Breast Neoplasms

Objective: To evaluate expression of p53 and Ki67 proliferative index in triple negative breast carcinoma. Study Design: Cross-sectional analytical study. Place and Duration of Study: Department of Histopathology, AFIP Rawalpindi, from Jan to Jul 2018. Methodology: Fifty-two cases of triple negative female breast carcinoma were included in this study regardless of age of patient, histological type and grade of the tumor. Tumors such as malignant tumors with positive immunohistochemical staining for ER, PR and Her 2 neu, stromal tumors, skin squamous cell carcinomas, lymphomas, poorly fixed specimens and specimens with scanty tumor tissue were excluded. Results: The mean age of patients was 53.28 ± 7.69 years (range 40-71 years). Most of the patients were in the age group 41–50 years 21 (40.4%) and 51-60 years 21 (40.4%), followed by age group more than 60 years 10 (9.2%). High Ki67 index was seen in 34 (65.4%) of cases. In the rest of the cases 18 (34.6%) the proliferative index was...

The extraction and purification of parigidin-br3, a cyclotide analogue belonging to the "bracelet" subfamily, from Palicourea rigida leaves is discussed. Unlike conventional cyclotides, parigidin-br3 has free N- and C-termini, as identified by MALDI-TOF/TOF analysis and confirmed by gene structure elucidation, and is one of a small number of acyclotides discovered during recent years. Parigidin-br3 showed cytotoxic activity against MCF-7 (breast cancer) and CACO2 (colorectal adenocarcinoma) cells, with IC50 values of ∼2.5 μM and less than 10% hemolytic activity. Overall, parigidin-br3 is a promising new molecule with cytotoxic properties against tumor cell lines and, unlike many synthetic acyclic analogues, demonstrates that cytotoxic activity is not limited to conventional (i.e., cyclic) cyclotides.

BACKGROUNDThe literature offers discordant results regarding whether diagnostic biopsy is associated with the dissemination of cancer cells, resulting in local and/or distant metastasis. The long‐term outcomes of patients with breast cancer were compared between those who were diagnosed using either fine‐needle aspiration biopsy (FNAB) or core‐needle biopsy (CNB) during 2 decades: the 1970s and 1990s.METHODSIn the 1970s, the only diagnostic needle biopsy method used for breast cancer in Sweden was FNAB. CNB was introduced 1989 and became established in Stockholm Gotland County in the early 1990s. The authors compared the clinical outcomes of patients diagnosed using FNAB from 1971 to 1976 (n = 354) versus those of patients diagnosed using CNB from 1991 to 1995 (n = 1729). Adjusting for differences in various treatment modalities, mammography screening, tumor size, DNA ploidy, and patient age between the 2 decades, 2 strictly matched samples representing FNAB (n = 181) and CNB (n = 2...

While leukocyte telomere length (TL) has been associated with breast cancer risk, limited information is available regarding the role of genetically-determined TL on breast cancer risk. We investigated whether aggregated TL-associated variants are associated with the risk of breast cancer in 2,865 breast cancer cases and 2,285 controls from the Shanghai Breast Cancer Genetics Study. Six genetic variants, identified through a genome-wide association study (GWAS) of TL in European-ancestry participants, were included in the study. A separate sample [n = 1,536, from the Shanghai Women's Health Study (SWHS), for whom information on both phenotypical leukocyte TL and genetic information was collected] was used to evaluate the association of six variants with TL in Asians. Three genetic risk scores (GRSs), based on the number of alleles associated with shorter TL that each individual carries for the six variants, were derived for the study: un-weighted, internally weighted (from the S...

In mammalian cells, the level of estrogen receptor α (ERα) is rapidly decreased upon estrogen treatment, and this regulation involves proteasome degradation. Using different approaches, we showed that the Mdm2 oncogenic ubiquitin-ligase directly interacts with ERα in a ternary complex with p53 and is involved in the regulation of ERα turnover (both in the absence or presence of estrogens). Several lines of evidence indicated that this effect of Mdm2 required its ubiquitin-ligase activity and involved the ubiquitin/proteasome pathway. Moreover, in MCF-7 human breast cancer cells, various p53-inducing agents (such as UV irradiation) or treatment with RITA (which inhibits the interaction of p53 with Mdm2) stabilized ERα and abolished its 17β-estradiol–dependent turnover. Interestingly, our data indicated that ligand-dependent receptor turnover was not required for efficient transactivation. Altogether, our results indicate that the Mdm2 oncoprotein and stress-inducing agents complexly ...

Women with primary breast cancer associated with extensive axillary node involvement or large primary tumors have a very poor prognosis despite treatment with standard-dose adjuvant chemotherapy. In an attempt to improve the outlook of these patients, we investigated the safety and feasibility of delivering three cycles of high-dose epirubicin and cyclophosphamide supported with filgrastim-mobilized peripheral blood progenitor cells (PBPC). Fifteen previously untreated women, median age 50 (range, 30-58) years, with poor prognosis early stage breast cancer received filgrastim (12 microgram/kg daily for 6 days) prior to chemotherapy to mobilize progenitor cells. Patients were then given three cycles of epirubicin (200 mg/m2) and cyclophosphamide (4 g/m2) at planned 28-day intervals, each followed by infusion of one third of the PBPC collected and daily administration of filgrastim (5 microgram/kg s.c.). Three leukaphereses collected a median of 114.9 (range, 22.7-273.5) x 10(4) granu...

More Glycine, Please To better characterize metabolic properties of cancer cells, Jain et al. (p. 1040 ; see the Perspective by Tomita and Kami ) measured systematically the concentrations of hundreds of metabolites in cell culture medium in which 60 different cancer cell lines were growing. The fastest growing cancer cells tended to consume glycine, whereas more slowly growing cells excreted some glycine. The rapidly growing cancer cells appeared to need glycine for synthesis of purine nucleotides required for continued synthesis of DNA. Interfering with glycine metabolism slowed growth of the rapidly proliferating cancer cells. Thus, an increased dependence on glycine by rapidly growing cancer cells could potentially provide a target for therapeutic intervention.

Isolated avulsion fractures of the pelvic ring are rare and occur predominantly in adolescent athletes. Isolated fractures of the lesser trochanter are reported to be pathognomic for tumor diseases in adults. We present a case of a female patient with an isolated avulsion of the lesser trochanter after treatment by her chiropractor. After staging examination, we determine the diagnosis of a left-sided carcinoma of the mamma. Additional imaging shows multiple metastases in liver, spine and pelvis. Palliative therapy has started over the course of time. We suggest, on suspicion of a malignant metastatic process, further investigation.

Background In South Africa, breast cancer is the most commonly diagnosed cancer and cervical cancer the leading cause of cancer mortality. Most cancers are diagnosed at a late-stage and following symptomatic presentation. The overall purpose of the study was to inform interventions aimed at improving timely diagnosis of breast and cervical cancer. Methods In-depth interviews were conducted with women with potential breast or cervical cancer symptoms from urban and rural South Africa. Participants were recruited from a community-based cross-sectional study on breast and cervical cancer awareness. Data were analysed using a thematic analysis approach. Results Eighteen women were interviewed (10 urban, 8 rural): the median age was 34.5 years (range 22–58). Most were unemployed, and five were HIV positive. Themes included impact and attribution of bodily changes; influence of social networks and health messaging in help-seeking; management of symptoms and help-seeking barriers. Breast c...

Recent studies suggest that HER-2/neu specifically promotes the invasive capacity of tumor cells by up-regulating secretion of the proteolytic enzyme, urokinase-type plasminogen activator (uPA), or its inhibitor, plasminogen activator inhibitor-1 (PAI-1), in colon and gastric cancer. It was the purpose of this study to: (a) evaluate the association between HER-2/neu and uPA and PAI-1 expression in a large primary breast cancer cohort; (b) perform the first multivariate analysis, including HER-2/neu, uPA, and PAI-1 in breast cancer; and (c) define the effect of HER-2/neu overexpression on uPA and PAI-1 expression in breast cancer cells. HER-2/neu, uPA, and PAI-1 were measured as continuous variables by ELISA in primary breast cancer tissue extracts from 587 patients with clinical follow-up and analyzed for correlations with clinical outcome. Furthermore, a full-length human HER-2/neu cDNA was introduced into five human breast cancer cell lines to define the effects of HER-2/neu overe...

Trastuzumab and lapatinib provide clinical benefit to women with human epidermal growth factor receptor 2 (HER)–positive breast cancer. However, not all patients whose tumors contain the HER2 alteration respond. Consequently, there is an urgent need to identify new predictive factors for these agents. The aim of this study was to investigate the role of receptor tyrosine kinase signaling and phosphoinositide 3-kinase (PI3K)/AKT pathway activation in conferring resistance to trastuzumab and lapatinib. To address this question, we evaluated response to trastuzumab and lapatinib in a panel of 18 HER2-amplified cell lines, using both two- and three-dimensional culture. The SUM-225, HCC-1419, HCC-1954, UACC-893, HCC-1569, UACC-732, JIMT-1, and MDA-453 cell lines were found to be innately resistant to trastuzumab, whereas the MDA-361, MDA-453, HCC-1569, UACC-732, JIMT-1, HCC-202, and UACC-893 cells are innately lapatinib resistant. Lapatinib was active in de novo (SUM-225, HCC-1419, and H...

INTRODUCTION Ultrasound-guided, vacuum-assisted biopsy has a definitive role in the diagnosis of breast lesions. Its role in the treatment of benign breast lesions like fibroadenomas has not been established. PATIENTS AND METHODS This is a retrospective review of patients undergoing ultrasound-guided, vacuum-assisted biopsy for clinically benign breast lesions. The procedures were performed in all cases by two consultant radiologists with special interest in breast radiology between February 2002 and January 2004. Patients were followed up in the clinic 6 weeks after the procedure. RESULTS Seventy-six patients had ultrasound-guided, vacuum-assisted excision of clinically benign breast lesions during this 2-year period. Mean age of the patients was 31 years. Altogether, 86 procedures were performed. Six patients with larger lesions (> 2 cm) had two procedures on separate sitting and 4 patients had separate lesions excised on a later date. Fifty-six patients were identified to have...

OBJETIVO: Avaliar se a Paullinia cupana diminui o número e a gravidade dos fogachos em mulheres após diagnóstico de câncer de mama. MÉTODOS: Estudo piloto prospectivo fase II realizado com mulheres que sobreviveram ao câncer de mama, que completaram o tratamento pelo menos 3 meses antes e que apresentavam ao menos 14 episódios de fogachos por semana. Utilizando o desenho de Simon para que a primeira etapa fosse considerada positiva, ao menos 9 de 15 mulheres deveriam ter a gravidade dos fogachos diminuída em pelo menos 50%. As pacientes receberam 50mg do extrato seco de Guaraná oralmente 2 vezes por dia por 6 semanas. Foram avaliadas, a gravidade e a frequência dos fogachos. RESULTADOS: Dezoito pacientes iniciaram o tratamento com Paullinia cupana e 15 completaram o estudo. Três pacientes deixaram o estudo imediatamente após iniciarem o tratamento em razão de dificuldade na participação e não adesão. Das 15 pacientes que completaram o estudo, 10 obtiveram diminuição de mais de 50% d...