Breast cancer is the most prevalent cancer among Iranian women. Early diagnosis of the disease is vitally important in successful treating of it and reducing its mortality and care-cost burden. In our country, the major causes of mortality and other unfavorable complications of the disease are due to late referring of women. Breast Self -Examination (BSE) is a low-cost, low-risk, self-performed screening, which, according to the evidence from the literature improves the prospects for women’s survival. A content analysis with a qualitative approach was conducted in depth on women through semi-structured  interviews. Based on the result analysis, one them related to women’s prospect BSE: Including Fearful feeling, with 2 Sub-themes A: Change body image B: Uncertain future. Training courses on breast cancer and BSE screening program for women (vulnerable poor population) is necessary so as to change their beliefs and culture in order to promote this health behavior. Breast cancer is a stressful experience that leads to emotional anxiety and destructs one’s performance in performing daily tasks. The world’s statistics indicate increased number of breast cancer infection and quicker spread of it in developing countries, which have had low rate of breast cancer before . DespiteThe purpose of this phenomenological study was to explore experiences of Women screening tests such as breast self-examination. A phenomenological approach was used to explore the essence of the participants’ experience of this phenomenon. Semi-structured interviews were conducted to gain a deeper understanding of those experiences.Interpretative Phenomenological Analysis served as the methodology for this study by providing a structure for gathering detailed descriptions on how women providing a structure for gathering detailed descriptions on how women experience screening tests such as breast self-examination and how they perceive this underlying belief of s experience. The notion that there are multiple realities and gives meaning to people’s lives are the scholars in qualitative research , 10. In To obtain the desired information, each participant was individually interviewed, face-to face, using a semi-structured interview. All participants gave verbal and written consent to be audio taped prior to the interview. The interview questions were developed by the researcher I answered all of the questions by discussing them with my dissertation chair to eliminate any bias as I have disclosed personal experiences related to the phenomenon. The interview questions were based on the participants’ prospect related to screen breast cancer.The initial interviews were no more than one hour in length. Participants were provided the opportunity to review the questions before the scheduled interview session.A face-to-face, follow-up interview, lasting approximately 30 minutes, was conducted with each participant purposes of verification and clarification. Preliminary findings were shared with the for participants during the follow-up interview to ensure agreement with themes and to give the participants the opportunity to correct any misrepresented ideas or interpretations. Follow-up interviews were not recorded. The Written informed consent was obtained from each participant informed consent was summarized verbally for each participant to ensure that she understood her involvement in this process. Prior to e ach interview, the participant was asked to personal characteristics questionnaire attached to the informed consent. The personal complete the characteristics questionnaire consisted of items pertaining to the participants’ age, marital status, educational level.I explained that this study will help to increase awareness of self- examination breast and how affects women of jiroft city.The participants were informed that if at any time they did not feel comfortable with answering a question, they were not obligated to do so. They were also informed that each participant would be given a pseudonym to protect her identity.The interview protocol was reviewed at the end to make certain that all the information was covered.Thus, after completing interviews were transcribed immediately transcribed. At this stage, the interview was reviewed several times to gain a general sense of the text. Data were read verbatim and the first level coding process with emphasis on implicit and explicit content was bone by highlighting and identifying the sentences and paragraphs of the units of analysis. For each analysis, a higher code was given and the codes were extracted. Then the codes based on differences and similarities were classified. Depending on the relationship between the subset, a great number of subclasses were organized in other classes, in coding process, the codes were repeatedly controlled by the research team and in cases of contradictions, and inconsistencies were resolved by discussion and dialogue. After classification, classes were put together in form of a significant conceptual model. And the relationships between the classes were identified and the source code appeared -15. To dAfter the data analysis, one of them was obtained from the data. It was fearful feeling, with 2 Sub-themes A: Change body image B: Uncertain future.Non-delayers experienced far less ambiguity about the implications of their symptom discovery and expressed more concern that the change they found might represent a serious health threat.The women participating in this study stated that educating people to stay away from known risk factors, and encouraging them to healthy habits are among the first steps towards the prevention and control. And breast cancer screening is the best strategy for reducing cancer mortality. Similar findings emerge from the breast cancer screening literature which suggests that attenders for screening have more faith in the health care system than non- attenders, perceiving positive, rather than negative, consequences as the likely outcome of screening.Some informants have expressed their unhappiness and distress on loss of body image due to the surgical treatment with one breast being removed or the scar that remained on her chest.The theme category of altered body image included loss of feminine characteristic, long-lasting psychological effect, and stigmatization. Meanwhile, our informants also held the same view, which they have revealed the negative feeling of body image due to the surgical treatment of the breast cancer. Although some literature have suggested that women undergoing breast cancer.Although some literature have suggested that women undergoing breast conservation surgery have better outcomes on selected psychosocial and quality of life measures then those of mastectomy.We found that women with a history of breast cancer in the family had a higher degree of susceptibility regarding breast cancer in our study. Some of the informants have expressed their worries towards uncertain future with their loss of control over life and fear of recurrence Table .This study is important as it defines the breast cancer-related behaviors and beliefs of women.The present study was conducted by the aim Women’s prospect of Breast Self-examination the. The results of the study showed that BSE to prevent breast cancer in addition to awareness dimension has psycho-mental dimension which is influenced by the social context and experience of each individual and is special to him. Since breast cancer is as a health threat and one of the major causes of death in women, it has caused great concerns and it is needed to raise people’s attitude . In geneAn attempt should be made to develop programs that are related heightening breast cancer knowledge, attitudes and practice of BSE . In a stEducation as an important factor in changing the attitude and approaches toward health and sanitation behavior. Culture and attitude can have an influence on health behavior such as BSE , 23. TheLaimian stated that as the mission of health education guidelines are to warn against health threats, the requisite for effective training in controlling and preventing of breast cancer is attention to the structure of attitudes of women and proposed approach to encourage health monitoring .Parsa (2008) recommends designing educational interventions based on famous psychological theories for breast cancer screening in developing countries  and TavaWith careful attention to the importance of early preventive interventions for detection of diseases in which there is a special place for self-care and the high incidence and prevalence rates of breast cancer in the human population, experiences and researches, and emphasis on new scientific resources to promote the conduct of Obstetrics and Gynecology, (BSE) among women, especially women at risk for breast cancer is an undeniable necessity. And using this type of intervention, given that the costs involved in comparison to the benefits are affordable, can be given priority in the health care system.Several studies suggest that improving the public’s attitude towards women screening for breast cancer can have a positive effect on behavior .It can be concluded that upgrading and modifying women’s health attitude, followed by creation of health behavior can guarantee a family’s health.


Genome-wide miRNA expression may be useful for predicting breast cancer risk and/or for the early detection of breast cancer.P=0.06). These risk-related miRNAs were enriched for HER-2 and estrogen-dependent breast cancer signaling.A 41-miRNA model distinguished breast cancer risk in the discovery study (accuracy of 83.3%), which was replicated in the independent study . Among the 41 miRNA, 20 miRNAs were detectable in serum, and predicted breast cancer occurrence within 18 months of blood draw , and applied to an independent replication study (n=71). The model was then assessed using serum samples from the nested case-control study (n=410).MiRNAs were assessed in two cross-sectional studies of women without breast cancer and a nested case-control study of breast cancer. Using breast tissues, a multivariate analysis was used to model women with high and low breast cancer risk (based upon Gail risk model) in a discovery study of women without breast cancer (Studying breast tissues of women without breast cancer revealed miRNAs correlated with breast cancer risk, which were then found to be altered in the serum of women who later developed breast cancer. These results serve as proof-of-principle that miRNAs in women without breast cancer may be useful for predicting breast cancer risk and/or as an adjunct for breast cancer early detection. The miRNAs identified herein may be involved in breast carcinogenic pathways because they were first identified in the breast tissues of healthy women. Breast cancer is the most common cancer among women in the US, except for non-melanotic skin cancer, and is the second leading cause of cancer-related mortality in women . KnowingOne approach to improve life-time breast cancer risk prediction and/or the early detection of breast cancer is to utilize molecular signatures from normal tissue, before women develop clinical abnormalities –18. For In this report, we hypothesized that the identification of miRNAs in healthy women associated with breast cancer risk can be one way of developing models for breast cancer risk assessment, and/or be used as an adjunct for enhancing early detection. To address this hypothesis, two independent cross-sectional studies of women undergoing reduction mammoplasty (RM) who had no prior history of breast cancer were used to build and evaluate a multi-miRNA model for breast cancer risk  prediction. We subsequently analyzed the National Institute of Environmental Health Science's Sister Study cohort  , using aP = 0.0005 and P = 0.032, respectively).The characteristics of the participants are shown in Table P < 0.05), but none of these remained statistically significant after adjustment for multiple comparisons  were differentially expressed in high vs. low risk women in the discovery study . IPA canonical pathway analysis revealed significant enrichment in HER-2 signaling and estrogen-dependent breast cancer signaling, as well as other important cancer pathways such as PI3K/AKT signaling, PTEN signaling, and TGF-beta signaling  of the 41 miRNAs associated with increased Gail breast cancer risk. Given that a single miRNA can target many genes, the focus herein was on experimentally validated targets (based on the IPA knowledge base) of the top 10 miRNAs, ranked by their weights in the sPLS-DA model . Five ouFor the other five miRNAs that had no experimentally validated targets, they had 98 predicted targets that are involved in breast cancer pathway .n = 205 cases and 205 controls), 34 of the 41 breast miRNAs identified in the discovery study were profiled in the serum of the Sister Study cohort. There were 20 of 34 miRNAs detected above background level in more than 50 women; these 20 miRNAs were then used to build a new classification model in the discovery RM set, rather than the 41 miRNAs. This model had 81.1% accuracy, 81.3% specificity, and 80% sensitivity. The 20-miRNA model was then locked and applied to classify women in the breast cancer cohort subjects. The 20-miRNA model correctly identified 74.6% of women who remained cancer-free and 31.7% of women who were diagnosed with breast cancer (Table P = 0.06). To be applicable in the clinical setting, we derived continuous risk scores based on the sPLS-DA model prediction. Women in the highest quartile of this score had a 53% increased risk for breast cancer , albeit based on small numbers of subjects and a statistically non-significant result.Shifting from breast tissue to serum analysis for the prediction of actual breast cancer in the Sister Study cohort using a nested case-control design  and was reported to be dramatically higher in ESR1 negative breast cancer cells, inhibiting ERα expression . miR-222Three prior cohort studies have investigated miRNA expression in prospectively collected blood samples for breast cancer risk prediction, including the Sister Study Cohort used herein , 46, 47.P-value < 0.10. This most likely due to the small number of women in the discovery study (and limited number of high breast cancer risk women without breast cancer) that were used to train the model. Moreover, transition from breast tissue to blood where some miRNAs may be expressed differently, the detection method differences, the broader range of ages and BMI, and the time from blood collection to diagnosis all could influence the results.The performance of the model applied to two independent studies is very modest albeit significantly better than random chance at Findings from this study should be considered in light of some limitations. The first relates to the use of the Gail risk model, which has limited accuracy, despite the fact that it is a widely used model. Other models could have been used, such as Tyrer-Cuzick  and BRCAThis study approaches the discovery of breast cancer risk miRNA models by first studying breast tissues of women without breast cancer providing comprehensive molecular measurement in target tissue. The results indicate modest concordance of miRNA expression between breast tissues and serum of women who later develop breast cancer, but given the reasons discussed above while applying breast modeling results to serum in different studies, the results indicate that the novel approach used herein has the utility to provide corroborative evidence for the ultimate development of a miRNA model for predicting breast cancer risk and/or early detection. Future prospective cohort studies with large sample size and long follow-up data are needed to confirm the promise of miRNAs in breast cancer risk prediction and early detection.Healthy women with no prior history of breast cancer who underwent RM were studied, as described previously , 50. BriWomen ages ≥35 who underwent RM at Baystate Medical Center  between 2007 and 2009 were studied, as previously described . ParticiA cohort study for breast cancer where there are publically-available serum-based miRNA profiles were then analyzed in relation to miRNA model identified from the above RM discovery study, using a nested case-control study design. The National Institute of Environmental and Health Sciences (NIEHS) Sister Study   includesAll participants in the three studies provided informed consent and studies were approved by the Institutional Review Boards of all participating institutions.® Technologies, Seattle WA), with 10 % duplicates for quality control purposes. Coefficients of variation (CV) were calculated to assess assay reliability .Total RNA was extracted from the two RM studies using formalin-fixed paraffin embedded (FFPE) tissues according to the manufacturer's instructions . miRNA expression was quantified using the nCounter digital detection miRNA expression assay  algorithm. [To confirm that patient characteristics in the RM studies were similar, chi-squared tests were used to compare the categorical characteristics between participants in the two studies. Two-sided Wilcoxon rank sum tests were used to compare expression of each miRNA individually between high and low risk women. gorithm.  An FDR vIn order to build a multi-miRNA model associated with breast cancer risk in the discovery study, we used a projection-based multivariate sparse partial least squares discriminant analysis (sPLS-DA ) approacIn order to replicate the findings of the RM discovery study, the miRNA model which was developed in the discovery study was used to predict the breast cancer risks of women in the replication study. The accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the miRNA model were calculated to evaluate the discriminatory performance of the miRNA panel in classifying women with low versus high Gail risk . To asse® used for the Sister Study and NanoString for the RM studies were matched based on their sequences to identify available miRNAs for further analysis. Since only 20 out of 41 miRNAs were detected above background by the Affymetrix method in serum, we used these 20 miRNA to build a sPLS-DA model in the discovery study. This model was then applied to classify women into breast cancer and cancer-free categories in the Sister Study cohort. Finally, the same permutation test as described above was applied to assess whether the performance of our model was better than what chance alone could produce. Continuous risk scores were derived by taking the difference of the two outcomes variables predicted by sPLS-DA. Logistic regression was used to estimate breast cancer odds ratios (OR) and 95% confidence intervals (CI) for comparisons of the second through fourth quartiles of the risk score relative to the first. All analyses described in this section were performed in the R statistical environment v3.1.1. Further details are available in the Supplementary Information.To assess whether the miRNA panel can prospectively predict breast cancer risk using serum in the Sisters Study, miRNAs by Affymetrix® QIAGEN Redwood City, www.ingenuity.com). miRNA targets were identified using TarBase [® knowledge base. Methodology and approaches are described in detail in Supplementary Information.Functional analysis was performed using QIAGEN's Ingenuity Pathways Analysis (IPA TarBase , miRecor TarBase , TargetS TarBase  and Inge


What cheaper alternative breast screening procedures are available to younger women in addition to clinical breast examination (CBE) in Sub-Saharan countries? In 2009, we first described BreastLight for screening and reported high sensitivity at detecting breast cancer. Due to limitations of BreastLight, we have since 2014 been using the more technologically advanced Breast-i to screen 2204 women to find cheaper screening alternatives. First, the participant lies down for CBE and then, in a darkened room, Breast-i was placed underneath each breast and trained personnel confirm vein pattern and look out for dark spot(s) to ascertain the presence of suspicious angiogenic lesion(s). CBE detected 153 palpable breast masses and Breast-i, which detects angiogenesis, confirmed 136. However, Breast-i detected 22 more cases of which 7 had angiogenesis but were not palpable and 15 were missed by CBE due to large breast size. Overall confirmed cases were 26, with Breast-i detecting 7 cases missed by CBE. Breast-i and CBE gave sensitivities of 92.3% and 73%, respectively. Breast-i with its high sensitivity to angiogenesis, reliability, and affordability will be an effective adjunct detection device that can be used effectively to increase early detection in younger women, thereby increasing treatment success. Breast cancer, a genetically and clinically heterogeneous disease , is the In Ghana, breast cancer is now the most common malignant disease in women accounting for a majority of cancer related deaths . ReportsThe mean age for breast cancer diagnosis in Ghana is 39 years  suggestiThe use of transillumination as an aid in the diagnosis of breast lesions was first shown by Cutler in 1929  followedThis is an experimental study carried out from September 2014 to February 2017. Participants were recruited from Central and Greater Accra regions of Ghana but mainly from Central because of location and accessibility to a particular age group in the population. Secondly, we wanted participants found to have suspicious lumps to be able to have access to treatment centres for further evaluation and possible treatment if needed. Lastly, due to limited funding, we could not include more participants as we desired.The study was a partnership between Mammocare, a nongovernmental Organization in Ghana, and Highland Innovations of Scotland, producers of the Breast-i on one side, together with Ministries of Women and Children and Health of Ghana. The Ministries' Joint Trustee Board for breast cancer awareness and early detection having been approved by the Ministries' Ethical Review Committee granted authority to Mammocare to conduct the study. Mammocare was required to organize an awareness talk, explain all procedures involving the Breast-i, and respond to participant's questions before the screening process. Discussions included painless and harmless procedural process, no coercion, ability to withdraw at one's own will, no invasion of privacy or involvement of deception, and absence of monetary rewards. After all of this, only willing participants who picked and completed a consent form were included in the study. The Breast-i had been approved by the Ghana Standards Authority as a breast screening device.In Central Region, we contacted the Women's Group of Churches for the awareness talk and participation. We also contacted the Women's Commissioner and Female Hall Presidents in the tertiary institutions. Lastly, in October, which is the breast cancer awareness month, we set up temporary stations all over town where women walk in for free screening. In the Greater Accra region, our activities are restricted more to the churches upon invitation. Willing females between 18 and 70 years who consented after the talk or after thoroughly explaining the procedures of CBE and Breast-i first underwent CBE followed by examination with the Breast-i in an adjoining room. In addition to screening, participants respond to questionnaires which captured health status, knowledge and perception of breast cancer and its symptoms, and socioeconomic and geographical information. All in all, we had accurate information on 2204 ladies who were screened with CBE and Breast-i over the period.CBE was first used to examine the breast and any suggestion of the presence of a palpable lump or suspicious lesion(s) was noted as per the information on the questionnaire. Next, in a darkened room Breast-i was pressed gently against the inferior surface of the female breast for illumination  and idenAll cases of either dark spots/shadows and/or palpable masses were considered as suspicious lesions and referred to the collaborating surgeons at the regional health facilities for histopathological confirmation. Results of the confirmation enabled the assessment of the efficacy of Breast-i as an adjunct screening tool which could be adopted by low resource Sub-Saharan countries in addition to CBE especially for the younger population. Follow-ups by phone were made to participants who were positively diagnosed with breast cancer to encourage them to attend the health centres and comply with the treatment regimen prescribed. This was the best we could do due to the limited resources at our disposal.The mean ages of the study participants were 34 and 41 years for Central and Greater Accra regions, respectively. This is because the study was skewed towards screening younger women as we wanted to determine the efficacy of Breast-i in this group who could not use mammography services. In central region, most of the participants were either students in tertiary institutions or staff of secondary and tertiary institutions. Hence, most of the participants were educated, lived in the urban areas, and had above adequate knowledge of breast cancer. In Greater Accra region, most of the participants were from churches and the figures are quite evenly spread. All of this is summarized in Figures Neoplastic lesions have the ability to form new blood vessels (angiogenesis) from existing ones to support the characteristic rapid cell divisions and growth. Angiogenesis also facilitates the spread of malignant tumour cells to distant organs (metastasis). If Breast-i has the capability of detecting haem and blood vessels then it should be capable of showing angiogenesis around neoplastic lesions. Bloody nipple discharge is one of the symptoms of possible breast cancer that should always be evaluated further. In some cases the bloody discharge may not be accompanied by a palpable mass. We therefore decided to ascertain whether Breast-i could predict or detect the source of the bloody discharge. The images in Figures The average age of breast cancer diagnosis in Ghana is 39 years  meaning Of the 22 suspicious cases detected by Breast-i alone , 7 were Overall, 26 breast cancer cases were confirmed at the referral and treatment centre and Breast-i detected 24 giving it a sensitivity of 92.3% at detecting breast cancer. CBE picked 19 cases and thus had a sensitivity of 73% .  Table Breast cancer is a devastating disease that impacts in a monstrous destructive way victims, families, and developing nations as a whole. Therefore any procedure or device that will increase early detection and therefore improve survival outcome, even if it is for one person, should not be ignored but evaluated and adopted if tests confirm its efficacy. In Sub-Saharan Africa, breast cancer, the most diagnosed cancer in women, most likely occurs in premenopausal women, with peak incidences around 39 years , 31, 32 Participants for this study were mainly drawn from tertiary institutions in Cape Coast and from churches in Accra, the capital city of Ghana. Most of the participants in Cape Coast were having or had had tertiary education as they were affiliated to universities and had adequate knowledge of breast cancer . SurprisBreast-i was developed to overcome the deficiencies of BreastLight. It must therefore produce the expected images for every lady screened irrespective of age, skin tone, breast density and size, lactation, or late pregnancy. Figures Breast-i was developed as an adjunct tool to see the “inside” of breasts for angiogenic detection of suspicious lumps. As seen from In conclusion, the study set out to answer questions such as whether Breast-i will be an effective alternative screening tool especially in dense, dark breasts of younger Black women, whether it can pick up suspicious lesions missed by CBE, and whether it can be recommend for usage in the population as an adjunct screening device. Our results reveal that Breast-i is a much more effective screening device especially by being able to pick up both nonpalpable lesions and very small lesions in larger breast which are often missed by CBE. Due to detection of angiogenesis, Breast-i pickups always warrant further evaluation as it is potentially cancerous. Furthermore, being battery operated and emitting no radiation, Breast-i can be used on all women from 15 years and above, pregnant or lactating. Finally, due to its high sensitivity and specificity coupled with the screening procedures being more acceptable by women, we will recommend Breast-i for both routine and mass screening in Ghana and possible other sub-Saharan countries. We see Breast-i as the future of screening and early detection of breast cancer in sub-Saharan countries to reduce late presentations and improve survival.


P > 0.05). In parallel, the significant effects were observed between mTOR rs2295080 polymorphism and breast cancer risk in the allele, codominant, and recessive models (P < 0.05). We detected no significant correlations between rs2536 polymorphism and the clinical parameters of breast cancer patients, while rs2295080 polymorphism was associated with lymph node (LN) metastasis. The Crs2536Grs2295080 haplotype was correlated with a significantly decreased risk of breast cancer (P < 0.05). In sum, the findings suggested that mTOR rs2295080 had a protective role on breast cancer susceptibility among Chinese population, while rs2536 polymorphism had no association with breast cancer risk.Mammalian target of rapamycin (mTOR) gene polymorphisms exert the major effects on the regulation of transcriptional activity and miRNA binding or splicing, which may be associated with cancer risk by affecting mTOR gene expression. However, inconsistent results have been previously reported. The present study evaluated the correlation between mTOR rs2536/rs2295080 polymorphisms and breast cancer risk. This case-control study was performed with 560 breast cancer patients and 583 healthy controls from the northwest of China. mTOR polymorphisms (rs2536 and rs2295080) were genotyped by Sequenom MassARRAY. We assessed the associations with odds ratios (ORs) and 95% confidence intervals (95% CIs). The association between mTOR rs2536 polymorphism and breast cancer risk was undetectable in our study ( Interestingly, there was a significant difference for the body mass index , suggesting the possibility that breast cancer is not linked to overweight women. The genotypic frequencies for rs2536 and rs2295080 among the controls were in Hardy-Weinberg equilibrium .The general characteristics of the participants were summarized in Table P > 0.05). For rs2295080, both GT and GG genotype had lower frequencies in the cohort of breast cancer patients as compared to controls. In addition, there was a significant association between rs2295080 and decreased risk of breast cancer .The genotypic and allelic frequencies of mTOR polymorphisms in breast cancers and controls were shown in Tables P = 0.005; GG vs. TT: OR = 0.65, 95 % CI = 0.67–1.36, P = 0.001; GT + GG vs. TT: OR = 0.56, 95% CI = 0.38–0.82, P = 0.003).We also analyzed the relationship between mTOR genetic polymorphisms and clinicopathological characteristics, including tumor size, lymph node metastasis, and the statuses of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor type-2 (Her-2). When the TT genotype used as the reference, we found no significant correlations between rs2536 and clinicopathological parameters of breast cancer patients Table . When thrs2536Grs2295080 haplotype was associated with a significantly decreased risk of breast cancer . We did not detect any associations of other haplotypes with the risk of breast cancer.We analyzed the association between mTOR haplotypes and the risk of breast cancer. Table rs2536Grs2295080 haplotype was associated with a significantly decreased risk of breast cancer.Understanding the associations between genetic alterations and cancers can improve prevention, treatment, and prognosis. Genome-wide association studies have revealed genetic markers for many different cancers. This case-control study examined the association between mTOR rs2536/rs2295080 polymorphisms and breast cancer risk. A total of 560 patients with breast cancer and 583 healthy individuals were involved in the assessment of cancer risk. It is noteworthy that the genotype T > G of rs2295080 was associated with decreased cancer risk. In contrast, no significant association was found between rs2536 and breast cancer. Furthermore, we analyzed the association between mTOR haplotypes and the risk of breast cancer and detected that the Cin vitro, resulting in lower mTOR mRNA expression in renal tissues [The mTOR/PI3K signaling pathway is commonly overactivated in human cancers to promote proliferation and survival , 21, 22. tissues . Recentl tissues , 28. Con tissues , our dat tissues , 29. HowAdditionally, increased mTOR expression was correlated with a poor prognosis in several human cancers, including renal cell cancer, lung cancer, laryngeal squamous cell carcinoma, neuroendocrine tumors, biliary tract adenocarcinoma, and colorectal cancers . It was Some limitations of this study is supposed to be noted. Firstly, the effect of a relatively small sample size was unavoidable since the sample size was approximately 500. Secondly, all cancer cases and controls originated from a single hospital; therefore, an inherent selection bias is likely to exist. Thus, it is important to validate these findings in a population-based prospective study. A large-scale multicenter study with detailed individual data is needed to further validate gene-gene and gene-environment interactions between mTOR genetic polymorphisms and cancer risk.In conclusion, our present study provides evidence of the association between mTOR polymorphisms and breast cancer risk. The rs2295080 polymorphism was associated with a decreased risk of breast cancer in a Chinese population, whereas the rs2536 polymorphism had no association with breast cancer risk.The present study was approved by the Ethic Committee of the second affiliated hospital of Xi'an Jiaotong University. The research protocol was carried out in accordance with the approved guidelines. All participants  as we described previously , 31 wereThe blood samples of 560 Chinese women with sporadic breast cancer (mean age: 49.09 ± 11.02) were collected from the second affiliated hospital of Xi'an Jiaotong University, Xi'an, Shaanxi province, P.R. China. A total of 583 age and sex-matched, healthy individuals (mean age: 48.80 ± 8.28) without any history of autoimmunity or malignancies were included in this group . DNA concentration was measured by spectrometry . Two tag-SNPs, rs2536 and rs2295080, were selected for the present study. Sequenom MassARRAY Assay Design 3.0 Software was used to design Multiplexed SNP MassEXTEND assay. SNP genotyping was performed using the Sequenom MassARRAY RS1000 according to the standard protocol recommended by the manufacturer. The corresponding primers used for each SNP are listed in Table 2 + 2pq + q2 = 1; where p is the frequency of the wild-type allele and q is the frequency of the variant allele) by using the χ2 test with degree of freedom equal to one among cases and controls, respectively. Pearson's χ2 test was used to determine whether there was any significant difference in allele and genotype frequencies between patients and controls. The relative risk associated with alleles, genotypes, and haplotypes was estimated with an OR and 95 % CI. We evaluated the risk in the dominant model (AA+Aa vs. aa), the recessive model (aa vs. Aa+AA), and the allele model (a vs. A), where A equals the major allele and a equals the minor allele). Phase2.1 software was used to conduct all common haplotypes and SPSS software was used to estimate the ORs and 95 % CIs for each haplotype. For all tests, a two-sided P < 0.05 was considered statistically significant.All statistical analyses were performed using the SPSS software package . Hardy-Weinberg equilibrium (HWE) was evaluated by comparing expected and observed frequencies with algorithms in the Alrequin 3.1 program . The observed genotype frequencies were compared to expected values calculated from HWE theory (p


BRCA1/2 mutation carrier status was not available. In a large, population-based, case-control study, we evaluated whether tumor characteristics of the first primary breast cancer are associated with risk of developing second primary asynchronous CBC, overall and in subgroups of interest, including among BRCA1/2 mutation non-carriers, women who are not treated with tamoxifen, and women without a breast cancer family history.Previous population-based studies have described first primary breast cancer tumor characteristics and their association with contralateral breast cancer (CBC) risk. However, information on influential covariates such as treatment, family history of breast cancer, and BRCA1/2 mutations.The Women’s Environmental Cancer and Radiation Epidemiology Study is a population-based case-control study of 1521 CBC cases and 2212 individually-matched controls with unilateral breast cancer. Detailed information about breast cancer risk factors, treatment for and characteristics of first tumors, including estrogen receptor (ER) and progesterone receptor (PR) status, was obtained by telephone interview and medical record abstraction. Multivariable risk ratios (RRs) and 95% confidence intervals (CIs) were estimated in conditional logistic regression models, adjusting for demographics, treatment, and personal medical and family history. A subset of women was screened for BRCA1/2 mutation non-carriers, women younger than 45 years of age, women without a breast cancer family history, and women who were not treated with tamoxifen.Lobular histology of the first tumor was associated with a 30% increase in CBC risk (95% CI 1.0–1.6). Compared to women with ER+/PR+ first tumors, those with ER-/PR- tumors had increased risk of CBC . Notably, women with ER-/PR- first tumors were more likely to develop CBC with the ER-/PR- phenotype , and risk remained elevated in multiple subgroups: BRCA1/2 mutation carriers. Hormone receptor status, which is routinely evaluated in breast tumors, may be used clinically to determine treatment protocols and identify patients who may benefit from increased surveillance for CBC.Having a hormone receptor negative first primary breast cancer is associated with increased risk of CBC. Women with ER-/PR- primary tumors were more likely to develop ER-/PR- CBC, even after excluding The online version of this article (doi:10.1186/s13058-017-0874-x) contains supplementary material, which is available to authorized users. BRCA1 and BRCA2 (BRCA1/2), [Among women with a first breast cancer, risk of a second primary tumor in the contralateral breast is greater than risk of a first primary breast cancer in the general female population, –3 and coRCA1/2), , 12 younRCA1/2),  nulliparRCA1/2),  and obesRCA1/2), . We and RCA1/2), , 16 and RCA1/2),  are assoRCA1/2), . We furtRCA1/2), .BRCA1 mutation carriers in this group [Additionally, some features of first breast tumors may predict CBC risk. Lobular histology of the first primary tumor has been associated with higher CBC incidence in several , 19, 20 is group , 31. ER is group .BRCA1/2 mutation carrier status, breast cancer family history, and treatment for first breast cancer [Several previous studies have examined characteristics of first breast tumors in relation to CBC risk, using cancer registry data, primarily the US National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Registry Program. Despite large sample sizes, these studies generally lacked detailed information on potentially important covariates including t cancer , 28, 29.The Women’s Environmental Cancer and Radiation Epidemiology (WECARE) Study is a multicenter, population-based case-control study in which UBC controls were individually matched to (cases) with asynchronous CBC. The study design of the first phase (WECARE I Study) has been described in detail elsewhere;  the secoCases were participants who were: (1) diagnosed between 1985 and 2008 with a first invasive breast cancer that had not spread beyond regional lymph nodes at diagnosis and a second contralateral primary breast cancer at least 1 year after the first diagnosis; (2) younger than 55 years at first diagnosis; (3) without previous or intervening cancer diagnosis except non-melanoma skin cancer or cervical carcinoma in situ; (4) alive at contact; (5) willing to provide informed consent and a biospecimen; and (6) residents of the same cancer registry reporting region for both diagnoses. Controls with an intact contralateral breast were identified using the same eligibility criteria, and individually matched to cases  on the following criteria: diagnosis age (5-year strata), diagnosis year (4-year strata), cancer registry region, and race/ethnicity. To improve statistical efficiency, WECARE I Study cases and controls were additionally counter-matched on cancer-registry-reported treatment with radiation such that two members of the case-control triad had received radiation therapy for their index breast cancer.We identified a total of 2354 CBC (cases) and 3599 UBC controls eligible for the study. Of those, 1521 patients and 2212 controls provided written informed consent, completed the interview, and provided a biospecimen.Study participants were interviewed by telephone using a structured questionnaire to evaluate known or suspected breast cancer risk factors, including demographics, medical history, reproductive history, breast cancer family history, hormone use, smoking and alcohol intake. Detailed data on treatment, tumor characteristics including HR status were abstracted from pathology and surgical reports, radiation oncology clinic notes, and systemic adjuvant treatment reports. Information on tumor characteristics was also obtained from SEER registry records for US participants and from the Danish Breast Cancer Cooperative Group records for Danish participants. HER2 status was available only for WECARE II Study participants. ER, PR and HER2 status were each reported as “positive” (+), “negative” (-) or “unknown”. Self-reported treatment data were used for participants with missing information in their medical records .BRCA1/2 mutations using denaturing high-performance liquid chromatography [BRCA1/2 mutations were defined based on the presence of variants known or predicted to truncate the protein including frameshifts and premature termination codons, mutations occurring within 2 bp of an intron/exon boundary, and missense substitutions known to have deleterious functional effects.Participants in the WECARE I Study were screened for tography . CarrierBRCA1/2 deleterious mutations, and repeated the analysis excluding BRCA1/2 mutation carriers. The association of HR status of the first breast tumor with CBC risk and subtype-specific CBC was additionally adjusted for BRCA1 deleterious mutation status in a post-hoc analysis. Likelihood ratio tests were utilized to assess heterogeneity for potential effect modifiers, including differences in all tumor characteristics and tamoxifen between the WECARE I and WECARE II Studies . Analyses were conducted using SAS v9.4 .Data from the two study phases were combined for the analyses presented here. Multivariable conditional logistic regression models were fit to estimate adjusted risk ratios (RRs) and corresponding 95% confidence intervals (CIs). Models included the following known or suspected CBC risk factors: age at first breast cancer diagnosis, breast cancer family history, age at menarche, parity, menopausal status, lobular histology of first breast cancer, and treatment for first breast cancer . To account for the counter-matched design of the WECARE I Study, models included a log-weight covariate. WECARE II Study participants (who were not counter-matched) were assigned an offset term of 1 . During Our analysis includes 1521 CBC cases and 2212 UBC controls. There were 2107 participants in the WECARE I Study and 1626 participants in the WECARE II Study. Median age at first diagnosis was 46 years and median time to CBC diagnosis among cases was 6.3 years (Table Pheterogeneity = 0.045). Other features of the first tumor, including grade, stage, nodal involvement, and tumor size, were not associated with CBC risk.Lobular histology of the first breast cancer was associated with elevated CBC risk  Table . This asWomen whose first primary tumor was HR- had a higher risk of CBC than women with HR+ disease Table . ER- firPheterogeneity = 0.43) or diagnosis age .Although there was no statistically significant heterogeneity, for HR- tumors, the increased CBC risk was greatest in the first 10 years following the first breast cancer diagnosis, with no association seen among women who were diagnosed with CBC more than 10 years after their first diagnosis  Table . SimilarWomen diagnosed with an ER-/PR- first breast cancer were less likely than women with an ER+/PR+ tumor to develop ER+/PR+ CBC  Table . In contBRCA1/2 mutations, 185  were mutation carriers. Excluding these women attenuated the increased RRs for CBC observed among all women when comparing HR+ to HR- first breast cancers, but the increased risk of ER-/PR- CBC following a diagnosis of an ER-/PR- first tumor, compared to an ER+/PR+ first tumor, persisted  . Excluding only BRCA1 carriers yielded an effect of similar magnitude for the risk of ER-/PR- CBC following an ER-/PR- first primary (results not shown).Among the women screened for In the WECARE Study, an HR- first breast cancer was associated with greater CBC risk than an HR+ first breast cancer. In particular, having a first tumor that lacked both ER and PR expression was associated with a more than fivefold greater risk of developing a CBC with the same HR-defined phenotype than first tumors that expressed both markers. Similar patterns of association between HR- first primary tumors and overall and subtype-specific CBC risk were observed when women treated with tamoxifen were excluded, suggesting that these associations were not due to lower CBC risk following tamoxifen treatment for ER+ first tumors. A lobular versus non-lobular histologic assessment at first diagnosis conferred a 30% increased CBC risk. Other features of first breast cancers were not associated with CBC risk.Our analysis benefits from the collection of detailed data on treatment history and potential confounders, including reproductive and family history. Many previous analyses have relied on data from cancer registries, including SEER, which records only limited covariate data and intended first course treatment. Similar to our results, the preponderance of studies indicate that HR- first breast tumors are associated with increased CBC risk. In a population-based case-control study that adjusted for treatment information available in SEER, Saltzman et al. reported that women with ER-/PR- first breast cancer were 60% more likely to be diagnosed with CBC than those with ER+/PR+ tumors,  a risk eBRCA1 mutation carriers, [BRCA1/2 mutation carriers. BRCA1 mutation carriers also tend to develop breast cancer at a relatively young age and other studies have reported that risk of HR- CBC among those with an HR- first tumor was higher among younger women [Consistent with our findings that women with ER-/PR- first breast cancers are at particularly high risk of ER-/PR- CBC, several other studies have found high concordance between HR status of the first and second primary breast cancers , 29, 39.arriers, , 31 whicer women , 27, 39;Histologic identification of lobular cancer in situ and invasive first breast cancer has frequently been implicated as a risk factor for CBC. Here, we observed a statistically significant 30% increased CBC risk associated with histologic identification of a lobular first tumor, even after adjusting for treatment and other risk factors. This result is consistent with that observed in previous studies , 20, 43,BRCA1/2 mutation data for WECARE II Study participants, reducing the statistical power to detect associations among non-carriers. Small numbers of ER+/PR- tumors also limited our ability to examine associations with this subtype. Additionally, HR status was evaluated by the pathology departments of treating hospitals, and was not assessed centrally using a standardized protocol. However, previous work has shown good agreement between HR status reported in cancer registries and HR status determined in a single academic reference laboratory, particularly for ER+/PR+ and ER-/PR- subtypes [Our study population included women under age 55 years at diagnosis of their first primary tumor. Therefore, the results of this study are most relevant for young women with breast cancer. A limitation of our study is the lack of subtypes . Additiosubtypes . TherefoBRCA1 mutation carriers are known to be at high risk of HR- tumors and CBC, but these associations were also seen in BRCA1/2 non-carriers. These results suggest that HR status may be useful for informing counseling and screening strategies for CBC risk among women with a first breast cancer. Future work should focus on more refined classification of both first and subsequent primary breast cancers in order to clarify whether these tumors arise from similar etiologic pathways and to identify patients at high risk of CBC.In summary, we observed that HR status and lobular histology of a first breast cancer are predictive of CBC risk. In particular, after adjusting for known CBC risk factors including treatment, women with an ER-/PR- first breast cancer were at a high risk of developing a second breast cancer that was also ER-/PR-. As HR status is a key factor in treatment choice, and ultimately prognosis, these results are informative for risk stratification. Notably,


ZNRD1-AS1) have been associated with cancer development. In this meta-analysis, we more precisely estimated the associations between three expression quantitative trait loci SNPs in ZNRD1-AS1  and cancer susceptibility. The data for three SNPs were extracted from eligible studies, which included 5,293 patients and 5,440 controls. Overall, no significant associations between SNPs in ZNRD1-AS1  and cancer risk were observed. However, in further subgroup analyses based on cancer type, we found that the A allele of rs3757328 increased the risk of some cancer in both allele contrast  and recessive models . The A allele of rs6940552 and the G allele of rs9261204 also increased the risk of some cancer in an Asian population in allele contrast  and recessive models . Thus, rs3757328, rs6940552, and rs9261204 in ZNRD1-AS1 are all associated with increased some cancer risk in an Asian population.Single nucleotide polymorphisms (SNPs) in human zinc ribbon domain containing 1 antisense RNA 1 ( HULC promotes the epithelial-to-mesenchymal transition phenotype and tumorigenesis in both pancreatic and gastric cancer cells [Long noncoding RNAs (lncRNAs) are a class of RNAs greater than 200 nucleotides in length that are not translated into proteins . The exper cells , 6.HOTAIR was found to increase breast cancer susceptibility [CARD8 are susceptibility markers for cervical cancer [POLR2E was associated with a decreased risk of esophageal squamous cell carcinoma [Single nucleotide polymorphisms (SNPs) in lncRNAs can also promote cancer development and progression. For example, the TT genotype of rs12826786 in arcinoma . CollectZNRD1) is involved in the development of multiple cancers [ZNRD1-AS1 , which lies in the upstream region of the ZNRD1 gene, were found to inhibit ZNRD1 expression and decrease the risk of cervical cancer [ZNRD1-AS1 increased the risk of hepatocellular carcinoma (HCC) [ZNRD1-AS1 need to be further studied. Therefore, we investigated the effects of rs3757328, rs6940552, and rs9261204 in ZNRD1-AS1 on cancer susceptibility in this study.Human zinc ribbon domain containing 1 ( cancers . Interesl cancer . Howeverma (HCC)  and lungma (HCC) . These cFour case-control articles –13, whicZNRD1-AS1  and cancer risk. The genotyping methods included TaqMan in one study, PCR-restriction fragment length polymorphism in two studies, and the Sequenom MassARRAY iPLEX platform in two studies  except cervical cancer (occurs only in women) both in the recessive model  and additive genetic model . The A allele of rs3757328 was significantly associated with an increased risk of some cancers compared with G allele.We next evaluated the effect of the rs3757328 polymorphism on the risk of cancer among the subgroups by cancer type. We observed the rs3757328 in ZNRD1-AS1 and cancer risk .Similar to the results for rs3757328, no significant association was observed between rs6940552 in ZNRD1-AS1 and cancer risk was found .No significant association between rs9261204 in We also performed sensitivity analyses through removal of the individual study one by one. The results indicated that the study by Guo et al.  predominPotential publication biases was evaluated using the Egger’s and Begg’s tests. The results provided statistical evidence for the absence of publication bias in all models Table .ZNRD1-AS1 and cancer risk. Our data indicated that these SNPs are correlated with an increased risk of several cancers in an Asian population.SNPs in lncRNAs contribute to the development of various cancers , 8, 14. ZNRD1 protein contains two zinc ribbon domains [ZNRD1 expression was observed in human gastric cancer [ZNRD1 was found to suppress CDK4, Cyclin D1, and p21 [ZNRD1-AS1 contribute to tumorigenesis through negative regulation of the ZNRD1 gene [ZNRD1-AS1 regulate of ZNRD1 expression [The  domains . It cata domains , 17. Redc cancer , 19. Int and p21  and inhiRD1 gene . EQTLs apression , 23.ZNRD1-AS1  have been associated with an increased risk of several cancers. Wen et al. [ZNRD1-AS1 decreased the risk of cervical cancer [ZNRD1-AS1 were associated with increased risk of some cancer types  except cervical cancer.Three SNPs in n et al.  demonstrl cancer . In thisThe meta-analysis had limitations. First, only five individual studies  were included in our analysis, which impacted the quality of our results. Second, our analysis was limited to individuals of Asian descent. Therefore, the effects of the SNPs on non-Asian populations are not yet clear, and further studies are necessary to confirm our results.ZNRD1-AS1 were correlated with an increased risk of several cancers. These results must be further evaluated in large-scale, randomized controlled trials involving different ethnic populations and cancers.In conclusion, our data indicate that three SNPs in ZNRD1-AS1 and cancer risk. This comprehensive literature search was performed using free-text words combined with Medical Subject Headings, such as “ZNRD1”, “ZNRD1-AS1”, or “lncRNA” and “cancer”, “carcinoma”, “tumor”, “tumour”, or “neoplasm” and “polymorphism”, “variation”, “variant”, “SNP”, “mutation”, or “genotype”. The references cited in the retrieved articles were also reviewed to identify additional eligible studies  provided sufficient data for the allele and genotype frequencies ; (4) published in English with the full-text article available; and (5) involved human subjects. The exclusion criteria were: (1) review article or commentary; (2) non-English publication; (3) replication of a previous study; and (4) non-human subjects.The study inclusion criteria were the following: (1) case-control design; (2) evaluated associations between SNPs in Two investigators (PYW and JHL) independently extracted the data from each study, including the surname of the first author, publication year, type of cancer, numbers of cases and controls, ethnicity, genotype platform, and SNP genotype. Disagreement was resolved through a discussion with a third reviewer (YML).The methodological quality of each eligible study was evaluated using the NOS. Each study was evaluated based on the selection, comparability, and exposure scores. Summary scores ranging from 0 to 9 points were calculated. Higher score were indicative of a lower risk of bias.ZNRD1-AS1 and cancer risk. We calculated ORs and 95% CIs in order to estimate the strength of the associations. The significance of the ORs was determined using Z tests. Heterogeneity between studies was assessed using the Chi square-based Q statistic. A random effects (DerSimonian-Laird method) or fixed effect (Mantel-Haenszel method) model was used to calculate pooled effect estimates in the presence (P < 0.10) or absence (P > 0.10) of heterogeneity, and subgroup analysis by cancer type was further performed. Sensitivity analysis was performed by excluding one study at a time and recalculating the risk effect. Begg’s and Egger’s tests were performed to evaluate publication bias. Data analysis was performed using the Stata software, version 12.0 . A P value < 0.05 was considered statistically significant.Allele contrast, dominant, recessive, homozygous, and heterozygous models were used to analyze the associations between SNPs in


Up to 65% of newly diagnosed breast cancer patients had not been screened correctly before diagnosis resulting in increased stage of cancer at presentation. This study assessed whether their primary relatives are, in turn, assessed appropriately.An ethically approved prospective study involving 274 primary relatives of women diagnosed with breast cancer, between 2009–2012, at a symptomatic breast unit in Ireland. Telephone interview established: demographics, menstrual history, family history verification, breast screening history. Personal risk level was calculated and whether current screening met screening guidelines. Participants were enrolled into appropriate screening programs if currently not in one and results analyzed.US in 16. Four underwent a biopsy and to date none had cancer. Surveillance was: annual screening in 48%; national screening program and General Practitioner (GP) in 33%; GP only in over 65s in 13%; 6% await further assessment at specialist genetics clinics where their surveillance will be decided.Two hundred and fifteen of the 280 (76.8%) newly diagnosed patients responded giving details of their 274 primary relatives; this made up the study cohort. Mean age 50 ± 10 (35–75). Thirty two percent were low risk, 64% moderate and 4% high. 190/274 (69%) were being screened appropriately. Seventy five relatives were then assessed with: mammography in 55, Mg and This study has identified an opportunity to improve the delivery of appropriate screening to higher risk primary relatives of patients with breast cancer. This necessitates an integrated national approach involving providers of primary care, patients and screening breast programs. Governments globally have advocated screening for certain common cancers, in particular breast and bowel cancer, to allow earlier detection and improve outcome. This process has been tailored to those in the highest risk age group; usually in the 50–70 year olds. This screening is costly and discussions regarding over diagnosis are common  were contacted by letter and requested to offer the details of their primary female relatives between the ages of 35–70. Demographics, stage at diagnosis, tumor grade and triple negative disease incidence were documented in this cohort.All their primary relatives were then contacted with a view to enrolment into this ethically approved prospective study of their breast care. Following receipt of written consent from willing primary relatives a structured telephone interview was carried out to establish the participants’ demographics, menstrual history, family history verification and breast screening history.Two additional questions were asked at the interview of the primary relative: (1) if you visited a General Practitioner (GP) since turning aged 35, for any health reason, was a family history recorded? (2) If you visited a GP since turning aged 35, for any health reason, was a clinical breast examination (CBE) performed?Using the information collected at the interview National Institute for Health and Clinical Excellence  and IBISAn assessment was then carried out to determine whether the participant's current screening regimen concurred with international screening guidelines relevant to their risk group. The criteria used to determine whether optimal screening and risk assessment practices were currently being delivered are shown in Table The screening modalities utilized, results and follow‐up screening plans were analyzed. Breast screening modalities commonly used included mammography (Mg), ultrasound and ultrasound guided biopsy. Mammograms were classified and reported using the UK 5‐point breast imaging classification  of newly diagnosed breast cancer patients responded, their mean age was 61 ± 15 (29–92). 221 breast cancers were diagnosed in 215 women. Their stage at diagnosis, tumor grade and triple negative disease incidence is shown in Table 75/84 (89.3%) proceeded to have breast screening performed and 9/84 (10.7%) declined. Modes of assessment included mammography alone in 55/75 (73.3%), with ultrasound in 16/75 (21.3%) and with image guided biopsy in 4/75 (5.4%).n = 75.31/72 (43.1%) were classified on imaging as R1, 39/72 (54.2%) R2 and 2/72 (2.8%) R3. Three had radiological classification data missing, no breast cancers were detected in this index round of breast screening in In line with current international practice surveillance breast screening was planned annually in 48% and biennial in 33%. Six percent await further assessment at specialist genetics clinics where their surveillance will be decided and 13% have no planned surveillance.When attending their GP 26% of participants had their family history recorded, 6% of GPs were already aware of their family history and in 68% no family history was recorded. A CBE was performed in 52% of participants; 39% when they were asymptomatic and 13% when they consulted their GP with breast related symptoms. Forty eight percent did not have a CBE.This study identified over 2/3 of primary relatives of symptomatic breast cancer patients were being screened appropriately. The participants in this study are self‐selected and introducing some bias; they are very interested in their risk of breast cancer with 69% already engaged in appropriate breast screening. Walker et al.  found thOur population cohort size is small, however, the region is rather unique with only a single hospital providing symptomatic breast care services; this facilitated invitation of primary relatives into our study. The exceptions are the primary relatives of the 41/321 (12.8%) of patients who had deceased within 4 years of diagnosis; this is comparable to the reported 12.5% in the unstandardized 4 year survival rates found in breast cancer patients in Ireland from 2006–2012 NCRI, . The iniTo evaluate family history risk and need for assessment we used a combination of both NICE criteria and the Tyrer‐Cuzick IBIS Risk Evaluation Tool version 6 IBIS . NICE prSixty eight percent of our primary relatives were in the moderate or higher risk groups. Evans et al.  risk assThe guidelines for breast screening vary internationally. The American Cancer Society makes strong recommendations for annual screening for ages 45–54 then biennial until life expectancy is less than 10 years  is a great tool to help personalize disease prevention in multifactorial diseases not only breast cancer; heart disease (Mulders et al. Controversy remains with respect to the efficacy of CBE as a screening tool. No RCTs have been performed. There is inadequate evidence to say that CBE reduces breast cancer mortality, however, there is sufficient evidence to say that it shifts the stage distribution of tumors detected toward a lower stage (Lauby‐Secretan et al. General Practitioners appear to be missing proactive opportunities in regards to recording family history and performing CBEs. GPs had knowledge of the individual's family history in only 32%. This is much lower than that reported in the 2007 New South Wales Population Health Study where 64.9% had discussed their FHH with their GP (Dunlop et al. This study has identified that there is an opportunity to improve the delivery of appropriate screening to higher risk primary relatives of patients with breast cancer. This necessitates an integrated national approach involving providers of primary care, patients themselves and screening breast programs.All authors have indicated they have no potential conflicts of interest to disclose.


This article investigated different dimensions of breast cancer and its associated factors. It revealed that breast cancer was and continues to be among the most prevalent and growing malignant diseases among Iranian women in the past four decades. In this article, required information was collected through literature review and keyword  query in credible scientific websites such as SID, Google Scholar, and comprehensive portal of human sciences.This disease affects all physical, mental, and social aspects of women life. On the other hand, such factors as social and family supports during the illness can reduce its damages. Although, the [exact] etiology of breast cancer is unknown, its associated risk factors were identified. Such factors as aging, history of breast cancer in the family, specific changes in breast(s), gene changes, history of productivity and menopause, lack of physical activity, alcohol consumption, obesity, nutrition, race, and radiation therapy to chest are risk factors of breast cancer. The incidence of this disease in developed countries varies from 1 to 2 percent, with almost 5% yearly increase in less developed countries [2]. According to estimates, more than 7 million people globally die from cancer. It is predicted that the number of new cancerous cases rises from 10 to 15 million by 2020 . Meanwhile, breast cancer is the most prevalent type of malignant neoplasms among women [5] with more than one million new cases per year [6]. In Iran, breast cancer accounts for the major type of cancer among women with the incidence of 21.4 [7], or 32% [8]. Breast cancer is the most common type of cancer among women in the US with the incidence rate of 12.5%. The risk of an individual dying from breast cancer is 1-in-35 [9]. At present, the chance of developing breast cancer over lifespan is 12% (1-in-8) in the United States [10]. Regarding the importance of this issue, this study sought to investigate breast cancer and its associated factors.Increased incidence of cancer in recent years and its impact on different physical, mental, and social dimensions of human life have turned it to a major problem of the century [Cancer and quality of life11]. Cancer affects patients’ quality of life to varying degrees. The major problems affecting patients' life quality are the mental and emotional impacts of illness, diagnostic and therapeutic measures, stress, pain, depression, and disease consequences on family, marital, and social relations, as well as the induced economic burdens, nutritional issues, and treatment complications . Determination of the quality of life of cancer patients can provide medical staff with a new solution in helping them become independent in performing life affairs under critical and non-critical situations [14]. Improvement of quality of life of cancer patients is the primary objective of medical and therapeutic cares. Maximization of job capabilities and improvement of functional status and quality of life of the patients are of the important tasks of health care team [15].The World Health Organization (WHO) defines the quality of life as an individual's perception of his/her position in life in the context of the culture and value systems in which he/she lives and in relation to his/her goals, expectations, standards, and concerns [Breast cancer and its etiology16], and is the second leading cause of cancer-induced death. The incidence of breast cancer is almost 1-in-8 women, requiring complete tissue removal, chemotherapy, radiotherapy, and hormone therapy most of the time [17]. Breast cancer is a type of tissue cancer that mainly involves inner layer of milk glands or lobules, and ducts (tiny tubes that carry the milk) [18]. The primary risk factors of cancer include age [19], high hormone level [20], race, economic status, and iodine deficiency in diet [21-23]. Breast cancer is a multi-stage disease, in which viruses play a role in one stage of this pathogenic process [24]. In general, viruses are involved with different cancer types [25].Breast cancer is the most common type of cancer and the second leading cause of death. This disease is the primary cause of mortality among women aged 45–55 years [Social support and breast cancer26]. Breast cancer is among diseases with severe psychological impact, in which the thoughts of death and mastectomy cause fear and anxiety in the patient. A cancer patient goes through various psychological stages in coping with and diagnosing this disease. The world of a woman with cancer dramatically collapses in the blink of an eye. The patient becomes confused and her small hopes fade away to great disappointments. Nobody can deeply understand her feelings ; while, she strongly needs support. Studies show that support is a vital and multi-dimensional need that should frequently be provided to clients. Nurses and physicians usually prioritize physical support; whereas, psychological-mental supports are polled as more important than other things by such patients. Researchers in the field have addressed hidden suffering of the afflicted women and analyzed their description of the disease and suffering. They collected different reports of change in life cycle and style, in which various concepts such as transition, transformation, overcoming and exploration of meaning have been defined. The discovered meanings functioned as ways by which the patient obtained the accuracy, truth, balance, and integrity [29]. In a qualitative study, Hamilton et al. used the grounded theory methodology to investigate the attitude of men as husband, life partner, father, and caregivers about the breast cancer and chemotherapy of their partners. They used semi-structured guided interviews, in which two major subjects were identified: Concentration on the partner's illness, caring for her, and paying attention to family to maintain its flow [30]. In a qualitative study, Landmark and Wall analyzed experience of 10 women newly diagnosed with breast cancer (aged 39-60 years). They aimed to improve nurses’ perception of mechanism of the patients' experience. Results revealed some aspects of their life. These experiences included emotional reactions, physical changes of body, mental image change, feminine identity, main activities, and social network. Understanding these experiences is very important for nurses as supporters of patients during the treatment and improvement process. Nurses should learn this knowledge and use it as much as possible in helping women with breast cancer and their families in gaining access to adaptive methods [31]. Regarding the deep impacts of this phenomenon on the patient and her family, and to provide them with appropriate support, putting effort to understand the experience of the involved people is very important. This is because a successful management of them and their family requires a comprehensive understanding of their experience [32]. Although medical team members may have acquired experience from their personal and professional life, functioning based on these experience limits the power of thinking and judgment [33]. Along with the concept of therapy, it is believed that therapists are required to understand the suffering of all people and even themselves as individuals to be capable of providing services in an emotional and empathic framework [34].The incidence of breast cancer is 1-in-9 women over lifespan. There are no accurate statistics on the incidence of the disease in Iran, but studies show that breast cancer is the second prevalent type cancer [Family and breast cancer35]. To women, the loss of breast means losing feminine identity. In addition, although chemotherapy is an important cancer treatment method, it dramatically affects the quality of life of patients and impairs their physical, mental, social, and spiritual well-being [36].Breast cancer is of the most important factors that risk physical, mental, and social health of women. Some therapeutic complications affect the patient's self-awareness, self-confidence, and sense of self-worthlessness and -acceptance. Suffering from disease, concerning about family future, fear of death, therapeutic complications, reduced performance, and mental imagery disorder are among factors that impair the mental health of patients with breast cancer [30]. Chronic disease of a family member dramatically affects the whole family. In such circumstances, several factors including role change, doubt, losing the sense of control, stepping into an unfamiliar environment, economic issues, etc. lead to family crisis [37]. According to Landmark and Wall, many women wish that their life patterns become normal, the same as before. This is also true to the whole family and can be seen as an adaptive approach. Women consciously choose activities that bring meaningful experience to their body and spirit. These activities vary from fantasizing to engaging in routine housekeeping duties. In their study, the role of supportive systems has been emphasized. They classified such systems into different categories namely family, other women, as well as institutions and organizations including department of surgery and insurance. The majority of patients find support from relatives. It is a valuable support that encourages women to take up against their illness more seriously [31].Cancer is a disease that involves the whole family. Different studies have reported disruption in daily life of family caregivers. In a qualitative study, two main concepts were found from the experience of partners: concentration of the partner's illness and caring for her, and concentration on family to maintain it. Some marginal concepts in this study included presence, reliance on medical team, decision-making, and handling financial affairs [38].Results from another study have shown the salient role of family and doctors for several patients. Many participants have mentioned the valuable role of receiving information and support from specialists. Several patients have reported that they have received romantic care and huge support from their families, helping them in adapting to new situation and returning to life. Partners and children, especially daughters, have been an enormous help. Yet, all patients have not had supportive family and have been even left alone [Religion and breast cancer39].Religion is a positive framework for grasping hidden meaning in disease. In the mentioned study, faith was considered as a powerful resource that alleviates concern and stress, and brings real comfort, which can be effective in adaptation with and return to the life [Cigarette smoking and breast cancer40]; however, the role of cigarette has not been considered as a cause until recently [41]. Increased incidence of breast cancer parallel with lung cancer in women in recent decades have attracted researchers towards increased rate of female smokers, aiming at finding a similar cause for this ascending trend. It is almost for two decades that researchers have addressed the relationship between breast cancer and cigarette smoking, leading to at least 22 published articles only by the late 80s. Different studies have suggested a weak relationship, lack of relationship, or supportive effect. The emphasis of these articles has been on active cigarette smoking and breast cancer. Investigation into indirect correlation of cigarette smoking with breast cancer has been less undertaken, but has delivered fixed results. Women exposed to cigarette smoke during childhood or married to a cigarette smoker are more prone to breast cancer . In a meta-analysis by Kuder et al. into indirect exposure to cigarette-smoke and the risk of breast cancer, a weak relationship was found; therefore, further studies are required to prove this causal relationship [44]. Results of Reynold et al.’s study on 116,544 women showed increased chance of developing breast cancer in cigarette-smokers, corroborating the role of cigarette in breast cancer etiology [45]. Rousseau et al. determined the susceptibility of breast tissue through growing and differentiating it [46]. Breast cells differentiated from the parts 1 and 2 are susceptible to chemical mutagens that occur before menopause; whereas, those differentiated from the part 3 are mutagen-immune. According to this study, it is supposed that exposure period to breast carcinogens determines susceptibility to carcinogenesis. For example, an early exposure, especially before the first pregnancy, may end in breast cancer, due to genotoxic mechanisms; whereas, the subsequent exposures have protective effects because of anti-estrogenic characteristic of cigarette. However, it should be considered that the duration of cigarette-smoking may neutralizes this effect. As a result, it is very important to determine whether the exposure to cigarette smoke was direct or indirect. The discovered relationship of cigarette-smoking with breast cancer (1984) confirmed this protective effect [47]. A study (1990) showed that the relative chance of developing breast cancer in cigarette-smokers versus non-smokers was 1-in-12 in case studies and 1-in-14 in cohort studies [48]. The onset of smoking in younger age increases the risk of cancer breast. Women who started smoking at 10-14 years were more prone to breast cancer [49]. The risk of breast cancer is higher in women with family history of breast cancer, ovarian cancer, or both [50].Identification of Breast cancer, as the most important cancer in women, and exploring its risk factors have interested researchers for many years [Cancer and genetic factors51].Breast cancer is a highly heterogeneous disease that is developed by mutual impact of genetic risk factors and environmental factors. It leads to progressive aggregation of genetic and epigenetic changes in breast cancer cells. Although epidemiological evidence highlight the presence of risk factors , family history of breast cancer is the strongest one. Almost 20% of all breast cancers have family origin, and etiologically are dependent to a specific predisposing gene of that disease [Nutritional factors and breast cancer52]. For the first time in 1940, research findings showed that increased use of fat leads to breast tumor in animals [53]. Howe and Goodwin reported a positive correlation between high fat intake and the risk of breast cancer [54]. Another study reported a positive significant relationship between animal protein intake and the risk of breast cancer [55]. In general, the relationship with the risk of breast cancer development is uncertain [56]. On the one hand, calorie intake leads to weight gain and obesity; on the other hand, it results in increased height in childhood and preterm menopause. Both factors can establish the context for cancer development in future [57].Among the nutritional factors, weight gain and high calorie intake are two causes of breast cancer development. Kopans and Greenwald put that obesity and high BMI in post-menopause increases the risk of breast cancer; whereas, there is not such relationship in pre-menopause women [BRCA1 and breast cancer58], and (2) estrogen can proliferate cells in precancerous and cancerous lesions through its hormonal activity. In addition, since an important part of breast carcinoma is estrogen-receptor-negative (or ER-), other mechanisms are also involved in the development of breast cancer [59]. Mutation of BRCA1 raises the risk of breast cancer to 51% and 85% by the age 50 and 70 years, respectively; it also raises the risk of ovarian cancer to 23% and 63% by the age 50 and 70 years, respectively [60].The main risk factors of non-genetic breast cancer have hormonal origin. For example, gender, the age at menarche and menopause, reproductive history, breast-feeding, and the use of exogenous estrogen  can be mentioned. In most cases, non-genetic breast cancer occurs among menopausal women who have high expression of estrogen receptor. Estrogen has at least two main roles in breast cancer development: (1) Estrogen metabolites can mutate or generate DNA-damaging free radicals [Immune system and breast cancer61]. The immune system is totally able to combat tumors and many immunological parameters applying cytokines for example IL-12 & IFN-γ play major roles in this regard. IL-12 is also the major cytokine responsible for the differentiation of TH1 cells, which are potent producers of IFN-γ, IFN-γ in turn has a powerful enhancing effect on the ability of phagocytes to produce IL-12 as well as having an important role in cellular immune response [Breast cancer in Iran62]. Although Iran has lower incidence of breast cancer, as compared to other countries, recent increase of this problem has turned it into the most common type of lesion among Iranian women. This cancer affects Iranian women at least one decade earlier than their counterparts in developed countries (more than 30% of the patients are younger than 30 years) .The incidence of this disease is about 20-in-1000 per year in Iran. Therefore, the probability of new cases with breast cancer is 6,000 , out of 30 million women in the country [MethodologyIn this article, required information was collected through literature review and keyword  query in credible scientific websites such as SID, Google Scholar, and comprehensive portal of human sciences.Breast cancer was and continues to be among the most prevalent and growing malignant diseases among Iranian women in the past four months. Breast cancer is a disease that involves the patient, family, and community, and wastes many financial and spiritual resources. This cancer is developed in breast tissues including ducts (tiny tubes that carry the milk) and lobules (milk-producing glands). Breast cancer is not gender-specific, but rarely develops in men. Although the exact cause of breast cancer is unknown, specific risk-factors have been identified. Different types of cancer have different risk factors. Some of these risk factors such as cigarette-smoking, alcohol use, and diet can be changed and depend on life style. However, other factors like age, race, gender, and family history are fixed and unchangeable. Having one or more of these risk factors does not necessarily mean infliction.Although many of these risk factors increase the chance of breast cancer development and progress, its exact mechanism is not clear. It seems that hormone plays a very important role in some types of breast cancer; however, its development and progress mechanisms are not very clear. In general, it can be said that such factors as aging, history of breast cancer development in family, certain changes in breasts, genetic changes, history of productivity and menopause, lack of physical activity, alcohol-use, diet and nutrition, race, and radiation therapy to chest are risk factors of breast cancer.This disease affects different physical, mental, and social aspects of women life. On the other hand, such factors as social and family supports during the illness can reduce its negative impacts.


Metabolomics is emerging as an important tool for detecting differences between diseased and non-diseased individuals. However, prospective studies are limited.BRCA status, and menopausal status. Duplicate samples were included for reliability assessment. We used a liquid chromatography/gas chromatography mass spectrometer platform to measure metabolites. We calculated intraclass correlations (ICCs) among duplicate samples, and coefficients of variation (CVs) across metabolites.We examined the detectability, reliability, and distribution of metabolites measured in pre-diagnostic plasma samples in a pilot study of women enrolled in the Northern California site of the Breast Cancer Family Registry. The study included 45 cases diagnosed with breast cancer at least one year after the blood draw, and 45 controls. Controls were matched on age (within 5 years), family status, p < 0.05), although these associations were not significant after adjusting for multiple comparisons.Of the 661 named metabolites detected, 338 (51%) were found in all samples, and 490 (74%) in more than 80% of samples. The median ICC between duplicates was 0.96 (25th – 75th percentile: 0.82–0.99). We observed a greater than 20% case-control difference in 24 metabolites  contains supplementary material, which is available to authorized users. Metabolomics is the systematic survey of the small molecules  that are the products of metabolism in biological systems . A metabMost metabolomics studies of breast cancer to date have been conducted in tumor tissues or cell lines and with the goals of distinguishing cancer from normal tissue and cancers with metastasis from those without, as well as identifying therapeutic targets –11. DataPre-diagnostic plasma samples were obtained from the BCFR, an international prospective cohort of breast cancer families established in 1995  16]. Fo. Fo16]. Plasma samples obtained from cases and matched controls were aliquoted into 200 μl ethylenediaminetetraacetic acid (EDTA) plasma vials. Case-control sets were assayed in the same batch and adjacent to each other in sequence. Samples were identified by specimen ID only, and laboratory technicians were masked to the case-control status of samples. The samples were assayed on the Discovery HD4 platform, a mass spectrometry-based metabolomics profiling platform, at Metabolon . This method combines automated sample extraction processing, an ultrahigh performance liquid chromatography/electrospray ionization tandem mass spectrometry (UHPLC/MS) with additional gas chromatography mass spectrometry (GC/MS) platform. Peaks were quantified using area-under-the-curve and metabolite levels were generated. The metabolite data were normalized to a median of 1.00 to correct for variation resulting from instrument tuning differences. Metabolites not detected in individual samples were imputed with the minimum value for that metabolite. The data were then log-transformed to reduce non-normality. Duplicates from 10 controls were included to assess assay reproducibility. Data from the duplicates were used to assess intra-class correlation (ICC) and were averaged for the case-control analysis.To assess the reliability of our assay results, we calculated coefficients of variation (CVs) and ICCs across duplicate samples. Coefficient of variation is a measure of dispersion, that describes the amount of variability relative to the mean. For samples measured using the same method, a low (~ 10%) variability within subjects and high variability across subjects is desirable. Intra-class correlations describe the degree to which duplicate samples agree: a value between 0.75 and 1 indicates excellent agreement.We used the variance component from a one-way analysis of variance (ANOVA) model to estimate the ICC for replicate samples, and estimated confidence intervals for the ICCs using the Smith method  in R  were detected in all the samples, and 490 (74%) were detected in greater than 80% of the 90 study samples. These metabolites include amino acids and lipids, and some related to microbiome influences and xenobiotics metabolism . Metabolites including 3-(cystein-S-yl)acetaminophen (xenobiotics pathway), 4-acetylphenol sulfate (xenobiotics pathway), and cysteine s-sulfate (amino acid pathway) were significantly higher in cases, whereas indoleacetylglutamine, (amino acid pathway), 2-ethylphenylsulfate (xenobiotics pathway), and sphingosine (lipid pathway) were significantly higher in controls  but modest associations were observed between some metabolites and age at blood draw; for example, age explained 13% of the variation in 1--2-oleoyl-GPC (P-16:0/18:1) .Among the metabolites that showed a greater than 20% case-control difference, we also examined differences among hypothesized predictors of breast cancer risk, including differences by age at blood draw, the number of affected first-degree relatives Table , ER statp < 0.001).We examined whether metabolites differed by the number of affected first-degree relatives. Overall, there was no clear monotonically increasing or decreasing pattern by the number of affected relatives: mean levels were similar for women with one or three affected relatives, and lower or higher for those with two affected relatives. For example, for 2-ethylphenylsulfate, the mean levels were 0.68, 0.97, and 0.64, for women with one, two, or three affected relatives, respectively (p = 0.04). Conversely, the mean indoleacetyleglutamine level was lower for ER+ breast cancer cases than ER- cases .In some metabolites, we found differences by ER status. For example, cases with ER+ breast cancer had higher mean laurylcarnitine level than those with ER- breast cancer . For adrenate (22:4n6), the mean level for PR+ cases was 1.07 compared to 0.69 for PR- cases, and for N-(2-furoyl)glycine, the mean level for PR+ cases was 2.87 compared to 7.54 for PR- cases. However, none of the associations remained significant after adjusting for multiple comparisons.Finally, we examined whether metabolite levels differed by PR status. The mean asparagine level for PR+ cases was 1.12, compared to 1.18 for PR- cases glycine in the xenobiotics pathway) differed by key breast cancer risk factors such as the number of affected family members, although these associations were not significant after adjusting for multiple comparisons, likely due to the small sample size. Taken together, these results suggest that a large-scale study (~ 1000) would be well-powered to detect meaningful biological and statistically significant differences between cases and controls to provide a better understanding of breast cancer etiology across a wide spectrum of risks, and among high-risk women in particular.Metabolomics profiles are becoming increasingly utilized in epidemiological studies to predict the risk of chronic diseases, including breast cancer; however, data from prospective studies are limited. In the first prospective study of metabolomics and breast cancer risk, Kuhn et al.  found thThe assay performance on our samples, measured by ICCs and CVs, is consistent with earlier studies that have examined the utility of metabolomics in epidemiological research among participants of the Shanghai Physical Activity Study . In thatBRCA1-associated tumors. However, studies utilizing human plasma are limited.Consistent with our observation that age at blood collection was associated with metabolite levels, Saito et al.  also repOne notable limitation of our study is that we did not match on the duration of storage time between cases and controls. Post-hoc analysis revealed that among case-control pairs, 35 pairs (78%) had a difference of less than 3 years of storage duration, while 1 pair had a difference of more than 10 years. Further analyses showed that while there were no appreciable differences in the analyses by age, there were differences in 5 metabolites when evaluating levels by the number of affected relatives. Future studies should match on calendar year of blood draw (hence storage duration) within case-control matched sets.Our study is among the first to examine the association between metabolomics and breast cancer risk using pre-diagnostic plasma samples. Despite the limited sample size, we were able to find a larger than 20% case-control difference in several metabolites, although we cannot rule out the possibility that the presence of asymptomatic preclinical breast cancer may have affected metabolite levels in cases. Such bias is possible but should be minimal as we excluded cases diagnosed with breast cancer within 12 months after the blood draw in order to limit the potential for preclinical disease to influence metabolite levels. Finally, our study is also among the first to examine reliability across more than 600 metabolites.In conclusion, findings from this study suggest that metabolomics can be used reliably in large-scale epidemiologic studies of breast cancer to detect meaningful differences in risk.Additional file 1:TableS1. Number of metabolites measured in plasma of BCFR participants (DOCX 17 kb)