Combining Molecular and Traditional Prognostic Factors: A Holistic Approach to Breast Cancer Prognostication.

Breast cancer is a heterogeneous disease with various morphologies and molecular features, and it is the second leading cause of cancer death in women in developed countries. According to the literature, we currently lack both prognostic biomarkers and therapeutic targets. The most important prognostic factors are disease stage and Nottingham grade. We conducted a retrospective analysis involving 273 patients with BC who underwent neoadjuvant therapy before proceeding to curative surgical treatment between 1 January 2014 and 31 December 2023. Pathological procedures were conducted at the Department of Pathology, Emergency County Hospital of Targu Mureș, Romania. A statistical analysis was performed. Regarding the relationship between Nottingham grade and Ki67, grade I was associated with a Ki67 of less than 14. The relationship between tumor grade and luminal was similar (p = 0.0001): Grade I was associated with luminal A. Regarding TNM stage, it was statistically significantly correlated with TILs (p = 0.01) and RCB (p = 0.0001). Stages III and IV were associated with a high RCB and poor prognosis. Regarding the prognostic value, Nottingham grade 3 and TNM stages III and IV were correlated with low overall survival and disease-free survival, with poor prognosis, and, among the molecular variables, RCB played the most important prognostic role.

Conventional Tools for Predicting Satisfactory Response to Neoadjuvant Chemotherapy in HR+/HER2- Breast Cancer Patients.

Aim: The aim of the study was to assess the role of Magee Equation 3 (MagEq3), IHC4 score, and HER2-low status in predicting "satisfactory response (SR)" to neoadjuvant chemotherapy (NAC) in HR+/HER2- breast cancer (BC) patients. Methods: In a retrospective study, female patients of any age with T1-4, N0-2, M0 HR+/HER2- BC who received NAC and underwent adequate locoregional surgical treatment were included. Patients were grouped according to 2 outcomes: (a) overall response to NAC in breast and axilla by using residual cancer burden (RCB) criteria and (b) axillary downstaging after NAC by using N staging. 2 cohorts for overall response were overall SR (RCB 0-1) and no SR (RCB 2-3). On the other hand, for axillary downstaging, 2 cohorts constituted from axillary SR (ypN0 and ypN0i+) and no SR (ypNmic-N3). MagEq3 and IHC4 scores were calculated from their pathological tumor slides in each patient. HER2 status was categorized as either "no" or "low." In addition, patient age, family history, tumor histology, stage at admission, and Ki-67 status were compared between cohorts according to predefined outcomes. Results: In a total of 230 BC patients, 228 patients were included to compare according to their RCB levels. The mean age of patients with overall SR was significantly lower than those without. Patients with high Ki-67 expression, high (>30) MagEq3 score, high ICH4 quartile, and HER2-low status had significantly more overall SR. On the other hand, only patients with high Ki-67 expression had significantly more axillary SR. MagEq3 score levels, ICH4 quartiles, and HER2 status were similar between patients with axillary SR and not. Conclusion: MagEq3 and IHC4 tools seemed to be useful to predict those HR+/HER2- BC patients who are most likely to get benefit from NAC. But, only high Ki-67 expression level significantly predicted satisfactory axillary downstaging in HR+/HER2- BC patients.

Can Morphological and Molecular Parameters of the Primary Breast Tumor Predict the Positivity of Nonsentinel Lymph Nodes After Positive Sentinel Lymph Node Biopsy?

Background: Sentinel lymph node (SLN) biopsy is the gold standard in the evaluation of the axillary status in patients with breast cancer. In cases meeting the Z0011 criteria, no further surgery is needed, while in the remaining cases axillary dissection is required. The aim of the study was to evaluate which morphological and molecular parameters of primary breast tumor or positive SLN can predict the positivity of nonsentinel lymph nodes (NSLN) in order to avoid unnecessary axillary lymphadenectomy. Methods: We conducted a retrospective study on 170 consecutive invasive breast carcinomas, in which SLN biopsy was performed for staging. Results: 42 (24%) cases presented SLN metastases, of which 11 were micrometastases, 6 cases met the Z0011 criteria, requiring no subsequent surgery. 25 patients underwent subsequent ANLD, but only 7 cases (28%) had positive NSLN. In this series, only the tumor diameter 20 mm can predict positive nonsentinel lymph nodes (p= 0.058; CI: 0.05787 to 0.8224). Other parameters such as patient's age (p=0.280; CI:0.7544 to 7.998), histological type (p=0.231; CI: 0.05374 to 9.271), histological grade (p=0.929; CI: 0.2351 to 3.515), molecular profile of the tumor (p=0.362; CI: 0.2416 to 4.663), number of positive SLN (p=0.378; CI: 0.1083 to 1.570), presence of extracapsular extension (p=0.625; CI: 0.5066 to 13.96) and lymph node ratio (p=0.656; CI: 0.5068 to 5.768) cannot predict the presence of metastasis in the NSLN. Conclusion: In cases in which the patient does not meet the Z0011 criteria and/or these criteria are not used, axillary lymph node dissection is the surgical treatment of choice.

The Accuracy of the Preoperative Axillary Ultrasound Examination in Predicting the Status of the Sentinel Lymph Node Involvement in Patients with Infiltrating Breast Carcinoma.

Background: we aimed to determine the accuracy of preoperative axillary ultrasound (US) in predicting the presence of sentinel lymph node (SLN) metastasis in breast cancer patients. Methods and Results: out of 54 cases, visible nodes on US were identified in 35 cases of which, 15 had metastasis. In 19 cases no axillary lymph nodes were visible on US. Of these, only 3 had metastasis. Moreover, our results demonstrated that neither the maximum diameter (p=0.738 Fisher exact test) nor the ratio between the longitudinal and transverse axes (p=0.728 Fisher exact test) can predict the positivity of the SLN. Conclusion: US cannot predict the positivity of the SLN.

ER-/PR+ subset of invasive breast carcinoma (IBC): a distinct phenotype with good prognosis.

The expression of the estrogen (ER) and progesterone (PR) receptors in IBC patients represents a well-know prognostic and predictive factor. The existence of ER-/PR+ as a distinct phenotype, however, is controversial as well as is its prognostic significance. The aim of the study was to assess the incidence and prognosis in patients with ER-/PR+ IBC. One hundred and twelve patients with IBC were analyzed regarding ER/PR profile and survival. GraphPad prism 6 for Windows and Kaplan Mayer curve were used to determine overall survival (OS) and disease-free survival (DFS), with p < 0.05 as statistically significant. Of the 112 IBC patients, 75% were ER+/PR-, 16.07% were ER-/PR-, 7.14% were ER+/PR- and only 1.78% were ER-/PR+. OS was 100% in the ER-/PR+ group and 91.6% in the ER+/PR+ group. The lowest OS was found in the ER-/PR- group (72.2%), while OS was 100% in ER-/PR+ group. Regarding DFS, there were no statistically significant differences in the four groups (p = 0.11), although the highest DFS was found in the ER-/PR+ group (100%). ER-/PR+ tumors were associated with younger age (p = 0.72), smaller tumor diameter (p = 0.27), absence of lymph node metastases, and HER2 overexpression. Our results suggest that ER-/PR+ cases represent the rarest phenotype in IBC cases but its association with the best OS and DFS in other ER/PR phenotypes indicates an independent predictive value of PR for treatment considerations.

Encapsulated papillary breast carcinoma in a male patient in association with microdeposits of carcinoma cells in the needle track and sentinel lymph node treated conservatively.

We present an encapsulated papillary breast carcinoma in a male patient, in association with microdeposits of carcinoma cells within the needle track, in the lymphatic spaces of the breast parenchyma and subcapsular sinus of two sentinel lymph nodes in which conservative treatment has been recommended. Both in females and males, papillary tumours and particularly encapsulated papillary breast carcinoma can be associated with microdeposits mechanically displaced, which have to be differentiated from true invasion and metastases and treated conservatively.

Obtaining adequate surgical margin status in breast-conservation therapy: intraoperative ultrasound-guided resection versus specimen mammography.

BACKGROUND AND AIM: The purpose of breast-conserving surgery (BCS) for women with cancer is to perform an oncological radical procedure with disease-free margins at the final histological assessment and with the best aesthetic result possible. Intraoperative resected specimen ultrasound and intraoperative resected specimen mammography may reduce the rates of positive margins and reexcision among patients undergoing conserving therapy. Our objective is to compare the two methods with the histopathological results for a preset cut off and asses which parameters can influence the positive margin status. METHOD: A prospective study was performed on 83 patients who underwent breast conservation surgery for early breast cancer (pT1-3a pN0-1 M0) between 2014 and 2016. After excision the specimen was oriented in the operating room by the surgeon. Metallic clips and threads were placed on margins: one clip and the long thread at 12 o'clock, two clips and the short threads at 9 o'clock. The next step was intraoperative ultrasound assessment of the specimen. For the margins under 2 mm we performed selective margin shaving, followed by mammography to identify and document the lesion and finally histopathological examination of the specimen with reporting the gross and microscopic margins. The positive margins required re-excision or boost of radiation at the posterior or anterior margins, depending on the case. RESULTS: We set a cut-off at 2 mm. The sensitivity and specificity of the intraoperative margin assessment via the ultrasound method were 90.91% (95% CI 70.84-98.88%) and 67.21% (95% CI 54-78.69%) respectively. The sensitivity and specificity of the intraoperative margin assessment via the mammographic procedure were 45.45% (95% CI 24.39-67.79%) and 85.25% (95% CI 73.83-93.02%) respectively. There was positive correlation between the histopathological and intraoperative ultrasound exam (p=0.018) and negative correlation between the histopathological exam and the post-operative mammographic exam (p=0.68). We found a positive correlation between the positive margin status and age (<40), preoperative chemotherapy, intraductal carcinoma, inflammatory process around the tumor, and the immunohistochemical triple negative profile. CONCLUSIONS: According to our results, the intraoperative ultrasound of the breast specimen for a cutt-off at 2 mm can decrease the rates of margin positivity compared to the mammographic procedure and has the potential to diminish the number of subsequent undesired re-excisions.

The Revisited Role of Ultrasound Guided Core Needle Biopsy in the Breast Cancer Diagnosis.

Background: Core needle biopsy (CNB) is an alternative to surgical biopsy in establishing the histopathological diagnosis of mammary lesions. AIM OF THE STUDY: The aim is to determine the accuracy of ultrasound guided CNB (US-CNB) in establishing breast cancer diagnosis. MATERIALS AND METHODS: We retrospectively analyzed the data of US-CNB patients between May 2012 - December 2014. One hundred sixty-three biopsies were performed in 155 patients. To assess the diagnostic accuracy of US-CNB, the results were correlated with the gold-standard of surgical excision of the breast lesions, thus, 90 patients (94 breast lesions) were included in the study group. We calculated the concordance of the results using the Kappa Coefficient, sensitivity and specificity using the ROC curve and the false-negative rate. Results: US-CNB identified 74 (79%) malignant lesions, 1 (1%) precursor high-risk lesion, and 19 (20%) benign lesions. Concordance between histopathological results was 96.8% (kappa: 0.91). The 94.2% (kappa: 0.80) consensus of the histological type could be calculated for 70 invasive carcinomas. The 61.8% (kappa: 0.41) concordance of the histological grade could be calculated for 55 invasive carcinomas. Sensitivity and specificity were 98.6%, and 100%, respectively. The false-negative rate was 1.3%. Conclusions: US-CNB is an excellent alternative to surgical biopsy in establishing the histopathological diagnosis of breast lesions, provided it is performed by a specialized team and there is clinical-radiological-histopathological concordance in all cases.

Discordance Rate in Estrogen Receptor, Progesterone Receptor, HER2 Status, and Ki67 Index Between Primary Unifocal and Multiple Homogenous Breast Carcinomas and Synchronous Axillary Lymph Node Metastases Have an Impact on Therapeutic Decision.

BACKGROUND: We aimed to demonstrate that in breast carcinomas the tumor profile is not stable during the metastatic process, with impact on therapeutic decisions. MATERIALS AND METHODS: We analyzed the estrogen receptor (ER), progesterone receptor (PR), and HER2 status and Ki67 index in 41 primary unifocal (PU) and 37 primary multiple (PM) breast carcinomas with identical immunohistochemical profiles among multiple tumor foci and the matched axillary lymph node metastases. We defined as concordant cases in which the primary tumor (PU or PM) and lymph node metastases displayed identical positivity or negativity for ER, PR, HER2, Ki67 and as discordant cases in which there was a mismatch in at least 1 biological parameter among PU and PM tumor and lymph node metastases. Moreover, we defined as concordant cases in which the molecular profile (based on the immunohistochemical evaluation of ER, PR, HER2, and Ki67) was concordant among PU and PM tumors and lymph node metastases and mismatch cases as those in which the molecular profile of the primary tumor differs from one of the lymph node metastases in at least 1 lymph node. RESULTS: The positivity for the biological markers is not stable during the metastatic process. In this study the total rate of discordant cases was 92.7% in PU tumors and 75.7% in PM homogenous tumors (P=0.058, odds ratio=0.245, 95% confidence interval, 0.06-0.991). The total rate of shifted cases was 64.9% in PM tumors and 82.9% in PU tumors. The highest rate of shifting was encountered from Luminal B-like to Luminal A-like. In 11 out of 37 (29.7%) PM and in 17 out of 41 (41.5%) PU cases the subtype shifted to a poorer one with respect to prognosis. CONCLUSIONS: The patients in whom the primary tumor is hormone receptor and/or HER2 negative but is positive for these markers in the axillary lymph nodes could become eligible for hormonal treatment and/or trastuzumab treatment, which may significantly improve the patient's outcome.

[Experimental study on the resistance to intraluminal pressure between handsewn and stapled anastomosis. In vitro experimental study]. / A bélrendszer kézi és gépi anastomosisainak nyomással szembeni ellenálló képességének felmérése. In vitro kísérletes tanulmány.

Intoduction and aim: The aim of the study was to compare the resistance to pressure of stapled and manually handsewn intestinal suture lines on in vitro pig intestine model. METHOD: We performed different types of stapled and manual sutures and the pressure level was measured using a differential pressure manometer. RESULTS: Although the hand-sewn end-to-end suture turned out to be the most resistant to pressure, statistical analysis revealed no significant differences compared to stapled suture (p = 0.49). In stump closure techniques, we observed a statistically high significance in resistance to pressure in the favour of manual stump closure (p = 0.004).Regarding side-to-side sutures we did not find any statistically significant differences in resistance to pressure between the techniques (p = 0.06). CONCLUSION: We can conclude that regarding the stump closure, the most resistant to pressure is the hand-sewn procedure, but in the other types of anastomosis, no significant differences was found between the stapled and hand-sewn techniques. Orv Hetil. 2017; 158(42): 1674-1680.

Review on Practical Approach in Multiple Breast Carcinomas: Does Each Focus Matter?

Breast carcinoma is the most frequent form of cancer encountered in women worldwide. In the routine practice, most of breast carcinomas are diagnosed as unifocal, however, a variable proportion is represented by multiple tumor foci. Since data regarding the incidence, definition, morphological and molecular profile, treatment and prognosis of multiple breast carcinomas are currently contradictory we are presenting a practical approach for pathologists dealing with such a lesion, which may display morphological and molecular heterogeneity among multiple foci with an impact on management and prognosis. Multiple tumor foci should be reported separately and taken into account when establishing the treatment.

Does the Surgical Management of the Intercostobrachial Nerve Influence the Postoperatory Paresthesia of the Upper Limb and Life Quality in Breast Cancer Patients?

The aim of our study was to evaluate the extent to which the preservation or the section of the intercostobrachial nerve (ICBN) influences the development of postoperatoryparesthesia and to assess whether the development of paresthesiamay change the patient's life quality after surgical treatment for breast carcinoma. MATERIAL AND METHODS: We performed a nonrandomized retrospective study including 100 patients who underwent axillary lymph node dissection for infiltrating breast carcinoma associated with axillary lymph node metastases. Using a questionnaire we studied the patients general life quality in the postoperative period. For the statistical analysis we used GraphPad Prism, Fisher'™s exact test and Chi square test. Results: 100 patients were included in our study with a mean age of 59.7 years. In 50 cases, the ICBN was preserved (Group 1),while in the remaining 50 cases the ICBN was sectioned during surgery (Group 2). Significantly more patients from Group 2 complained about postoperative paresthesia (p=0.026). In our series, the management of the ICBN cannot be significantly correlated with the impairment of the patients daily activities (p=0.2), sleeping cycle (p=0.2), and general life quality after surgery (p=0.67). We can conclude that the management of ICBN has a great influence on the development of postoperative paresthesia. Although the paresthesia does not have a negative effect on the patient'™s life quality in the postoperative period, in our opinion it is important to preserve the ICBN in order to prevent postoperative paresthesia.

Correlation between obesity and prognostic/predictive parameters with emphasis on the importance of lymph node metastases in patients with invasive breast carcinoma.

We aimed to evaluate whether obese women experience more advanced invasive breast carcinoma (IBC) with a higher number of involved lymph nodes, higher range of axillary lymph node ratio (LNR) and presence and size of extracapsular extension as it may have an impact on prognosis and management. 245 patients diagnosed with IBC were divided into normal weight (NW), overweight (OW) and obese (OB) groups. Patients were divided into high range of LNR (LNR over or equal to 0.2) and low LNR (LNR less than 0.2). The extracapsular extension dimensions were measured on the original slides of each case and grouped into ≤ 1 mm and > 1 mm. 84 patients (33.07%) were OW, 72 (29.38%) OB and 91 (37.14%) NW. 45.7% of cases had macrometastasis in the axillary lymph nodes. NW patients had significantly fewer metastatic lymph nodes (p = 0.05) than in the OW/OB groups. There was no statistically significant difference between BMI groups according to the LNR (p = 0.66). Out of 111 cases with macrometastasis, 58 cases (52.25%) had extracapsular extension (ECE) (11.7% NW, 24.32% OW and 16.22% OB). Significantly more OW patients presented extranodal invasion (p = 0.04). We found no statistically significant relationship between the extracapsular extension diameter and BMI groups (p = 0.1).

Intratumoral Heterogeneity for Ki-67 Index in Invasive Breast Carcinoma: A Study on 131 Consecutive Cases.

INTRODUCTION: In addition to conventional histopathologic parameters, the assessment of proliferation is a major factor in treatment decision in breast carcinoma patients. The aim of this study was to assess whether Ki-67 heterogeneity in invasive breast carcinomas could have an impact over treatment decision. MATERIALS AND METHODS: Immunohistochemistry for Ki-67 was evaluated in resection specimens of 131 consecutive invasive breast carcinomas. Heterogeneity was defined as the presence of a low (<17%) and high (>35%) proliferative activity within the same tumor in the same histologic section. The rest of the cases were defined as homogenous. Clinical-pathologic features were also analyzed. RESULTS: A total of 107 (81.67%) of the cases were homogenous and 24 of 131 cases (18.32%) showed heterogeneity as defined above. Among these, 10 (41.6%) cases showed a gradient of increasing staining toward the tumor edge and 14 (58.4%) cases showed hot spots. In general, the proliferative activity varied from 1% to 90% in different areas of the tumor. A higher incidence of breast carcinoma was observed after menopause in both groups (83.33% in heterogeneous cases and 79.43% in homogeneous cases) (P=0.783). These groups were similar as far as the most frequent histologic types were concerned: no special type (95.83% vs. 56.07%) (P=0.0001). Tumor histologic grade, T and N stage were similar in both groups. We noted a higher proportion of stage N3 cases in the heterogeneous tumor group (54.16% vs. 34.57%) (P=0.14). Prognostic markers analysis in the heterogeneous cases revealed 100% positivity for hormone receptors (compared with 94.65%) and a much higher proportion of HER2-negative cases (87.5% vs. 73.83%) (P=0.19). CONCLUSION: As Ki-67 heterogeneity can be encountered in breast carcinomas and Ki-67 value could have an impact on clinical decisions, it is mandatory to evaluate the whole specimen and not only the core biopsy specimen and to correlate it with mitotic count.

Indications of a Defunctioning Stoma in Colorectal Anastomosis--Our Experience and Review of the Literature.

BACKGROUND: Defunctioning stomas can prevent consequences of anastomotic leakage, but they are not free of complications. OBJECTIVES: The identification of high-risk patients to establish criteria for strong and relative indications for the formation of a defunctioning stoma. METHODS: Two hundred fifty consecutive colorectal anastomoses were performed between 2004 and 2015; 95.2% of these were for colorectal cancer. In 130 cases, mechanical anastomosis was used. A protective stoma was performed in only 15 cases. The incidence of anastomotic leakage was evaluated according to multiple parameters, as were the postoperative complications related to protective stomas. The outcomes were compared to those reported in the literature. RESULTS: Symptomatic anastomotic leakage occurred in six patients (2.4%) and resulted in four deaths. None of the patients with a protective stoma developed serious complications related to the colorectal anastomosis. However, serious ileostomy-related complications occurred in two cases (15.38%). CONCLUSIONS: Protective stomas should be used only according to the risk criteria of the patients. Strong indications are: anastomotic imperfections, anastomosis under tension, previous pelvic irradiation, ultralow anastomosis in patients older than 70 years, patients over 80 years, and significant co-morbidities.

Clinical implications of multifocality as a prognostic factor in breast carcinoma - a multivariate analysis study comprising 460 cases.

BACKGROUND: Multifocality is not listed among prognostic factors in international breast cancer guidelines. This study aims to analyze survival in multiple breast carcinomas (MFMC cc) compared to unifocal ones (UF cc), in order to assess the prognostic impact of multifocality. METHODS: The study included 460 breast carcinomas (2002-2006) with a median follow-up time of 104 months (74-134 months). We assessed mortality rates, overall survival at 5 years and 10 years in general, overall survival at 5 and 10 years in MFMC cc compared to UF cc, as well as median survival and survival rate according to age, T status and axillary lymph node status in MFMC cc compared to UF cc. We carried out a multivariate analysis in order to identify independent predictor factors for survival. RESULTS: 69/460 (15%) of cases were MFMC cc. Mortality rates were 56.5% in MFMC cc versus 45.1% (UF cc) (P = 0.08). 5-year overall survival was 55.9% in MFMC cc vs. 64.7% UF cc, and the 10-year overall survival was 34.9% MFMC cc vs. 52.7% UF cc (P = 0.27). Median survival in MFMC cc was 78 months (6.5 years), whereas in UF cc it was 126 months (10.5 years). However, in the multivariate analysis, survival was independently influenced only by tumor size and the presence of axillary lymph node metastases (P < 0.0001). CONCLUSION: Breast cancer multifocality is associated with higher general mortality rates, lower 5 and 10-year overall survival, yields a lower median survival, but it does not constitute an independent prognostic factor in multivariate analysis.

Multifocal/multicentric breast carcinomas showing intertumoural heterogeneity: a comparison of histological tumour type and Nottingham histological grade of primary tumour and lymph node metastasis.

Our study aimed to compare the histological tumour type and Nottingham histological grade of invasive tumour foci in multifocal/multicentric breast carcinomas with those in corresponding axillary lymph node (LN) metastases. We reassessed slides from consecutive multiple breast carcinomas surgically treated with axillary LN dissection (2007-2012). 155 (19.23%) of 806 cases had multiple breast cancer, of which 115 (74.19%) cases had identical morphology. Of these, 85 (73.91%) cases had axillary LN metastases morphologically identical to the originating breast tumours. 32 of the 40 (80%) cases with different morphology had axillary LN metastases; in most heterogeneous cases with differences in grade (87.5%), the grade of metastases was identical to the grade of the tumour foci with the highest histological grade, and in 33.33% of cases the grade in LN was concordant with the grade of smaller foci. Among the 18 cases heterogeneous in histological type with axillary metastases, 33.33% presented heterogeneous histological types in LN, and 22.22% of them were only concordant with the histological type of the smaller tumour foci. The morphological aspects of axillary LN metastases correspond to the highest histological grade and/or histological tumour type with unfavourable prognosis, which does not necessarily appear in the largest tumour focus.