The differences between pure and mixed invasive micropapillary breast cancer: the epithelial-mesenchymal transition molecules and prognosis.

PURPOSE: Invasive micropapillary carcinoma (IMPC) of the breast is known for its high metastatic potential, but the definition of pure and mixed IMPC remains unclear. This retrospective cohort study aims to investigate the prognostic significance of the micropapillary component ratio and the expression of critical molecules of epithelial-mesenchymal transition (EMT), including E-cadherin (E-cad), N-cadherin (N-cad), CD44s, and ß-catenin (ß-cat), in distinguishing between pure and mixed IMPCs. METHODS: We analyzed 100 cases of locally advanced IMPC between 2000 and 2018 and excluded patients who received neoadjuvant chemotherapy. Pure IMPC was defined as having a micropapillary component of over 90%. A comprehensive recording of prognostic parameters was conducted. The IMPC areas were analyzed using the immunohistochemical (IHC) staining method on the microarray set for pure and mixed IMPC patients. Pearson's chi-square, Fisher's exact tests, Kaplan-Meier analysis, and Cox proportional hazards analysis were employed. RESULTS: The comparative survival analysis of the entire group, based on overall survival (OS) and disease-free survival (DFS), revealed no significant difference between the pure and mixed groups (P = 0.480, HR = 1.474 [0.502-4.325] and P = 0.390, HR = 1.587 [0.550-4.640], respectively). However, in the pure IMPC group, certain factors were found to be associated with a higher risk of short survival. These factors included skin involvement (P = 0.050), pT3&4 category (P = 0.006), a ratio of intraductal component (> 5%) (P = 0.032), and high-level expression of N-cad (P = 0.020). Notably, none of the risk factors identified for short OS in pure IMPC cases were observed as significant risks in mixed cases and vice versa. Furthermore, N-cad was identified as a poor prognostic marker for OS in pure IMPCs (P = 0.002). CONCLUSION: The selection of a 90% ratio for classifying pure IMPCs revealed significant differences in certain molecular and prognostic parameters between pure and mixed groups. Notably, the involvement of N-cadherin in the epithelial-mesenchymal transition (EMT) process provided crucial insights for predicting OS and DFS while also distinguishing between the two groups. These findings strongly support the notion that the pure IMPC subgroup represents a distinct entity characterized by unique molecular characteristics and behavioral patterns.

Comprehensive Immunohistochemical Analysis of Epithelial-Mesenchymal Transition Biomarkers in the Invasive Micropapillary Cancer of the Breast.

Background: Invasive micropapillary carcinoma (IMPC) of the breast is commonly associated with a poor prognosis due to its high incidence of lymphovascular invasion and lymph node metastasis (LNM). Our study is aimed at investigating the prognostic significance of the expressions of E-cadherin (E-cad), N-cadherin (N-cad), CD44s, and ß-catenin (ß-cat). In addition, it is aimed at deciphering the consistency of these markers between the IMPC, the invasive breast carcinoma, no-special type (IBC-NST), and LNM components in the same IMPC cases. Methods: Sixty-two IMPC cases with LNM from 1996 to 2018 were analyzed. Immunohistochemical staining was performed separately on the three regions for each patient. Statistical analyses included Kaplan-Meier, Cox regression, and McNemar's statistical tests. Results: Loss of CD44 expression in IMPC, IBC-NST, and LNM areas was associated with poor prognosis in overall survival (OS) (p = 0.010, p < 0.0005, p = 0.025). Loss of CD44 expression in the IBC-NST, gain of N-cad expression in the IMPC, and loss of ß-cat expression in the LNM areas were indicators of poor prognosis in disease-free survival (DFS) (p = 0.005, p = 0.041, p = 0.009). Conclusion: Our evaluation of this rare subtype, focusing on the expression of key epithelial-mesenchymal transition (EMT) molecules, revealed that it shares characteristics with the IBC-NST component within mixed tumors. Notably, contrary to expectations, a reduction in CD44 expression was found to adversely affect both OS and DFS. By conducting staining procedures simultaneously across three regions within the same patient, a novel approach has provided valuable insights into the mechanisms of EMT.

The Oncologic Safety of Sentinel Lymph Node Biopsy in Patients with Node-Positive Breast Cancer with Complete Response to Neoadjuvant Chemotherapy: A Single-Center Experience.

Objective: To evaluate the efficiency and safety of sentinel lymph node biopsy (SLNB) in patients with breast cancer with complete response to neoadjuvant chemotherapy (NAC). Methods: Ninety-two consecutive (T1-4 and N1-2) patients with breast cancer who had pathologic and/or clinical and radiologic axillary lymph node involvement were included. All patients received NAC. Patients with a clinical and radiologic complete response in the axilla after NAC underwent SLNB. Pathologic complete response (ypCR) was defined as the absence of residual invasive and in situ cancer, and near-complete response (ypNCR) represented in situ and/or ≤ 1 mm residual tumor in the breast and/or presence of malignant cell clusters (≤0.2 mm) and/or micrometastases (≤2.0 mm) in the axillary lymph nodes (ALN) (ypTis/T1mi, ypN0i+/pN1mi). Results: The mean age of the 92 patients was 49.6 ± 10.3 years and the mean follow-up was 34.0 ± 17.8 months. With respect to breast tumors, 23 (25.0%) patients had complete and 14 (15.2%) had a near-complete response to NAC. Complete response in ALN was obtained in 39 (42.4%) patients and near-complete in six (6.5%) patients. The overall survival of the 33 patients who achieved ypCR and ypNCR was 100% and the remaining 59 patients with partial or no response to NAC was 83.1% at a mean follow-up of 34 months (p=0.063). Conclusions: In this study, no event developed in cases with ypCR and ypNCR in the breast and axilla. The persistence of the same results in long-termfollow-ups may enable the use of ypNCR as a positive prognostic marker in addition to ypCR.

Biomarker Discordances and Alterations Observed in Breast Cancer Treated with Neoadjuvant Chemotherapy: Causes, Frequencies, and Clinical Significances.

PURPOSE: Biomarker discordances and alterations can be encountered between tru-cut biopsy and residual tumor in breast cancer treated with neoadjuvant chemotherapy (NACTx). We aimed to investigate the effect of NACTx on major biomarker expression (ER, PR, HER2, Ki-67) and tumor grade, the frequency and causes of receptor discordances, and the clinical significance of changes in terms of adjuvant therapy need and chemosensitivity. METHODS: In this retrospective study, ER, PR, HER2, and Ki-67 expression and tumor grades were compared between pre- and post-NACTx tumor samples using the Wilcoxon signed-rank test. The frequencies of receptor discordances and the need for new adjuvant therapy due to discordances were calculated. The effect of patient and tumor characteristics and NACTx regimens on discordances was investigated using multivariate analysis. Using histopathological examinations, residual tumors were divided into chemotherapy-responsive and chemotherapy-unresponsive tumors. Biomarker changes in both groups were analyzed for predictability of chemosensitivity. RESULTS: Of the 169 patients who received NACTx, 102 patients having enough residual tumors in the surgical pathology specimen were enrolled in the study. Histopathologically, about 70% of tumors were partially responsive to NACTx and 30% were unresponsive (chemo-resistant). The concordance and discordance rates were 95.1% versus 4.9% for ER (p = 0.180), 97.1% versus 2.9% for PR (p = 0.083), and 89.2% versus 10.8% for HER2 (p = 0.763), respectively. In addition, 15% of hormone receptor (HR)-negative patients became HR(+) and 5.7% of HER2(-) patients became HER2(+) in the residual tumors, requiring adjuvant endocrine or anti-HER2 therapy. In particular, 18% of triple-negative patients became HR(+) and 12% became HER2(+). HER2 loss was detected in 40% of HER2(+) patients. Multivariate logistic regression analysis revealed that lower estrogen expression (p = 0.046), a smaller tumor size (p = 0.029), and anti-HER2 therapy (p < 0.001) have independent efficacy on ER discordance, PR discordance, and HER2 discordance, respectively. Ki-67 and PR expression significantly decreased in chemotherapy-responsive tumors (p = 0.001 and p = 0.004), and the tumor grade increased in chemotherapy-unresponsive tumors (p = 0.034). CONCLUSIONS: Approximately 3-5% of HR discordance and about 10% of HER2 discordance can be observed in breast cancer after currently used NACTx regimens. Discordances are bi-directional (from positive to negative and vice versa), and their causes are multifactorial; they should be assessed accordingly. The NACTx effect alone cannot explain observed discordances but can cause biomarker alterations. The change in receptor status from positive to negative, especially HER2 loss, is mainly associated with the NACTx effect. However, the shift from negative to positive is thought to be primarily related to intratumoral heterogeneity. Receptor statuses becoming positive are of more clinical importance due to adjuvant therapy requirements. Biomarker alterations in PR, Ki-67, and tumor grade can provide predictive information about tumor chemosensitivity.

Gastrointestinal Tract Metastases of Invasive Lobular Carcinoma of the Breast: An Immunohistochemical Survey Algorithm.

Invasive lobular carcinoma (ILC) accounts for almost 15% of all breast carcinomas. The potential of ILC to metastasize to the gastointestinal system is significantly greater than that of invasive ductal carcinoma. Gastric metastasis occurred in the ninth year of the follow-up in a patient who was operated on the right breast due to ILC. The patient was investigated for simultaneous masses in the stomach and colon, and a random mass was found in her right breast.

The Importance of the Pathological Perspective in the Management of the Invasive Lobular Carcinoma.

Background: Invasive lobular carcinomas (ILC) account for 10-15% of all breast cancers and are the second most common histological form of breast cancer. They usually show a discohesive pattern of single cell infiltration, tend to be multifocal, and the tumor may not be accompanied by a stromal reaction. Because of these histological features, which are not common in other breast tumors, radiological detection of the tumor may be difficult, and its pathological evaluation in terms of size and spread is often problematic. The SSO-ASTRO guideline defines the negative surgical margin in breast-conserving surgeries as the absence of tumor detection on the ink. However, surgical margin assessment in invasive lobular carcinomas has not been much discussed from the pathological perspective. Methods: The study included 79 cases diagnosed with invasive lobular carcinoma by a Tru-cut biopsy where operated in our center between 2014 and 2021. Clinicopathological characteristics of the cases, results of an intraoperative frozen evaluation in cases that underwent conservative surgery, the necessity of re-excision and complementary mastectomy, and consistency in radiological and pathological response evaluation in cases receiving neoadjuvant treatment were questioned. Results: The tumor was multifocal in 37 (46.8%) cases and single tumor focus in 42 (53.2%) cases. When the entire patient population was evaluated, regardless of focality, mastectomy was performed in 27 patients (34.2%) and breast-conserving surgery (BCS) was performed in 52 patients (65.8%). Of the 52 patients who underwent BCS, 26 (50%) required an additional surgical procedure (cavity revision or completion mastectomy). There is a statistical relationship between tumor size and additional surgical intervention (p < 0.05). BCS was performed in 7 of 12 patients who were operated on after neoadjuvant treatment, but all of them were reoperated with the same or a second session and turned to mastectomy. Neoadjuvant treatment and the need for reoperation were statistically significant (p < 0.05). Additional surgical procedures were performed in 20 (44.4%) of 45 patients in BCS cases who did not receive neoadjuvant therapy. Conclusions: Diagnostic difficulties in the intraoperative frozen evaluation of invasive lobular carcinoma are due to the different histopathological patterns of the ILC. In our study, it was determined that large tumor size and neoadjuvant therapy increased the need for additional surgical procedures. It is thought that the pathological perspective is the determining factor in order to minimize the negative effects such as unsuccessful cosmesis, an additional surgical burden on the patient, and cost increase that may occur with additional surgical procedures; for this reason, new approaches should be discussed in the treatment planning of invasive lobular carcinoma cases.

Prognostic Value of Receptor Change After Neoadjuvant Chemotherapy in Breast Cancer Patients.

Objective: The aim of this study was to investigate the relationship between hormone receptors (HR) and human epidermal growth factor receptor 2 (HER-2) discordance with prognosis, before and after neoadjuvant chemotherapy (NAC) in breast cancer patients. Materials and Methods: Histopathological data of 142 breast cancer patients attending a single center between 2001 and 2018 and were operated after NAC were evaluated retrospectively. Results: The median (range) age of patients was 58 (32-69) years. In patients who underwent Tru-cut biopsy before NAC, 77 patients were ER+, 30 were ER (-), 73 were PR (+), 33 were PR-, 14 were HER-2 (+), and 94 patients were HER-2 (-). In terms of ER change, five patients were found to have changed status and 85 had no receptor change. The mean overall survival of patients with receptor changes was 31 months against 60 months in patients with no receptor changes, which was not significant (p = 0.351). In sub-group analysis of patients undergoing receptor change, the ER (+) → (-) group had significantly shorter survival (p = 0.003). For PR change, mean survival was 38 months in seven patients with a receptor change and 59 months in 87 patients without a receptor change, which was not significant (p = 0.603). Sub-group analysis of PR status change showed that survival was significantly shorter in the PR (+) → (-) group (p = 0.012). Conclusion: These results suggest there is a need for reassessment of HR and HER-2 status in surgical samples from patients following NAC, and that NAC-induced changes in the HR state may be used as a prognostic factor.

Breast cancer patients with isolated bone metastases and oligometastatic bone disease show different survival outcomes.

In this study, we planned to investigate the clinical course of patients with breast cancer with oligometastatic bone disease (OMBD). The patients were grouped according to the characteristics and the sites of metastases. Group I included 928 patients without metastasis. Group II, the OMBD group, included 68 patients. Group III, the widespread metastasis group, comprised 185 patients with multiple bone metastases and/or solid organ metastases. The mean overall survival of the groups was 16.7 ± 0.3 years in group 1, and 7.8 ± 0.8 and 5.9 ± 0.4 years in groups 2 and 3, respectively (p < 0.001 for the comparison of all three groups together; p < 0.001 for group 1 vs. 2 and 3) and (p = 0.037 for group 2 vs. group 3). In the subgroup survival analysis of patients in group 2 (OMBD), the mean and median survival was 5.5 ± 0.8 and 4.0 ± 0.8 years vs. 9.2 ± 0.98 and 9.0 ± 1.05 years in patients with more than one bone metastasis and single bone metastasis, respectively (p = 0.019). OMBD seems to be a different disease than breast cancer with isolated bone metastases. The high risk of developing OMBD, especially following locoregional recurrence, increases the importance of locoregional therapy in large T and N stage tumors.

Axillary metastasis in clinically node-negative breast cancer.

AIM OF WORK: This study investigates the factors related to metastasis detection in a sentinel lymph node biopsy (SLN) in patients without clinical axillary involvement. PATIENTS AND METHODS: The medical records of patients who underwent an SLN biopsy after diagnosis with early-stage breast cancer were evaluated retrospectively. The study sample included 64 patients divided into two groups according to the histopathological examination of the SLN biopsy: Group I (positive for axillary metastasis) and Group II (negative for axillary metastasis). RESULTS: The frequency of lymphovascular invasion was significantly higher in Group I (57%) than in Group II (13%) (p = 0.003). The progesterone receptor status (p = 0.036), tumor T-stage(p = 0,047), and Ki-67 index differed significantly (p = 0.045) between the two groups. While in univariate analysis, lymphovascular invasion, T-stage and KI-67 index were significant, in multivariate analysis only lymphovascular invasion was found to be significant. No significant differences were found in terms of estrogen receptor and HER2 considering tumor invasion type, histologic grade, vascular invasion, neural invasion, multifocality or bilaterality, hormone receptor status, menopause status, total number of lymph nodes, presence of non-sentinel lymph nodes and the number of SLNs in the groups (p > 0.05). CONCLUSIONS: The results of this study indicate that lymphovascular invasion is associated with axillary metastasis, based on an SLN biopsy.