Cases Of Benign Breast Disease Research Articles

Expression and clinical significance of serum interleukin-6 in triple negative breast cancer

Objective To evaluate the expression and clinical significance of interleukin-6 (IL-6) in triple negative breast cancer (TNBC). Methods One hundred and fifty-six cases including 52 cases of TNBC, 79 cases of non-triple negative breast and 25 cases of benign breast disease. Serum IL-6 level was detected by using enzyme linked immunosorbent assay (ELISA). The difference of IL-6 level in the three groups was analyzed. The correlation between serum IL-6 level and clinicopathological parameters of TNBC including age, menopause status, tumor size, lymph node metastasis and TNM stage was examined. Results The serum IL-6 level in groups of benign breast disease, non-triple negative breast cancer and TNBC was (13.3±4.7), (79.9±19.5), (114.2±21.9) pg/ml respectively. The difference between the three groups differed significantly (P=0.000). The level of serum IL-6 in TNBC with tumor size>2 cm and lymph node metastasis was higher than that with tumor size≤2 cm and no lymph node metastasis, and the difference differed significantly (P=0.000, 0.020). Conclusion IL-6 level was highly in the serum of TNBC and it maybe a diagnosis marker and therapeutic target. Key words: Interleukin-6; Triple negative breast cancer; Serum

Abstract LB-337: Adipose inflammation and the risk of benign and malignant breast disease in African American women

Abstract Introduction: Obesity is associated with an increased breast cancer (BrCa) incidence. Adipose inflammation, marked by crown-like lesions in the breast (CLS-B) or dying adipocytes surrounded by macrophages, has been previously associated with BMI, aromatase expression, and systemic inflammation - all BrCa risk correlates. However, CLS-B has not been well described in normal or pre-malignant tissue, nor ever described in African American women (AAW). Here we examined whether CLS-B is associated with risk of benign breast disease (BBD) and BrCa in AAW, who suffer a higher incidence of breast cancer, poorer breast cancer outcomes, and a higher prevalence of obesity than women of other ethnicities. Methods: We assessed breast biopsies from three age-matched groups including 50 AAW with no history of BBD or BrCa from the Komen Normal Tissue Bank (KTB) and AAW with BBD from our Detroit cohort who developed cancer (55 BBD cases) or did not develop breast cancer (47 BBD controls). Slides were assessed by pathologists (KK, RAF) for CLS-B presence. Associations between tissue type and CLS-B presence among KTB and BBD samples were assessed using chi-square tests. Association between tissue types and CLS-B adjusting for BMI was assessed using the Mantel-Haenszel test. Results: The KTB, BBD controls and BBD cases groups were matched for age, consisted of approximately 15% <45, 43% 45-55, and 42% 55+ year old AAW. Our study of KTB, BBD control and BBD case groups predominately consisted of overweight (22, 17, and 32%, respectively) and obese women (60, 57, and 47%, respectively). Our data show that CLS-B presence is associated with BBD: significantly more BBD biopsies (29/89=32.6%) were CLS-B positive than KTB biopsies (4/44=9.1%; p=0.006). Among BBD biopsies, fewer BBD controls (11/45=24.4%) were CLS-B positive than BBD cases (18/44=40.9%; p=0.159). After controlling for BMI, CLS-B presence showed an increasing trend among KTB, BBD control and BBD case biopsies (p=0.002, see Table). CLS-B presence by study group and BMIKTBBBD controlsBBD casesN (%) with CLS-B presenceN=44N=44N=42BMI<250/8 (0%)1/10 (10.0%)4/9 (44.4%)BMI 25-291/9 (11.1%)1/8 (12.5%)4/13 (30.8%)BMI 30+3/27 (11.1%)9/26 (34.6%)9/20 (45.0%) Conclusions: These findings suggest that CLS-B may serve as an important histological marker of BrCa risk in benign breast biopsies. Our study population exhibited higher rates of obesity than other BBD and CLS-B studies of European American women highlighting the need to include diverse populations in future studies examining BrCa risk. These findings have potential implications for modeling BrCa risk, particularly among AAW, for whom obesity is prevalent. Citation Format: Asra N. Shaik, Katrin Kiavash, Karri Stark, Julie L. Boerner, Julie J. Ruterbusch, Rouba Ali-Fehmi, Michele L. Cote. Adipose inflammation and the risk of benign and malignant breast disease in African American women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-337.

Plasma soluble cluster of differentiation 147 levels are increased in breast cancer patients and associated with lymph node metastasis and chemoresistance.

Cluster of differentiation 147 (CD147) contributes to breast cancer invasion, metastasis, and multidrug resistance. Recent studies have shown that peripheral soluble CD147 (sCD147) is increased in hepatocellular tumour and multiple myeloma patients and correlated with disease severity. The primary aim of our study was to assess the level, as well as the biological and clinical significance of sCD147 in breast cancer. We tested plasma sCD147 levels in 308 breast cancer patients by enzyme-linked immunosorbent assay between February 2014 and February 2017. A subset of 165 cases of benign breast diseases was included as a control group at the same period. We analysed the clinical significance of plasma sCD147 with relevance to clinicopathological factors of breast cancer patients. Plasma sCD147 levels were significantly higher in patients with primary breast cancer than those with benign breast diseases (P=0.001), in patients with locally advanced breast cancer (T3-T4 tumour) than those in early breast cancer (T1-T2 tumour; P=0.001), in patients with lymph node metastasis than in those without (P<0.001), and in patients with high recurrence risk than those with medium recurrence risk (P<0.001). Plasma sCD147 levels were also significantly higher in the chemotherapy-resistant group than in the chemotherapy-sensitive group (P=0.040). Plasma sCD147 was an independent predictor for lymph node metastasis in breast cancer patients (P=0.001). This is the first study to demonstrate that plasma sCD147 levels are elevated in breast cancer patients. Soluble CD147 is also associated with tumour size, lymph node metastasis, high recurrent risk, and chemoresistance. Our findings support that plasma sCD147 is an independent predictive factor for lymph node metastasis.

Spectrum of Benign Breast Lesions in a Tertiary Care Hospital of Lahore

Women with benign breast diseases (BBD) are at a high risk of developing breast cancer.&#x0D; Objective: Purpose of the study was to analyze the spectrum of BBD in a tertiary care hospital of Lahore to understand the prevalence of inflammatory lesions, benign neoplasms and their age-wise comparison.Methodology: The study was carried out at Pathology Department, King Edward Medical University, Lahore. Data of 368 cases of BBD during a time span of 3 years (2011-2014) was obtained retrospectively.Results: There were 190 patients of fibroadenoma (FA), 81 of fibrocystic disease (FCD), 64 of breast abscess (BA), 12 of granulomatous mastitis (GM), 7 of lipoma, 5 of phylloides tumor (PL), 4 of fibrosis (F), 2 of intraductal papilloma (IDP) and 3 of accessory breast with Fibrocystic (FC) changes. The relation between theages and frequency of the different types of lesions was also analyzed to understand the association between predisposing factors and the nature of lesions.Conclusions: Out results demonstrated that the FA is the most frequent benign breast lesions and is common among young females with age ranges from 10 to 20 years. FCD is the second most common lesion, while FA and FCD are less common among women older than 40 years. Benign neoplasms are more frequentamong women of the Lahore. There were only three cases of sclerosing adenosis, 2 of microglandularadenosis, 3 of hyperplasia and no case of radial scar.

Macrophagic "Crown-like Structures" Are Associated with an Increased Risk of Breast Cancer in Benign Breast Disease.

In breast adipose tissue, macrophages that encircle damaged adipocytes form "crown-like structures of breast" (CLS-B). Although CLS-B have been associated with breast cancer, their role in benign breast disease (BBD) and early carcinogenesis is not understood. We evaluated breast biopsies from three age-matched groups (n = 86 each, mean age 55 years), including normal tissue donors of the Susan G. Komen for the Cure Tissue Bank (KTB), and subjects in the Mayo Clinic Benign Breast Disease Cohort who developed cancer (BBD cases) or did not develop cancer (BBD controls, median follow-up 14 years). Biopsies were classified into histologic categories, and CD68-immunostained tissue sections were evaluated for the frequency and density of CLS-B. Our data demonstrate that CLS-B are associated with BBD: CLS-B-positive samples were significantly less frequent among KTB biopsies (3/86, 3.5%) than BBD controls (16/86 = 18.6%, P = 0.01) and BBD cases (21/86 = 24%, P = 0.002). CLS-B were strongly associated with body mass index (BMI); BMI < 25: 7% CLS-B positive, BMI 25-29: 13%, and BMI ≥ 30: 29% (P = 0.0005). Among BBD biopsies, a high CLS-B count [>5 CLS-B/sample: 10.5% (BBD cases) vs 4.7% (BBD controls), P = 0.007] conferred a breast cancer OR of 6.8 (95% CI, 1.4-32.4), P = 0.02, after adjusting for adipose tissue area (cm2), histologic impression, and BMI. As high CLS-B densities are independently associated with an increased breast cancer risk, they may be a promising histologic marker of breast cancer risk in BBD. Cancer Prev Res; 11(2); 113-9. ©2017 AACR.

The Intact® breast lesion excision system as a therapeutic device for selected benign breast lesions.

The aim of this paper is to evaluate our Unit's initial experience using the Intact breast lesion excision system as a therapeutic excision option for benign or borderline breast lesions, which otherwise would entail open operative excision. The study includes the first 111 patients who underwent therapeutic excision with the intact radiofrequency system between December 2012 and May 2016 performed at the Meirav Center for Breast Health, at the Chaim Sheba Medical Center, Ramat Gan Israel. The indications for the procedure included those patients who have benign, or atypical high risk lesions following a previous core needle biospy (CNB) who would have normally undergone conventional excision biopsy. After reviewing each case separately, we found that the use of the BLES system as a treatment device permitted the avoidance of operations that would have been otherwise indicated, in 98 cases of the total 111 in the cohort (88.3%). Thirteen cases eventually had to undergo surgical excision. In eight cases pathology was upgraded from the initial CNB to invasive or noninvasive carcinoma. Although the INTACT sysytem is most commonly used as an alternative biopsy technique for its diagnostic capabilities, this study assessed its clinical role as a definitive therapeutic excisional modality in selected cases of benign breast disease. It proved valuable in the majority of cases with avoidance of surgery where it was traditionally indicated, (98/111, 88.3%) and as definitive fibroadenoma management in a further 28 patients.

Alterations in the Immune Cell Composition in Premalignant Breast Tissue that Precede Breast Cancer Development.

Purpose: Little is known about the role of the immune system in the earliest stages of breast carcinogenesis. We studied quantitative differences in immune cell types between breast tissues from normal donors and those from women with benign breast disease (BBD).Experimental Design: A breast tissue matched case-control study was created from donors to the Susan G. Komen for the Cure Tissue Bank (KTB) and from women diagnosed with BBD at Mayo Clinic (Rochester, MN) who either subsequently developed cancer (BBD cases) or remained cancer-free (BBD controls). Serial tissue sections underwent immunostaining and digital quantification of cell number per mm2 for CD4+ T cells, CD8+ T cells, CD20+ B cells, and CD68+ macrophages and quantification of positive pixel measure for CD11c (dendritic cells).Results: In 94 age-matched triplets, BBD lobules showed greater densities of CD8+ T cells, CD11c+ dendritic cells, CD20+ B cells, and CD68+ macrophages compared with KTB normals. Relative to BBD controls, BBD cases had lower CD20+ cell density (P = 0.04). Nearly 42% of BBD cases had no CD20+ B cells in evaluated lobules compared with 28% of BBD controls (P = 0.02). The absence of CD20+ cells versus the presence in all lobules showed an adjusted OR of 5.7 (95% confidence interval, 1.4-23.1) for subsequent breast cancer risk.Conclusions: Elevated infiltration of both innate and adaptive immune effectors in BBD tissues suggests an immunogenic microenvironment. The reduced B-cell infiltration in women with later breast cancer suggests a role for B cells in preventing disease progression and as a possible biomarker for breast cancer risk. Clin Cancer Res; 23(14); 3945-52. ©2017 AACR.

Clinical study on the relationship between hepatitis B virus infection and risk of breast cancer: a large sized case-control and single center study in southwest of China.

PurposeChronic hepatitis C virus (HCV) infection is reported to be associated with early-onset breast cancer, while, as a hepadnavirus, hepatitis B virus(HBV) infection is more common than HCV in China. In this article, it is aimed to study the relationship between HBV infection and risk of breast cancer in China.MethodsThe clinical data of 2452 cases of initially diagnosed breast cancer and 1926 cases of benign breast disease (as controls) with the consecutive reports of HBV serological markers and liver function tests, available in the Electronic Medical Records of the Breast Cancer Center of Chongqing, the southwest of China, from January 2011 to March 2015, were collected for analysis.ResultsThe average age of the initially diagnosed breast cancer patients was 50.3±11.3 years with the age peaking about 40- 49yeaers (39.7%). The positive rate (8.2%) of hepatitis B surface antigen in breast cancer patients was relatively higher than that (7.8%) in controls (P>0.05). While, the positive rate (66.4%)of hepatitis B core antibody in breast cancer patients was significantly higher than that (53.7%) in controls (P<0.05), so were the similar results in the age groups of 40-49 years, after multiple layer analysis stratified by age and compare HBV markers adjusting age with binary logistic regression. Meanwhile, the status of albumin, aminotransferase and aspartate transaminase (41.4 g/L, 22.9 U/L, 22.0 U/L) in breast cancer patients were significantly poorer than those (44.1 g/L,16.8 U/L, 19.2 U/L) in controls (P<0.05).ConclusionsExposure to HBV infection may be a risk factor for breast cancer and may be also related to the earlier age onset of breast cancer (peaked around 40-49 years) among Chinese females.

Abstract 2577: Expression of P53/PTEN/c-Myc in peripheral blood leukocytes from patients with breast cancer and its clinical significance

Abstract Breast cancer remains the most frequently diagnosed malignancy and leading cause of cancer deaths in women worldwide. Current data showed that the morbidity of breast cancer has been rising shifting with younger age in the last decades, therefore early detection is urgently needed to improve the management of breast cancer as what has been working on many other malignancies. Dysfunction of tumor suppressor gene and/or oncogene might play vital roles in tumorigenesis and cancer progression, such as P53, PTEN and c-Myc. In this study we aim to detect the expression of P53/PTEN/c-Myc mRNA in peripheral blood leukocytes from patients with breast cancer and benign breast diseases, and investigate its correlation with the clinicopathologic characteristics, further to explore the potential clinical application significance. In this study, fluorescent quantitation Real-time Polymerase Chain Reaction (FQ-RT-PCR) was employed to detect the expression of P53/PTEN/c-Myc mRNA in peripheral blood leukocytes from 304 cases, including 105 patients with breast cancer, 107 cases of benign breast diseases and 92 healthy women as control. 2-ΔΔCT was used to calculate the relative quantitative gene expression and Mann-whitney U test was carried to distinguish the differences among the independent cohorts. The results showed that P53 and PTEN mRNA were significantly reduced in both breast cancer group and benign breast diseases group, respectively(P&amp;lt;0.01), moreover, the P53 mRNA in benign breast diseases was even lower than that in breast cancer(P&amp;lt;0.01). However, c-Myc didn’t show any obvious difference among the three groups. Further investigation the genes expression with clinicopathologic characteristics, we found that PTEN in patients with breast cancer was correlated with lymph nodes metastasis and clinical stage as well. Among those breast cancer patients without lymph node metastasis, the level of PTEN mRNA in peripheral blood leukocytes was obviously lower than that in patients with metastatic lymph node positive (P&amp;lt;0.05), on the other hand, breast cancer patients with ductal carcinoma in situ and earlier stages(0+I+II) showed lower PTEN mRNA than those in later or advanced stages (III+IV) (P=0.01). Above results indicated that P53 and PTEN mRNA in peripheral blood leukocytes displayed apparent difference among patients with breast cancer, benign breast diseases and healthy control, and dysregulation of P53/PTEN was found in patients with benign breast diseases, even more obvious than that in breast cancer patients. Moreover, down-regulation of PTEN might predict and/or display the early events of breast cancer carcinogenesis and lymph nodes metastasis. Our findings suggest that detection of tumor related genes in peripheral blood leukocytes would serve as a unique potential approach in early and noninvasive diagnosis of tumors, also would be very promising in clinical applications as well. Note: This abstract was not presented at the meeting. Citation Format: Guangcheng Huang, Qiang Ma, Jiang Zou, Ru Sun, Lihua Yao, Lei Xu, Dongsheng Wang, Xiaolan Guo. Expression of P53/PTEN/c-Myc in peripheral blood leukocytes from patients with breast cancer and its clinical significance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2577. doi:10.1158/1538-7445.AM2017-2577

Abstract P4-04-09: CD4 and CD8 T cell densities are increased in benign breast disease compared to normal breast tissue

Abstract Introduction: CD4+ and CD8+ T cells are important effector cells in the adaptive immune response against cancers. In premalignant proliferative breast tissues, the role of the immune system remains relatively undefined. In this study, we sought to investigate and quantify the presence of CD4 and CD8 expressing immune cells in benign breast tissues and their association with breast cancer risk. Method: Archived breast tissue samples from women with benign breast disease (BBD) or no clinical breast disease [Komen Tissue Bank (KTB)] were obtained for this age-matched case-control study. BBD samples included BBD cases (subsequently developed breast cancer) and BBD controls). Tissue sections were characterized for non-proliferative or proliferative disease and degree of lobular involution. CD4+ and CD8+ cell densities (cells/mm2) were obtained by digital image quantitation for up to 10 individual lobules per sample and a per-sample estimate of cell density was calculated as the median cell density across lobules within a sample. Statistical analysis was performed using Wilcoxon signed-rank and Kruskal-Wallis tests. Results: Among 267 women (median age 52, range 35-75) comprising 89 age-matched triplets, 2417 lobules were evaluated [783 KTB, 804 BBD case, 830 BBD control]. 1372 (57%) lobules were normal and 1045 (43%) were fibrocystic. CD4+ cells were present in 1903 (79%) lobules while CD8+ cells were present in 2214 (92%) lobules. CD4 and CD8 densities showed a moderate positive correlation (r = 0.39) with each other, but overall, lobules showed a lower density of CD4+ than CD8+ cells (mean difference -54 cells/mm2, 95% CI: -68 to -39 cells/mm2). At the per sample level (see Table), BBD controls showed significantly higher levels of both CD4+ (p=0.009) and CD8+ cells (p=0.0001) compared to KTB samples. In contrast, the BBD cases only showed elevated CD8 (p=0.007) and not CD4 (p=0.21) cell infiltrates compared to KTB samples. Comparing BBD cases to BBD controls, BBD cases showed significantly lower CD8 cell density as compared to BBD controls (p=0.002) and cases had lower CD4 cell density but the difference was not significant (p=0.07). Despite these differences in the cell densities, the ratio of CD4:CD8+ cells did not differ significantly across groups (p=0.83). The CD4:CD8+ ratio also did not differ significantly by histologic impression (p=0.74), degree of involution (p=0.27), or age (p=0.32). KTBBBD ControlsBBD CasesMedian (IQR)(n=89)(n=89)(n=89)CD4+ cells/mm240 (17-95)60 (25-124)49 (21-92)CD8+ cells/mm285 (49-131)157 (84-225)134 (80-168)Ratio (CD4:CD8)*0.45 (0.14-0.96)0.41 (0.15-0.81)0.40 (0.19-0.70)*Ratio is missing for n=7 samples (3 KTB, 2 BBD control, 2 BBD case) with undefined ratio due to zero CD8+ cells for all lobules in the sample. Conclusion: Our findings suggest that BBD is associated with increased infiltration of T cells into the breast tissue. Furthermore, these immune responses appear more robust in BBD patients at lower risk of developing breast cancer. Citation Format: Pena Jimenez A, Hoskin TL, Arshad MA, Visscher DW, Brahmbhatt RD, Miller EE, Stallings Mann ML, Carter JM, Murphy LM, Winham SJ, Radisky DC, Denison LA, Knutson KA, Degnim AC. CD4 and CD8 T cell densities are increased in benign breast disease compared to normal breast tissue. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-04-09.

Circulating Tumor Cells in Breast Cancer: Correlation with Clinicopathological Parameters, Hormone Profile and MicroRNA Polymorphisms.

Circulating tumor cells are isolated tumor cells in the peripheral blood that serve as important prognostic indicators for many kind of tumors. The study was conducted to know the rate of detection of circulating tumor cells among breast cancer patients in comparison with benign breast diseases and control subjects and to know the association between CTC positivity and various clinicopathological parameters, hormonal profile and microRNA polymorphisms. In the present case control study, we included 182 healthy controls, 108 cases of benign breast disease and 114 breast carcinoma cases. Various clinicopathological details of cases were recorded. Immunohistochemistry was performed for estrogen (ER) and progesterone receptors (PR) and Her-2 neu. Circulating tumor cells were analyzed using flow cytometry (EpCAM, CK, CD45). Genotypic frequency of micro RNA polymorphisms was determined by PCR-RFLP assay. Circulating tumor cell positivity was observed in 11/114 (9.64%) breast cancer cases but absent in benign and control groups, and was significantly associated with tumor size, histologic type, tumor grade, metastasis and skin infiltration (p < 0.05). Circulating tumor cell positivity did not show any correlation with the immunohistochemical profile. No significant associations between pre-miRNA genetic variations miR-196a2 C/T (rs11614913), miR-146a G/C (rs2910164) and miR-499 T > C (rs3746444) polymorphisms and circulating tumor cell positivity were observed. The flow cytometry protocol for detection and molecular characterization of circulating tumor cells is a time and cost-effective technique, suitable for routine clinical use. However, more elaborate studies are needed to establish the findings as our study was limited by small sample size.

Abstract B34: CD56+ immune cell infiltration is decreased in benign breast lobules with fibrocystic changes

Abstract Introduction: CD56+ lymphocytes (a defining marker of natural killer cells) have a predominantly cytotoxic phenotype and a hypothetical role in breast tumor immunosurveillance. Here we investigate whether CD56+ staining density varies in nonmalignant breast lobules according to confirmed breast cancer risk factors- age, and histologic features of fibrocystic change and lobular involution. Methods: Archived breast tissue samples were obtained from 94 women with benign breast disease (BBD). The sample set was selected as a nested case-control study (47 cases, 47 controls) from within a large BBD cohort; cases were those who developed breast cancer subsequent to their benign breast biopsy; controls were matched to cases on age at biopsy, year of biopsy, and length of breast cancer free follow-up at least as long as the time-to-cancer in the matched case. Up to 10 representative lobules in each sample were characterized by H&amp;E for fibrocystic changes and the degree of epithelial proliferation (normal, nonproliferative, proliferative, atypia) and for degree of lobular involution (none, partial, complete). Consecutive sections were immunostained for CD56 and hematoxylin. Using digital image analysis, CD56 staining was quantified on a per lobule basis by pixel ratio (PR) (positive stain:total lobule). Statistical analysis was performed using linear mixed effects regression on the rank transformed density to account for correlations among multiple lobules from the same patient in assessing the association of density with lobule characteristics and using conditional logistic regression for association with case-control status. Results: Among 94 women (median age 52, range 35-73), 876 lobules were evaluated: 431 in BBD cases and 445 in BBD controls. Overall, 391 lobules (45%) were normal and the remaining 485 (55%) demonstrated fibrocystic changes. Among fibrocystic lobules, 247 (51%) had nonproliferative changes, 218 (45%) had epithelial proliferation, and 20 (4%) had atypical hyperplasia. Among normal lobules, 61 (16%) had no involution, 139 (36%) had partial involution, and 191 (49%) had complete involution. The vast majority of lobules (861/876, 98%) demonstrated presence of CD56+ cells, while only 15 of 876 lobules in 11 patients had zero CD56+ cells [7 cases (15%) versus 4 controls (8.5%) OR 1.75, p = 0.37]. The median CD56+ PR was 0.55% overall. Fibrocystic lobules as a group showed significantly lower median CD56+ PR compared to normal lobules (0.37% vs 0.85%, p &amp;lt; 0.0001). Among subcategories of fibrocystic lobules, the median CD56+ PR was lower in proliferative lobules (0.29%) compared to non-proliferative (0.42%), but this difference was not statistically significant (p = 0.55). Older women (age &amp;gt; 55) showed the highest CD56+ PR (median of 0.92%), as compared to 0.38% in women 45-55 (p=0.02), and 0.52% in women age &amp;lt;45 (p = 0.26). Among normal lobules, median CD56+ PR was similar between lobules with no involution (0.55%) and partial involution (0.52%) but was considerably higher among lobules with complete involution (1.3%, p = 0.09 and p = 0.05, respectively). In a multivariable model, CD56+ PR differences between fibrocystic and normal lobules remained significant (p = 0.0002) and also remained significant between age groups of &amp;gt; 55 and 45-55 (p = 0.02), while involution was non-significant. Median CD56+ PR was lower in cases (0.43%) compared to controls (0.72%), but this was not statistically significant (p=0.19) in our sample of 47 case-control pairs. Conclusions: Breast lobules with fibrocystic changes show less CD56+ cells, raising a question of possible immune suppression induced by early epithelial abnormalities. These findings encourage further investigation to improve understanding of the immune microenvironment in premalignant breast tissues. Citation Format: Rushin D. Brahmbhatt, Daniel Kerekes, Tanya L. Hoskin, Alvaro Pena, Daniel W. Visscher, Melody L. Stallings-Mann, Derek C. Radisky, Linda M. Murphy, Vernon Shane Pankratz, Keith L. Knutson, Marlene Frost, Amy C. Degnim. CD56+ immune cell infiltration is decreased in benign breast lobules with fibrocystic changes. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr B34.

Abstract 2364: CD68+ immune cells show different infiltration patterns in tissue samples from women with no clinical breast disease and those who have benign breast disease

Abstract Introduction: The role of macrophages in the tumor microenvironment is of increasing interest for tumor progression and invasion. Here we investigated the difference in CD68+ cell density in tissue samples from women with Benign Breast Disease (BBD) and women with no clinical breast disease from the Komen Tissue Bank (KTB) at Indiana University. Method: Archived breast tissue samples from women with BBD and no clinical breast disease were obtained for this age-matched case-control study. BBD samples included cases [later got Breast Cancer (BC)] and controls (did not get BC). Samples were characterized via H&amp;E stain for epithelial proliferation [normal (N), fibrocystic non-proliferative (NP), proliferative (P), or atypia (A)]. CD68+ cell density was obtained by digital image quantitation on a per lobule basis (Total CD68+ cells/mm2). Statistical analysis was performed with mixed effects regression. Results: Among 276 women (median age 53, range 35-79) comprising 92 age-matched triplets, 2508 lobules were evaluated [789 KTB, 839 BBD case, 880 BBD control]. 1407 (56%) lobules were normal and 1101 (44%) were fibrocystic {NP [613 (56%)], P [448 (41%)] and A [40 (4%)]}. Out of 2508 lobules analyzed, 2362 (94%) had CD68+ cells, while 146 (6%) showed zero CD68+ cells [19 (2%) BBD cases, 20 (2%) BBD controls, 107 (14%) KTB, p&amp;lt;0.0001]. KTB samples showed significantly lower (p&amp;lt;0.0001) CD68+ density (median 136 cells/mm2) as compared to BBD cases (median 313 cells/mm2) and BBD controls (median 299 cells/mm2). (See Table) For each lobule type, KTB samples had lower CD68+ density compared with the same lobule type in BBD samples (p&amp;lt;0.0001). Conclusion: CD68+ cells are more frequent in breast lobules from women with BBD compared to normal donors. This finding in premalignant breast tissues is consistent with inflammation as a driver of tumorigenesis. BBD case (n = 92 patients)BBD control (n = 92 patients)KTB(n = 92 patients)n lobulesMedian (IQR)n lobulesMedian (IQR)n lobulesMedian (IQR)Overall839313 (165 - 538)880299 (164 - 527)789136 (55 - 272)By Lobule TypeNormal344310 (177 - 557)434331 (177 - 567)629128 (55 - 255)All non-normal/fibrocystic lobules combined495314 (157 - 527)446274 (152 - 478)160159 (58 - 393)Fibrocystic non-proliferative231319 (153 - 543)263274 (140 - 496)119163 (71 - 359)Fibrocystic proliferative246295 (153 - 496)169277 (153 - 478)33128 (30 - 385)Atypia18484 (313 - 739)14260 (223 - 375)8216 (0 - 493)IQR - Interquartile range (25th percentile - 75th percentile) Citation Format: Muhammad A. Arshad, Daniel W. Visscher, Tanya L. Hoskin, Rushin D. Brahmbhatt, Alvaro Pena Jimenez, Melody L. Stallings Mann, Erin E. Miller, Linda M. Murphy, Jodi M. Carter, Stacey J. Winham, Keith L. Knutson, Derek C. Radisky, Amy C. Degnim. CD68+ immune cells show different infiltration patterns in tissue samples from women with no clinical breast disease and those who have benign breast disease. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2364. doi:10.1158/1538-7445.AM2015-2364

Caracterización histopatológica de lesiones benignas de la mama en mujeres del departamento de Sucre, Colombia. Periodo 2012-2013

El presente trabajo reclasificar el patrón histopatológico de las lesiones benignas de mama en mujeres del departamento de Sucre, en el período 2012-2013. Se trata de un estudio observacional-descriptivo-transversal, retrospectivo, en pacientes con reporte de patología de lesión benigna de mama, atendidas en el laboratorio de patología Patólogos Asociados de Sucre Ltda, Sincelejo-Sucre. Se revisaron las placas de archivos de casos de patología benigna de mama. Se reconfirmó el diagnóstico y se reclasificó de acuerdo con Page y Dupont y se encontró lesión no proliferativa en 376 (82,27%), lesión proliferativa sin atipias en 67 (14,66%) y lesión proliferativa con atipias en 14 (3,06%). Las lesiones no proliferativas son las lesiones benignas de mama más frecuentes en el departamento de Sucre y la más común en este estudio fue el fibroadenoma. Los informes de patología se deben reportar según la clasificación de Page y Dupont, para la mejora de la predicción y estratificación de riesgos y el mejor asesoramiento de reducción de riesgo para las mujeres con hiperplasia atípica. Se debe realizar seguimiento con mamografías preventivas de rutina en estos grupos de alto riesgo.

Preoperative Peripheral Blood Count in Breast Carcinoma: Predictor of Prognosis or a Routine Test.

Background. Peripheral blood count is the first investigation to be done in every patient before surgery. As strong relationship exists between cancer and immune response of the body, clinical stage at presentation and altered hematological parameters can influence the progression of cancer and vice versa. Settings and Design. It is a case control study of total 50 cases (35 cases of carcinoma breast and 15 cases of benign breast disease). Methods. A case control study was carried out; 35 cases of breast cancer patients were taken prior to surgery and chemotherapy with 15 cases of benign breast disease as control. Clinical staging according to the tumor, node, and metastasis classification (TNMc) was done and was correlated with complete blood count (CBC). Results. All the cancer patients were females with overall mean age of 47.96 ± 13.84 years. Amongst all altered blood parameters, correlation of absolute lymphocytic count (p value 0.001) with TNMc staging was found significant. Particularly, decrease in absolute leucocytic count was observed with increase in stage of breast carcinoma. Conclusions. The stage-specific mean values of absolute lymphocytic counts of preoperative breast cancer patients can be used as an economical tool to know the evolution of disease.

Abstract 1652: Immune infiltration of normal and benign breast lobules varies in breast tissues based on cancer risk

Abstract Introduction: Histologic characteristics of nonmalignant breast tissues (epithelial proliferation and involution) are associated with future breast cancer (BC) risk. We evaluated immune infiltration (lobulitis) in benign breast lobules and its association with features of BC risk. Methods: We analyzed archived nonmalignant breast tissue samples from 81 women in age-matched groups of varying cancer risk: 27 with benign breast disease (BBD) who later developed BC (cases), 27 with BBD without subsequent BC (controls), and 27 normal women without clinical breast disease from the Komen Tissue Bank at Indiana University (KTB). Up to 10 lobules in each sample were characterized by H&amp;E for lobulitis, involution (none, partial, complete), and fibrocystic (FC) status (normal, nonproliferative, proliferative). Lobulitis was defined by H&amp;E staining as lymphocyte nuclei in the intralobular stroma at low magnification and between adjacent acini at high magnification. Data was analyzed by mixed effects logistic regression. Results: Median age was 57 years (range 37-70). Among 81 breast tissue samples, 750 lobules were evaluated: 249 in BBD Cases, 265 in BBD Controls, and 236 in KTB donors. 56% of lobules were normal and 44% were FC, with 87% of FC lobules occurring in BBD samples. Lobulitis was present in 44% of lobules and varied according to subject age and individual lobule features. Younger women were more likely to have lobulitis (p=0.002); among women &amp;lt;50 the median proportion of lobules with lobulitis was 50%, versus 30% among women 50+. Lobulitis was less frequent in lobules with complete involution (37%) compared to partial (74%) or no involution (84%), p&amp;lt;0.0001. Lobulitis was common in normal lobules (52%) and decreased with increasing epithelial abnormality-39% of nonproliferative lobules and 27% of proliferative lobules (p&amp;lt;0.0001). In multivariate analysis including all 3 variables, all 3 remained significantly associated with lobulitis: age (p=0.03), proliferation (p&amp;lt;0.0001), and involution (p=0.0001). Lobules with lobulitis were less frequent in groups of women with increased breast cancer risk-55% of lobules in normal KTB samples, 43% in BBD controls, and 35% in BBD cases (p = 0.02). Conclusion: Lobulitis is common in normal and benign breast tissue lobules but varies with age, involution status, and epithelial abnormality. Further work is needed to understand the role of immune infiltrates in breast cancer risk. Citation Format: Rushin D. Brahmbhatt, Daniel W. Visscher, Tanya L. Hoskin, Derek C. Radisky, Linda M. Murphy, Melody L. Stallings Mann, Erin Miller, Vernon S. Pankratz, Lynn C. Hartmann, Marlene H. Frost, Amy C. Degnim. Immune infiltration of normal and benign breast lobules varies in breast tissues based on cancer risk. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1652. doi:10.1158/1538-7445.AM2014-1652

Adolescent physical activity and inactivity: a prospective study of risk of benign breast disease in young women.

In previous investigations of adolescent activity recalled in adulthood, modest reductions in risk of benign breast disease (BBD) and premenopausal breast cancer were seen with moderate-strenuous activity during high school. We therefore investigated physical activity, walking, and recreational inactivity (watching TV-videos, playing computer-videogames) reported by adolescent girls in relation to their subsequent risk for BBD as young women. The Growing Up Today Study includes 9,039 females, 9-15years at study initiation (1996), who completed questionnaires annually through 2001, then in2003, 2005, 2007, 2010 and 2013. Annual surveys (1996-2001) obtained data on physical and sedentary activities during the past year. Beginning in 2005, women (≥18years) reported whether they hadever been diagnosed with BBD confirmed by breast biopsy (n=133 cases, to 11/01/2013). Logistic regression (adjusted for baseline adiposity and age; additional factors in multivariable-adjusted models) estimated associations between adolescent activities (moderate-vigorous, walking, METS, inactivity) and biopsy-confirmed BBD in young women. Girls who walked the most had significantly lower risk of BBD (multivariable-adjusted OR=0.61, ≥30 vs ≤15min/day;p = .049). We observed no evidence that inactivity (≥3 vs <2h/day OR=1.02, p=.92) or METS (top vs bottom tertile OR=1.19, p=.42) were associated with BBD. Accounting for factors including family history, childhood adiposity,and other activities and inactivities, adolescent girls who walked the most were at lower risk for BBD. We found no evidence that high moderate-vigorous activity might reduce risk, nor did we observe any association with inactivity. Continued follow-up will re-evaluate these findings as more BBD cases, and ultimately breast cancer, are diagnosed.

Evaluation of serum PSA levels as a biomarker for breast carcinoma in north Indian females

Objective: Breast cancer has emerged as the most common malignancy among females during the last few years. Early diagnosis is essential for disease management so research is underway to identify potential serological bio markers with acceptable sensitivity and specificity. The current study was undertaken to compare the levels of serum PSA in patients with benign breast diseases, carcinoma breast and normal controls. Methods: The study was conducted jointly by the departments of Biochemistry and Surgery. Fifty patients of breast carcinoma were enrolled in the study, along with 50 cases of benign breast disease and 50 healthy controls. Serum PSA levels were estimated by Roche Elecsys modular Cobas e 411(electrochemiluminescence immuno assay) (Manheim Germany). Results: We did not find any significant differences in the PSA levels between normal controls, patients with benign breast disease as well as females presenting with breast carcinoma. No correlation was observed between serum PSA levels with clinical staging as well as histopathological grading. Conclusions: According to previous published studies, tumor levels of PSA are valuable for breast cancer patient prognosis, since patients with PSA positive tumors have much longer disease-free and overall survival. PSA levels in the serum of breast cancer patients are not significantly different from the PSA levels in the serum of normal women. Based on these data we conclude that serum PSA levels are not useful for breast cancer patient diagnosis or monitoring. DOI: http://dx.doi.org/10.3126/ajms.v5i4.7800 Asian Journal of Medical Sciences 2014 Vol.5(4); 25-28

Expression of midkine in serum of patients with breast cancer and its clinical significance

Objective To investigate the serum midkine (MK) level in patients with breast cancer and its clinical significance.Methods The serum level of midkine was measured by using enzymelinked immunoadsobent assay in 100 healthy controls,50 cases of benign breast disease,and 120 cases of breast cancer before and after Surgery.Results The expression rate of midkine in serum of patients with breast cancer (65.52％) was significantly higher than in patients with benign breast disease (6.00％) and healthy controls (4.00％) (both P ＜0.01).The level of midkine in serum of patients with breast cancer before surgery [1 372 (896,324 6) ng/L] was significantly higher than that in patients with breast cancer after surgery [784 (563,890) ng/L] or breast benign disease [465 (420,574) ng/L] or healthy controls [450 (400,554) ng/L] (all P ＜0.01).The level of midkine in serum in patients with tumor recurrence [2 358 (1 123,4 787) ng/L] was obviously higher than that in patients with breast cancer before surgery (P ＜0.01).The preoperative level of midkine in serum of breast cancer patients was associated with clinical TNM stage,histological grade,axillary lymph nodes metastases and tumor size.Conclusion Surgery,clinical stages,histological grades,lymph nodes metastases and tumor recurrence were associated with the level of midkine in serum.Serum midkine level can be applied in the diagnosis and monitoring of breast cancer. Key words: Breast cancer; Midkine

Benign breast diseases in Warri Southern Nigeria: A spectrum of histopathological analysis

Background: Benign breast diseases (BBDs) constitute a source of morbidity and mortality among women globally. Most of these lesions are common in women of reproductive age and are associated with hormonal influences. However, studies have reported an increasing incidence of these lesions in children and adolescents. Aims: The aim was to highlight the spectrum and histological patterns of BBDs among women in Delta State and other Southern states of Nigeria as seen at central hospital, Warri. Materials and Methods: This study was a 7-year retrospective analysis of all histologically diagnosed breast diseases in women. Request forms were scrutinized for clinical bio-data, diagnosis. Hematoxylin and eosin stained-slides of breast biopsies carried out at the central hospital, Warri were archived and studied. Results: A total of 905 breast lesions were received during this 7 years period in the Pathology Department. Of these, 644 cases accounting for (71.2%) were benign lesions, while 261 cases (28.8%) were malignant giving a ratio of 2.5:1. A total of 638 cases occurred in female while only 6 cases occurred in males. The mean age was 31.2 ± 8.4 years, and the peak age incidence was 20-29 years constituting 49.8% cases of BBDs. Fibroadenoma was the most common BBD accounting for 302 cases (46.9%). Fibrocystic disease was the second majority and constituted 126 cases (19.6%). Conclusion: Fibroadenoma constituted the most common histopathological patterns of BBDs in children and adolescents in our environment.