Breast Cancer

RT after surgery kills any cancer cells that could remain in the breast, the chest wall, or nodal basins. RT for early stage disease can allow for breast preserving surgery instead of mastectomy. In Phase III breast trials for DCIS, moderate dose RT has been shown to eradicate residual microscopic disease in the breast. This reduces the chance that the cancer will come back, thus allowing patients the ability to conserve the breast. Likewise, Phase III trials for stage I-II breast cancer have proven that adding RT to lumpectomy dramatically reduces breast cancer recurrence in the breast over lumpectomy alone, and that survival is identical between mastectomy and lumpectomy plus RT. Post-mastectomy RT (PMRT) is indicated for stage III disease (high risk patients with cancers > 5 cm or involving lymph nodes). RT is also used for recurrent breast cancer and in stage IV disease to palliate symptomatic sites. The most common way RT is delivered is via external beam using either photons or electrons. A typical curative course lasts 6 weeks, with daily treatments delivered Monday- Friday, and about 15 minutes is required per treatment. Ongoing trials are assessing the value of shorter course partial breast irradiation. In the palliative setting, RT can be delivered in a much shorter course, typically over 2 weeks.

Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and pre- vention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest avail- able genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57–1.65) with area under receiver-operator curve (AUC) ¼ 0.630 (95%CI: 0.628–0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Good- ness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs.

and men [11]. However, it is in sexually selected traits, such as breasts, that the highest values of FA may be found [12-14]. Sexually selected traits are more liable to be disrupted during development because they often show rapid growth rates, are generally elaborate in design and are highly susceptible to mutation that results from rapid cellular proliferation and the action of sex steroids [15-17]. Breasts develop rapidly just prior to and during puberty and the importance of estrogen in the development, growth and carcinogenesis of the mammary gland is well established [18]. The role of local estrogen pro- duction in breast cancer is now more apparent [19-22]. Sym- metrical breast development may well be an indicator of an individual's ability to tolerate 'disruptive' hormonal variation whilst maintaining developmental stability. Møller and col- leagues [23] found that large breasts had more FA than small breasts, breast FA was higher in nulliparous women, and that breast FA was a predictor of fecundity.

The data were analysed using the SPSS v.13 and Stata v.8.2 statistical packages (SPSS Inc., Chicago, Illinois, USA; Stata- Corp. LP, Texas, USA). Using two conditional logistic regres- sion models (for absolute breast FA and relative breast FA) the crude and adjusted relative odds of breast cancer were esti- mated for each breast FA variable and other known potential risk factors and confounders, together with 95% confidence intervals (95% CI). For the purposes of this analysis, because a 1 ml change in breast volume FA is very small, the results for breast volume FA are presented as the change in relative odds for a 100 ml change in breast volume FA. In addition, given the strong effect of age at menopause on breast cancer risk, this was controlled for in additional models containing only post- menopausal women. The effect of age at first pregnancy was modelled using another set of conditional logistic regression models for the subset of women who had ever been pregnant, and again age at menopause was controlled for in an addi- tional analysis including only post-menopausal, ever pregnant women. A case-control stratum was excluded from the analy- sis if the information for either the cases or controls was not known for the variable in question. The variables were entered together into the multivariable regressions, and then factors that did not contribute significantly after consideration of other potential cofactors were removed from the model only if they were found not to influence the FA associations. The models containing all risk factors are presented and only minor changes to the parameter estimates in the main findings resulted if insignificant terms were removed.

HER-2 may be a paramount gene to subatomic focusing on medicine for breast malignant [37]. Determination of ER status about obtrusive breast carcinoma may be suitable as a prognostic and predictive figure, and ER+ predicts for a light of endocrine help for example, such that antiestrogen (tamoxifen) organization alternately ovarian concealment. Similarly, mankind’s epidermal development component receptor 2 (HER2) positivity is handy for selecting focused on treatment with monoclonal immune response (trastuzumab) against HER2. Recently, microarray profiling from claiming obtrusive breast carcinoma need distinguished five different subtypes from claiming morphologically comparative breast malignancy (luminal A, luminal B, typical breast-like, HER2-overexpressing, furthermore the basal-like subtype), representing something like 15% for breast malignant situations furthermore portrayed toward cynicism for ER, PR, furthermore HER2, is connected with combative histology, poor prognosis, What’s more lethargy of the ordinary endocrine therapies, shorter survival, and BRCA1-related breast malignancy [38,39]. Exactly breast malignancy needs a shelter amount for HER2 receptors. The additional HER2 receptors animate those malignancy units will separate What’s more developed. When there would be higher levels of the HER2 protein done a breast cancer, it is known as HER2 certain breast malignant. The HER2/erbB2 gene, cell surface receptor tyrosine kinase is a pro-oncogene for signal transduction in cell development and division [40,41].

69. Ingthorsson, S., Sigurdsson, V., Fridriksdottir, A.J., Jonasson, J.G., Kjartansson, J., Magnusson, M.K. & Gudjonsson, T. 2010, "Endothelial cells stimulate growth of normal and cancerous breast epithelial cells in 3D culture.", BMC Research Notes, vol. 3, pp. 184. 70. Dirat, B., Bochet, L., Dabek, M., Daviaud, D., Dauvillier, S., Majed, B., Wang, Y.Y., Meulle, A., Salles, B., Le Gonidec, S., Garrido, I., Escourrou, G., Valet, P. & Muller, C. 2011, "Cancer-Associated Adipocytes Exhibit an Activated Phenotype and Contribute to Breast Cancer Invasion", Cancer Research, vol. 71, no. 7, pp. 2455-2465. 71. Man, Y. 2007, "Focal degeneration of aged or injured myoepithelial cells and the resultant auto-immunoreactions are trigger factors for breast tumor invasion", Medical hypotheses, vol. 69, no. 6, pp. 1340-1357.

To evaluate the performance of each potential PRS, we standard- ized the PRSs to have unit standard deviation (SD) in the valida- tion set of control subjects. The association of the standardized PRSs was evaluated in the validation and test (prospective studies) datasets, by logistic regression. We used a Cox proportional haz- ards regression model to assess the association with risk of breast cancer in UK Biobank. Models were also compared in terms of the area under the receiver operator characteristic curves (AUC), adjusted for study, calculated using the Stata command comproc. Meta-analysis of study-specific effects was carried out using the Stata command metan.

Abstract: Breast cancer is the most frequent type of cancer in women. Great progress has been made in its treatment but relapse is common. One hypothesis to account for the high recurrence rates is the presence of cancer stem cells (CSCs), which have the ability to self-renew and differentiate into multiple malignant cell types. This study aimed to determine genes that are expressed in breast cancer and breast CSCs and to investigate their correlation with stemness. RNA was extracted from established breast cancer cell lines and from CSCs derived from five different breast cancer patients. DNA microarray analysis was performed and any upregulated genes were also studied in other cancer types, including colorectal and lung cancer. For genes that were expressed only in breast cancer, knockdown-based experiments were performed. Finally, the gene expression levels of stemness transcription factors were measured. The outcome of the analysis indicated a group of genes that were aberrantly expressed mainly in breast cancer cells with stemness properties. Knockdown experiments confirmed the impact of several of these on NANOG, OCT3/4, and SOX2 transcription factors. It seems that several genes that are not directly related with hormone metabolism and basic signal transduction pathways might have an important role in relapse and disease progression and, thus, can be targeted for new treatment approaches for breast cancer.

We also found that a significant proportion of breast cancer patients in Italy might be receptive to the idea of taking HRT. However, there is a diffuse sceptical attitude in the lay public and also in the medical community about the safety of this treatment for breast cancer survivors. Indeed, the majority of women had been advised against HRT by their physicians, who also very rarely did inform the patients about the existence of alter- native non-hormonal remedies. We believe that at least part of the reluctance to prescribe HRT in patients with previous breast or endometrial cancers may be attributed to the fact that national health guidelines usually state that estrogens are contraindicated in these patients.

freedom. The associations between risk of breast cancer and risk factors and CYP17 genotypes were assessed by multiple linear logistic regression, adjusting for the potential confound- ers reference age, body mass index, family history, education level, country of birth, benign breast disease, and age at men- opause in postmenopausal women. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with and with- out adjustment for measured risk factors. Logistic regression was also used to assess, in controls, the associations of hor- mone-related risk factors with genotype after adjusting for the above potential confounders. The statistical significance of interaction terms was assessed by the likelihood ratio test. All analyses were conducted with Stata version 8.0. All statistical tests were two-sided and the P values quoted are nominal; that is, no attempt was made to adjust for multiple compari- sons, either in terms of the number of covariates or in terms of the number of modes of inheritance being considered. A visual comparison between the results of the ABCFS and those of the WNYBCS was conducted by plotting the corre- sponding log OR estimates from each study against one another, using R version 1.6.2. The size of the points was pro- portional to the average of the inverse of standard errors of the two studies for that particular risk factor's estimate, so that larger points were those for which there was more precision. A positive correlation between the data points would be evi- dence for replication of findings.

mice, and, conversely, that aromatase expression and activity are increased by transgenic COX-2 over-expression. Together these datasets definitively establish that Cox-2 can regulate aromatase in vivo in mammary tissues [56,62]. Peripheral aromatization is largely responsible for estrogen production in postmenopausal women, and mammary adipose tissue is a particularly important local estrogen source. Therefore, regulation of mammary aromatase synthe- sis by COX/PG signaling is most likely to be important in the context of postmenopausal breast cancer. The ability of COX- derived PGs to increase aromatase expression and hence local estrogen levels may provide a partial explanation for reports of reduced incidence of breast cancer associated with NSAID use [5-12], because COX inhibition is predicted to decrease mammary estrogen levels and hence restrict the growth of estrogen-dependent tumors. This mechanism is expected to be operative irrespective of COX-2 expression status because COX-1 is constitutively expressed in human breast tissues [21,25]. Importantly, the idea that both COX isoforms can impact on tumorigenesis is supported by genetic evidence obtained using Cox-1 and Cox-2 knockout mouse strains [32,40,63,64]. Intriguingly, Neugut and colleagues [65] have identified differential sensitivity of breast cancers to NSAID-mediated protection according to hormone receptor status. Specifically, they found that aspirin use was associated with a decreased risk of hormone receptor positive breast cancer, but did not affect the incidence of hormone receptor-negative disease, in a population-based case-control study. These data support the concept that COX inhibition reduces mammary neoplasia at least in part through suppression of estrogen biosynthesis. Figure 4

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26. Husin N, Helali T, Domi M, Bedri S, Cervical cancer in women diagnosed at the national health laboratory, sudden: A call for screening, Sudan journal of medical science, 2011; (6): 183-190. 27. Abudu EK, Banjo AAF, Izegbu MC, J.Agboola AO, Anunobi CC, Jagun OE, Histopathological pattern of carcinoma of cervix in Olabisi Onabanjo University Teaching Hospital, Sagamu, Nigeria, Nig Ot j Hosp Med, 2006; 16(3): 35-40.

Background: Helicobacter pylori is a pathogenic gram negative bacteria found in human stomach. It is present in almost 50% of human population worldwide and its infection is linked to development of various diseases ranging from gastrointestinal disorders to gastric cancer. The objective of the present study was to assess the epidemiology and genomic variability of H. pylori strains prevalent in patients of Jammu (J&K).

The present study showed a significant male preponderance with male to female ratio 4.03:1. which is comparable to other studies. However many earlier Indian studies were showing sex ratio 5.76:1 to 6.67:1. This over the years change in ratio can be explained due to rising trends of lung malignancies in females, while most of them were never smoker or passive smokers. The most common etiological association of lung carcinoma found worldwide is tobacco consumption in form of smoking, with increasing risk by early age at initiation, duration and per day use. By the present study we found that 59% of lung cancer patients were smokers. Hence there is a strong need of conduction of more awareness programmes and tobacco control regimens. Our study showed a higher number of adenocarcinomas i.e. 53.44% of all NSCLC, while Squamous Cell Carcinoma comprised 36.91% of all NSCLC. These results favouring a morphological shift from Squamous Cell Carcinoma to adenocarcinoma of lung, which has been confirmed by many other studies. 14,18

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Most of the literature studying the association of Down syndrome with parental consanguinity concluded that no such association existed. The association of consanguineous marriages with late onset complex diseases such as diabetes, cardiovascular disorders, schizophrenia and cancer requires further studies to precise any existing risks because currently unambiguous evidence-based conclusions are difficult to establish. 18 In the