Breast carcinoma grading on core needle biopsy - to grade or not to grade?

Core needle biopsy (CNB) is well established as an important diagnostic tool in diagnosing breast cancer and it is now considered the initial method of choice for diagnosing breast disease and the basis for the treatment planning. The concordance rate between CNB and surgical excision specimen in determination of histological grade (HG) varies widely across literature, ranging from 59-91%. The aim of our study was to investigate the level of concordance between CNB and surgical excision specimen for the determination of HG for breast cancer patients. The study population included 157 women with a breast tumor who underwent a core needle biopsy for breast carcinoma and a subsequent surgical excision of the tumor. The concordance level between core needle biopsy and surgical resection specimen for overall histologic grading was 73%: for tubule formation - 71%, for nuclear pleomorphism - 91%, for the mitotic index - 59%. Our study shows that our institution's histologic grading of CNBs and surgical excisions shows a fairly good correlation and is useful for the planning of treatment.

Dendritic Cell Subpopulations Are Associated with Prognostic Characteristics of Breast Cancer after Neoadjuvant Chemotherapy-An Observational Study.

Breast cancer (BC) is the most prevalent malignancy in women and researchers have strived to develop optimal strategies for its diagnosis and management. Neoadjuvant chemotherapy (NAC), which reduces tumor size, risk of metastasis and patient mortality, often also allows for a de-escalation of breast and axillary surgery. Nonetheless, complete pathological response (pCR) is achieved in no more than 40% of patients who underwent NAC. Dendritic cells (DCs) are professional antigen-presenting cells present in the tumor microenvironment. The multitude of their subtypes was shown to be associated with the pathological and clinical characteristics of BC, but it was not evaluated in BC tissue after NAC. We found that highe r densities of CD123+ plasmacytoid DCs (pDCs) were present in tumors that did not show pCR and had a higher residual cancer burden (RCB) score and class. They were of higher stage and grade and more frequently HER2-negative. The density of CD123+ pCDs was an independent predictor of pCR in the studied group. DC-LAMP+ mature DCs (mDCs) were also related to characteristics of clinical relevance (i.e., pCR, RCB, and nuclear grade), although no clear trends were identified. We conclude that CD123+ pDCs are candidates for a novel biomarker of BC response to NAC.

Dendritic Cell Subpopulations Are Associated with Morphological Features of Breast Ductal Carcinoma In Situ.

Ductal carcinoma in situ (DCIS) is the preinvasive form of breast cancer (BC). It is disputed whether all cases of DCIS require extensive treatment as the overall risk of progression to BC is estimated at 40%. Therefore, the crucial objective for researchers is to identify DCIS with significant risk of transformation into BC. Dendritic cells (DC) are professional antigen presenting cells and as such play a pivotal role in the formation of immune cells that infiltrate in breast tumors. The aim of this study was to investigate the relationship between the density of DCs with different superficial antigens (CD1a, CD123, DC-LAMP, DC-SIGN) and various histopathological characteristics of DCIS. Our evaluation indicated that CD123+ and DC-LAMP+ cells were strongly associated with maximal tumor size, grading and neoductgenesis. Together with CD1a+ cells, they were negatively correlated with hormonal receptors expression. Furthermore, the number of DC-LAMP+ cells was higher in DCIS with comedo necrosis, ductal spread, lobular cancerization as well as comedo-type tumors, while CD1a+ cells were abundant in cases with Paget disease. We concluded that different subpopulations of DCs relate to various characteristics of DCIS. Of the superficial DCs markers, DC-LAMP seems particularly promising as a target for further research in this area.

Presence of Dendritic Cell Subsets in Sentinel Nodes of Breast Cancer Patients Is Related to Nodal Burden.

BACKGROUND: Sentinel lymph nodes (SLNs) are both the first site where breast cancer (BC) metastases form and where anti-tumoral immunity develops. Despite being the most potent antigen-presenting cells, dendritic cells (DCs) located in a nodal tissue can both promote or suppress immune response against cancer in SLNs. METHODS: In SLNs excisions obtained from 123 invasive BC patients, we performed immunohistochemistry (IHC) for CD1a, CD1c, DC-LAMP, and DC-SIGN to identify different DCs populations. Then we investigated the numbers of DCs subsets in tumor-free, micrometastatic, and macrometastatic SLNs with the use of a light microscope. RESULTS: We observed that CD1c+ and DC-SIGN+ DCs were more numerous in SLNs with a larger tumor size. More abundant intratumoral DC-LAMP+ population was related to a higher number of metastatic lymph nodes. Conversely, more abundant CD1a+ DCs were associated with a decreasing nodal burden in SLNs and a lower number of involved lymph nodes. Moreover, densities of the investigated DC populations differed with respect to tumor grade, HER2 overexpression, hormone receptor status, and histologic type of BC. CONCLUSIONS: According to their subtype, DCs are associated with either lower or higher nodal burden in SLNs from invasive BC patients. These relationships appear to be dependent not only on the maturation state of DCs but also on the histological and biological characteristics of the tumor.

Primary bilateral angiosarcoma of the breast treated with neoadjuvant chemotherapy combined with propranolol.

A case report of bilateral primary angiosarcoma treated with neoadjuvant chemotherapy was presented. A routine diagnostic mammography and ultrasound examinations indicated abnormalities in both breasts of the patient, confirmed on MRI as large bilateral masses. Core needle biopsy revealed angiosarcoma G1. The treatment agreed during the interdisciplinary meeting involved chemotherapy combined with simultaneous blockade of beta-adrenergic receptors, followed by bilateral simple mastectomy. This case highlights the importance of a patient-focused care.

Composition of tissue fatty acids of phospholipids depends on tumor localization and disease progression in colorectal patients.

OBJECTIVES: Fatty acids play a role in development and progression of colon cancer. The aim of this study was to assess the relation between tissue fatty acids (saturated fatty acids, unsaturated fatty acids, the ratio of C18 to C18:1 - index of fatty acids saturation, SI), colorectal tumor localization and disease progression. METHODS AND RESULTS: Total of 49 patients (14 with proximal colon, 13 with distal colon and 22 with rectal tumor localization) were studied. One year after surgery 24 patients had the disease progression. Tissue levels of saturated fatty acids and unsaturated fatty acids were measured before surgery by gas-chromatography. These fatty acids were determined in cancerous tissue (CA) and non-cancerous tissue (NCA). The most significant differences in the mean values of fatty acids of phospholipids between CA and NCA in patients with proximal tumor localization were noted. The mean value of C18 was significantly lower while C18:1 was significantly higher in CA as compared to NCA in patients without disease progression (p<0.02; p<0.03; respectively). SI was significantly lower in CA as compared to NCA only in patients without disease progression (p<0.02). CONCLUSION: Fatty acids of tissue phospholipids' fraction, as well as SI, strongly depend on tumor localization and might be useful as potential markers of the disease progression in colorectal cancer patients.

Lymphoid environment in molecular subtypes of breast cancer.

Recently, a large body of evidence has shown that the microenvironment of invasive breast carcinoma affects its development and the patient's outcome, and vice versa - cancer cells express factors that modulate tumour milieu in terms of its composition and function. We performed an immunohistochemical (IHC) staining of 108 formalin-fixed, paraffin-embedded (FFPE) tissue samples to investigate the relationships between T-cell, B-cell, and NK-cell infiltrate, invasive breast carcinomas molecular subtypes, and other prognostic indicators. The main findings of our study were as follows: the significantly higher infiltrate of the analysed immune cell subsets in triple-negative (TNBC), HER2-positive, non-luminal and luminal B/HER2+ breast carcinomas than in luminal A cancers; their higher densities in poorly differentiated lesions; correlations between lymphoid cells and the expression of hormonal receptors, HER2 receptor status, and marker of cancer proliferation. Furthermore, we observed T-cell numbers to be associated with greater tumour diameter. In summary, the results of our study indicate associations between tumoural lymphoid infiltration and the unfavourable intrinsic subtypes as well as other detrimental prognostic factors in invasive breast carcinomas.

Preferring fried dishes increases risk of benign breast disease, but not breast cancer.

BACKGROUND: Unhealthy diet and cooking method used may influence the risk of breast cancer (BC), but there is only limited evidence with regard to benign breast disease (BBD). The aim of this study was to assess a relationship between cooking technique, especially fried to boiled meals ratio in the diet, and the risk of BC and BBD in a group of Polish women. MATERIAL AND METHODS: A case-control study involving 34 BC cases, 81 BBD cases and 122 healthy controls was conducted between July 2007 and November 2011. All the women were asked about their nutritional habits, especially the way of preparing meat and fish dishes. Then the ratio of fried to boiled meals was calculated. RESULTS: High fried to boiled ratio was associated with increasing risk of BBD, but not BC. Women consuming fried dishes more often than boiled dishes had elevated risk of BBD: OR = 3.04 and OR = 3.65 for the second and the third tertile, respectively. Adjustment for the other confounders only slightly altered this relationship. CONCLUSION: Women who preferred frying as a cooking technique had increased risk of benign breast disease, but not breast cancer. There is a need of more precise investigation to confirm this association.

Pigmented Paget's disease of the nipple.

Pigmented Paget's disease of the nipple (PPD) is an uncommon variant of Paget's disease. An accumulation of melanin within the lesion imparts a brow color to the affected area, so the lesion might clinically as well as histologically mimic melanoma. We present a case of PPD in a 60-year-old woman.

[Preoperative quality of life in women with pathological alteration in breast]. / Jakosc ycia kobiet ze zmianami patologicznymi piersi w okresie przygotowawczym do zabiegu chirurgicznego.

The aim of the study was to assess the similarities or differences in the psychosocial response to primary diagnosis of malicious or benign tumor in breast significantly influenced the quality of life in women in preoperative period. Health-related quality of life has been studied in the preoperative period in the group of 59 patients with malicious tumor and in the group of 130 women with benign tumor in comparison to 126 healthy women. Study was performed using self-administered questionnaire consists of The Rand Mental Health Inventory (three distress scores include depression, anxiety and loss of behavioral or emotional control; two well-being scores include general positive affect and emotional ties), COOP Charts (measuring nine dimensions of QOL), subscale focus on social support was used for the presented analysis; additionally questions concerning demographic and social characteristics of women as well as questions on illness behaviors have been involved. Statistical analysis was performed using multidimensional models of logistic regression. Results based on multidimensional logistic regression models showed higher risk of anxiety (OR=4,0; 95% CI=(1,8; 8,6)), depression(OR=3,0; 95% CI=(1,4; 6,2)) and distress (OR=2,5; 95% CI=(1,2; 5,3)) in women with malicious tumor in comparison to healthy women. Comparatively, higher risk of anxiety (OR=1,8; 95% CI=(1,0; 3,2)) and depression (OR=2,0; 95% CI=(1,2; 3,5)) among women with benign tumor in regard to healthy ones. Further examination of determinants of components of mental health among three analyzed group of women showed that among women with benign tumor higher risk of anxiety (OR=3,5; 95% CL=(1,2; 10,5)), depression (OR=3,2; 95% CI=(1,2;9,1)) and loss of behavioral or emotional control ((OR=4.3; 95% CI=(1,5;12,0)) as well as distress (OR=4,3; 95% CI=(1,5;13,0)) was related with considerable reduction of receiving support. Women with malicious tumor also indicated that slightly reduction of the received support was associated with higher risk of the loss of behavioral or emotional control (Isz=6,6; 95% PU=(1,4; 30,8)). Results confirmed that also diagnosis of benign tumor in breast is perceived as an event which significantly decreased quality of life in preoperative period. Interactions between medical staff - and patients with any change in breast should based on good verbal communication, giving information which help understanding by patients all aspects of diagnosis and expected treatment.

Neoductgenesis in Ductal Carcinoma In Situ Coexists with Morphological Abnormalities Characteristic for More Aggressive Tumor Biology.

Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer that is generally indolent, however, could advance to invasive carcinoma in more than one-third of cases if left untreated. Thus, there is continuous research to find DCIS characteristics that would enable clinicians to decide if it could be left without intensive treatment. Neoductgenesis (i.e., formation of the new duct of improper morphology) is a promising, but still not sufficiently evaluated indicator of future tumor invasiveness. We gathered data from 96 cases of DCIS (histopathological, clinical, and radiological) to assess the relationship between the neoductgenesis and well-established features of high-risk tumor behavior. Furthermore, our intention was to determine which degree of neoductgenesis should be considered clinically significant. Our major finding was that neoductgenesis is strictly related to other characteristics that indicate the invasive potential of the tumor and, to achieve more accurate prediction, neoductgenesis should be accordingly recognized to less strict criteria. Therefore, we conclude that neoductgenesis is another important revelator of tumor malignancy and that it requires further investigation during prospective controlled trials.

Evaluation of serum concentrations of vascular endothelial growth factor (VEGF) in breast cancer patients.

The aim of the study was to assess the value of vascular endothelial growth factor (VEGF) measurements in breast cancer patients with respect to recognized clinicopathological prognostic factors. The study was conducted in 87 women with histologically confirmed breast cancer who underwent surgical treatment and 37 healthy women. Vascular endothelial growth factor concentration levels in the blood samples of patients were correlated with the size of the primary tumor, lymph nodes in the armpit, cancer stage, histological type, grading, multifocality, status of estrogen and progesterone receptors and HER-2 protein expression. Statistical analysis did not show any correlation between concentrations of VEGF and any of the selected parameters. The comparison of VEGF concentrations showed a slightly raised level of VEGF in women with the disease as opposed to the healthy subjects but the differences were not statistically significant (p = 0.472). Similar results were obtained for marker CEA (p = 0.09), while the level of Ca 15-3 in both groups differed significantly (p < 0.001) reaching higher values in the patients with diagnosed breast cancer. Vascular endothelial growth factor concentrations in breast cancer patients do not correlate with recognized clinicopathological prognostic factors and CEA and Ca 15-3 markers, which does not preclude the potential role of VEGF as an independent prognostic factor.

Comparison of two minimally invasive biopsy techniques - Breast Lesion Excision System and vacuum-assisted biopsy - for diagnosing and treating breast lesions.

Introduction: The vacuum-assisted biopsy (VAB) and the Breast Lesion Excision System (BLES) are minimally invasive biopsy techniques, both used as diagnostic and therapeutic tools. The aim of the study is to compare these two methods and assess them in the context of discomfort, early and late complications and their diagnostic and therapeutic potential. Material and methods: The study involved 173 patients who underwent a VAB or a BLES breast biopsy in the period between 2009 and 2016. Approximately 3 months after the biopsy, the patients completed a questionnaire in which they assessed the procedure for discomfort associated with the procedure and the final cosmetic outcome. The cosmetic effect of the biopsy was also assessed by a surgeon. Results: The BLES and the VAB breast biopsies did not differ in terms of pain, duration, and discomfort of the procedure, breast bruising, breast tenderness about 24 h after the procedure or pain lasting over 3 months after the biopsy. Subsequently, the biopsies were evaluated in terms of the cosmetic effect assessed by the patient and by a surgeon and no differences were observed. There were no significant differences between the VAB and the BLES breast biopsies in the course of the procedure, early and late complications and cosmetic effect. Conclusions: Since the BLES breast biopsy makes it possible to evaluate the margins, it is a good alternative to the open breast biopsy.

Breast cancer chemotherapy induces vascular dysfunction and hypertension through a NOX4-dependent mechanism.

Cardiovascular disease is the major cause of morbidity and mortality in breast cancer survivors. Chemotherapy contributes to this risk. We aimed to define the mechanisms of long-term vascular dysfunction caused by neoadjuvant chemotherapy (NACT) and identify novel therapeutic targets. We studied arteries from postmenopausal women who had undergone breast cancer treatment using docetaxel, doxorubicin, and cyclophosphamide (NACT) and from women with no history of such treatment matched for key clinical parameters. We explored mechanisms in WT and Nox4-/- mice and in human microvascular endothelial cells. Endothelium-dependent, NO-mediated vasodilatation was severely impaired in patients after NACT, while endothelium-independent responses remained normal. This was mimicked by a 24-hour exposure of arteries to NACT agents ex vivo. When applied individually, only docetaxel impaired endothelial function in human vessels. Mechanistic studies showed that NACT increased inhibitory eNOS phosphorylation of threonine 495 in a Rho-associated protein kinase-dependent (ROCK-dependent) manner and augmented vascular superoxide and hydrogen peroxide production and NADPH oxidase activity. Docetaxel increased expression of the NADPH oxidase NOX4 in endothelial and smooth muscle cells and NOX2 in the endothelium. A NOX4 increase in human arteries may be mediated epigenetically by diminished DNA methylation of the NOX4 promoter. Docetaxel induced endothelial dysfunction and hypertension in mice, and these were prevented in Nox4-/- mice and by pharmacological inhibition of Nox4 or Rock. Commonly used chemotherapeutic agents and, in particular, docetaxel alter vascular function by promoting the inhibitory phosphorylation of eNOS and enhancing ROS production by NADPH oxidases.

[Sentinel lymph node biopsy as a new approach to colorectal cancer treatment]. / Biopsja wezla wartowniczego--nowy aspekt w chirurgicznym ieczeniu raka jelita grubego.

Some concepts considering sentinel lymph node excision in colon and rectal carcinoma are presented in the paper. Arguments pro and contra were exposed and interpret separately. The problem is still open. Current knowledge indicates that lymphatic system in colon and rectum can be very different in many patients. There is no evidence that sentinel node biopsy in this group can be useful. In patients with advanced colorectal carcinoma (T3, T4 according to TNM classification) sentinel node biopsy cannot replace regional lymph node dissection. Sentinel lymph node biopsy and localization of metastases allows to change the qualification of the NO patients to N1 (upstaging). This means the change of cancer staging in these patients and qualification to chemotherapy. In conclusion we underline that there is still too little knowledge to implement these procedures in clinical practice, that problem needs more consideration.

Nodal status in luminal A invasive breast cancer: relationships with cytotoxic CD8 + and regulatory FOXP3 + cells tumor-associated infiltrate and other prognostic factors.

Luminal A breast cancers are generally associated with low metastatic potential and good prognosis. However, there is a proportion of patients, who present with metastases in lymph nodes. The aim of our study was to determine the association between the number of positive lymph nodes and infiltrates of tumor-associated cytotoxic CD8 + (CTLs), regulatory FOXP3 + T cells (Tregs), as well as other prognostic factors. Immunohistochemistry (IHC) for CD8 + and FOXP3 + was performed in 87 formalin-fixed paraffin-embedded primary breast cancer tissues, and cell infiltrate was assessed under light microscope. We observed that node-positive cases were associated with higher numbers of Treg cells and lower CTL/Treg ratio. There was also an inverse correlation between the CTL/Treg ratio and the number of metastatic lymph nodes. Similar relationships were found between the number of metastatic lymph nodes and Treg density or CTL/Treg ratio in pT1 BC. An elevated intratumoral CTL/Treg ratio was associated with pN0 stage. The relationship between lymphovascular invasion (LVI) and Treg density was also noted in node-negative tumors. In addition, more advanced nodal stage was related to LVI, higher pT, and lower PR expression. The numbers of CD8 + and FOXP3 + were also associated with tumor size, histologic grade, PR expression, and mitotic index. The results of our study suggested that the levels of tumor-infiltrating regulatory and cytotoxic cells as well as the balance between them play a role in lymphovascular spread of luminal A breast cancers.

Dendritic Cells Are Associated with Prognosis and Survival in Breast Cancer.

Dendritic cells (DCs) constitute a part of the tumour microenvironment, but we are still far from understanding their complex role in immune response to the tumour. This study aimed to investigate the density of DCs expressing CD1a, CD83, CD123, DC-LAMP3 (CD208) and DC-SIGN (CD209) in breast cancer. The correlations between DC density and molecular subtype of breast cancer, its hormone receptor status, spatial location and their associations with clinical and pathological prognostic factors were evaluated. We have shown that intratumoural CD1a+ cells were significantly associated with progression-free survival. For LAMP3+ and CD123+ DCs, higher cell densities were associated with non-luminal as compared to luminal cancer phenotype. In contrast, dense CD83+ DC infiltrate was observed in luminal tumours. The number of CD1a+ DCs in both locations was the highest in luminal B/HER2+ cancers. The highest positive cell count of LAMP3+ cells was observed in the triple-negative subtype in both locations. We found higher numbers of LAMP3+ DCs both intratumourally and at the invasive margin, as well as CD123+ DCs intratumourally in tumours with negative expression of oestrogen or progesterone receptors. Our study demonstrates associations between DC subpopulations and histological and clinical characteristics, as well as molecular subtypes in breast carcinoma.

A Prospective Pilot Study on Use of Liquid Crystal Thermography to Detect Early Breast Cancer.

Background: Breast cancer is the most common cancer in women. While mammography is the standard for early detection in women older than 50 years of age, there is no standard for younger women. The aim of this prospective pilot study was to assess liquid crystal contact thermography, using the Braster device, as a means for the early detection of breast cancer. The device is intended to be used as a complementary tool to standard of care (sonography, mammography, etc). Patients and Methods: A total of 274 consecutive women presenting at Polish breast centers for prophylactic breast examination were enrolled to receive thermography; 19 were excluded for errors in thermographic image acquisition. The women were divided according to age (n = 135, <50 years; n = 120, ≥50 years). A control population was included (n = 40, <50 years; n = 23, ≥50 years). The primary endpoint, stratified by age group, was the C-statistic for discrimination between breast cancer and noncancer. Results: In women with abnormal breast ultrasound (n = 95, <50 years; n = 87, ≥50 years), the C-statistic was 0.85 and 0.75, respectively (P = .20), for discrimination between breast cancer and noncancer. Sensitivity did not differ (P = .79) between the younger (82%) and older women (78%), while specificity was lower in the older women (60% vs 87%, P = .025). The false-positive rate was similar in women with normal and abnormal breast ultrasound. Positive thermographic result in women with Breast Imaging Reporting and Data System (BIRADS) 4A on ultrasound increased the probability of breast cancer by over 2-fold. Conversely, a negative thermographic result decreased the probability of cancer more than 3-fold. Breast size and structure did not affect the thermography performance. No adverse events were observed. Conclusions: Thermography performed well in women <50 years of age, while its specificity in women ≥50 years was inadequate. These promising findings suggest that the Braster device deserves further investigation as a supporting tool for the early detection of breast cancer in women younger than 50 years of age.

Intraductal papilloma of the breast - management.

In light of the growing availability of ultrasound testing and invasive diagnostic methods of the breast in everyday gyneco- logic practice, lesions of uncertain malignant potential, classified histologically as B3, have become a significant health issue. Intraductal papillomas (IPs) are the most common pathology in that group of lesions. Despite their benign histologic appearance, IPs may accompany malignant growths and the diagnosis made on the basis of biopsy material carries the risk of breast cancer (BC) underestimation. The article presents a review of the available literature on the management of patients diagnosed with intraductal papilloma at a standard core needle biopsy or vacuum-assisted core needle biopsy. The management is not uniform and depends not only on the verification technique or the accompanying pathological growths, but also on the result of clinical-pathological correlations. As it turns out, open surgical biopsy should not necessarily be recommended to every affected woman, and a growing number of sources have recently suggested that a control program would be sufficient in many cases. Thus, it is vital for gynecologists to be able to differentiate between those women who may be included in the annual ultrasound control program and those who require further surgical management.

Triple negative breast cancer with ACTH-dependent Cushing's syndrome - case report.

INTRODUCTION: Endocrine and metabolic paraneoplastic syndromes in the course of malignant tumors result from ectopic production of hormones or hormone precursors in tumor cells. Production of hormones by endocrine tumors is relatively frequent, while such production by adenocarcinoma cells is definitely rare. The study presents a case of triple-negative invasive breast cancer, with the ectopic secretion of ACTH (adrenocorticotropic hormone), which provokes serious metabolic disorders. MATERIALS AND METHODS: The patient was admitted to hospital with symptoms of Cushing`s syndrome. Diagnostic tests revealed that the cause of metabolic disorders was breast cancer. After proper preparation, the patient was qualified for surgery. RESULTS: After the mastectomy, the patient's metabolism stabilized. The patient underwent adjuvant chemotherapy and radiotherapy. Four months after the last cycle of systemic treatment, cancer dissemination was found. The patient was treated with second-line chemotherapy, however, control CT revealed progression. The patient died 20 months after surgery and two months after the last cycle of chemotherapy. CONCLUSIONS: The case reported in this study - triple-negative invasive breast cancer, responsible for ectopic production of ACTH and causing Cushing's syndrome - is a rare phenomenon. Treatment of patients with breast cancer showing hormonal activity should not differ from general rules applied for breast cancer. However, due to accompanying metabolic disturbances, the patients need individualized oncological approach, precise diagnostic tests, and adequate preoperative preparation.