The Breast Cancer Screening Beliefs Questionnaire (BCSBQ) has been designed as a culturally appropriate instrument for assessing women’s beliefs, knowledge and attitudes to breast cancer and breast cancer screening practices. While it has proved to be a reliable instrument when applied to women of Chinese, Arabic and Korean origin living in Australia, its psychometric properties among women from African backgrounds have not been tested. The aim of this study is to examine the psychometric properties of the BCSBQ among African Australian women.The BCSBQ was administered to 284 African Australian women who were recruited from a number of African community organizations and churches. Factor analysis was conducted to study the factor structure. Construct validity was examined using Cuzick’s non-parametric test while Cronbach alpha was used to assess internal consistency reliability.Exploratory factor analysis results demonstrated that the African-Australian BCSBQ can be conceptualized as a 4-factor model. The third factor, viz. “barriers to mammography”, was split into two separate factors namely, “psychological” and “practical” barriers. The results indicated that the African-Australian BCSBQ had both satisfactory validity and internal consistency. The Cronbach’s alpha of the three subscales ranged between 0.84-0.92. The frequency of breast cancer screening practices  were significantly associated with attitudes towards general health check-ups and perceived barriers to mammographic screening.Our study provided evidence to support the psychometric properties of the BCSBQ.in African Australian women. The study moreover demonstrated that the use of the instrument can help health professionals to understand the beliefs, knowledge and attitudes to breast cancer among African Australian women and also the factors that impact on their breast cancer screening practices. While Europe and Asia have traditionally been the largest sources of migration to Australia, there also has been large-scale immigration from Africa over the last two decades. As a result, since 2005 people of African origin have become one of the top ten immigrant populations in Australia . The sigYet breast cancer is a health concern for all women regardless of their ethnic background and in fact is the most common form of cancer among first generation female immigrants living in Australia . AlthougThe bulk of studies on the incidence of breast cancer among immigrant African women emanate from the United States of American (USA) and suggest that the incidence of breast cancer in this group is lower than among Caucasian women . HoweverLate detection may be due to lack of participation in breast cancer screening measures. To ascertain whether this is the case, there has been considerable research effort mostly in the USA –10 but aAfrican immigrants may have different model of health care that influences their ideas about illness and health seeking behaviours , 17. ManStudies have also demonstrated that African immigrant women often have little or no knowledge about breast cancer screening measures , 27. ThiAs in the case of other minority groups, international studies have also identified common barriers to mammographic screening such as lack of transport, lack of English proficiency, the likely costs in the absence of health insurance and fear of cancer diagnosis , 29, 30.This situation leads us to assert that a culturally sensitive instrument to assess African Australian women’s knowledge of and attitudes towards early breast cancer detection measures is essential. The aim of the present study was to assess and report the psychometric properties of the Breast Cancer Screening Beliefs Questionnaire [BCSBQ] among African Australian women. Recently, the BCSBQ has been validated among Arabic , Korean A cross sectional study design was used in this study.African Australian women refers to any female of self-reported African descent who has migrated to Australia.The participants of this study were African Australian women who met the following criteria: (1) being aged 18 years and over; (2) were resident in Sydney and (3) had no history of breast cancer. Women in the last category were excluded because of the possibility that their cancer diagnosis might have changed their beliefs, knowledge and attitudes toward breast cancer and screening behaviours. The term Convenience sampling was utilised in recruiting the participants for the study. Leaders of African community women’s organisations and associations in Sydney and also African churches were approached to gain access to their female members. The second author, who is from African background, provided details of the study to community leaders and explained its aims and procedures to them. While some leaders offered assistance in distributing the questionnaire, some preferred the second author’s personal attendance in meetings at which the questionnaires were distributed, completed and collected. Participants also had the option of returning the questionnaire in a stamped, addressed envelope. Other means of gaining participation included personal networking and attendance at African community events and end-of-the-year activities.Data were collected between October 2013 and December 2014. Prior to data collection, the participants were notified that ethics approval for the study had been obtained. An information sheet containing detailed information was given to the women and a participant’s completion of the questionnaire was considered to constitute her written consent.Attitudes towards general health check-ups, with a subscale of four items designed to determine the participants’ attitudes to undergoing such checks in the absence of signs and symptoms of disease; 2) Knowledge and perceptions about breast cancer, with a subscale of four items designed to elicit information on the participants’ cultural beliefs regarding breast cancer; 3) Barriers to mammographic screening practices, with a subscale of five items covering what participants perceive as psychological and practical barriers that prevent or at least discourage them from participating in mammographic screening. For the purpose of this paper, the term “The African-Australian BCSBQ” is used.The BCSBQ, first developed in English, is a 13-item instrument designed to investigate behaviours in terms of three subscales as follows: 1) Figure In addition to the information obtained from the African-Australian BSCBQ, demographic information about age, length of stay in Australia, English language proficiency and highest level of educational attainment was collected. The participants were also asked about the frequency with which they undertook the basic screening practices of breast awareness , clinical breast examination (CBE) and mammography.We planned to recruit over 200 participants to ensure an adequate sample size required for factor analysis of the 13-item BCSBQ, using the rule of thumb of 10 subjects per item . ApproxiThe demographic characteristics of the participating women were summarized using descriptive statistics. The originally designed 3-factor structure of the BCSBQ questionnaire was first examined using a CFA of this cohort. The covariance matrix of the 13 items was first computed and then factor-analyzed using maximum likelihood method. Goodness-of-fit of the factor model was assessed by the fit indices with respective common criteria, namely the root mean square error of approximation (RMSEA ≤ 0.06), standardized root mean square residual (SRMR ≤ 0.08), comparative fir index (CFI ≥ 0.95), and non-normed fit index (NNFI ≥ 0.95), which addressed the parsimony correction, absolute fit, and comparative or incremental fit, as recommended , 37. WheThe subscale scores of the questionnaire were then calculated on the same basis as the original version previously reported by Kwok et al. . The halAttitude subscale score; (2) those who achieved higher education levels would be more knowledgeable about breast cancer screening and thus record higher Knowledge subscale scores; (3) those who had more frequent screening practices were associated with fewer barriers to breast cancer screening, which resulted in a higher Barriers subscale score. Because of the ordinal-type nature of the frequency of screening practices and education level, the trend was tested by a Cuzick’s non-parametric test [Construct validity was also examined by testing three hypotheses regarding the association between the subscale scores and the frequency of screening practices and/or education level: (1) those who performed breast awareness exercises and/or presented themselves for CBE and mammograms more frequently, were likely to have a more proactive attitude towards breast cancer screening as reflected by a higher ric test . All staThe research project was approved by the Human Ethics Committee of Western Sydney University – number H9759.The demographic characteristics of the 264 participants who completed the questionnaire are summarized in Table p-value < 0.001), RMSEA = 0.19  = 0.18 to 0.21), SRMR = 0.15, CFI = 0.78 and NNFI = 0.72. After examining the modification index, a covariance between Q10 and Q11 was added to the factor model and the fit statistics improved but still did not satisfy the pre-specified criteria: chi-square statistic = 422.1 , RMSEA = 0.15 (95 % CI = 0.14 to 0.17), SRMR = 0.13, CFI = 0.87 and NNFI = 0.83. The final CFA model is shown in Figure The CFA of the hypothesized 3-factor structure of the African-Australian BCSBQ resulted in a chi-square statistic = 680.9 ,” “I don’t want to go for a mammogram because I would need to take off my clothes and expose my breasts (Q12)” and “Having a mammogram is embarrassing (Q13)”. The fourth factor consisted of two items related to practical barriers: “It would be difficult to arrange transportation for getting a mammogram (Q10)” and “I don’t want to have a mammogram because I can’t speak English (Q11)”. Therefore, apart from examining the main Barrier scale, we split the remaining validation into two “daughter” subscales, namely Psychological and Practical barriers.Since the hypothesized 3-factor structure could not be confirmed through the CFA, an EFA was performed as planned. The eigenvalues for the first five factors were 6.04, 2.21. 1.31, 1.03 and 0.56. Having examined the scree plot, a 4-factor model was identified, the varimax-rotated loadings of the four factors being presented in Table Barriers subscale and its two daughter subscales. The subscales under Attitude and Knowledge had a range from 0 to 100, while the Barrier subscale had a minimum score of 5. There were very mild (≤3 %) floor and ceiling effects for the three original as well as the Psychological barriers subscale, but 15.5 % of the women attained the maximum score of 100 for the Practical barrier subscale. The Cronbach’s alpha of the Attitude, Knowledge and Barriers subscales were 0.92, 0.91 and 0.77 respectively. However, after splitting the Barriers subscale into two, the Cronbach’s alphas improved to 0.84 for Psychological barriers and 0.86 for Practical barriers.Table p-values < 0.01). The Attitude subscale score was significantly higher among those who had more frequent CBEs and mammograms, but marginally insignificantly higher among those who performed more frequent breast awareness exercises . The main Barriers subscale score in contrast, was significantly associated only with the frequency of breast awareness exercises  and not with frequency of CBEs  and mammography . However, after splitting this factor into two daughter subscales, the Practical barrier score showed itself to be significantly associated with all three screening practices .The mean scores of the three original subscales and two daughter subscales, stratified by the participants’ education levels and frequency of screening practices, are shown in Table Increasing cancer screening rates among minority populations is vital because early detection is central to reducing morbidity and mortality. This fact lends particular importance to our BCSBQ-based study because it constitutes the first step towards investigating breast cancer screening behaviour and practices among the fast-growing population of African immigrants to Australia.Barriers to mammography, needed to be split into two factors namely Psychological and Practical barriers. The three items on the Psychological  subscale proved to be of little help in evaluating the participants’ thinking on this issue and in fact masked the effect of the two items on the Practical barriers  subscale. This became clear after the three Psychological items were effectively removed from the main Barriers factor which had revealed that the Cronbach’s alpha improved and the three hypothesis tests became (more) significant. Practical barriers such as transportation and English proficiency, had a greater impact on African Australian women’s screening behaviours than the Psychological barriers set out above. This finding is in agreement with those of overseas studies conducted among African immigrant women [practical barriers subscale does include an item relating to concerns about English. It may be that language concerns occur within the technical and medical context of mammograms, and/or that women of African ancestry find it difficult to discuss their modesty concerns. Our findings may indicate that in the future use of this instrument for African participants, the three main Psychological barrier items can be regarded as a separate factor that is separate from the Practical barrier items. This is in line with a similar modification of the BCSBQ conducted among Hong Kong Chinese in which the two Practical barrier items were not included because they had proved to be irrelevant [In contrast to the BCSBQ studies conducted among Korean, Indian and Arabic immigrant populations in which the results supported the original 3-factor model, the EFA results of the present study demonstrated that the African-Australian BCSBQ could be conceptualized as a 4-factor model. The third subscale, viz, arriers Q, Q11 subnt women , 30. Desrelevant .Barrier subscale into two, the Cronbach’s alpha improved to 0.86 for Practical barriers. However, one drawback of the division of the main Barrier factor was the inflation in the ceiling effect which increased from 1.1 % in the original to 15.5 % under the new the Practical factor. This was not surprising since one of the two items related to concerns about English and more than half the African Australian women in this cohort had attained tertiary or higher education qualifications, spoke English at home and rated their English level as very good. Although the subscale score could not be distinguished among this proportion of participants, it had better reliability and discriminative power than the original main Barrier factor across the whole spectrum as evidenced by the Cronbach’s alpha and the three hypothesis tests. This again supported the separation of the main Barrier subscale into two daughter factors.Similar to the original and other versions, the internal consistency of the three subscales proved excellent, with Cronbach’s alpha ranging from 0.77 to 0.92, comfortably above the acceptable level of 0.70 recommended by Hair et al. . After sPractical barrier subscale was more significantly associated with breast cancer screening practices, rather than Psychological barriers. This is consistent with the findings of overseas studies which have demonstrated that transportation and language appear as key barriers to mammographic screening among African immigrant women [The African-Australian BCSBQ also demonstrated good construct validity with the associations between the three subscales and the frequency of screening practices. In line with studies focused on Chinese, Arabic, Korean and Indian immigrant women, the Attitudes subscale showed significant associations with both CBE and mammographic screening. Our findings on this score are supported by the claim that immigrant women often have different concepts of preventive care and that having cancer screening while asymptomatic is foreign to their health practices , 43, 44.nt women , 29.Our findings also demonstrate that as in the validation study conducted among Korean Australian women , the eduThe limitations of this study should be noted when applying the findings. Firstly, participants were born in African countries but resided in Australia. Therefore, these results may not be generalizable to African women living in their home countries. Secondly the study utilised self-reported measures of breast cancer screening practices that could have been over or under-reported. Further studies with adequate verification of self-reported information built into their design, are warranted.The psychometric properties assessment of the African-Australian BCSBQ reported in this paper confirm that the instrument is a valid and reliable tool for assessing breast cancer beliefs and attitudes towards screening practices among African-Australian women.


Breast cancer is the most common cancer in women worldwide. We investigated the association of hormonal contraceptive use and breast cancer in Thai women.A cohort study was conducted in Khon Kaen, Thailand. There were 70 cases of histologically confirmed breast cancer among 11 414 women aged 30 to 69 years who were recruited as participants in the cohort study during the period from 1990 through 2001. The study population was followed-up until December 31, 2011. To identify factors associated with incidence of breast cancer, hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using a Cox proportional hazards model.The 11 414 women provided a total observation time of 157 200 person-years. Breast cancer risk among women with a history of hormonal contraceptive use was 1.31 times that of women without such a history, but the difference was not statistically significant . No type of hormonal contraceptive was associated with a significant increase in breast cancer risk as compared with women who had never used hormonal contraceptives , and there was no relationship between duration of hormonal contraceptive use and breast cancer.There was no association between hormonal contraceptive use and breast cancer; however, this finding should be viewed with caution due to the small number of cases. In the most recent decades breast cancer incidence has increased rapidly in many developing countries but only slowly in developed countries.2 In Thailand, the age-standardized incidence rate (ASR) of breast cancer is highest in Bangkok (34.1) and lowest in Nakhonphanom (13.1).3 As in other countries, breast cancer remains a public health problem for Thai women.Breast cancer is the most common cancer in women worldwide. Globally, breast cancer accounts for 23% of all cancers in women.4 body mass index,5,6 family history of breast cancer,7 early menarche and late menopause,8 age at first childbirth,9 and shorter lifetime duration of breastfeeding in premenopausal women.10 A meta-analysis of case-control studies reported that oral hormonal contraceptive use increased the risk of premenopausal breast cancer.11Study of the epidemiology and risk factors of breast cancer is very important for prevention. Hormonal contraceptive use is a risk factor for breast cancer, but the magnitude of the risk is unclear. Other possible risk factors include age,12In 2005 the IARC reported that the global mean percentage of current use of oral contraception was 7.3% and that the rate was higher in developed (15.7%) than in developing (5.8%) regions. The mean rate for Southeast Asia was higher (12.8%) than that for Asia as a whole (4.5) but below that for the United States/Canada (15.5%) and Europe (17.4%). The rate for Thailand was surprisingly high (23%) and was similar to the mean for Australia/New Zealand (23.3%).13It is unclear whether breast cancer risk differs according to the type of hormonal contraceptive used . One study found a high risk for a small group of women who had reported using implants.In this study we investigated the association between hormonal contraceptive use and breast cancer development in a Thai population. We expect that the findings will be valuable for breast cancer prevention and family planning programs.14 Within the cohort there were 11 414 women with complete data on hormonal contraceptive use, and the analysis was done based on this number of participants. According to reports supplied by the Khon Kaen provincial cancer registry, there were 70 cases of histologically confirmed breast cancer among the 11 414 women. Follow-up was completed for all participants.This is an analytical study of data from a prospective cohort study, the Khon Kaen Cohort Study (KKCS), which is administered by the Cancer Unit of the Faculty of Medicine, Khon Kaen University, Thailand, and was established in 1991–2001. During this period, women aged 30 to 69 years living in Khon Kaen Province were invited to join the KKCS.15,16Variables of interest were age at recruitment, marital status, family history of breast cancer, breastfeeding history, age at first childbirth, age at menarche, and history of hormonal contraceptive use , and duration of use. Data for these variables were extracted from the KKCS dataset, which had been collected on recruitment into the cohort. All cohort participants were followed up until the end of the study, on December 31, 2011. Cohort participant data were linked to the Khon Kaen Cancer Registry to identify participants who had become breast cancer patients. The Khon Cancer Registry is the second population–based registry to be started in Thailand and was established in 1988 to represent the northeastern region of the country. Like the other 8 Thai cancer registries, it adheres to the procedures established by the IARC and International Association for Cancer Registration.All breast cancer diagnoses were histologically confirmed, and the date of diagnosis was obtained from medical records. Person-times were calculated from date of recruitment, date of diagnosis, date of loss to follow-up or withdrawal, and date at the end of the study.Multivariate analysis was used to investigate associations between hormonal contraceptive use and cancer development, and adjustments were made for age at recruitment, marital status, family history of breast cancer, and breastfeeding history. The Cox proportional hazards model was used to calculate risks of breast cancer in terms of hazard ratios (HRs) and 95% confidence intervals (CIs).The study was conducted in accordance with the principles of the 1975 Declaration of Helsinki and was approved by the Khon Kaen University Ethics Committee for Human Research .The study population of 11 414 provided a total observation time of 157 200 person-years; there were 70 cases of histologically confirmed breast cancer.The demographic characteristics of the participants are summarized in Tables The final results are shown in Table No type of hormonal contraceptive was associated with a significantly higher risk of breast cancer as compared with never use of hormonal contraceptives , and there was no relationship between duration of hormonal contraceptive use and breast cancer. Regarding age at beginning of follow-up, neither younger nor older women showed evidence of an association between hormonal contraceptive use and breast cancer risk.17 of 1423 women aged 40 to 60 years from families with hereditary familial breast cancer there were 380 cases of breast cancer, and ever use of oral contraceptives was unrelated to breast cancer risk . However, among those who had last used this form of contraception 15 or more years previously, there was actually a reduced risk, and statistically significant increased risks were found for subgroups of more recent users (5–9 years and 10–14 years previously). A US population-based case-control study of 4575 women with invasive breast cancer and 4682 controls aged 35 to 64 years18 found that use of injectable progestin-only contraceptives was unrelated to breast cancer risk . This absence of an association was found among current users , those who began contraceptive use during the previous 5 years , and those who began use before age 35 years . Another study19 that used the same database found no association between breast cancer and oral contraceptive use among current or previous users .To our knowledge, this is the first study of the association between hormonal contraceptive use and breast cancer risk in Thai women. Our study did not find an association between hormonal contraceptive use and subsequent development of breast cancer. Similar results were reported in other studies. In a Norwegian studyOther studies reported a positive association between hormonal contraceptive use and breast cancer risk. In a US study of 6150 female relatives of probands diagnosed with breast cancer during the period from 1944 to 1952, breast cancer developed in 242 relatives during the follow-up period. Ever use of oral contraceptives was associated with increased breast cancer risk in sisters and daughters  but not in second-degree or no consanguineous relatives (HR = 1.2 for both). The authors noted that the increased risk among first-degree relatives was particularly evident among those who had used oral contraceptives before 1976, a period when they were likely to contain higher levels of estrogen and progestins. In a large prospective cohort study of 103 027 randomly selected Scandinavian women aged 20 to 49 years, 1008 women received a diagnosis of breast cancer during the duration of follow-up. Ever-use was associated with increased risk .13,20 The absence of a statistically significant linear relationship between duration of hormonal contraceptive use and breast cancer risk was also reported by others.21–23 However, 1 study found a weak, but statistically significant, trend toward increased risk with longer duration of use,24 and a Canadian study reported a significant inverse association.25The present lack of an association of breast cancer with oral and injected contraceptive use is similar to findings from other studies.n = 70) limited the power of this study.The lack of consistency in past and present findings is difficult to explain but is probably due to differences between the populations studied, such as recency of use, family history, and number of cases. Furthermore, the data on hormonal contraceptive use in our study came from a single interview at cohort recruitment. This might be a limitation, because some women may have started using hormonal contraceptives after baseline, and a subgroup analysis showed that HRs for hormone use differed between younger and older women. The statistical power of the test was calculated based on the Cox proportional hazards model with an expected HR of 1.5, but the small number of breast cancer cases (In conclusion, we found no association between hormonal contraceptive use and breast cancer; however, this finding should be viewed with caution due to the small number of cases.


This study was undertaken to evaluate the association between components defining insulin resistance and breast cancer in women.We conducted a systematic review of four databases  for observational studies evaluating components defining insulin resistance in women with and without breast cancer. A meta-analysis of the association between insulin resistance components and breast cancer was performed using random effects models.Q2 vs. Q1 0.96, 0.71 to 1.28; OR Q3 vs. Q1 1.22, 0.91 to 1.64; OR Q4 vs. Q1 0.98, 0.70 to 1.38). Likewise, there were no differences for quartiles of non-fasting/fasting C-peptide levels . Homeostatic model assessment (HOMA-IR) levels in breast cancer patients were significantly higher than in people without breast cancer .Twenty-two studies  were selected. Fasting insulin levels were not different between women with and without breast cancer . Similarly, non-fasting/fasting C-peptide levels were not different between the two groups . Using individual odds ratios (ORs) adjusted at least for age, there was no higher risk of breast cancer when upper quartiles were compared with the lowest quartile (Q1) of fasting insulin levels (OR Higher levels of fasting insulin or non-fasting/fasting C-peptide are not associated with breast cancer in women. HOMA-IR levels are slightly higher in women with breast cancer. Breast cancer is the most common malignancy and the second leading cause of cancer death among women in the US. According to estimates for the year 2014, 235,030 breast cancer cases are expected to be newly diagnosed and 40,000 women will die from the disease in the US Insulin, a peptide hormone secreted by beta cells of the pancreas, promotes glucose absorption by cells and plays a central role in carbohydrate and fat metabolism. High insulin levels are a hallmark of insulin resistance. Insulin resistance is defined clinically as the inability of insulin to increase cellular glucose uptake and utilization, thereby leading to compensatory and chronic hyperinsulinemia Several epidemiologic studies have shown association between obesity and breast cancer in postmenopausal women Reliability of insulin and/or C-peptide levels as biomarkers of breast cancer has been a subject of controversy. Few studies report an association between these insulin resistance components and risk of breast cancer A comprehensive literature search using PubMed-Medline from 1960 through December 15, 2012, EMBASE from 1980 through December 15, 2012, The Web of Science from 1980 through December 15, 2012, and Scopus from 1960 through December 15, 2012 was conducted by three authors . The following keywords were used: hyperinsulinemia, breast cancer and breast carcinoma.(“hyperinsulinaemia”[All Fields] OR “hyperinsulinism”[MeSH Terms] OR “hyperinsulinism”[All Fields] OR “hyperinsulinemia”[All Fields]) AND ((“breast neoplasms”[MeSH Terms] OR (“breast”[All Fields] AND “neoplasms”[All Fields]) OR “breast neoplasms”[All Fields] OR (“breast”[All Fields] AND “cancer”[All Fields]) OR “breast cancer”[All Fields]) OR ((“breast”[MeSH Terms] OR “breast”[All Fields]) AND (“carcinoma”[MeSH Terms] OR “carcinoma”[All Fields])))The following predetermined inclusion criteria was used: (i) observational studies evaluating the risk of components associated with insulin resistance and breast cancer, (ii) study population of patients ≥18 years; (iii) study in any language. Our exclusion criteria were: (i) no control group; (ii) fasting insulin, non-fasting/fasting c-peptide or HOMA-IR  data were not available or could not extracted for the study groups. Controls are defined as patients without breast cancer.A list of retrieved articles was reviewed independently by 3 investigators  in order to choose potentially relevant articles, and disagreements about particular studies were discussed and resolved by consensus.Two reviewers (VP and AD) independently extracted data from studies. The following information was extracted: age, gender, body mass index (BMI), menopausal status, insulin and/or c-peptide levels, method of diagnosis of breast cancer, fasting status when blood samples were collected, and assays for quantifying insulin and c-peptide. Information regarding homeostatic model assessment (HOMA-IR) scores was also collected, whenever available. One other author (AVH) reviewed the extractions for inconsistencies, and the three authors  reached consensus.The quality of the selected studies was assessed independently by two authors (V.P. and A.V.H.) using the Newcastle–Ottawa scale (NOS). The NOS uses two different tools for case–control and cohort studies and consists of three parameters of quality: selection, comparability and exposure/outcome assessment. The NOS assigns a maximum of four points for selection, two points for comparability and three points for exposure or outcome. NOS scores of ≥7 were considered as high quality studies and NOS scores of 5–6 were considered moderate quality. Any discrepancies were addressed by a joint re-evaluation of the original article.2), Cochran Chi-square (χ2) and the I2 statistic 2 values of 30–60% represented a moderate level of heterogeneity. A P value of <0.1 for χ2 was defined as indicating the presence of heterogeneity. Tau2 provides an estimate of between-study variance in random-effects meta-analysis. If Tau2 is >1, it suggests presence of substantial statistical heterogeneity. Publication bias was explored with the funnel plot and tested with the Egger's test of funnel plot asymmetry Our systematic review and meta-analysis follow the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) collaboration. DerSimonian and Laird random effects models were used for all meta-analyses Our search identified 525 publications . After rUsing the NOS scale, all but 2 studies The funnel plot did not suggest the presence of publication bias, and the formal test of asymmetry of this plot was not significant .2 = 95% and 99%, respectively) for these two associations. Using individual ORs adjusted for age at least, there was no increased risk of breast cancer when the higher quartiles were compared with the lowest quartile (Q1) of fasting insulin    (2 = 0)  were not different between women with and without breast cancer  . Further (2 = 0) .In this systematic review we did not find differences between fasting insulin or non-fasting/fasting C-peptide levels and women with and without breast cancer. There was no higher adjusted risk of breast cancer between higher quartiles of fasting insulin or non-fasting/fasting C-peptide levels and their lowest quartile levels. Finally, fasting HOMA-IR levels were slightly and significantly higher in women with breast cancer in comparison with women without breast cancer.Insulin and IGF-1 are peptide hormones that stimulate proliferation of tissues and levels higher than normal (i.e. hyperinsulinemia) have been linked with carcinogenic properties in animal models A meta-analysis has linked diabetes mellitus and breast cancer risk Another recent meta-analysis evaluated the relationship between metabolic syndrome and breast cancer We did not find any association between markers of insulin resistance and breast cancer. Fasting insulin levels and non-fasting/fasting C-peptide levels may shadow the state of stress that the pancreas has in presence of insulin resistance. We believe that measuring insulin levels in the 3-hour period after a sugar load test can provide better information and potentially peak levels of insulin or the area below the 3-hour insulin curve may be associated with breast cancer risk. Higher fasting insulin levels have been slightly associated with higher risk of endometrial cancer  Load tests may give higher chances to find an association not found with current measurements. Previous research has shown an association between glycemic load and breast cancer risk in a meta-analysis We did not evaluate fasting glucose individually, but we did evaluate HOMA-IR scores, which is proportional to glucose x insulin levels. A very small, although significant association between HOMA-IR scores and breast cancer was found. Unfortunately, we could not explore the association between higher quartiles and the lowest quartile of HOMA-IR scores, as they were not available in the selected studies. Again, we propose that glucose and insulin levels may be both measured after a sugar load test and these values may provide a better estimate of the association of insulin resistance and breast cancer risk.A recent meta-analysis found no evidence of an association between serum insulin and C-peptide concentration and breast cancer in 6 prospective studies with 1,890 cases Our study has several limitations. First, the observational nature of the included studies may weaken our conclusions, especially because most are case-control studies. However, the risk of bias of included studies was low. Second, although we compared insulin, C-peptide levels and HOMA-IR scores univariably between women with and without breast cancer, we also meta-analyzed risks measures of breast cancer between quartiles that were adjusted at least for age, and in most of cases for several essential confounders. Third, there was substantial clinical and statistical heterogeneity among included studies. Previous meta-analyses In observational studies, higher levels of fasting insulin or non-fasting/fasting C-peptide were not found to be associated with the presence of breast cancer in women, even after adjustment for important confounders. HOMA-IR levels are slightly higher in women with breast cancer.Checklist S1PRISMA Checklist.(DOC)Click here for additional data file.File S1Supporting tables. Table S1, Newcastle-Ottawa Scale. Table S2, Study Quality Assessment.(DOC)Click here for additional data file.


The possibility of developing breast cancer is a concern for all women; however, few studies have examined the relationship between cancer worry and the stages of adoption for breast cancer screening in Korea. Here, we investigated the associations between cancer worry, the stages of adopting breast cancer screening, and socio-demographic factors known to influence screening behaviors.This study was based on the 2013 Korean National Cancer Screening Survey, an annual cross-sectional survey that utilized nationally representative random sampling to investigate cancer screening rates. Data were analyzed from 1,773 randomly selected women aged 40–74 years. Chi-squared tests and multinomial logistic analyses were conducted to determine the associations between cancer worry and the stages of adoption for breast cancer screening and to outline the factors associated with each stage.Korean women were classified into the following stages of adoption for breast cancer screening: pre-contemplation (24.7%), contemplation (13.0%), action/maintenance (50.8%), relapse risk (8.9%), and relapse (2.6%). Women in the action/maintenance stages reported more moderate to higher levels of worry about getting cancer than those in the pre-contemplation stage. Further, age of 40–49 years and having private cancer insurance were associated with women in the action/maintenance stages.Interventions to address breast cancer worry may play an important role in increasing participation and equity in breast cancer screening. Breast cancer is one of the most common cancers around the world. According to GLOBOCAN fact sheets, 25% of all of the new cancer cases involve the breast. While breast cancer is the most frequent cancer among women of both highly and less developed nations , there aIn Korea, even though the incidence of breast cancer is not as high as that of Western countries, it is rapidly increasing. Breast cancer is the second most common type of cancer and the fifth leading cause of cancer death among Korean women . In KoreAlthough organized breast cancer screening is offered, breast cancer screening rates for Korea (70.9% for the entire nation) are still below those for other developed countries , 7. In aIn addition to achieving high initial rates, the maintenance of participation rates at subsequent rounds of screening is equally as important . AccordiIn this study, via a transtheoretical model, we aimed to examine the stages of adoption for breast cancer screening to outline the extents to which breast cancer worry affect the decisions of Korean women to undergo breast cancer screening or not. We also investigated associations between the stages of adopting breast cancer screening and socio-demographic factors known to influence screening behaviors. We suspect that providing detailed information on stages of adoption and factors influencing breast cancer screening will help researchers tailor health communication to increase participation in breast cancer screening.Data were acquired from subjects included in the 2013 Korean National Cancer Screening Survey (KNCSS). The KNCSS is an annual cross-sectional survey performed to investigate screening rates among Koreans for five common cancers  through nationally representative random sampling. Men aged ≥40 years and women ≥30 years were selected based on Resident of Registration Population data for July 2013 compiled by Statistics Korea, using multistage random sampling according to sex, age, geographic area, and size of population per area. The survey was conducted from September 26 to October 18, 2013, at which time investigators from a professional research agency went door-to-door to recruit residents. At least three attempts were made to contact individual residents. The 2013 KNCSS included 4,100 participants among a total of 23,238 random samples . The response rate after making contact was 64%, excluding those who were absent  or who did not meet the criteria for this survey (296). Of the respondents, 1,773 cancer-free women aged ≥40 years were finally included in the current study, since the NCSP only provides breast cancer screening for individuals aged ≥40 years.Witten informed consent was obtained from all study participants before the face-to-face interview. This study was approved by the Institutional Review Board (IRB) of the National Cancer Center, Korea . Informed consent was documented via the use of a written consent form approved by the IRB and signed by all study participants.Pre-contemplation, had never undergone breast cancer screening and did not plan to within the next 2 years;Contemplation, had either never undergone breast cancer screening or had not in the last 1–2 years, but are planning to within the next 2 years;Action/Maintenance, had undergone breast cancer screening within the last 24 months and were planning on undergoing another test within the next 2 years;Relapse risk, had undergone breast cancer screening within the last 24 months, but were not planning on undergoing another test within the next 2 years;Relapse, had undergone one or more breast cancer screening test in the past, but were now off schedule and had no plans to undergo breast cancer screening within the next 2 years.The stages of adoption for breast cancer screening were assessed via a modified five-stage process related to the subjects’ reported histories of breast cancer screening and their current intentions to undergo screening within the next 2 years, as recommended by Rakowski et al. in 1996 . The parTo develop survey questions related to cancer worry and perceived risk, we reviewed previous research. Since measurements of cancer worry and perceived risk were not available in the Korean language, questionnaires written in English were first translated into Korean and then translated back into English to confirm the accuracy of the translation. Further, we conducted a pilot survey to assess understanding of these questions among respondents. In the present study, Lerman’s Cancer Worry Scale modified to reflect cancer worry in Korea was used , 24, 25.We also examined several socioeconomic  and health-related factors  to assess their influence on screening behaviors. Further, private cancer insurance and awareness of the NCSP were also measured to assess the accessibility of breast cancer screening. Although the NHIS provides universal coverage to all Koreans, many Koreans pay for supplementary private health insurance in the event of illness  due to insufficient coverage with the NHIS .P-value of <0.05 in univariate analysis were included in the multinomial logistic regression model as potential predictors. These variables included age, monthly household income, residence area, private cancer insurance, regular health checkups, and cancer worry. Additionally, we conducted trend analysis for the ordinal categorical variables to investigate the significance of any trends. Statistical analyses were performed using STATA software , and all P-values <0.05 were considered statistically significant.Descriptive statistics were assessed to characterize the study population. For comparison of cancer worry levels with worry levels for five major non-communicable diseases, ANOVA and Tukey’s post-hoc analysis were conducted. Chi-squared tests were used to compare the distributions of the stages of adoption according to socioeconomic and health-related factors. To investigate factors related to one’s stage of adoption, we grouped participants into four groups: 1) pre-contemplation; 2) contemplation; 3) action/maintenance; and 4) relapse risk/relapse group. Multinomial logistic analysis was conducted to identify associations between breast cancer worry and the stages of adoption for breast cancer screening, as well as factors associated with each stage. In this analysis, we combined the relapse risk and relapse stages, because the number of women who were in the relapse stage was too small to conduct multivariate analysis. Further, women in the relapse risk and relapse share the same experience in that they have already been in action or maintenance. We assessed the adjusted odds of being in the action/maintenance group or relapse risk/relapse group rather than the pre-contemplation group. All variables with a Descriptive data for the subjects according to their levels of cancer worry are presented in In the present study, we classified respondents according to stage of adoption for breast cancer screening. Among the study population, 24.7% were classified in the pre-contemplation stage, 13.0% in the contemplation stage, 50.8% in the action/maintenance stage, 8.9% in the relapse risk stage, and 2.6% in the relapse stage. Age, monthly household income, private cancer insurance, regular health checkups, and cancer worry were significantly different across the stages of adoption of breast cancer screening .P for trend = 0.021). Meanwhile, no statistically significant difference in cancer worry levels was noted among women in the pre-contemplation, contemplation, and relapse risk/relapse stages.Between the pre-contemplation and contemplation stages, only private cancer insurance was significantly different; women who had private cancer insurance were more likely to be in the contemplation stage than the pre-contemplation stage. In comparison of the pre-contemplation and action/maintenance stages, women aged 40–59 years who had private cancer insurance and who reported higher levels of cancer worry were more likely to stay in the action/maintenance stage than the pre-contemplation stage. However, between the pre-contemplation and relapse risk/relapse stages, no statistically significant difference was noted.In the present study, we assessed the associations between cancer worry and stages of adoption for breast cancer screening in the general Korean population. Although previous studies have investigated the importance of the role of breast cancer worry in promoting participation in cancer screening –10, few Across the stages of adoption, several factors were shown to influence differences in the distribution thereof in the present study. Mainly, subjects who reported relatively greater concerns for getting cancer were more likely to be classified in on-schedule stages (contemplation and action/maintenance). Additionally, age, monthly household income, private cancer insurance, undergoing regular health checkups, and cancer worry were significantly different across the stages of adoption for breast cancer screening. Meanwhile, perceived risk showed no significant difference across the stages of adoption. Reviewing previous studies, the effect of perceived risk on intention to undergo mammography was still unclear, though it has been studied as a promoter of preventive health behavior –31. For In summary of the percent distribution across the stages of breast cancer screening adoption for Korean women, only about 63.8% reported on-schedule screening , while 36.2% did not . These screening rates are much lower than those for on-schedule screening in the United States (84.0%) . One preAmong our results from multinomial logistic analysis, we found that cancer worry played a role in boosting cancer screening behaviors overall. Compared to those with relatively low cancer worry, subjects with relatively high levels of cancer worry were more likely to be classified in the action/maintenance stage than the pre-contemplation stage. Between the pre-contemplation stage group and the relapse risk/relapse stage group, those who reported relatively greater concerns for getting cancer were more likely to be classified in the relapse risk/relapse stages, suggesting that women with little to no concerns for getting cancer had not even considered undergoing breast cancer screening, in the past or the future. As introduced above, despite the existence of several contradictory results, cancer worry has predominantly been shown to play a critical role in motivating screening behavior, with which our results agree , 34. AmoP for trend = 0.001). Additionally, women who had private cancer insurance and had higher household income (P for trend = 0.051) were more likely to be in the action/maintenance stage that the other stages, potentially indicating a health disparity related to the economic status of women.Herein, we also examined socio-economic factors in relation to their effects on breast cancer screening behavior. In doing so, we discovered that Korean women aged 40–59 years, who are at high risk for breast cancer, are more likely to remain in the action/maintenance stages than the pre-contemplation stage (Our study has a number of limitations. First, the cross-sectional design of this study hindered our ability to implicate any causal relationship for the observed associations. Thus, future studies with a longitudinal design should be conducted to track patterns in breast cancer screening behaviors. Second, because of memory bias, we assessed only the most recent breast cancer screening event and did not collect information on screening events that preceded the most recent one. Therefore, we could not distinguish between the action and maintenance stages. Further, we only measured overall cancer worry not breast cancer-specific worry, as we were concerned that there might be somewhat different trends between overall cancer worry and breast cancer-specific worry. Thus, studies that distinguish between worry for individual types of cancer are needed, as are validation studies to develop reliable and capable measures of predicting unique variances in cancer-relevant worry in the Korean population.Despite these limitations, this study is important in that it is the first to assess breast cancer worry specifically in relation to its effects on screening behavior among Korean women. As well, this study provides new insights that may be of use in guiding the development of intervention strategies for improving compliance with breast cancer screening recommendations at the population level. Our results demonstrated that cancer worry is associated with continued breast cancer screening among women in Korea. Additionally, we showed that age, household income, private cancer insurance, and regular health checkups are positively associated with the stages of breast cancer screening adoption among Korean women. Interventions to address breast cancer worry may play an important role in increasing participation and equity in breast cancer screening.


Population attributable risks (PARs) are useful tool to estimate the burden of risk factors in cancer incidence. Few studies estimated the PARs of oral cavity cancer to tobacco smoking alone, alcohol drinking alone and their joint consumption but none performed analysis stratified by subsite, gender or age. Among the suspected risk factors of oral cavity cancer, only PAR to a family history of head and neck cancer was reported in two studies. The purpose of this study was to estimate in France the PARs of oral cavity cancer to several recognized and suspected risk factors, overall and by subsite, gender and age.We analysed data from 689 oral cavity cancer cases and 3481 controls included in a population-based case–control study, the ICARE study. Unconditional logistic regression models were used to estimate odds ratios (ORs), PARs and 95 % confidence intervals (95 % CI).−2, never tea drinking and family history of head and neck cancer explained 35.3 % (25.7 %–43.6 %), 30.3 % (14.4 %–43.3 %) and 5.8 % (0.6 %–10.8 %) of cancer burden, respectively. About 93 % (88.3 %–95.6 %) of oral cavity cancers were explained by all risk factors, 94.3 % (88.4 %–97.2 %) in men and only 74.1 % (47.0 %–87.3 %) in women.The PARs were 0.3 %  for alcohol alone, 12.7 % (6.9 %–18.0 %) for tobacco alone and 69.9 % (64.4 %–74.7 %) for their joint consumption. PAR to combined alcohol and tobacco consumption was 74 % (66.5 %–79.9 %) in men and 45.4 % (32.7 %–55.6 %) in women. Among suspected risk factors, body mass index 2 years before the interview <25 kg.mOur study emphasizes the role of combined tobacco and alcohol consumption in the oral cavity cancer burden in France and gives an indication of the proportion of cases attributable to other risk factors. Most of oral cavity cancers are attributable to concurrent smoking and drinking and would be potentially preventable through smoking or drinking cessation. If the majority of cases are explained by recognized or suspected risk factors in men, a substantial number of cancers in women are probably due to still unexplored factors that remain to be clarified by future studies. Oral cavity cancer  is an imPopulation attributable risks (PARs) are useful tool to estimate the burden of risk factors in cancer incidence. Although several epidemiological studies examined the joint effect of tobacco and alcohol consumption and found evidence of an interaction on an additive  or multiThe few available studies on HNC related to alcohol and tobacco consumption which provided separate PARs of oral cavity cancer did not include French data, and none performed analysis on oral cavity cancers stratified by gender, age or anatomic location. However, concerning the carcinogenic effect of tobacco smoking and alcohol drinking, differences between oral subsites have been observed in some epidemiological studies , 20–25. In a previous analysis , we repoUsing data from the ICARE study, we conducted the present analysis to (i) estimate in France the proportion of oral cavity cancers attributable to the effect of tobacco smoking alone, alcohol drinking alone and to their joint effect; (ii) assess the PARs due to several potential risk factors previously observed in this study population ; (iii) examine differences in PARs, if any, by subsite, gender and age.The study design, study population and data collection methods of the ICARE  study have been described in details elsewhere . Brieflyth revision [ICD-10] codes C01-C06 [The present analysis included only cases with oral cavity cancer , and anthropometric measurements . Ever smokers were defined as subjects who had smoked at least 100 cigarettes in their lifetime, or who had smoked at least one pipe, cigar or cigarillo per week for at least one year. Ever alcohol and tea drinkers were defined as subjects who had consumed at least one drink per month for at least one year. To ascertain the medical history, study participants were asked if, throughout their lives, they had ever had one or more diseases among those mentioned in a list, including oral candidiasis. To ascertain the family history of cancer, subjects were asked if their biological mother and father and their full brothers or sisters had ever had a cancer. If the answer was “yes”, the subjects were asked to specify the type of cancer.A summary version of the questionnaire was used when the subject was too sick to answer the complete questionnaire (83 cases (10.8 %) and 74 controls (2.1 %)). This questionnaire did not include information about anthropometric measurements, family and medical history, and tea consumption. Therefore, these subjects were excluded from the present analysis that finally included 689 cases and 3481 controls.−2/≥ 25 kg.m−2), family history of HNC in first degree relatives (yes/no), personal history of oral candidiasis (yes/no) and tea drinking (never/ever). The choice of adjusting for these variables was justified by our previous results that showed lower risks of oral cavity cancer in overweight/obese subjects compared to normal/underweight subjects [Unconditional logistic regression models were used to estimate ORs, PARs and their 95 % CIs. The models included the variables age , gender, area of residence (10 administrative areas), education level , alcohol and tobacco consumption , alcohol but never tobacco use  and tobacco and alcohol use (joint effect)), BMI two years before the interview . Polytomous regression modes were used to estimate ORs, PARs and 95 % CI by subsite .All statistical tests were two-sided. Analyses were performed using the Stata Statistical Software release 10.0 .Men represented more than two thirds of both cases and controls . Cases were younger and had lower education level than controls . The most frequent tumour location was the floor of the mouth (27.7 %), followed by the mobile tongue (23.2 %), the base of the tongue (18.8 %), other parts of the mouth (11.5 %) and soft palate (10.8 %). Gums and hard palate represented only 5.7 % and respectively 2.3 % of cancer locations.ORs, 95 % CIs and PARs of oral cavity cancer to alcohol drinking alone, tobacco smoking alone and their joint consumption, and the multiplicative interaction parameter are presented in Table Differences between subsites were observed: the greatest PARs to tobacco consumption alone, joint and total consumption of alcohol and tobacco were observed for floor of the mouth cancer (15.5 % (6.7–23.6) for tobacco consumption alone, 79.6 % (70.8–85.7) for alcohol and tobacco consumption, and 95.6 % (82.3–98.9) for alcohol and/or tobacco consumption). The lowest PARs to tobacco consumption alone, joint and total consumption of alcohol and tobacco were found for gum cancer (11.1 % (−30.1–39.2) for tobacco consumption alone, 26.2 % (−13.9–52.2) for joint consumption of alcohol and tobacco, and 36.4 % (−62.3–75.0) for alcohol and/or tobacco consumption). For the base of the tongue and soft palate, oral subsites generally grouped with the oropharynx, the PARs were similar to that observed for mobile tongue and other parts of the mouth; for example, the total PAR was 79.6 % (50.6–91.6) for base of the tongue, 75.7 % (51.3–87.9) for mobile tongue, 82.3 % (44.9–94.3) for soft palate and 87.6 % (50.1–96.9) for other parts of the mouth. With respect to the exclusive alcohol drinking, the PARs were low and some negative values were found when the ORs were below 1 for base of the tongue, mobile tongue and gum cancers.The PARs were lower in women than in men for both the joint and total consumption of alcohol and tobacco . Concerning the PARs stratified by age, it was difficult to conclude to any difference between subjects younger than 45 compared to subjects aged 45–60 or older because CIs are large and overlapped.−2. Since the confidence intervals overlapped, it is not possible to conclude to significant differences between subsites. Among men, the corresponding PAR was 39.9 % (30.0–48.3). No association was observed in women between BMI and oral cavity cancer (OR = 1.1 (0.6–2.0)), leading to a small PAR . No significant differences were observed in PAR stratified by age.ORs, PARs and 95 % CI for oral cavity cancer associated with other risk factors than alcohol and tobacco are presented in Table Only few oral cavity cancers were attributable to having a family history of HNC in first degree relatives . No noticeable differences were observed in PAR by subsite or by age. The PARs were 6.8 % in men and 2.1 % in women with overlapping CIs.Very few oral cancer cases were attributable to a personal history of oral candidiasis . We did not find any significant difference in PARs stratified by subsite, gender or age.The PAR associated with never drinking tea was 30.3 % (14.4–43.3). The highest ORs and PARs were observed for soft palate and other parts of the mouth but confidence intervals were large and overlapped and it was difficult to conclude to any difference. The PAR was 38.0 % in men and only 13.9 % in women, confidence intervals overlapping. Analysis stratified by age did not show significant differences in PAR.The PAR to all factors combined was around 93 % (95 % CI 88.3–95.6) with the lowest value of 78.5 % (95 % CI 15.2–94.6) for the gum cancer and the highest value of 98.0 % (95 % CI 91.4–99.5) for the floor of the mouth cancer  are not modifiable or can hardly be subject to preventive measures. In addition, obviously, it is not possible to recommend a weight gain that was inversely associated with the risk oral cavity cancer, because of the negative consequences on many other diseases. However, the objective here was to assess the impact of each risk factor, prioritize them, and determine the proportion of oral cavity cancers that remains to be possibly explained by other unexplored factors.Our results have shown that the proportion of risk attributable to tobacco smoking alone was greater than that attributable to alcohol drinking alone. Smoking was an independent risk factor for oral cavity cancer while drinking, in the absence of smoking, conferred little and no significant risk. These results are similar to those reported in other studies , 31, 32.The proportion of cases attributable to the joint effect of tobacco and alcohol was around 70 %, confirming that tobacco and alcohol together explain the majority of oral cavity cancer burden in France. This result is consistent with that reported by one case–control study conducted in Latin America , but higDifferences in PARs by gender were observed, particularly with regards to the attributable risks to tobacco and alcohol. The PAR to their joint consumption was higher in men than in women , consistent with previous studies , 15, 17.Conversely to the available studies , 15, 19,In our study, PAR of oral cavity cancer to family history of HNC was around 6 %, greater than that reported for HNC overall in the pooled analysis within INHANCE Consortium (around 2 %) . This diLow versus high BMI and never versus ever consumption of tea appear to be responsible for a significant number of oral cavity cancers, especially in men. The possible role of body fat in the distribution of the lipophilic carcinogens derived from tobacco smoke  and the Approximately 93 % of cases of oral cavity cancer overall, 94 % in men and only 74 % in women, are explained by all the studied factors. This leaves about 7 % of cases to be explained by other risk factors that we have not been able to take into account, of which 6 % in men and 26 % in women. This result emphasizes the role of other risk factors in women, such as human papillomavirus (HPV) infection, diet, hormonal factors or specific genetic factors of cancer susceptibility.Strengths of our study are the multicenter design and the study size that allowed us to perform stratified analyses by anatomic subsite, gender and age.Some limitations of our study exist. The subjects self-reported their own consumption of tobacco, alcohol and tea, anthropometric measurements, medical and family history. Thereby, recall bias could not be ruled out and it is possible that the cases had a higher motivation than the controls to recall tobacco and alcohol consumption as well as medical and family history, known as potential risk factors of cancer. Nevertheless, we do not think that underreporting of alcohol consumption may explain its negligible impact because alcohol drinking is socially accepted in France. In France, only 8.4 % of people reported never having drunk alcohol , a propoInformation about other suspected or known risk factors for oral cavity cancer such as HPV infection or diet was not collected in our study and residual confounding cannot be excluded. HPV infection is a recognized risk factor for base of the tongue and tonsils cancers, but less for the other HNC . HoweverWhile we did not observe an independent effect of alcohol on oral cavity cancer risk in our study, concurrent smoking and drinking are responsible for the majority of oral cavity cancers, especially among men. In terms of public health, this study suggests that a reduction of combined tobacco and alcohol consumption could result in a significant decrease of oral cancer. Ninety-three percent of cases overall and 94 % in men are explained by known or suspected risk factors. However, a substantial proportion of oral cavity cancer among women (26 %) cannot be attributed to either established or suspected risk factors. Still unexplored factors conferring oral cancer risk among women remain to be clarified by future studies.


To assess the knowledge of nurses involved in the care of oncology patients in apublic university hospital, regarding breast cancer and hereditary breast cancer,and to verify the use of such knowledge in their daily practice.  This is a descriptive cross-sectional study. Data were obtained through astructured, self-administered questionnaire. Out of 154 nurses, 137 (88.9%) agreedto participate in the study. Two questionnaires were excluded such that 135questionnaires were analyzed.  The global percentage of correct answers was not associated with age (p=0.173) ordegree/specialization (p=0.815). Questions were classified into categories. Incategories involving knowledge of established breast cancer risk factors andindicators of hereditary breast cancer, the rate of correct answers was 65.8% and66.4%, respectively. On the practice of genetic counseling, 40.7% of thoseinterviewed were not sure about the definition of genetic counseling and 78.5%reported never having identified or referred a patient at genetic risk forspecialized risk assessment. Practice of educational actions regarding thissubject was reported by 48.5% of those interviewed.  This study reinforces the need to develop qualifying actions for nurses, so thatstrategies to control breast cancer become effective in their health carepractice. In Brazil, it is the most frequent tumor in women of the Southeastern(69/100.000), Southern (65/100.000), Midwestern (48/100.000) and Northeastern regions(32/100.000). According to the Brazilian National Cancer Institute (INCA), estimates for 2012/2013 indicate that 52.680 new cases of female breastcancer will be identified, corresponding to the occurrence of 52 cases per 100.000women. Despite being considered a tumor with good prognosis in most instances and ifdiagnosed and treated in time, breast cancer is still associated with a high mortalityrate in Brazil. The most probable cause for this observation is that the disease isstill being diagnosed in advanced stages, and multiple barriers to diagnosis andtreatment exist for most women who rely on the public health care system(-). Cancer is the leading cause of death due to non-transmitted diseases worldwide and thusan important public health problem both in developed countries and in underdeveloped ordeveloping countries. Breast cancer is the most frequent type of cancer in women and thesecond cause of death in this population group worldwide. In Braregions3/100.000, increasingage, high breast tissue density and family history of cancer, especially breastcancer. Additional factors that modulate breast cancer risk include nutritionalfactors, physical activity, history and duration of breast feeding, obesity inpost-menopause, smoking, alcohol consumption, exposure to ionizing radiation andsocio-economic level.Breast cancer is a multi-factorial disease in which genetic and environmental factorscontribute to its occurrence. In a s disease. Sporadheworld. It is t cancer. Establtcancer,5-6ic level,6-7BRCA1 and BRCA2 genes. Women with mutations in oneof these genes present a cumulative risk of between 55% and 85% of developing breastcancer until the age of 70 and a 15% to 65% risk of developing ovarian cancer, dependingof the type and location of the mutation. Features of the family history that suggest hereditary predisposition tobreast cancer include, among others, early age at diagnosis, multiple synchronic ormetachronic primary tumors, male breast cancer and association with other tumors such asovarian and prostate cancers. In Brazil, the breast cancer screeningprotocol recommended by the Ministry of Health includes annual clinical breastexamination for asymptomatic women aged 40-50 and bi-annual mammographic screening forwomen aged 50-69. Recommendations for women at high risk for developing breast cancerare less clearly defined in Brazil. Clinical breast examination (CBE) and annualmammography (MMG) have been suggested from the age of 35 years, but different protocolsare usually recommended according to the specific cause of risk. There is no evidence tosupport breast self-examination (BSE) as an isolated strategy for early detection ofbreast cancer. Hereditary breast cancer corresponds to approximately 10-15% of all malignant breasttumors. Among these are the tumors caused by highly penetrant germline mutations in the(-). Knowledge and identification of risk factors for sporadic breast cancerand focus on risk assessment for the genetic aspects of hereditary breast cancers arekey challenges for health promotion and cancer prevention within nursingpractice(-). Nurses have a central role in the multidisciplinary team involved in the care ofpatients with breast cancer, as well as those at increased risk for the disease.Therefore, it is essential to invest in the education and training of nurses, both inthe recognition of risk factors and in criteria for referral of patients to maximizerisk-reducing practices, especially in high-risk individuals-11. Kpractice-13. . An Excel for Windows(r) file was created and populatedwith data from the questionnaires. Data were analyzed using SPSS(r)version 18.0 software, mainly with simple descriptive statistics. For the assessment ofthe normality of quantitative variables (demographic data), the Kolmogorov-Smirnov testwas applied. Due to the non-Gaussian presentation of the remainder of the data, thesewere presented as median and interquartile intervals. The chi-square test was performedto assess the association between the overall percentage of correct answers in relationto age and specialization. Spearman correlation was used to evaluate the associationbetween the overall percentage of correct answers and the number of years aftergraduation. In all analyses, P<0.05 was considered significant. This is a descriptive transversal study performed with nurses of a public universityhospital in Southern Brazil  who wereinvolved with the care of oncology patients in their practice. The study was approved bythe Research Ethics Committee of the Institution (HCPA GPPG protocol number 120507).Knowledge in the areas of breast cancer and hereditary breast cancer was assessedthrough a questionnaire consisting of 29 questions distributed as follows: objectivequestions (mostly multiple choice) about demographic data and professional training (5questions), about cancer and breast cancer (10 questions) and about cancer genetics andhereditary breast cancer (14 questions). In relation to breast cancer, the questionnaireassessed knowledge about disease epidemiology, risk factors, diagnosis, screening andtreatment. Regarding hereditary breast cancer, knowledge about diagnostic and referralcriteria was assessed. Recruitment and data collection occurred between March andSeptember of 2013. The estimated minimum sample size at baseline was 103 nurses, and thetotal amount of nurses who were active in clinical and surgical hospitalization,radiotherapy, chemotherapy and outpatient units and who were involved with the care ofadult oncology patients in the HCPA was 154 nurses during the study period. Allprofessionally active nurses involved with care of oncologic patients in the institutionwere invited for this study, and 137 (88.9%) agreed to participate. After the nursessigned informed consent, researchers provided the questionnaire, which was answeredindividually by each participant. Data obtained were compiled, analyzed and comparedwith the existing knowledge about the topicsOf the 154 professionals who were active in the care of cancer patients during theperiod, 137 nurses (88.9%) participated in the research. Two (1.4%) questionnaires wereexcluded due to inconclusive answers; thus, 135 questionnaires were analyzed. Theoverall percentage of correct answers was not associated with age (p=0.173) orspecialization in oncologic care (p=0.815). However, an inverse association  was observed between years since the end of training and number of correctanswers. The overall median of correct answers for each participant was calculated bycombining both questions of knowledge about breast cancer and inherited breast cancer.The lowest percentage of correct answers by a participant was 37.9% and the highest,91.1% (average = 67.98%: SD 8.91). The results were categorized according to the mainareas of knowledge considered in the study: breast cancer and hereditary breast cancer.Age was concentrated in the 40-49 age group; number of years since graduation variedfrom 1 to 50 years (median=15 years) and the length of time in care of oncology patientsvaried from <1 to 40 years (median=10 years). In relation to knowledge about hereditary breast cancer, most of the participants (54%)reported that knowledge about hereditary breast cancer had been acquired during graduatestudies, and a small percentage reported exposure to the topic in extracurricularactivities or during their post-graduation courses. A group of participants (13%)reported never having received information on the topic. Nevertheless, the blocks ofknowledge "characteristics of hereditary breast cancer" and "indicators of higher riskof developing hereditary breast cancer" had the highest levels of right answers . Two questions presented the lowest rate of correct answers inthose blocks . DetaileAs for the approach of including familial breast cancer history in routine anamnesis,108 (80.6%) of nurses reported performing this approach. Still within the subject ofhereditary breast cancer, When questioned about the professional role of nurses in carrying out educationalactions to help in the prevention of breast cancer, 134 (99.3%) participants reportedthat these should be part of their professional activity. However, less than half of them effectively perform this type of preventive action in their dailyprofessional practice. The actions effectively performed, according to reports of theparticipants, are described in Finally, when questioned about their interest in receiving more information aboutgenetic risks for breast cancer and training strategies in the area, 98.5% ofparticipants expressed their interest in training through lectures given by specialists(61.7%), seminars with discussion of illustrative cases (46.6%) and long-distancetraining (46.6%). . Although one might expect that more mature professionals would have moreknowledge in this area, we observed the opposite: more experienced professionals hadlower performance in the questionnaire. This finding may reflect a lack of knowledge inolder professionals due to deficiencies in undergraduate training and indicates the needfor the ongoing education for nurses. This need was also highlighted in the previousstudy. The demographic data profile of participants in this study showed a predominance ofprofessionals with considerable training and experience in the field of oncology, whichis not surprising for staff nurses at a university hospital. This profile was similar tothe participants in a previous study that assessed knowledge, attitudes and practice ofphysicians and nurses from the Family Health Strategy (FHS) program in the State of RioGrande do Norte (city of Mossoró), Brazil, in relation to early detection of breastcancer. In that study, the average time since graduation was 17 and 15 years forphysicians and nurses, respectively. Althouusstudy. . Regarding the knowledge of nurses about breast cancer in general, althoughthe overall percentage of correct answers was higher than 65%, highly compromised areaswere identified, such as risk factors and current breast cancer screening strategies. An important fact that may explain the relative lack of knowledge of participants inspecific areas is the low percentage 11%) of professionals who had taken aspecialization course in oncology in this series. This fact is most likely associatedwith the type of activity of most nurses interviewed: generalized assistance in clinicaland surgical units. In these sectors, the experience with oncology patients allows themto develop educational and assessment actions in terms of risk factors within thehealth/illness context, without the need for specific academic knowledge. Meanwhile,breast cancer is an action area of the nurse while also being a public health problemand an area with multiple opportunities for risk-reducing interventions% of prof. A recent case-control study about women's knowledge of breast cancer riskfactors performed in a regional university in the Brazilian state of Rio Grande do Sul(RS) observed that women with breast cancer had less previous knowledge about riskfactors than women without the disease and concluded that information is an importantmeans of reducing breast cancer incidence and enabling early diagnosis.Risk factors for breast cancer, even those established in the scientific literature, arenot well known and not often discussed with women and patients in general. A studyconducted in the city of Dourados (MS), Brazil, with 393 female users of the FHS Programaged 40-69 years, found that nearly half of the participants did not know any of thebreast cancer risk factors and approximately 30% knew only one factor. A receiagnosis.. Within that context, the nurse has a central role, considered by someauthors as a duty, in promoting the development of such educational abilities, togetherwith the female population. Secondary prevention is also important in the control ofbreast cancer. An important finding of this study was the significant lack of knowledgeregarding current guidelines for breast cancer screening proposed by the Ministry ofHealth (MH) in Brazil. This observation allows us to infer that nurses might not be familiar withthese protocols. The aforementioned study also identified low levels of knowledge regarding the recommended strategyof mammography screening in women. In the Mossoró study, 93.6% of the participatingnurses reported that the starting age for screening mammography is 40 years. It may bethat this result, as well as the low number of correct answers of the participants inthe present study regarding the correct starting age and periodicity of screening asrecommended by the MH, is related to the controversy over the recommendations of the MHversus those of the Brazilian Mastology Society (BMS), which recommends initiation ofscreening at age 40 years. This recommendation is based on Law No. 11.664, of April 29, 2008, whichensures the performance of mammography in all women from the age of 40 years on, by thepublic health care system in Brazil, Sistema Único de Saúde (SUS), contrary to the guidelines of the MH. Finally, a revision of the barriersto access to breast cancer screening programs and the role of nursing demonstrated thatthe educational intervention of nurses, together with patient awareness, results in ahigher patient adherence to mammographic screening.Considering that primary prevention, which aims to prevent exposure to risk factors,especially modifiable ones, such as diet and physical activity, has the potential toreduce the incidence of cancer by up to 28%, health promotion is one of the fundamentalstrategies to empower women to understand and intervene in determinants of their ownhealth. WithinBrazil,. This oed study also id40 years. This rde (SUS), contracreening.(20)noted that 97.55% of the women interviewed agreed about the importance of the roleof nurses as health educators, but only 35% of patients effectively received guidancefrom nurses regarding breast cancer prevention. In relation to educational actions for the prevention of breast cancer described in thepresent study, although the vast majority of participants recognized that educationalactivities should be an integral component of nursing care, only half of themeffectively performed these actions in their daily practice. These results are inaccordance with the observations of another study on the knowledge of breast cancer inusers of the public service, in the city of Bauru, São Paulo, Brazil. That work. A study about the characteristics of women diagnosed with breast cancerattended in reference health services in north Minas Gerais, Brazil, indicated that20.1% had a family history of breast cancer. Another study performed in an outpatient cancer-risk evaluation programlocated in a teaching hospital in the state of São Paulo showed that 35.3% of women withbreast cancer also had a positive family history of the disease. A study performed in Porto Alegre also found a relationship between breastcancer and family history. According to the study, a family history suggestive of hereditary breastcancer was identified in 6.2% of the cancer-unaffected women visiting basic health careunits in the periphery of the city of Porto Alegre. In assessing nurses' knowledge of hereditary breast cancer and indicators of increasedrisk of hereditary predisposition to cancer, most of the questions had a high percentageof correct answers. The questions with a lower performance were related to frequency ofhereditary breast cancer  and theoccurrence of breast cancer in men (a frequent myth being that it does notoccur),8. A t cancer. Anothe disease. A stud history. Accord. The nurse involved in the care of oncology patients can be the initialidentifying agent of a high-risk patient, facilitating the referral to aspecialist. Therefore, proper training of nurses in genetic risk identification and inthe importance of referrals to high-risk programs, are crucial to enable timelyreferrals and use of proper risk reducing interventions. Uncertainty and lack of knowledge of nurses about the role of geneticcounselling and the criteria and methods for referral of patients at risk, which wereall identified in this study, are an important barrier to the effective performance ofthese professionals.Timely identification of patients at risk for developing hereditary breast cancer allowsimplementation of multiple strategies aimed at prevention or early diagnosis, both in aproband and in his/her family members. The nuecialist. Therefventions. Uncert.Finally, an interesting and very positive finding of this study was the great interestnurses demonstrated in learning more about this area. A review of publications in thecurrent bibliographic data bases  in the fields of nursingand knowledge about breast cancer risk factors and screening strategies showed that theyare under-represented and that the main focus is on knowledge of the patients affectedby the disease. The same was evident in review articles that highlight the lack ofpublications in Latin America on this subject and the need for training of nurses inrelation to risk factors and implementation of screening actions in routine nursingcare,,25.Cancer prevention and control are among the most important scientific and public healthchallenges of the present. For strategies of prevention and early detection of breastcancer to result in real benefits, it is imperative to take a multidisciplinaryapproach, where nurses need to be aware of and knowledgeable about their educational andclinical role in the prevention and early detection of breast cancer, especiallyhereditary breast cancer. The assessment of knowledge and actions currently performed bynurses in this area is critical to defining the necessary training that theseprofessionals need.


Pregnancy produces a protective effect against breast cancer in women who had their first full term pregnancy (FTP) in their middle twenties. The later in life the first delivery occurs, the higher the risk of breast cancer development. Also, transiently during the postpartum period, the risk of developing breast cancer increases. This transient increased risk is taken over by a long-lasting protective period. The genomic profile of parous women has shown pregnancy induces a long-lasting “genomic signature” that explains the preventive effect on breast cancer. This signature reveals that chromatin remodeling is the driver of the differentiation process conferred by FTP. The chromatin remodeling process may be the ultimate step mediating the protection of the breast against developing breast cancer in post-menopausal years. Breast cancer affects women of all ages, races, and nationalities –3. The wEpidemiological, clinical, and experimental data have uncovered that one of the risks of developing breast cancer is the reproductive history –14. PregThe aggressive form of breast cancer called triple-negative breast cancer is more common in young women under the age of 40. It is not understood why young women are more likely to be diagnosed with this aggressive form of breast cancer .Despite the decrease of risk for breast cancer in lifetime, approximately 30% of breast cancer patients are diagnosed up to 5 years after giving birth . This wiThis review will address the mechanisms that determine the long-lasting preventive effect of pregnancy against breast cancer, and the transient increase of risk in the years that follow pregnancy.In experiments performed in rats, which is the gold standard animal model for induction of mammary gland differentiation, pregnancy (which takes 21 ± 3 days) has to be completed in order to prevent carcinogen-induced mammary cancer development. In Sprague-Dawley rats, it has been demonstrated that when their first pregnancy was interrupted 12 days after conception and cancer was induced by 7,12-Dimethylbenz(a)anthracene (DMBA) 21 days later, the number and weight of the tumors per animal in pregnancy-interrupted rats and age-matched virgin rats were similar. However, rats that completed their pregnancy had a significantly reduced amount of tumors . CompletEpidemiological studies have demonstrated that a female’s reproductive history is closely linked to breast cancer risk , 10, 13.The above mentioned findings show that the first FTP occurring during the high risk susceptibility window, but before exposure to a carcinogen, prevents mammary cancer initiation. This observation is equivalent to the widely reported protective effect of an early first FTP in women , 19, 33.In the past, we have addressed the morphological, physiological, and genomic changes that occur during and as a consequence of pregnancy. This hormonally induced differentiation of the breast stamps a mark on breast cancer risk , 33–36. The breast of both post-menopausal nulliparous and parous women contains mainly Lob1 after the regression of the mammary gland subsequent to lactation in the latter group. However, despite its close morphological resemblance, these Lob 1 structures have to be different biologically as parous and nulliparous women differ in their susceptibility to carcinogenesis . This coThe cells from the parous breast contain higher chromatin condensation (heterochromatin), while the breast parenchyma of post-menopausal nulliparous women contains predominantly euchromatin nucleus (EUN) cells  Figure , which d+CD24−/low breast cancer cells had the ability to form new tumors with as few as a couple hundred cells whereas tens of thousands of cells with alternate phenotypes failed to produce tumors  and trimethylation of histone 3 in lysine 27 (H3K27me3)    . Histone3K27me3) .N-methytransferase, which acts as a gene silencer by adding three methyl groups to lysine 27 of histone 3, a modification that leads to chromatin condensation  and Chromobox homolog 3 (CBX3) , 39. Theensation –69.Recent studies have demonstrated that some non-coding RNA molecules are at the center of nuclear assembly and recruit PcG complexes to the locus of transcription . Indeed,The spliceosome machinery, stored in the nuclear paraspeckles, plays a critical role in the differentiation process of mouse embryonic stem cells . Post-trCyclin L1 (CCNL1) and L2 (CCNL2) interact with splicing factors localized in the nuclear speckles . The epiThe chromatin modifications observed in the parous breast are accompanied by higher expression of genes related to cell adhesion and differentiation, such as laminins, desmocollin-3, cytokeratin 5, and GATA binding protein 3 (GATA3) , 36, 39.Finally, numerous downstream genes that are regulated by the estrogen receptor α (ER-α) were found to be up-regulated in the parous breast . Among tThe regulatory mechanisms highlighted in this section are key to the decrease in susceptibility of the epithelial cell to carcinogenesis. However, more studies need to be conducted to identify the specific pathways involved in this process. Data discussed here emphasizes the relevance of transcriptional and post-transcriptional regulatory mechanisms as critical to the differentiation of the breast. Increasing amount of data is revealing how the combination of genetic and epigenetic modifications is responsible for driving transformation, eventually leading to cancer. Therapeutic strategies that target a combination of genetic mutations together with chromatin modifications, splicing factors, and lncRNA regulation will lead to more effective treatments. In addition, agents which induce changes in the breast cells similar to those induced by pregnancy could potentially be used to protect healthy women considered at high risk of breast cancer (BRCA 1/2 mutation carriers). One example is hCG, which induces cell differentiation in the mammary gland in Sprague-Dawley rats .The differences in gene expression between parous and nulliparous women were also studied in premenopausal women . Gene exIt is not surprising that during the first 5 years after FTP, activation of several genes related to immune response is observed. Growth factors, hormonal signaling and cytokines/chemokines are known to participate in mammary gland differentiation and lactation . HoweverPregnancy exerts a protective effect in women who had an early FTP. However, approximately 30% of breast cancer patients are diagnosed up to 5 years after giving birth .The genomic profile of nulliparous and parous women in the premenopausal and post-menopausal period have shown that some groups of genes are only activated during the first years after FTP , while oThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


In conclusion, a longer duration of current HRT use was associated with a higher risk of breast cancer independent of the birth-cohort difference.Menopausal hormone replacement therapy (HRT) increases the risk of breast cancer in Western countries; however, there are fewer reports from the Asian population, which has a lower incidence of breast cancer. A population-based retrospective cohort study was conducted by analyzing longitudinal National Health Insurance claim data of a 200,000-person national representative cohort. A total of 22,929 women aged ≥45 years in 1997 without previous diagnosis of breast cancer were enrolled and stratified into two birth cohorts born before or after 1933. HRT prescriptions were traced in outpatient data files and incident breast cancer cases were identified from 1997 to 2004. The Cox proportional hazards model was used to analyze breast cancer hazard ratio (HR). HRT users were censored after they discontinued HRT. The results showed that women born during 1933–1952 had a twofold increased risk of breast cancer  compared with women born before 1933, when adjusted for HRT use. When adjusted for the birth-cohort difference, HRT users had significantly increased breast cancer HR  Both randomized controlled trials and observational studies conducted in Western countries have shown that menopausal hormone replacement therapy (HRT) increases the risk of breast cancer ,3,4,5,6,Single-payer National Health Insurance (NHI) implemented in Taiwan since 1995 has covered the health care of over 99.9% of the population. In this study, we analyzed a national representative cohort with eight years of longitudinal NHI claim data to investigate whether HRT increased the risk of breast cancer in the Asian population.The National Health Insurance Research Database (NHIRD) comprises NHI reimbursement claim data and registry records collected by the National Health Insurance Administration and processed by the National Health Research Institute for clinical and epidemiological research . All theversus non-users was analyzed using the Cox proportional hazards model, adjusted by birth cohort (birth after or before 1933). Kaplan–Meier estimates of cumulative breast cancer hazards of the middle-aged cohort were plotted after being stratified by HRT use. Breast cancer incidence was estimated by dividing the number of breast cancer cases by the total observed person-years. Data were analyzed using the PASW statistics 18 software . p values <0.05 (2-tailed) were considered statistically significant.The NHIRD has a 200,000-person national representative cohort sampled from 23,753,407 beneficiaries enrolled in NHI before 2001 by simple random sampling. All the longitudinal inpatient and outpatient claim data from 1997 to 2004 and cancer registry records in the NHI Catastrophic Disease Registry from 1995 to 2004 were retrieved. Women fulfilling the inclusion criteria of being female, alive, aged ≥45 years in 1997, and without a previous diagnosis of breast cancer, were enrolled. A total of 22,929 women fulfilled the inclusion criteria and were further stratified into two birth cohorts—those born from 1933 to 1952 (aged 45–64 years in 1997) and those born before 1933 (aged ≥65 years in 1997). Outpatient claim data from 1 January 1997 to 31 December 2004 were reviewed to identify the date, duration, and regimen of HRT prescriptions, including all estrogen and progestin types in oral or topical forms. The duration of HRT use was calculated only during 1997 to 2004, as there were no outpatient claim files before 1997 in the NHIRD. Women who were prescribed HRT continually for longer than 3 months during 1997 to 2004 were classified as HRT users; the others were classified as non-users. HRT users were followed from the date of commencing HRT until three months after discontinuation of HRT to cover time lag from diagnosis to registration to the National Health Insurance Administration. HRT users were censored after discontinuation of HRT because the risk of breast cancer dissipated after discontinuation of HRT use , where Pe is the proportion of HRT use in population, and RRe is the relative risk of breast cancer associated with HRT exposure.PAR = Pversus 153 cases per 100,000 person-years in non-users). The population-based risk of breast cancer attributable to HRT in the middle-aged cohort was 10.3% supposing that 78.6% of them did not use HRT, with the relative risk of breast cancer as 1, and there was a relative risk of 1.3 for the 15% that used HRT less than 5 years, and a relative risk of 1.9 for the 6.4% that used HRT longer than 5 years. In the elderly cohort, there were 0.7 additional cases of breast cancer for every 1000 person-years of HRT use. The population-based risk of breast cancer attributable to HRT use in the elderly cohort was 3.1%.In middle-aged women, there were 1.5 additional cases of breast cancer for every 1000 person-years of long-term HRT use  study ,2, our sThe use of HRT in Taiwan has declined since 2002 following the publication of the WHI results ,27; hencMore than four years of current HRT use can increase the risk of breast cancer in Asian women, independently of the birth-cohort difference. A longer duration of current HRT use is associated with a higher risk of breast cancer. Estrogen combined with progestin significantly increases the risk of breast cancer in middle-aged women, but not the use of estrogen alone.