compares the clinical features of ILC and IDC to evaluate ALN surgery considerations for ILC patients. Materials and Methods: We retrospectively analyzed 3543 patients who underwent upfront surgery for early breast cancer at Yonsei University Severance Hospital between January 2015 and December 2019. Multivariate logistic regression assessed factors linked to ALN metastasis, while Cox regression identified predictors of recurrence and survival. Results: Among the patients, 92.1% had IDC and 7.9% had ILC. T2-stage tumors were more prevalent in ILC (31.4% vs. 18.1%, p < 0.001). The rates of ALN metastasis were similar between the groups (IDC: 21.1%, ILC: 24.6%, p = 0.655); however, the presence of more than two metastatic ALNs was more frequent in ILC (9.6% vs. 5.0%, p = 0.004). Factors associated with having >2 metastatic ALNs included histology, suspicious axillary ultrasound, T stage, and lymphovascular invasion. The median follow-up period was 65 months, with no significant differences observed in 8-year recurrence-free survival (ILC: 95.2%, IDC: 94.1%, p = 0.134) or 5-year overall survival (ILC: 97.1%, IDC: 97.4%, p = 0.289). Conclusions: ILC features larger tumors and a higher nodal burden but has similar survival rates to IDC with proper treatment. Caution is essential in axillary surgery to avoid underestimating the nodal burden. Full article

Background and Objectives: Mixed ductolobular carcinomas (mDLCs) are tumors that contain both ductal and lobular components. The clinicopathological characteristics and impacts on survival of the two components, which have distinct biological behaviors, are still not clearly understood. This study aimed to compare the clinicopathological characteristics, recurrence/metastasis patterns, and survival outcomes of mDLC and invasive lobular carcinoma (ILC), as well as to investigate the prognostic significance of both histopathologies. Materials and Methods: The outcomes of 132 patients who were followed and treated between 2010 and 2021 were analyzed. Patients were examined in two groups, ILC and mDLC. Chi-square tests were performed to compare the baseline clinicopathological characteristics and treatments. Survival rates were subsequently analyzed using the Kaplan–Meier method and compared using the Cox proportional hazards model. Results: In this study, 80 (61%) patients had ILC histopathology, while 52 (39%) had mDLC histopathology. Differences between the groups were observed in median age (p = 0.038), N stage (p = 0.046), estrogen receptor (ER) status (p = 0.005), lymphovascular invasion (p = 0.007), median tumor diameter (p = 0.050), and frequency of distant metastasis (p = 0.029). The treatments, relapse patterns, and metastasis patterns were similar (p > 0.05). No differences in overall survival (OS) and disease-free survival (DFS) were observed. In the multivariate analysis, mDLC histopathology was identified as a poor prognostic factor (HR: 2.95, CI 95%: 1.10–7.88, p = 0.030). Histopathology (ILC vs. mDCL) was not identified as a prognostic factor in the Cox regression analysis for DFS. Conclusion: Although mDLC has poor clinicopathological features (younger age, more advanced N stage, more ER negativity, more lymphovascular invasion, and more frequency of metastases) and appears more aggressive than ILC, these changes do not affect survival in this study. However, mDLC histopathology seems to be associated with poor prognosis for OS. Full article

The purpose of this study was to evaluate the suitability of formalin-fixed and paraffin-embedded (FFPE) samples and fixed fresh (FF) samples for single-cell RNA sequencing (scRNAseq). To this end, we compared single-cell profiles from FFPE and matched FF tissue samples of one invasive carcinoma of no special type carcinoma (invasive ductal carcinoma–IDC) and one invasive lobular carcinoma (ILC) to assess consistency in cell type distribution and molecular profiles. The results were validated using immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and electron microscopy. Additionally, immune cell proportions identified by IHC were quantified using QuPath and compared to the scRNAseq results. FFPE- and FF-derived libraries demonstrated high-quality sequencing metrics, and cellular heterogeneity was similar. No exclusive cell populations were identified by either approach. The four samples analysis identified six types of epithelial cells, as well as tumoral microenvironment populations. The scRNAseq results from epithelial neoplastic cells were concordant with common IHC markers. The proportion of immune cells identified by IHC in FFPE sections were similar to those obtained by scRNAseq. We identified and validated a previously poorly recognized subpopulation of neoplastic multi-ciliated cells (MCCs) (FOXJ1, ROPN1L). Analysis of FOXJ1 in 214 ER-positive invasive carcinomas demonstrated protein expression in one third of tumors, suggesting frequent focal MCC differentiation. Our results support the suitability of scRNAseq analysis using FFPE tissue, and identified a subpopulation of neoplastic MCC in breast cancer. Full article

Invasive lobular carcinoma (ILC), accounting for up to 15% of diagnosed breast cancers, has garnered significant attention due to the loss of the epithelial cell–cell adhesion molecule E-cadherin. This loss contributes to its distinct biological, morphological, and clinical characteristics compared to non-lobular breast cancers. The use of immunohistochemistry (IHC) for E-cadherin and/or the associated cadherin–catenin complex, such as p120-catenin and beta-catenin, in morphologically equivocal cases, has been increasingly adopted in pathology practice. This approach has substantially improved diagnostic accuracy, interobserver reproducibility, and the identification of new morphologic variants of ILC. ILCs exhibit unique tumor biology, which presents considerable challenges in clinical management, especially in preoperative imaging evaluation, surgical management, and neoadjuvant treatment. Recent advances in translational and clinical research have enhanced our understanding of ILC and have spurred the development of new clinical trials specifically targeting these cancers. This review highlights recent progress in various aspects of ILC, including its unique molecular alteration, pathological classification and diagnostic approach, tumor biology and behavior, key clinical management challenges, and ongoing clinical trials, as well as the role of artificial intelligence in diagnosing ILC radiologically and pathologically. The goal of this review is to provide an updated understanding of the tumor biology, clinical manifestations, and molecular landscape of ILC and to help refine current tumor classification and diagnosis, subsequently improving management strategies and overall outcomes for lobular carcinoma patients. Full article

Objectives: To evaluate the neoadjuvant chemotherapy (NACTx) process in breast cancer (BC), its significant treatment-related adverse events (trAEs), tumor clinical response rates, and surgical and pathological outcomes, and to analyze factors influencing cavity shaving and axillary lymph node dissection (ALND) following sentinel lymph node biopsy (SLNB). Methods: A comprehensive retrospective study was conducted at a single center on patients who received NACTx for BC between 2015 and 2021. Results: Medical records of 242 patients were reviewed. Approximately one-fifth encountered grade ≥ 3 trAEs (21.5%), leading 3.3% to discontinue chemotherapy. Anthracycline cardiotoxicity (2.2%) caused one death (mortality rate = 0.4%). For clinical response and surgical and pathological outcomes, 229 patients were eligible. Clinical progression occurred in 3.9% of the patients (14% in triple-negative BC, p = 0.004). Breast-conserving surgery (BCS) was performed in 55% of the patients. There was no significant difference between the type of breast surgery (BCS vs. mastectomy) and molecular subtype, histology, tumor size, or tumor’s pathological response degree. Cavity shaving was required in one-fifth of the patients who underwent BCS (n = 134) due to an invasive tumor at the surgical margin (SM). Tumor histology (invasive ductal vs. invasive lobular carcinoma; OR: 4.962, 95% CI 1.007–24.441, p = 0.049) and tumor SUVMax value (OR: 0.866, 95% CI 0.755–0.993, p = 0.039) had significant independent efficacy on SM positivity. Initially, 75% underwent SLNB, but nearly half of them needed ALND. ALND rates were significantly higher in the luminal A and LB-HER2(−) groups (87% vs. 69%) than in the HER2(+) and TN groups (43% to 50%) (p = 0.001). All luminal A patients and those with lobular histology required ALND after SLNB, but no patients in the HER2-enriched group required ALND. ER positivity and higher PR expression levels were associated with an increased need for ALND after SLNB, whereas HER2 positivity and higher SUVMax values of LN(s) were associated with a significantly reduced need for ALND. About 27% of the patients achieved overall pCR. No pCR was achieved in the LA group. Conclusions: The BC NACTx process requires close monitoring due to severe AEs and disease progression. NACTx decisions must be made on experienced multidisciplinary tumor boards, considering tumor characteristics and expected targets. Full article

Breast cancer is a significant health challenge worldwide and is the most frequently diagnosed cancer among women globally. This review provides a comprehensive overview of breast cancer biology, genomics, and microbial dysbiosis, focusing on its various subtypes and racial differences. Breast cancer is primarily classified into carcinomas and sarcomas, with carcinomas constituting most cases. Epidemiology and breast cancer risk factors are important for public health intervention. Staging and grading, based on the TNM and Nottingham grading systems, respectively, are crucial to determining the clinical outcome and treatment decisions. Histopathological subtypes include in situ and invasive carcinomas, such as invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC). The review explores molecular subtypes, including Luminal A, Luminal B, Basal-like (Triple Negative), and HER2-enriched, and delves into breast cancer’s histological and molecular progression patterns. Recent research findings related to nuclear and mitochondrial genetic alterations, epigenetic reprogramming, and the role of microbiome dysbiosis in breast cancer and racial differences are also reported. The review also provides an update on breast cancer’s current diagnostics and treatment modalities. Full article

Background: Accessory breast cancer cases are rarely reported in the literature. Of the reported cases, the predominantly available ones are those localized in the axillary region. Methods: We present here a very rare case of metastatic accessory breast cancer. It was located in the infra-mammary region (IMR). IMR accessory breast cancer is a rare form of breast cancer. Although ectopic nipples are occasionally found in the IMR, because of the lack of ductal tissue malignant changes, they are rare. Results: In our case, the primary tumor was localized in the congenital accessory breast tissue (ABT). It was recognized as invasive lobular accessory breast cancer cT3N1M0 with a second NST carcinoma, cT2N0M0, Stage IIA, in the ipsilateral breast. A multi-modal approach was applied. Adjuvant chemotherapy was carried out with epirubicin, cyclophosphamide, and paclitaxel, with post-chemotherapy ultrasound followed by right radical mastectomy. Adjuvant radiotherapy was given to our patient in the form of 25 fractions of 50 GY for 25 days, followed by hormonal treatment with Letrozole, 2.5 mg/day, to be continued for 5 years. Conclusions: our case demonstrates that since it is rare to find accessory breast cancer in the infra-mammary region, early identification and management with a multi-modal approach can lead to a successful patient outcome. Full article

Invasive Lobular Carcinoma (ILC) presents a distinct subtype of breast cancer, representing 10–15% of cases, with unique clinical and molecular features. Characterized by a non-cohesive, single-file invasion pattern, ILC is typically estrogen receptor (ER)- and progesterone receptor (PR)-positive but human epidermal growth factor receptor 2 (HER2)-negative. Despite favorable prognostic features, its highly metastatic nature and predilection for atypical sites contribute to lower long-term survival compared to invasive breast carcinoma of no special type (NST). ILC’s genetic landscape includes mutations in various genes (CDH1, BRCA2, ATM, etc.) and signaling pathways that impact treatment responses, especially in endocrine treatment. Furthermore, the diverse ILC subtypes complicate its management. Current challenges in chemotherapy, along with the targeted therapies, are also discussed. The present article aims to comprehensively review the recent literature, focusing on the pathological and molecular aspects of ILC, including associated genetic mutations influencing disease progression and drug resistance. Full article

Fibroblast growth factor receptor 2 (FGFR2) has been associated with breast cancer. We performed in silico analyses to investigate the FGFR2 mRNA expression and splice variants associated with breast cancer subtypes. Online databases, including cBioPortal and TCGA SpliceSeq, were used to examine the association between the FGFR2 expression and splice variants with breast cancer subtypes. A higher FGFR2 mRNA was significantly associated with luminal, oestrogen receptor (ER)-positive breast cancers, and invasive lobular carcinomas, whereas a lower FGFR2 was associated with human epidermal growth factor receptor 2 (HER2)-positive breast cancer and invasive ductal carcinomas. The epithelial alternatively spliced FGFR2 IIIb isoform was significantly enriched in ER+ breast cancer, while the mesenchymal FGFR2 IIIc isoform was significantly prevalent in HER2+ cancer. Increased levels of FGFR2 and IIIb splice isoforms are associated with less aggressive breast cancer phenotypes, while decreased levels of FGFR2 and increased IIIc splice isoform are associated with more aggressive phenotypes. Full article

Invasive lobular carcinoma exhibits unique morphological features frequently associated with alterations in CDH1. Although some studies have identified abnormalities in adhesion factors other than E-cadherin, the molecular mechanisms underlying E-cadherin abnormalities in CDH1-unaltered invasive lobular carcinoma remain poorly understood. In this study, we investigated the molecular underpinnings of E-cadherin dysregulation in invasive lobular carcinoma in the absence of CDH1 gene alterations, using comprehensive bioinformatic analyses. We conducted a comparative study of CDH1-mutated and non-mutated invasive lobular carcinoma and evaluated the differences in mRNA levels, reverse-phase protein array, methylation, and miRNAs. We observed that invasive lobular carcinoma cases without CDH1 alterations exhibited a significantly higher incidence of the Claudin-low subtype (p < 0.01). The results of the reverse-phase protein array indicate no significant difference in E-cadherin expression between CDH1-mutated and non-mutated cases. Therefore, abnormalities in E-cadherin production also exist in CDH1 non-mutated invasive lobular carcinoma. Considering that there are no differences in mRNA levels and methylation status, post-translational modifications are the most plausible explanation for the same. Hence, future studies should focus on elucidating the mechanism underlying E-cadherin inactivation via post-translational modifications in CDH1 non-mutated invasive lobular carcinoma. Full article