We have been following this population for cancer incidence and mortality and as in the general Russian population, we found a significant temporal trend of breast cancer incidence. A significant linear radiation dose–response relationship was observed (P=0.01) with an estimated excess relative risk per Gray (ERR/Gy) of 5.00 , 0.80, 12.76). We estimated that approximately 12% of the 109 observed cases could be attributed to radiation.In the 1950s, the Mayak nuclear weapons facility in Russia discharged liquid radioactive wastes into the Techa River causing exposure of riverside residents to protracted low-to-moderate doses of radiation. Almost 10 000 women received estimated doses to the stomach of up to 0.47 Gray (Gy) (mean dose=0.04 Gy) from external  In a pooled analysis of several cohorts, an excess relative risk (ERR) per Gray (Gy) of 0.86 , 0.7, 1.04) was reported with individual study risks ranging from 0.06 to 1.94 .The Techa River Incidence cohort (TRIC) consists of 18 382 individuals born before 1950, who lived in villages on the Techa River in Chelyabinsk Oblast at some time between January 1950 and December 1960. The current analyses are based on the 9908 female cohort members with follow-up from 1956–2004. The study cohort and follow-up period were defined on the basis of the cancer incidence data availability.3 with a total activity of 1017 Bq (2.75 million Ci) for β-emitters (137Cs and the bone-seeking isotopes of strontium (89Sr and 90Sr), which accounted for 12.2 and 20.4% of the total discharge, respectively .Residents of the riverside areas received both external and internal radiation exposures. External exposures to Considerable migration among study cohort members because of compulsory re-settlement from highly contaminated to uncontaminated villages, and migration of younger cohort members primarily for educational or job opportunities presented a challenge in follow-up and therefore most work has focused on mortality data  are used for matching cancer case notifications to the TRIC. Copies of death certificates for deceased cohort members are obtained from the Regional Vital Statistics Registrar's Office archives. Additional information on cohort members who developed breast cancer is obtained from their medical charts stored at the URCRM clinical department.Analyses were based on a detailed classification of person-years and case counts stratified by ethnic group (Slavs and Tartars/Bashkirs), attained age (5-year groups through age 79 and 80 plus), follow-up period (5-year periods from 1956 through 2004), age at first exposure (10-year groups through age 59 and 60 plus), time of study entry (before and after 1.1.1953), number of live births , age at first pregnancy , and stomach dose (in Gy) with 5-year latency period, that is, dose received in ⩽5 years prior to cancer diagnosis was not considered in assessing breast cancer risk. The first 6 years of follow-up (1950–1955) were excluded from analysis, because cancer incidence data were not available. Women contributed person-years only when they were known to reside in the catchment area, as this reflected when a woman was at risk of having a breast cancer identified. Person-year accumulation began on 1 January 1956 or from the initial date of residence in a contaminated village after that date. The termination date for counting person-years was the date of death, or the earliest of the following: date of last known residence in the catchment area, or of breast cancer diagnosis, or 31 December 2004. Person-year computations and risk estimation were carried out using Epicure software =λ0(1+ρ(d)ε(z1)) where a is age at diagnosis, d is stomach dose in Gy, z0 represents factors  that could modify the baseline rates (λ0), and z1 represents factors that could modify the ERR. For analyses based on external comparisons the baseline rates were taken to be equal to the θRpop, where Rpop is the population rate for age a in year y, and θ is the estimated baseline SIR. For analyses based on internal comparisons, a log linear model was used to estimate baseline (zero-dose) risk with the rates to be proportional to age to a power that changes once women reach the age of 50 years. Ethnicity, number of live births, time of study entry and birth cohort were considered as potential modifiers of the baseline rates.Breast cancer incidence rates in the cohort were analysed using simple parametric excess relative risk (ERR) models. The basic ERR model for age-specific breast cancer incidence rates was λ(ρ1d). Tests for non-linearity in the dose–response were based on comparison of the linear and linear-quadratic dose–response models (ρ1d+ρ2d2). Because of the small number of observed and radiation-associated cases in this cohort, there is little power to assess effect modification. The primary analysis was based on a dose–response model without effect modification. However, we evaluated several factors that might modify the association between radiation and breast cancer, namely, age at exposure, ethnicity and age at diagnosis.The dose–response function was generally taken as a linear function of dose , 109 breast cancers were diagnosed among TRIC members, of which 79% were histologically confirmed, 16% by X-ray and clinical examinations, and 5% solely from death certificates.The majority of cohort members reported Slavic ethnicity (67%), 42% of women were less than 20 years old at the start of exposure, and 79% lived along the river during the period of maximum releases . At the end of follow-up 19% of the cohort were urban residents. The estimated stomach doses were below 5 mGy for 30% of the cohort members, whereas 16% had a dose of 50 mGy and over.vs 8% of non-migrants; cause of death unknown for 41% of deceased outside vs 13% of deceased within the catchment area), the analyses were limited to the periods in which cohort members were known to reside in the catchment area.P<0.001) with rates increasing on average by 50%  per decade increase of birth year. Without allowing for possible radiation dose effects, the number of cases was 37% more than predicted national rates for rural areas . However, when compared with general female population rates the observed number of cases was 19% lower than expected . Allowing for a linear dose–response, the baseline SIRs were somewhat lower, with estimates of 1.26   and 0.74  , respectively. Breast cancer SIRs based on Russian general and rural female population rates by follow-up period are presented in P=0.06). A significantly higher risk was found among women who arrived on the Techa River between 1953 and 1960  compared with those who lived in the area during the period of maximal radioactive contamination. The highest breast cancer risk was found in nulliparous women compared with women who had three or more children (P=0.008). Among parous women, there was no difference in risk by age at first birth (P=0.43).P=0.01) linear dose–response relationship was observed for breast cancer with little evidence of non-linearity (P>0.5). The estimated ERR/Gy was 4.99 . A significant  of the breast cancers observed were attributable to radiation exposure. The small number of breast cancers limited the ability to detect effect modification. Ethnicity, age at diagnosis, age at exposure and time since exposure did not significantly modify the breast cancer radiation risk estimate; however, women who were under age 10 at first exposure appeared to have the highest risk (data not shown).This is the first report describing breast cancer incidence patterns and radiation dose relations in a subgroup of the Techa River cohort. The main result from our study was a significant linear relationship between breast cancer incidence and radiation dose. This finding adds to the limited data on the carcinogenic effects from protracted environmental ionising radiation in the low-to-medium dose range.As neither Techa River residents nor health care providers were aware of dose levels and given the legal requirement for newly diagnosed malignancies to be reported to the Regional Oncology Dispensary, the likelihood of differential reporting for patients with high and low exposure is small. The power of the study is decreased by the reduction in person-years of follow-up because of relatively high migration from the study catchment area. Because of the nature of the address and cancer registration systems it is not possible to obtain complete information on cancer incidence, vital status or cause of death for cohort members living outside the study catchment area. For cohort members living in the study catchment area, vital status at the end of follow-up was known for 92% and among deceased subjects cause of death was ascertained for 87% . HoweverWe found a significant increase of breast cancer background risk with attained age, nulliparity, and follow-up time, as in the general Russian population and worldwide . Althougvs Tartars and Bashkirs) was marginally significant (P=0.06) suggesting that this is largely because of different reproductive patterns  using Russian rural rates, and lower  with the general Russian rates were used.γ-ray exposures and internal exposure to γ-rays from 137Cs distributed uniformly throughout the body), the breast and stomach doses should be similar. TRDS-2000 dose estimates should not be considered definitive, as efforts are currently underway to improve the dosimetry system by better characterisation of the radiation source term and using more information to individualise dose estimates  found in the pooled analysis of atomic bomb survivors and seven cohorts of medically irradiated women with 1502 breast cancers and 1.8 million person-years of follow-up , provided an ERR of 1.09/Sv  (Our study findings are in agreement with the hypothesis of linearity of radiation dose–response for breast cancer. The point estimate of the ERR per Gy is higher than that reported by others, but given our wide risk CIs, it is consistent with many other studies. Current dose estimates have limitations that could bias ERR estimates (In summary, an analysis of breast cancer incidence among women in the Techa River Incidence Cohort has shown a significant increase with age at diagnosis, birth cohort and reduction in incidence with increasing parity. A significant linear trend of risk with increasing radiation dose, is based on small numbers and requires cautious interpretation.


Many women in Iran have a relatively high body mass index. To investigate whether the condition contributes to excess breast cancer cases, a case-control study was conducted to assess the relationships between anthropometric variables and breast cancer risk in Tehran, Iran.All incident cases of breast cancer in the Iranian Centre for Breast Cancer (ICBC) were identified through the case records. Eligible cases were all postmenopausal women with histological confirmed diagnosis of breast cancer during 1996 to year 2000. Controls were randomly selected postmenopausal women attending the ICBC for clinical breast examination during the same period. The body mass index (BMI) was calculated based on weights and heights as measured by the ICBC nursing staff. Both tests for trend and logistic regression analysis were performed to calculate odds ratios and 95% confidence intervals as measures of relative risk.In all, 116 breast cancer cases and 116 controls were studied. There were no significant differences between cases and control with regard to most independent variables studied. However, a significant difference was observed between cases and controls indicating that the mean BMI was higher in cases as compared to controls (P = 0.004). Performing logistic regression analysis while controlling for age, age at menopause, family history of breast cancer and parity, the results showed that women with a BMI in the obese range had a three fold increased risk of breast cancer .The results suggest that obesity in postmenopausal women could increase risk of breast cancer and it merits further investigation in populations such as Iran where it seems that many women are short in height, and have a relatively high body mass index. Although anthropometric characteristics have been evaluated as possible determinants of breast cancer risk -3, studiStudies suggest that timing of weight gain in an individual may be more relevant to breast cancer risk than weight gain at any age . In otheHowever, not enough is known about the relationship between anthropometric variables and risk of breast cancer in Asian populations. An international study reported that in Asian populations with low breast cancer risk, both pre- and post-menopausal obesity was associated with a higher risk of breast cancer . SimilarOnly one study has reported on associations between body mass index and breast cancer risk in Iran . StudiesThis paper aims to examine the relationship between anthropometric variables and risk of breast cancer in postmenopausal women in Tehran, Iran where it seems that many women have a relatively high body mass index.2]. To avoid measurement error one of the authors carried out duplicate measurements at the same time and the two measurements were identical as noted by one of us. Based on the BMI, women were grouped into different categories as recommended by the WHO: normal range (BMI = 18.5–24.9 kg/m2), overweight (BMI = 25–29.9 kg/m2), and obese (BMI ≥ 30 kg/m2) [A retrospective case-control study was conducted to assess the relationships between anthropometric variables and breast cancer risk in Tehran, Iran. All incident cases of breast cancer in the Iranian Centre for Breast Cancer (ICBC) were identified through the case records. Eligible cases were all postmenopausal women with histologically confirmed diagnosis of breast cancer (both in situ and invasive disease) during 1996 to year 2000 and women with a previous breast cancer diagnosis were excluded. Controls were randomly selected from postmenopausal women attending the ICBC for clinical breast examination during the same period. Menopausal status was defined when there have been no menses for a year . Women with bilateral oophorectomy, hysterectomy, or who reported use of postmenopausal hormones were excluded from the study. Data on demographic, medical history and reproductive characteristics of breast cancer cases and controls were extracted from case records. The variables of interest were age, marital status, educational status, family history of breast cancer, age at menarche, parity, age at first live birth, number of live births, age at menopause, previous use of oral contraceptives, weight and height at diagnosis. The body mass index was calculated based on heights and weights as measured by the ICBC nursing staff [BMI = weight (kg)/height (m)The sample size was based on an assumption that at least 25% of breast cancer cases and 10% of women in the control group would be obese. As such, a study with a sample of 224 women (112 in each group) would have a power of 80% to estimate an odds ratio of 3 at 95 percent confidence level . The actTests for trend were performed to calculate odds ratio and 95% confidence intervals as measures of relative risk. The test calculates Chi-square for trend, the associated P value and the odds ratio for each category compared with the reference category . T-test The ICBC board approved the study and all patients were asked for consent to use their information for the study. In fact, since there was no interventions involved a member of the ICBC called each patient (116 cases and 116 controls) to ask for permission to use their information to be reviewed. All patients gave oral consent.In all, 116 breast cancer cases and 116 controls were studied. The characteristics of cases and controls are shown in Table The results obtained from multiple logistic regression analysis are shown in Table Overweight and obesity are common health conditions and their prevalence is increasing globally. The World Health Organization recently called for the continuous monitoring of BMI to assess the trends in obesity in populations across time . It is wWeight gain and obesity not only are risk factors for breast cancer, but also contribute to the diagnosis process. A study from Geneva Cancer Registry, Switzerland compared diagnostic characteristics of obese with non-obese breast cancer patients. The findings showed that obese patients presented significantly more often with advanced stage disease, experienced more surgical delay and prolonged hospital stay after surgery. The authors speculated that the more advanced stage at diagnosis could be due to the larger breast size of obese women, with more fatty tissue, which can lead to difficulties in palpating the primary tumor and the axillary lymph nodes. Also, obese women may be more reluctant to undergo physical examination because of embarrassment about their weight. They suggest there is a need to educate women and doctors that self-examination and clinical examination may be less reliable in obese women, and to think of strategies to prevent advanced disease at diagnosis for this growing group of patients .There are two measures which are significant to body mass index and its relation to breast cancer risk: weight and height. The strength of this study relates to the fact that all heights and weights were measured by the ICBC nursing staff rather than relying on self-reported weights and heights by the cases and controls. Anthropometric studies usually rely on self-reported measures and the evidence suggests that obese women tend to underestimate their weight gain as compared to lean adolescents . In contIt is argued that adult weight gain is a more important risk factor for breast cancer than BMI because body mass gained after young age is mainly adipose tissue (that increases the risk of breast cancer), while BMI is determined by fat tissue and lean body mass in combination (that might not be responsible for increased risk of breast cancer). Therefore, weight gain might be a better measure of adult obesity than BMI ,29 or boIn this study the breast cancer cases were shorter in height than controls and it seems that the height was the most significant factor that contributed to increased breast cancer risk in obese women Table . The finFinally, this study, as many investigations, showed elevated odds ratios for breast cancer associated with a number of known risk factors such as family history of breast cancer, younger ages at menarche, and older ages at first birth Table . HoweverThis study provided data on the fact that obesity could increase breast cancer risk in postmenopausal women in Iran. It seems that there is need to publicize obesity as an important risk factor for breast cancer in Iran. Indeed, this requires encouraging Iranian women to do more exercise and follow healthy diets.2: Square meter; Cm: Centimeter; BMI: Body Mass Index; OR: Odds Ratio; CI: Confidence Interval.ICBC: Iranian Center for Breast Cancer; Kg: Kilogram; mThe authors declare that they have no competing interests.AM was the main investigator, analyzed the data and wrote the paper. JS, FF, and FM contributed to the study design and analysis. MV contributed to the study design and helped in writing the final draft. MA, and AK collected the data. ME, SH and IH contributed to the data collection and patient recruitments for the study. All authors read and approved the final version of the manuscript.The pre-publication history for this paper can be accessed here:


To determine which aspects of breast cancer genetic counselling are important to Ashkenazi Jewish women, a discrete choice experiment was conducted. Participants consisted of 339 Australian Ashkenazi Jewish women who provided a blood sample for research used to test for Ashkenazi Jewish ancestral mutations in the genes BRCA1 and BRCA2, and were offered their genetic test result through a cancer genetics service. Main outcome measures were women's preferences for, and trade-offs between, the genetic counselling aspects of providing cancer, gene, and risk information (information); giving advice about cancer surveillance (surveillance); preparing for genetic testing (preparation); and, assistance with decision-making (direction). Respondents most valued information, about twice as much as advice about surveillance, four times as much as preparation for testing, and nine times as much as assistance with decision-making, which was least valued. Women's preferences were consistent with the major goals of genetic counselling, which include providing information and surveillance advice, and avoiding direction by facilitating autonomous decision-making. There were differences between the women in which aspects they most favoured, suggesting that counselling that elicits and responds to clients’ preferences is more likely to meet clients’ needs. Shortly after the cloning of the breast cancer susceptibility genes BRCA1 and BRCA2, three specific mutations in BRCA1 and BRCA2 were found to be 20 times more common in individuals of Ashkenazi Jewish descent than in the general population   of genetic counselling. These attributes were identified through reviews of the peer reviewed and policy/practice literature on genetic counselling, consultation with clinical geneticists, genetic counsellors, heads of genetic services, psychologists, and interviews with participants  from a series of pairwise choices. A probabilistic discrete choice model was used to analyse the data.Each discrete choice question asked respondents to choose between two hypothetical genetic counselling appointments described in terms of different levels of the four counselling attributes. Scenarios were paired randomly. Three attribute levels were used in the experimental design according to the amount of discussion – none, some, or a lot – devoted to each attribute during a counselling appointment. Respondents were therefore asked which of the two hypothetical genetic counselling appointments they would prefer, where alternative appointments were described in terms of different levels for the four attributes see . The SPEAn internal consistency test was included with the discrete choice experiment. This involved presenting a choice of counselling appointments with attribute levels such that all respondents should choose the same appointment. Only responses that showed internal consistency were included in the subset for analysis.A random effects probit regression model was used to analyse the discrete choice data  using StP<0.01) and were more likely to have had cancer (P<0.01). Younger women were more likely to have a university degree (P<0.01), and had better genetic knowledge (P<0.01). Recent death in the family was associated with a strong family history of cancer (three or more cases of breast or ovarian cancer in first- and second-degree relatives) (P<0.01) and recent cancer diagnosis in the family (P<0.01).Of the 339 AJBCS participants who were sent the follow-up questionnaire (average 44 months after enrolment in the study), 256 (76%) were completed and returned. Simple attribute-ranking preferences are presented elsewhere .Of the 209 women who completed all five discrete choice questions, 193 (92%) passed the consistency test. The random effects probit model was fitted using responses from these 193 respondents . All maiThe most important attribute was information, followed by surveillance, and then preparation . The leaβinfo/βdirn) of the main effects. In this study, women would give up 8.75 units of discussion of direction to get an extra unit of discussion of information. That is, information was found to be almost nine times as important as direction. Alternatively, it could be viewed that women would only give up 0.11 units of discussion of information to get an extra unit of discussion of direction. These data also show that discussion of information was more than three times as important as discussion of preparation, and more than twice as important as discussion of surveillance. Similarly, discussion of surveillance was four times more important than discussion of direction, and discussion of preparation was more than twice as important as discussion of direction.The effects of respondents’ personal characteristics and experiences on the relative value of attributes were examined to determine whether preferences vary systematically between respondents. This was performed by modelling potential interactions between characteristics and preferences in the regression model . Personal characteristics included demography, education, parity, psychological well-being, personal and family cancer history, mutation carrier status, and genetic knowledge. No statistically significant relationships were identified.Women had highest preference for information, valuing it almost nine times more than direction in decision-making about genetic testing. This is consistent with the major aims of cancer genetic services, which include providing cancer, genetic and risk information, and facilitating autonomous decision-making. Women also had high preference for discussion of breast and ovarian cancer surveillance options, valuing it twice as much as preparation for possible outcomes of genetic testing, and four times as much as direction in decision-making about genetic testing. This provides evidence that the shift towards a multidisciplinary team, which includes oncologists and surgeons able to provide surveillance advice is consistent with women's preferences for genetic counselling. The discrete choice experiment results are entirely consistent with results from attribute-ranking questions presented in Although many women preferred information most, and assistance with decision-making least, there were differences between women in which aspects they most favoured. In particular, we found that some women valued preparation highly, whereas others placed least value on this aspect of genetic counselling. Since analysing these data, we have become aware of another study which has similarly found that in general, clients preferred information most and emotional support least, although a subset had high preference for emotional support (The results from this study suggest that a uniform and structured genetic counselling appointment may not be the best method of service delivery, as preferences vary between clients, and fulfilment of clients’ preferences are important for achieving desired client outcomes. This has also been demonstrated recently by Participants of this study have undergone genetic counselling, and most have received their genetic test result, meaning that they are well placed to identify attributes of genetic services that are important to users of those services . The impa priori expectations, the discrete choice experiment results are plausible, and provide further evidence that the technique can be successfully applied in health care. Discrete choice experiments have been shown to provide internally valid and consistent responses (Given esponses , and theesponses . Althougesponses . ClearlyIt remains to be seen whether results from this study are generalisable to other populations and to other types of genetic testing, owing to differences in the characteristics of participants of this study and of other populations seeking cancer genetic counselling. Such differences include; specific testing with a more definitive outcome was conducted in the Ashkenazi Jewish population, whereas there is often no definitive outcome from BRCA1 and BRCA2 testing in the general population; the extent of family cancer history of participants may differ from other populations undergoing BRCA1 and BRCA2 testing; and, other cultural groups may value counselling outcomes differently. Nonetheless, a study of preferences for cancer genetic counselling in a Dutch population found that clients had similar preferences to those identified in this study of Australian Jewish women (The discrete choice experiment technique could be further used to elicit client preferences for a range of other health and nonhealth objectives relating to genetics services. In particular, access to genetics services may be improved if genetics testing becomes available through general practitioners on a widespread basis. However, this might be associated with a more limited service for clients, as most general practitioners will not have the time or level of genetics training as found in dedicated genetic clinics. A discrete choice experiment could be used to measure the value that clients place on improving access to genetics services relative to the amount of information and other aspects of genetic counselling that they would receive from their local family doctor compared to a genetic clinic.


MMR is responsible for the repair of base-base mismatches and insertion/deletion loops. Besides this, MMR is also associated with an anti-recombination function, suppressing homologous recombination. Losses of heterozygosity and/or microsatellite instability have been detected in a large number of skin samples from breast cancer patients, suggesting a potential role of MMR in breast cancer susceptibility.MSH3, MSH4, MSH6, MLH1, MLH3, PMS1 and MUTYH).We carried out a hospital-based case-control study in a Caucasian Portuguese population (287 cases and 547 controls) to estimate the susceptibility to non-familial breast cancer associated with some polymorphisms in mismatch repair genes  polymorphism GA (Leu/Pro) and AA (Pro/Pro) genotypes were associated with a decreased risk: OR = 0.65 (0.45-0.95) (p = 0.03) and OR = 0.62 (0.41-0.94) (p = 0.03), respectively.Using unconditional logistic regression we found that MSH3 Ala1045Thr/MSH6 Gly39Glu - AA/TC  associated with a decreased risk; and MSH4 Ala97Thr/MLH3 Leu844Pro - AG/AA , GG/AA , and GG/AG  all associated with an increased risk for breast cancer.Analysis of two-way SNP interaction effects on breast cancer revealed two potential associations to breast cancer susceptibility: It is possible that some of these common variants in MMR genes contribute significantly to breast cancer susceptibility. However, further studies with a large sample size will be needed to support our results. Breast cancer is the first leading cause of cancer mortality in women in the United States and Europe and current estimates suggest that one in eight American women will be diagnosed with breast carcinoma . VariousBRCA1 and BRCA2  and the heterozygous (Leu/Pro) was also associated with a protective effect .Regarding the SNP tests for association and the genotype specific risks, obtained by unconditional multiplicative logistic regression, there was no difference in cases and controls for 8 of the 9 SNPs tested , p = 0.01). Additionally, three interactions between MSH4 Ala97Thr/MLH3 Leu844Pro are associated with an increased risk for breast cancer , p = 0.01; GG/AA interaction: adjusted OR = 2.11, 95% CI (1.12-3.98), p = 0.02; and GG/AG: adjusted OR = 1.88, 95% CI (1.12-3.15), p = 0.02).The analysis for all SNP-SNP interactions between different genes  associated with individual risk for disease was assessed . However, in contrast to breast cancer, most of lung cancer cases are typically caused by smoking habits, and thus the aetiology of the two cancers is different. In any case, polymorphisms in DNA repair genes may modify cancer risk . It should be noted that the MSH3 and MSH6 genes act as MMR pathway sensors, detecting errors that occur during DNA replication, being implicated in postreplicative mismatch correction [MMR is achieved by several protein heterodimers. As such, it was important to evaluate a gene-gene interaction model in this study. The analysis of the genotype specific risks shows significant differences for two associations between different MMR genes. The rrection .MSH4 Ala97Thr/MLH3 Leu844Pro) associated with an increased risk for breast cancer. As described by Santucci-Darmanin et al. [MLH3 plays a role in mammalian meiotic recombination [We also found evidence for an interaction (n et al.  MLH3 is bination .It has been known for some years that the MMR pathway affects the efficiency of meiotic recombination . NeverthMSH4 Ala97Thr/MLH3 Leu844Pro interaction might be associated with an increased risk for breast cancer, modifying the progression of MMR pathway and therefore increasing the mitotic recombination rates in mammary gland cells. However, larger studies are required to verify the role of MSH4 and MLH3 genes in mammalian mitotic recombination.As a result, it is possible that structural or function modifications in the MLH3 gene, Leu844Pro, was associated with decreased risk for breast cancer. Interestingly, an observed decreased risk between common homozygous and heterozygous of the MSH3 Ala1045Thr/MSH6 Gly39Glu interaction and an increased risk between several combined genotypes of the MSH4 Ala97Thr/MLH3 Leu844Pro point towards a multiplicative gene-gene interaction model.In summary, we found that the genetic variant of the The association between cancer risk and several genotypes observed in this study reinforce the hypothesis for the role of the MMR pathway in breast cancer susceptibility. In fact, the MMR plays a key role in maintenance of genomic stability, contributing to tumour suppression by reducing mutations and promoting apoptosis in response to some DNA damage during replication and mitotic recombination processes ,35. DiffMMR: mismatch repair; SNP: single nucleotide polymorphism; MSI: microsatellite instability; IDLs: insertion/deletion loops; LOH: loss of heterozygosity; HNPCC: Hereditary Nonpolyposis Colorectal Cancer; HWE: Hardy-Weinberg equilibrium; MAF: minor allele frequency; CI: confidence interval; OR: odds-ratio.The authors declare that they have no competing interests.JC and SNS performed the experiments. APA, VT and JEP participated in the inclusion of patients and controls, and retrieved the information from the patients' records included. JFG and JR were responsible for the study concept and design, and JFG created the database for the study and carried out all of the statistical analyses. JC and SNS wrote the manuscript and JFG and JR also contributed to writing the manuscript. The manuscript had been read by all authors.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/9/344/prepubEffects in breast cancer susceptibility of combined genotypes between two polymorphisms within the same gene. The table provided depicts the genotype combination frequencies and the OR values between two polymorphisms within the same gene - MSH3 and MSH4.Click here for fileAll two-way SNP interaction effects on breast cancer risk. The data supplied represents the frequencies and the OR values for all SNP-SNP interactions between different genes associated with individual risk for breast cancer.Click here for file


Breast cancer is a major threat to Taiwanese women's health. Despite the controversy surrounding the effectiveness of breast self-examination (BSE) in reducing mortality, BSE is still advocated by some health departments. The aim of the study is to provide information about how women decide to practice BSE and their experiences through the training process. Sixty-six women aged 27-50 were recruited.A descriptive study was conducted using small group and individual in-depth interviews to collect data, and using thematic analysis and constant comparison techniques for data analysis.It was found that a sense of self-security became an important motivator for entering BSE training. The satisfaction in obtaining a sense of self-security emerged as the central theme. Furthermore, a ladder motivation model was developed to explain the participants' motivations for entering BSE training. The patterns of motivation include opportunity taking, clarifying confusion, maintaining health, and illness monitoring, which were connected with the risk perception for breast cancer.We recognize that the way women decide to attend BSE training is influenced by personal and social factors. Understanding the different risk assessments women rely on in making their health decisions is essential. This study will assist researchers and health professionals to gain a better understanding of alternative ways to deal with breast health, and not to be limited by the recommendations of the health authorities. As a means for early detection of breast cancer, breast self-examination (BSE) has shown that cancer may be discovered at anytime. Most women accept the idea that breast cancer may happen to any of them, yet at the same time, some of them fear discovering the disease. Although researchers have studied the determinants of BSE, there has been relatively little understanding about the motivation of women to learn breast self-examination.A more in-depth exploration of women's experiences in relation to BSE might provide an insight into their behavioral choices. Therefore, we have attempted to explore the reasons why women want to learn BSE skills, as well as explore and illustrate the patterns of how women make the decision to learn this technique. The research questions involved were 2-fold: (a) what are the overall approaches that women decide to enter a BSE training program? (b) what are the personal and social factors related to the motivation for making the decision? For this study, an overall approach was defined as a general way in which a person cognitively addresses a given decision-making task.Baxter  announceMotivation is defined as an internal state or condition that serves to activate or energize behavior . For exaBSE is represented as an opportunity for having some control in the face of a potentially life-threatening disorder. Vahabi and Gastaldo  noted thThus, the underlying assumption behind this philosophy is that women must have knowledge of their potential and covert possibility of breast cancer in order to protect themselves. According to Rothman and Kiviniemi , people'There has been little research published on how women make decisions regarding BSE. Most researchers have focused on factors associated with women's behavior related to BSE rather than on the decision-making process that preceded the behavior. For example, the low ratio of women who practice BSE monthly has been attributed to several other factors, such as inadequate knowledge about the risk of breast cancer and the life-saving advantages of BSE -8. The cThe above literature highlights the fact that BSE is a complex issue. It is not only a medical one, but a sociological one. In summary, much of the research in the field of BSE practice has focused on factors associated with BSE frequency using standardized questionnaires. Thus, ascertaining how women make decisions regarding BSE urgently requires more empirical study.This study was approved by the Institutional Review Board at National Taiwan University. The researcher obtained both written and oral informed consent from the participants. The paper constitutes part of the result of the BSE training project. To participate in this study, women were required to be < 50 years old, not previously diagnosed with breast cancer, and significantly from a high-risk and under-protected population among Taiwanese women. The mortality rate from breast cancer in women of this age group has been gradually increasing and yet they do not have access to free mammography. BSE therefore is potentially an easily available and accessible method for them.The researchers recruited participants who had a better knowledge and experience with the subject being studied. A purposeful sample was recruited for in-depth interviews. Interviewees had participated in a large (n = 203) community-wide BSE training project designed to increase BSE competency. This research has also shown that studying different age groups and education levels of women can bring greater variety to the results. Thus, recruiters were asked to select women participants from various categories, in age and education levels. The recruiters met to choose potential research participants and then the field researcher asked the selected women if they would participate. The number of interviewees was based on the principles of saturation. Since the qualified participants were collected while specifying with the 203 participants along with the interview and analyze. Therefore, the final number of participants was not pre-decided. After 28th group interview, it was hard to elicit new nuances from the interviews. It was considered that the investigation had reached a preliminary saturation point, and the collection of data was discontinued after the 31st group interview had finished. This final sample comprised 66 women aged between 27-50 years old. Most (87.6%) were married. Sixty-four women (96.9%) had at least a high school level of education. Eleven participants (16.7%) reported that they had a first-degree family history of breast cancer. About 35.6% of the participants had previously performed BSE before the training program, but only 3 women had been practicing BSE monthly. There were 22 women (33.3%) practicing BSE monthly after the training program.Interviews were held in the community meeting rooms, at the participant's or the researcher's home. The interviews took 30-120 min to complete and were audio taped. Of the 31 interviews conducted, 28 were used with a small group of 2-3 women, and 3 were conducted as one-on-one interviews. Some positive evidence revealed that data regarding these perceptions may be enriched in a group setting, where individual participation can be enhanced through group interaction . One-on-Participants began the interview by describing their reasons, decisions and motivations for entering the BSE training program, which had been launched in the community 4 months earlier by the field researcher. The women were encouraged to frame the issue of BSE broadly, and generate some topics for discussion which included (see AppendixI): (a) their reasons for deciding to attend the BSE training program; (b) experiences of their BSE at home; (c) their feelings while examining their own breasts; (d) favorable circumstances for their monthly BSE practices; (e) promising to practice BSE frequently thereafter and the compelling reasons for this; (f) sharing stories about their relatives, friends, and acquaintances with breast cancer; and (g) thinking about the risk of getting breast cancer. The same semi-structural questions were asked with the individuals and small groups.Thematic analysis and constant comparison techniques were employed. Thematic analysis, data analysis and the interpretation of data were facilitated using Benner's  paradigmThe transcripts were then examined in detail to identify basic patterns and recurrent themes using line-by-line coding to examine, compare and begin developing conceptual categories. Categories were developed inductively using the constant comparison method . This meHow do women face the threat of breast cancer? Our findings indicated that women's participation in BSE training was a purposeful action. Personal safety needs provided them with the principal motivation, i.e. a sense of self-security emerged as the central theme of participants' efforts to practice BSE. Each woman had her own personal reasons for participating in the BSE training. However, the common motivation related to how women assessed their risk of breast cancer, as influenced by individual and social factors. According to the level of the women's risk perception, a ladder of motivation was found in the results. The 4 patterns of motivation were identified as: taking opportunities, clarifying confusion, maintaining health, and illness monitoring. The 4-ladder motivation model and its intertwined dimensions are shown in Figure "I wanted to learn BSE so I can do self-examination without worries" (A28). A second woman said "I think if I learn the skills I can do it more often by myself, with my own feelings on them so that my mind can be released" (C56). In as much as women's existence is threatened by breast cancer, a self-examination procedure needs to be mobilized to give a sense of self-security. The study showed that satisfaction in a sense of self-security was related to autonomous decision making and action; as another participant explained, "I want to understand my body more" (D10). Therefore, in general women who understand how to self-examine and understand their own body condition could be important in the prevention of possible lesions.The results indicated that almost all of the women could not deny the possibility of having breast cancer, but living in a conservative society like Asia, most women deal with their worries on their own. Fon Shin (in Chinese), the description of storing your heart in a safe-keeping place carries a similar meaning to a sense of self-security in English. Fon Shin has also become the barrier in women with possible breast cancer to look for professional help as their bodies cannot be freely exposed to a stranger's eye. One woman explained PS: In parenthesis, the first letter labeled the level of ladder: A, opportunity taking; B, confusion clarifying; C, health maintaining; and D, illness monitoring. The second letter represented the number of cases. Ex. (A28) it refers the quotation from the 28 case in the opportunity taking ladder.Our findings indicate that the salient motivations for entering the program could be identified as: taking opportunities, clarifying confusion, maintaining health, and illness monitoring. These were connected with risk perception of breast cancer and were not isolated from one another. Indeed, they move back and forth dynamically, depending on individual and social conditions. Forty out of 66 women felt that health maintenance was the major motivation for their attending the project, whereas 9 participants said that they attended for illness monitoring, 2 for confusion clarifying, and 15 for opportunity taking.Some women claimed that they were taking advantage of an opportunity, and their participation in BSE was not solely based on medical considerations. Opportunity taking was expressed in 3 categories, as a lower risk perception, as suspicious to the efficacy of BSE, and as a passive or incidental attendance at the program.This concept is reflected in the women's discussion about the low prevalence of breast cancer among their family's members and friends. Fifteen participants intimated that they had no family history of cancer and regarded themselves as women with a lower risk, compared with the average woman. Furthermore, after comparing themselves to those stereotypical images about physical condition and lifestyle, they positioned themselves at a lower risk."What risk? I do not feel it is high for me because I neither have genetic inheritance nor those so-called cysts. As I do not have large breasts, I am not the target." (A46)"I am sort of mentally fluky, it derived from not having a family history of breast cancer and I have a healthy lifestyle, no smoking, no drinking; I also do exercise so, I believe that I am not at high risk." (A28)"Breast cancer, I feel it is impossible to occur to me (laugh). I am married and have given birth to children. I do not feel any changes or problems with discharge, and no pain." (A15)"Although my mother's sister had breast cancer, I have a faith, though a bit strange, that l probably will not get breast cancer. Furthermore, I watch my diet, and eat a lot of vegetables and fruit while avoiding meat and greasy foods." (A23)However, one woman, whose aunt (her mother's sister) had breast cancer still did not associate herself with high risk. She was able to reconcile herself with perceptions of being at a lower risk. Maybe she created an alternative explanation about the etiology of breast cancer. She stated that: As stated above, women mostly thought that their health is at low risk based on their medical knowledge and beliefs instead of observing changes in their own body.In this group, the participants did not perform BSE in the 6 months prior to BSE training. Some had used other screening methods and had been informed of no abnormal findings. However, a few women were suspicious, to the extent that they examined their breasts themselves."I have had done it twice by sonogram and been palpated by the doctor 2-3 years ago prior to the program. Anyway, only a doctor can conduct an efficient breast examination. I did not think that I could do so by myself. I attended this program since I wanted to know some of the skills for palpating breasts. I know that I have touched the bulk in my breast, and it made me nervous while I touched it." (A48)"It is my emotional obstruction, some of my friends said that it's ok enough to be checked out by physicians. They believe in an expert, not in themselves. I wondered at their inactivity to the learning resources...." (A46)"I doubted I could learn it well." (A21)These women stated that their participation in the program was influenced by external forces, such as those from ties, by friends and the media. For example:"I met Miss Lin [the assistant in this research], who invited me to join in your BSE project. I thought it is the age that I have to care about this disease. Generally, I did not pay attention to it. I was passive and just came to try it." (A15)"At first, I attended and supported the program just for taking my responsibility as a mother-volunteer in the school. I am not really interested in learning BSE." (A21)"In fact, I am not a health believer; I do not take care much about myself. Honestly, I thought this is a rare chance to learn something about breast examination. I entered the program just passively. Particularly, at the time when Mrs. Kuo [the richest entrepreneur in Taiwan] died of breast cancer, everyone was talking about it. It made me panic." (A28)"It was an important incentive that I could learn along with my peers." (A28)"I joined the training program because of being pushed by my friends." The data showed that women, who had a better chance of accessing some BSE programs or information, and especially to someone who is trustworthy, would gain more incentive to participate in the examination.Low risk perception, suspicion to efficacy, and passive/incidental attendance are the reasons for those women in the program who still hold some uncertainties toward their bodies, and explain their concerns about joining the program.Misunderstandings concerning the concept of breast mass have made participants confused about being at a higher risk.Two participants with no family history of breast cancer found buds inside their breasts. They had previously practiced BSE, but had not had a mammography or a sonogram before the training program. They had questions about breast traits, and did not know the characteristics of potential signs of breast cancer. They were panic about the mass existing in their breast."I heard that breast cancer might be found through lumps in advance. When I touched my breasts, I felt the mass in them. The mass is still there but there have not been any changes up to now. I think that techniques of BSE can be of help for self-examination." (B11)"I always palpated some masses in my whole breasts. They felt like in pieces. I wondered what those were. Are they normal or abnormal? Then I went to visit a doctor. The surgeon did not tell me anything (laugh). I asked for an examination, he replied he did not like to do a clinical breast exam. I thought maybe there was some difficulty in a male doctor palpating woman' breasts, although I am ok about it, he may be not. Then what? I do not know where I can ask for help. You know, nowadays there are few programs of breast self-examination for women." (B20)For women who wanted to increase their knowledge concerning breast cancer and avoid further confusion, they approached the BSE scheme when they found a breast mass and were unable to get answers by themselves or especially from professional doctors about their concerns.Of the 40 participants in this group, 17 women had practiced BSE at least once during the past 6 months, and 12 women had also previously had a mammography or sonogram before the training program. They claimed that they wanted to learn BSE for health protection as an early detection method. The concept was constructed in 3 dimensions, first perceiving the risk of breast cancer, second realizing the limitations of medicine, and third knowing the benefits of breast self-examination.In this group, all women expressed that they perceived the risk of breast cancer. However, the participants varied in assessing their risk of breast cancer. Seven women believed that their risks were connected with having a family history of breast cancer."My mother was diagnosed with a breast cancer last month." (C58)"I am a person with a high-risk because my mother and my elder sister had breast cancer." (C34)"I was nervous about having breast cancer because my mother had breast cancer, and had a mastectomy for one of her breasts last year. Also, I have used hormone replacement therapy." (C56)A negative family history does make a woman more concerned about their breasts. Many women expressed that their being conscious of the risk of breast cancer was influenced by their friends or relatives having breast cancer."Because those 2 relatives [my aunt and my sister-in-law] and a friend have breast cancer, I feel this is a crisis in a woman's life." (C49)"My neighbor next-door and a friend are having chemical treatments for breast cancer. I believe that women need to learn some skills of breast self-examination for early treatment. "(C5)"I am surprised that one of my colleagues, who [28 years old] is younger than me, was diagnosed with breast cancer. She was so young. That is why I want to learn the skills..." (C8)The perception of risk was irrespective of their age and more concerned with their understanding. The risk assessment was based on their assumptions about the characteristics of women."As a 47-year-old woman receiving hormone replacement therapy, this is time for me to take care of my breasts." (C62)"Although I am young [27 years], I cannot exclude the risk of breast cancer since I am a woman." (C7)"I found that women can have cancer at younger age. Yes, we have to protect our health from a young age." (C8)"In the beginning, I attended this training due to my large breasts. I have heard that enormous breasts increase the risk of breast cancer. My mother's breast cancer, which was diagnosed last month after I learned the BSE, made me pay more attention to it." (C58)The risk assessment was also influenced by social environment."Recently, breast cancer has been big news in the media since Mrs. Kuo - the richest entrepreneur's wife - died of breast cancer. That made me concerned about the breast self-examination. I want to learn how to do it." Therefore, we understood that women's conceptions of risk in breast cancer are constituted mostly by multiple sources such as past experiences of family members, relatives, friends, or others.The dominant screening modalities of breast cancer are mammography, sonogram, and clinical breast examination. Participants have realized the limitations of medicine and technology, as the following excerpts illustrate:"I feel that it is necessary to have a mammography, but I also have heard that mammography has its limitations, and the accuracy is not high. My friend had been in stage-II breast cancer, but it had not been detected by mammography, which was adopted one year and a half ago." (C35)"I had a breast examination by a doctor, but he took less than 3 minutes." (C17)"I felt uncomfortable when the doctor was doing a breast examination for me, because his facial expressions made me feel disgusted. I do not want to see that rotten doctor any longer." (C58)"I felt that the doctor did a breast examination for me lacked concern. He did not do it under standardized procedure. In general, the doctors depend on the sonogram as the principal screening equipment. Mrs. Kuo died of breast cancer, although she had had regular mammography and sonograms." (C5)"I was in hormone therapy and the doctor conducted a mammography for me. It showed no problem, but I am still so nervous when asking for a sonogram examination." (C65)As we have revealed more disadvantages in current medicine practice, so the lack of humanity in medical practice has become a vital issue for the women.Regarding to the perceived benefits of BSE as a protective strategy, most participants in this group know well that BSE can be helpful in finding the breast problem because their relatives and friends found the breast cancer by self-examination. BSE evidently works, as the following examples state:"My friend discovered her breast cancer by touching her own body. Unfortunately, her tumor had been growing. If it had been found earlier, everything could be different. I think that every woman should do breast self-examination." (C35)"The Vietnamese care-giver found the lump in my mother's breast, when she bathed my mother. She really did my mother a great favor. ...This is a good chance for me to learn these skills. I think that I can do it more often with my own fingers so that it might keep my mind at ease." (C56)"I want to say I did BSE just for health, not intending to argue with the size of my breasts. The incentive of health is still strong (laughs). By the way, I have recommended the skills to my friends. For example, I told my boy-friend that I could teach his sister; as we are all women, we have to protect ourselves..." (C7)Regarding breast cancer, even though most women never found any abnormal signs within their bodies, BSE can also eliminate the uncertainties of the disease, but learning BSE is also good for the health.In this group, all participants (9 women) had personal experience of abnormal clinical findings that were subsequently were diagnosed as benign. Although they did not report having a family history of breast cancer, having a breast with a benign lesion influenced their risk assessment. These participants considered themselves as being at higher than average risk. Illness monitoring became a motivation to their practicing BSE. The concept was composed of 3 elements: having breasts lesions, being concerned about breast lesions, and applying multiple monitoring strategies.Some women had experienced a benign lump caused by a fibro-cyst or fibro-adenoma, as well as nipple inversion and secretion."The mass in my breast was found by myself 10 years ago. The doctor believed that it was a fibrocystic problem." (D1)"Last year, I felt my breast was tender, and then I discovered a mass. Yes, it was almost 2.5 cm large. The diagnosis showed it was a fibro-cyst." (D3)"I had surgery for removing a fibro-cyst from my breast about 10 years ago." (D31)"Last year, nipple inversions occurred in both breasts. In addition, I had seen little milk-like secretions on my nipples for many years ago. My doctor noticed and said that it did not seem to be a good condition and I have to follow up and take care." (D66)From the above statements, we learn that women, especially those who have previously had a breast lesion, became motivated to monitor the condition of the breast regularly.Although the breast lesions of some participants were identified as benign, they were worried that the lesions would change from benign to malignant. Their considerations were associated with their knowledge."I have seen rotten breasts from pictures. Cancer can ulcerate the entire breast, how awful it is! You know, I am really worrying that I will get breast cancer and it will be too late to treat it. I am really worrying..." (D66)"I was diagnosed with a fibro-cyst. I was covered with a cloud of shadow as I read the report which said it would change from being benign to malignant in 5-10 years." (D1)Women expect regular breast screening to be an essential procedure in saving their lives against breast cancer, but obviously not all women believe that any single-modality can achieve this result. To supplement any potential missing accuracy, some women have used more than one screening technique to ensure their health. Multiple monitoring strategies have been reported. In this group, 7 out of 9 participants have practiced BSE, and 5 women had done BSE at least once during the last 6 months. Furthermore, 8 women have previously received other screenings, such as mammography, sonogram, and clinical breast examination. The following are examples of their statements:"I have been getting a mammography and sonograms annually now for > 10 years. I am so afraid of getting cancer. What can I do? I heard that the machines [mammography and sonogram] do not always work correctly. I happened to know there was a training program of breast self-examination, so I attended immediately. Feeling my breasts with my fingers seems better than seeing a doctor, who spends < 2 minutes for an examination." (D66)"I used to have sonograms and also physicians palpation my breasts. In addition to the medical examinations, I also added an item for breast tumor marker (CA153). It makes me less fearful since I have a complete screening. You know, I touched and found a lump in my breast several years ago. Through self examination, I can observe the change of my breasts and this helps me to understand my own physical condition." (D1)The study indicated that women's awareness of the threat of breast cancer or an abnormal breast finding, which caused them stress, would lead them to adopt coping strategies. The coping strategies are the learned behaviors of BSE, CBE , and mammography. Many participants have used more than one modality to monitor their breasts. Self-examination for breast cancer is one of the methods of early detection which helps women to understand their own body, along with information about what is happening to their breasts.BSE as a detector of breast cancer may save lives or be a trigger for fear and terror. What are the conditions that affect a women's decision-making? This study revealed that the motivation of all participants for entering BSE training was categorized into four patterns: taking opportunities, clarifying confusion, maintaining health, and illness monitoring. The ladder could be used to describe the risk perception that women feel at different levels. The greater the risk perception, the higher up the ladder motivation moved. The 4 motivation patterns have become interwoven with personal and social factors.Women in this category believed in the importance of self-care and expected to take control of their own health condition. Referring to Haselton's statement in adaptive rationality, he suggests that the mind is remarkably well designed to deal with the important problems of survival and reproduction, and is not fundamentally irrational . FurtherLeslie et al.  suggesteThis study showed that almost all the participants wanted to learn breast self-examination, especially those who had symptoms or a family history of breast cancer. Choi  noted thet al. [In this study, 15 out of 66 women thought that they were at a lower breast cancer risk than average. One woman claimed that she knew the characteristics of breast symptoms that were potential signs of breast cancer. Since she assessed her symptoms were without those characteristics, she concluded that it was not a sign of breast cancer and it did not threaten her health. Katapodi et al.  suggesteSome women indicated that they experienced confused feelings when they did a BSE. They neither understood how to do the examination, nor could they distinguish normal tissues from potentially dangerous lumps. Even though they had sought clarification from medical professionals, they remained unclear following their doctor's explanations. Therefore, the participants wanted to perfect their skills in performing a BSE so as to rely on their own evaluations. Some of these women even undertook a further strategy of multiple-monitors. They combined BSE with a mammography and sonogram to ensure greater reliability.Consistent with our findings, another study has revealed that women constructed their own personal meanings about the benefits and limitations of BSE, as well as their use of this self-care behavior within their daily lives . They usSumming up the reasons, we found that women may decide to enter BSE training as a coping strategy for dealing with the stress of perceived risk of mammary cancer. The ultimate outcome relevant to breast health behavior they desired was for breast health or the early detection of cancer. Results revealed that the sense of self-security became a great motivator.The decision to participate in BSE was not solely based on the concern with one's health. Rather, they were influenced by social factors. First, it depends on the social image of women's' breasts. For instance, when women's groups proposed the right to breast-feeding babies in the public, one male politician stated that: "Don't be shamed of feeding your baby in the public unless you are uncomfortable of your flat breasts. We, as men, have seen many kinds of women's breasts." Women's breasts are sexualized for male satisfaction. Thus, some women participate in BSE to escape the male doctor's gaze. Some women deny BSE because of feeling uncomfortable about exposing her breasts to other women. Secondly, doctors' work is overloaded in the current medical system; they have to see 30- 50 patients in a half-day, so each patient has only a few minutes for the examination. Some women turn to BSE due to their distrust in the doctor; even BSE is not recommended in the media.The question of why women regard BSE as a complex issue might be related to the way women are valued in society. This is reflected in the following social factors.Women do not like to talk about their breasts because it is taboo in Taiwanese society. Taiwanese women live in a society strongly influenced by a Confucian culture. They do not like to look at pictures of breasts; and when they think of breast health they think of cancer, which they do not like to talk about. In the interviews, many women expressed concern about disrobing or uncovering their breasts. The reason given was that they were struggling with what is socially acceptable. Exposure of the breasts was beset with embarrassment, sexual connotations and vulnerability. For example, one woman "felt embarrassed" because her breasts were small and flat. Another woman felt that exposure of her breast to strangers would bring her criticism, and some women might refuse to attend the BSE training because they thought the BSE procedure, perceived as having a sexual connotation, would be too uncomfortable for them.Some researchers indicated that the association of the breast with sex and extreme modesty influences a woman's conception of breast examination ,27. It wIn general, the media is the main source of healthcare information for the public ; use of It was found that Taiwanese women's body was facing an oppressive environment due to the linkage of women's breast with sex or shame. Under the dominance of modern medical technology, women's body care is forced to be medical oriented rather than self-care oriented. Kearney  indicateThis study makes several contributions to the current knowledge about BSE. It also provides empirical data concerning BSE in practice, highlighting how the medical environment interacts with social factors and personal factors was crucial to understanding a health preventive action regarding women's attitudes towards breast cancer.The selected group of women who attended the BSE program might have already had a positive attitude towards BSE, thus the interpretation of the findings was not able to be generalized. However, when many conflicting opinions between women's behavior and professional suggestions have been revealed, the results may assist researchers, health professionals, and the community to understand the actions of women from their perspective.It is important to keep in mind that this study addressed the underlying considerations that prompt women to learn BSE. We recognize that how women decide to attend BSE training is influenced by personal and social factors. Therefore, it is useful to integrate the individual elements and social context in the design of a BSE program. We are convinced that the knowledge and experience of BSE practitioners is very important. Women should neither be limited by, nor entirely dependent upon, medical and technological systems when facing these problems sine alternative solutions are available. We suggest that future research should focus more on the understanding of how women weigh the risks and benefits concerning the personal and social factors, before they deny the efficacy of practicing BSE.BSE: Breast Self-Examination; CBE: Clinical Breast-Examination.The authors declare that they have no competing interests.RJY conceived and carried out the study as part of her doctoral research. LHH participated in the design of the study. YSH participated in assembly of data and interpretation. UIC assisted with the study and synthesized analyses together with CSH. HDB supervised data analysis, interpretation and led the writing. All authors helped to conceptualize ideas, interpret findings, and review drafts of the manuscript.1. Could you tell me about your ideas and comments about BSE?2. Why did you decide to attend the BSE training program?What factors prompted you to learn BSE?Probe questions:How did you know the training program?What did you think about this training at that time?What were reasons for your decisions to attend this training?3. Could you describe your feelings for performing BSE at home the first time?4. What make it possible to perform BSE practice monthly (in regularity)?5. What experiences did you have regarding BSE, CBE, and mammography?The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6874/10/23/prepub


We have carried out a case-control study to evaluate the association between Wolfe's mammographic patterns and the risk of breast cancer, and to examine the influence of control selection and the radiologist who read the films upon the results obtained. Mammograms of the non-cancerous breast of 183 women with unilateral breast cancer were compared with mammograms from two age-matched control groups: a group of asymptomatic women attending a screening centre, and a group of symptomatic women referred for the diagnostic evaluation of suspected breast disease. Films were arranged in random sequence and independently classified by 3 radiologists. A strong and statistically significant association was found between mammographic dysplasia and breast cancer when controls from the screening centre were compared to cases, but not when cases were compared to women referred for the diagnostic evaluation of breast disease. This result appears to arise in part because of an association between symptoms of benign breast disease and mammographic dysplasia, and suggests that some previous negative studies of the association of mammographic patterns with breast cancer may have arisen from the inclusion of symptomatic subjects as controls.


A cross-sectional survey of all patients aged 30–65 in four general practices within one Local Health Care Co-operative in Fife, Scotland was undertaken to measure the prevalence of family history of colorectal, breast and ovarian cancer. A total of 7619 patients aged 30–65 responded to a postal questionnaire (response rate 59%). In all, 17% of respondents  reported a relative affected by colorectal, breast or ovarian cancer. Of those, 6%  met the Scottish guidelines for referral for genetics counselling. In all, 2%  of all individuals with an affected relative had received genetic counselling and risk assessment. Of these, 25%  met the moderate- or high-risk criteria for developing a cancer. In conclusion, the number of patients who are at a significantly increased risk of cancer on the basis of a family history is small  list). It is therefore unrealistic to expect GPs to develop expertise in genetic risk estimation. A simple family history chart or pedigree is one way that a GP can, within the constraints of a GP consultation, determine which patients should be reassured and which referred to the local cancer genetic clinic. Cancer is one of the three health priorities of the National Health Service in Scotland (NHSiS) . Local HCancer genetics is the fastest growing area of clinical genetics .A postal survey of all patients aged 30–65 years from four general medical practices covering over 99% of the population within one LHCC in Fife, Scotland was undertaken using a cancer family history questionnaire that had been developed and evaluated by a Cambridge-based research team (n=254) or in person by a genetic nurse (n=51) to check the consistency of the information collected via the postal survey. A fieldworker telephoned 101 of those reporting no family history to confirm that there was no family history of colorectal breast or ovarian cancer in their families.Patients were asked if they had any family members  who had had colorectal, breast or ovarian cancer and the age at which these cancers were diagnosed. Those with no affected relatives were requested to return the questionnaire at this point. Those with a family member affected were asked to complete a detailed family history including relationship to the affected individual, site of cancer and age at and date of diagnosis. In all, 305 randomly selected participants reporting a family history of cancer  were interviewed by telephone  were completed and returned  of those reporting a family history of colorectal cancer and 2% (95% CI 1–3%) reporting a history of any of the three cancers or 0.41% (95% CI 0.26–0.55%) of the population surveyed.In all, 27 of the female respondents met national guidelines for referral for risk assessment for breast cancer only, that is, 3% (95% CI 2–4%) of all female respondents reporting a family history of cancer or 0.64% (95% CI 0.40–0.88%) of the total female population surveyed.Two female respondents met the national guidelines for referral for risk assessment for ovarian cancer only, that is, 0.2% (95% CI 0–0.5%) of all females reporting a family history of cancer or 0.05% (95% CI 0–0.1%) of the total female population surveyed.In all, 18 female respondents met the national guidelines for referral for risk assessment, that is, 2% (95% CI 1–3%) of all female respondents reporting a family history of cancer or 0.43% (95% CI 0.22–0.62%) of the total female population surveyed.A validation study was undertaken in order to assess the consistency of this information. In all, 352 patients reporting a family history of cancer were randomly selected and asked to discuss their history with a genetic nurse either face to face or by telephone. Of these, 305 (87%) responded and their family history was verbally confirmed. Of these, 17  were assessed to be at a moderate to high risk of developing colorectal cancer and thus met the national criteria for referral for risk assessment, 28  met the referral criteria for breast cancer and three  for ovarian cancer.As a result of this group being interviewed by the genetic nurse, the risk of 21  of the respondents was altered. The estimated risk of one or more of the three cancers was increased for 16 of the respondents, although in six cases it was difficult to verify the risk due to incomplete information, for example, age of diagnosis of cancer in relative. For five respondents, the estimated risk of cancer was reduced. Only four  of the 101 respondents who originally reported no family history of breast, ovarian or colorectal cancer in the family history form subsequently mentioned a family history on interview with a fieldworker. All four were assessed to be at low risk of developing cancer.In all, 15% of respondents who reported a positive family history of these cancers had discussed their concerns with their GP, the great majority during the last 3 years. Out of these respondents, 86% (and 87% of the 30 respondents found to be at moderate or high risk) had raised the issue themselves (rather than their GP asking them about the family history of cancer). In all, 10% of respondents reporting any family history of cancer (and 22% of those at moderate/high risk) had been referred to a specialist to discuss their risk of cancer and 2% (25% of those at moderate/high risk) had received genetic counselling in the past.Using these results to estimate workload for GPs and cancer genetic clinics in the rest of Scotland, the following figures are obtained:Potentially, only one in 14 patients attending a GP with a positive family history of cancer needs to be referred to regional cancer genetics services for further risk assessment.vs 44 years), similar to that reported in the previous study which evaluated the family history of cancer questionnaire.9 The study made no allowance for multiple sampling of the same family, but the aim was to assess the burden of cancer genetics in a GP practice. Males with a family history of breast or ovarian cancer were assessed as low risk, as no clinical screening is indicated for them.A valid response rate of 59% was achieved for the postal questionnaire used in this study. This is considerably higher than that in a previously published study using a similar questionnaire where the response rate was 29% (We have recently shown in Scotland that such reports of a positive family history of cancer are rarely incorrect but may substantially underestimate the true prevalence of a history of cancer in relatives, especially among second-degree relatives, when compared to cancer registry records (It is interesting to note the higher incidence of moderate- or high-risk family histories in the subgroup of participants that agreed to be interviewed. This may reflect a greater interest in discussing their situation in the moderate- and high-risk groups.Prior to the study, it was anticipated that some respondents might experience anxiety concerning their own risk of cancer as a result of completing the family history questionnaire. Participants were invited to voice their anxieties by phone with the study team who could then arrange an appointment with a genetic nurse. However, it was only necessary for the genetic nurse to contact two respondents in relation to this issue and she was able to provide advice and reassurance in both cases. Discussion with GPs in the practices involved revealed no contact with patients worried by the results of the study. Many of the respondents did admit to worries about their family history when interviewed, but had not taken advantage of genetic counselling. In fact, those at the greatest risk were the ones who reported least use of the service.The majority of questionnaires were completed correctly and many respondents included a great deal of information about their family history of cancer, sometimes involving obtaining details from family members living abroad. For GPs faced with patients consulting with concerns about their family history, a suitable response would therefore be to ask the patient to complete a similar family history form and to rely on this in making a decision as to whether or not to refer the patient to the local cancer genetics clinic.Cancer genetics referral guidelines are quite complex. Therefore, computer programmes have been developed based on referral guidelines to support the decision-making by GPs. However, as GPs will see only a few patients a year, acquiring all of the skills necessary for genetic counselling or to operate such programmes may be unlikely to be accorded a high priority. In addition, newly acquired skills following training are likely to degrade over time without frequent reinforcement. We suggest that GPs could use a questionnaire to collect information and then pass it on to the local genetic nurse, primary care genetic clinician or cancer centre for a rapid assessment as to whether further action should be taken.The number of patients seeking genetic counselling has increased sharply over the last few years (


Tobacco smoke exposure may be associated with increased breast cancer risk, although the evidence supporting the association is inconclusive. We conducted a case-control study in Delaware, incorporating detailed exposure assessment for active and secondhand smoke at home and in the workplace.Primary invasive breast cancer cases diagnosed among female Delaware residents, ages 40–79, in 2000–2002 were identified through the Delaware cancer registry (n = 287). Delaware drivers license and Health Care Finance Administration records were used to select age frequency-matched controls for women <65 and ≥ 65, respectively. Detailed information on tobacco smoke exposure was obtained through telephone interviews.A statistically significant increased risk of breast cancer was observed for ever having smoked cigarettes . However, there was no evidence of a dose-response relationship between breast cancer risk and total years smoked, cigarettes per day, or pack-years. Neither residential nor workplace secondhand smoke exposure was associated with breast cancer. Recalculations of active smoking risks using a purely unexposed reference group of women who were not exposed to active or secondhand smoking did not indicate increased risks of breast cancer.These findings do not support an association between smoking and breast cancer. More than 180,000 cases of breast cancer are expected to be diagnosed in the U.S. in 2008 [While some epidemiologic studies have observed associations between cigarette smoking and breast cancer, more studies have not ,4. Most th revision (ICD-0) code 174) in 2000–2002. Cases were excluded from the study if they had a prior history of invasive breast cancer, lived in an institutional setting, or did not have a telephone. Physician approval was required prior to contacting cases. Potential participants were then mailed a letter and contacted by telephone 1–2 weeks later. Of the 1,076 potential cases identified through the Delaware Cancer Registry, physician permission was obtained to contact 617, of whom 217 could not be located or were not eligible for the study. Of the remaining 400 eligible cases, 28% refused to participate in the study, resulting in a final sample size of 287 cases. As compared to the cases who participated in the study, cases who were not contacted or refused to participate were somewhat less likely to be White, while no differences were observed between the groups by county or stage at diagnosis.Breast cancer cases were identified through the Delaware Cancer Registry, a statewide, population-based cancer registry maintained by the Delaware Division of Public Health. Cases were defined as female residents of Delaware, ages 40–79, diagnosed with microscopically-confirmed incident primary invasive breast cancer , currently known as the Center for Medicare and Medicaid Services, for women 65+ years. Controls were frequency-matched to cases on age within 10-year groups. Telephone numbers were obtained using reverse telephone directories, and letters were mailed to women with phone number matches, informing women of their selection into the study and the phone call that they should anticipate. Potential controls were then called 1–2 weeks after letters were mailed, and of those eligible controls contacted, 46% participated.Power calculations performed during the design phase of the study indicated that 300 breast cancer cases and 300 controls were needed in order to achieve 80% power to detect an odds ratio between active smoking and breast cancer of 1.6 at a significance level of p < 0.05, assuming the prevalence of exposure in controls was 47%, the proportion of women of similar ages as the proposed controls who reported ever smoking in the Delaware Behavioral Risk Factor Surveillance Survey .In accordance with the study protocol, which was approved by the human subjects review boards at the Johns Hopkins Bloomberg School of Public Health, the Delaware Department of Health and Social Services, and the University of Delaware, informed consent was completed by phone. Trained interviewers administered a detailed questionnaire with smoking questions modeled after the Missouri Women's Health Study ,31. EachSecondhand smoking in childhood (<18 years) and adulthood was based on enumeration of smokers living in the participant's household. Then, for each smoker, the number of packs, cigars or pipefulls smoked per day were recorded, in addition to the hours/day the participant was exposed. As with active smoking, new data were collected any time any aspect of exposure changed. Occupational exposure to secondhand smoke involved enumeration of jobs with exposure and, for each job, reporting of length of employment and average daily hours of exposure. Subjects also provided a subjective rating of exposure intensity  for each job. Other questions on demographics, reproductive history, family history, exogenous hormone use, alcohol consumption, physical activity, sleeping habits, meat cooking and consumption, and other dietary factors were also included.Categorical variables were compared between cases and controls using the chi-square test or the Mantel-Haenzsel chi-square test for trend. Total years smoked were calculated by summing the lengths of each reported period of smoking. Average cigarettes per day were calculated by weighting the number of cigarettes smoked per day in each period by the number of years in that period, divided by the total number of years. Total pack-years were calculated as the product of total years and average cigarettes per day.Secondhand smoking analyses were restricted to women who smoked less than 100 cigarettes in their lifetime. Total years of secondhand smoke exposure were calculated by summing years across all periods for which women reported residential secondhand smoke exposure. To facilitate comparison with findings from a previous study of detailed secondhand smoke exposure measures , a smokeAssociations between tobacco smoke exposure and breast cancer were estimated by using unconditional logistic regression. For initial active smoking analyses, never active smokers (women who never smoked 100 cigarettes) were the reference group. For secondhand smoke exposure, never active smokers unexposed to secondhand smoke comprised the reference group. Additional active smoking analyses were conducted, using three more restrictive reference groups based on secondhand exposure data; those with: 1) zero years of lifetime residential secondhand smoke exposure and zero years of occupational secondhand smoke exposure; 2) ≤ 10 years of lifetime residential secondhand smoke exposure, ≤ 10 years of moderate-level occupational secondhand smoke exposure, and ≤ 10 years of heavy-level occupational secondhand smoke exposure; or 3) zero years of residential secondhand smoke exposure before age of 18. Women missing data for any smoker in any period were coded to missing for the corresponding summary variable.Initial regression models included age and menopausal status, given their strong associations with breast cancer. Additional potential confounders were tested individually. If the risk estimate associated with smoking changed by 10 percent in either direction, that variable was included in a full model. If the smoking variables were multilevel, then a factor was included in the final model if it affected 1 out of 2 or 2 out of 3+ levels. Potential confounders were assessed separately for active and passive tobacco smoke exposure. Separate models were also constructed for pre- and postmenopausal women.Selected characteristics of cases and controls are presented in Table Among never active smokers, secondhand smoke exposure in the home during childhood was not associated with breast cancer risk, whether exposure was measured in total years, smoker-years, pack-years or weighted pack-years  and decreased rather than increased with use of more stringent reference groups excluding those exposed to secondhand smoke. Additionally, there was no evidence of a dose-response relationship between breast cancer risk and total years smoked, cigarettes per day, or pack-years. Residential exposure to secondhand smoke was not associated with breast cancer risk, whether the exposure occurred in childhood or adulthood. No increased risk of breast cancer was associated with heavy exposure to secondhand smoke at work. No large differences in breast cancer risk associated with secondhand smoke were observed by menopausal status.Our findings for secondhand smoke are consistent with the 2002 International Agency for Research on Cancer Monograph on Tobacco Smoking and Tobacco Smoke, which stated that existing evidence was inconsistent and did not support a causal association between passive smoking and breast cancer . In contAlthough a number of previous studies report no association between active smoking and breast cancer risk , thesSome have suggested that there may be a critical period for exposure to active and/or secondhand smoking at early ages, prior to the birth of a first baby when cellular differentiation within the breast is completed ,24. In oThe statistically significant increased risk of breast cancer we observed for ever smoking juxtaposed with the lack of a dose-response relationship observed for any measure of frequency or duration suggests that the former association may be due to confounding. In a recent cross-sectional analysis from the California Teacher's Study , active As mentioned earlier, there was also non-participation among cases. If smoking was related to a more aggressive form of breast cancer, a greater proportion of cases who smoked may have been excluded by physicians for medical reasons, resulting in a bias toward the null. However, the overall percentage of cases diagnosed at advanced stages was small, and stage distribution was similar across participants and non-participants. Alternatively, the null associations with breast cancer risk observed for quantitative measures of active smoking and secondhand smoke exposure may be due to negative confounding by unmeasured factors, although it is difficult to speculate what these confounders could be. Non-differential misclassification of tobacco smoke exposures could have also biased the results toward the null if both the cases and the controls had equal difficulty recalling their lifetime exposures to tobacco smoke.In conclusion, exposure to tobacco smoke, either through active or secondhand smoking, was not associated with breast cancer risk in this Delaware population. Women should still be encouraged to avoid tobacco smoke exposure to prevent other adverse health effects associated with both active and secondhand smoking.The authors declare that they have no competing interests.DER participated in the coordination of the study, performed the statistical analyses and drafted the manuscript. RCB and HLH participated in the design of the study and helped to draft the manuscript. CJN conceived of the study, participated in its design and coordination, and helped to draft the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:Secondhand smoke exposure at home among non-smoking breast cancer cases and controls from Delaware. Table.Click here for file


We conducted a population-based case-control study of breast cancer among Chinese-, Japanese- and Filipino-American women in Los Angeles County Metropolitan Statistical Area (MSA), San Francisco-Oakland MSA and Oahu, Hawaii. One objective of the study was to quantify breast cancer risks in relation to menstrual and reproductive histories in migrant and US-born Asian-Americans and to establish whether the gradient of risk in Asian-Americans can be explained by these factors. Using a common study design and questionnaire in the three study areas, we successfully conducted in-person interviews with 597 Asian-American women diagnosed with incident, primary breast cancer during the period 1983-87 (70% of those eligible) and 966 population-based controls (75% of those eligible). Controls were matched to cases on age, ethnicity and area of residence. In the present analysis, which included 492 cases and 768 controls, we observed a statistically non-significant 4% reduction in risk of breast cancer with each year delay in onset of menstruation. Independent of age at menarche risk of breast cancer was lower  among women with menstrual cycles greater than 29 days. Parous Asian-American women showed a significantly lower risk of breast cancer then nulliparous women (OR=0.54). An increasing number of livebirths and a decreasing age at first livebirth were both associated with a lower risk of breast cancer, although the effect of number of livebirths was no longer significant after adjustment for age at first livebirth. Women with a pregnancy (spontaneous or induced abortions) but no livebirth had a statistically non-significant increased risk (OR=1.84), but there was no evidence that one type of abortion was particularly harmful. A positive history of breastfeeding was associated with non-significantly lower risk of breast cancer (OR=.78). There are several notable differences in the menstrual and reproductive factors between Asian-Americans in this study and published data on US whites. US-born Asian Americans had an average age at menarche of 12.12 years-no older than has been found in comparable studies of US whites, but 1.4 years earlier than Asian women who migrated to the US. Asian-American women, particularly those born in the US and those who migrated before age 36, also had a later age at first birth and fewer livebirths than US whites. A slightly higher proportion of Asian-American women breastfed, compared with US whites. The duration of breastfeeding was similar in US-born Asians and US whites, but was longer in Asian migrants, especially those who migrated at a later age. Menstrual and reproductive factors in Asian-American women are consistent with their breast cancer rates being at least as high as in US whites, and they are. However, the effects of these menstrual and reproductive factors were small and the ORs for migration variables changed only slightly after adjustment for these menstrual and reproductive factors. These results suggest that the lower rates of breast cancer in Asians must be largely as a result of other environmental/lifestyle factors.