Breast cancer is the leading female malignancy in Nigeria. Screening for early detection has led to reduction in mortality from the disease. It is known that attitudes of physicians and motivation by community nurses influence uptake of screening methods by women. This study aims to investigate knowledge of breast cancer risk factors, beliefs about treatment and practice of screening methods among a cohort of female healthcare professionals in Lagos, Nigeria.A cross-sectional study was conducted using a self-administered questionnaire to assess the knowledge of breast cancer risk factors, beliefs about treatment and practice of screening methods among 207 female doctors, nurses and other healthcare professionals working in a university teaching hospital in Lagos, Nigeria. Stratified random sampling method was employed. Chi square test, analysis of variance and Mantel-Haenszel test were performed in data analysis using SPSS v10.0 and Epi Info version 6 statistical packages.Female doctors obtained a mean knowledge score of 74% and were the only professional group that had satisfactory knowledge of risk factors. Majority (86%) believed that early breast cancer is curable while half of participants believed that prayer can make breast cancer disappear from the affected breast. Eighty three percent practice breast self-examination (BSE) once a month and only 8% have ever had a mammogram. Age, knowledge of risk factors, profession and beliefs were not significantly associated with rate of BSE in this study.Results from this study suggest the need for continuing medical education programmes aimed at improving knowledge of breast cancer among female healthcare providers other than doctors. Breast cancer is the most prevalent cancer worldwide with about 1 million new cases annually . Many coAwareness and knowledge about breast cancer vary among communities and population groups worldwide. While studies conducted to assess breast cancer knowledge among women showed satisfactory level in some places ,4, otherEarly detection and treatment of breast cancer is associated with better chance of long-term survival . In NigeBreast self-examination (BSE), clinical breast examination (CBE) and Mammography are recognized screening methods for breast cancer . HoweverIn Nigeria, previous studies on breast cancer knowledge assessment were conducted mainly among community dwelling women ,18. RepoThe study was designed as a cross sectional survey of female healthcare professionals. The aims were to assess level of their knowledge about breast cancer risk factors, beliefs concerning breast cancer treatment and their practice of BSE, CBE and Mammography as screening methods.The study was conducted in January, 2007 at Lagos State University Teaching hospital in Lagos, Nigeria. The institution had 652 female healthcare professionals consisting 550 nurses, 64 doctors and 38 allied healthcare providers. Participants were selected using stratified random sampling method with proportional allocation. Sample size was calculated to achieve 95% confidence and 5% type 1 error. A total number of 207 participants were selected among all eligible healthcare professionals in ratio 7:2:1 for nurses, doctors and others respectively. Questionnaires were distributed to participants through their sectional heads using the attendance list in a monthly hospital programme. Names of those who participated were randomly selected from the list until the sample size allocated to each professional group was achieved. All those selected returned their questionnaires within 24 hours to their respective heads of section and were retrieved the same day they were returned. Written informed consent was obtained and assurance of confidentiality of responses was given to each respondent. The hospital Research and Ethics committee approved the conduct of the study.A self administered questionnaire prepared by the author was employed. Questions were partly drawn using information on breast cancer from the literature. Additional questions were adapted, after modification, from questionnaires used in similar studies conducted earlier in the country. Pre-test was conducted on 15 female healthcare professionals working in the hospital following which some questions were modified to improve clarity. Those that participated in the pre-test were not part of the study. The questionnaire was in four parts. The first part was to elicit socio-demographic data on age, profession, marital status and qualification of each study participant. Questions relating to knowledge of breast cancer risk factors were asked in the second part. Eight items with different levels of relative risk for breast cancer were included and they were to generate "Yes" "No" or "Don't know" response. Participants awareness of breast cancer and early detection methods were also assessed in this section. The third part of the questionnaire assessed participant's beliefs about breast cancer treatment. In the last part, questions were asked on the practice of BSE, CBE and Mammography among participants. Most of the questions in the third and fourth parts were also designed to elicit similar response of "Yes" "No" or "Don't know".Each respondent was scored on knowledge of risk factors based on the number of correct answers (n = 8). Out of a total score of 100, percentage score for each participant and mean score for different professional groups were calculated. Knowledge score of all the groups were compared while that of the two dominant groups i.e. nurses and doctors were also compared separately. A score of > 80% was considered as indicating "excellent" knowledge, scores between 60% and 80% was labelled "very good" knowledge, scores between 40% and 60% represented "good" knowledge while a score of < 40% was classified as "poor" knowledge. Response of participants belonging to different professional groups to questions on beliefs and practice of screening methods were also compared.SPSS V10.0 Statistical package was used in data analysis. Frequency distributions were produced for the variables. Statistical comparison was carried out using chi-square test for qualitative variables and proportions and analysis of variance for quantitative variables. Epi Info version 6 was also employed in conducting Mantel-Haenszel test to adjust for possible confounding effect of age on the variables. Stratified analysis was performed on each professional group after which summary chi square and p value were computed. Level of statistical significance was set at P < 0.05.Table Tables Responses of participants to questions on beliefs about breast cancer treatment are shown in tables Tables Excluding doctors, knowledge of breast cancer risk factors among female healthcare professionals in this study is poor. Reports from similar studies among female healthcare providers support this finding ,16. An eLevel of knowledge of breast cancer risk factors is similar among nurses, pharmacists, physiotherapists and laboratory scientists in this study. Nurses play key role in breast cancer information dissemination and care because of their more frequent interaction with patients and their relatives. Furthermore, this role has been expanded in some advanced countries with the evolution of specialist breast care nurse . AlthougParticipants in this study have positive perception of breast cancer treatment. Majority held the belief that early stages of the disease are curable and that surgery is the most effective method of treatment. These findings support the report from an earlier study among nurses in Lagos, Nigeria where 89% would agreed to have mastectomy should they develop breast cancer . In a moBelief in the efficacy of traditional methods of therapy and prayer in the cure of breast cancer is widespread among females in developing countries and African-American women ,12,25. IPractice of BSE by participants in this study is commendable. Ninety-five percent carried out the procedure at least once every month. This is an improvement over 89% reported in an earlier study among nurses in Lagos . HoweverPractice of CBE by study participants is rather poor. Only 26% have had the procedure in the past 1 year. Low rates of CBE were reported in earlier studies among nurses and community-dwelling women in Nigeria ,19. AzaiRates of BSE and CBE by participants in this study were found not to be influenced by age, profession or knowledge of risk factors. Although, association between older age and more frequent practice of BSE was reported by Jacob et al , other sMajority of participants in this study were aware of mammography as a screening method for early breast cancer. However, only 8% among participants ever had mammogram. Reports from developing nations often indicate low rates of mammography screening practice ,26. OkobBreast self-examination, CBE and mammography are recognised methods of screening for breast cancer and adoption of mammography screening has led to reduction in mortality from the disease in women over 50 years . AlthougWomen with breast cancer in Nigeria are relatively younger than their Caucasian counterparts ,9. ThereSmall proportion of study participants delayed return of the questionnaires for several hours. This may raise concern about reliability of their responses. However, efforts were made to ensure that majority responded promptly and returned the questionnaires immediately. The sample size in this study is skewed in favour of nurses and doctors because of relatively smaller number of other female healthcare professionals in the Institution. This challenge is addressed by comparing the two dominant groups separately in data analysis.Knowledge of breast cancer risk factors is satisfactory among doctors but inadequate among a large percentage of nurses and other allied healthcare professionals in this study. Considering their leading role in breast cancer awareness and information dissemination, efforts should be made by Government and Non-Governmental agencies to improve breast cancer knowledge among healthcare providers other than doctors. Frequent continuing medical education programmes on breast cancer at institutional level is desirable. In addition, greater emphasis needs to be placed on breast cancer in the curricula of nursing and other healthcare training institutions so that graduates of such schools are better informed about the disease.Significant proportion of participants in this study believed in the role of prayer and alternative medical therapy in the cure of cancer. This is a reflection of high level of spirituality and belief in tradition among Nigerians. Programmes to educate religious leaders and alternative medical practitioners about breast cancer should be encouraged. The advantage of early presentation and treatment of patients suffering from breast cancer should be emphasized during such interactions.Although, practice of BSE among participants in this study is satisfactory, female doctors, nurses and other allied healthcare professionals should be encouraged to adopt regular CBE as well. This will positively influence their role in motivating other women in the society who look upon them for advice and guidance in adopting the practice of screening methods.The authors declare that they have no competing interests.NAI designed the study, acquired data, performed statistical analysis and drafted the manuscript. OOO revised and contributed to the final draft of the manuscript and statistical analysis of data. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/9/76/prepub


Using an automated method for detecting mammographic mass, the authors evaluated the relation between quantitatively measured density and the risk of breast cancer in a case–control study among Japanese women. The case subjects were 146 women newly diagnosed and histologically confirmed with breast cancer at a general hospital. A total of 659 control women were selected from those who attended a breast cancer mass screening at this hospital. Significantly increased odds ratios (ORs) of breast cancer were observed for breast densities of 25–49 and 50–74%, but not for densities of 75–100% as compared with 0% in premenopausal women after controlling for covariates . In postmenopausal women, ORs were significantly increased for breast densities of 25–50% (OR=3.0) and 50–100% (OR=4.2). Total breast area was significantly associated with the risk of breast cancer independent of density percent or dense area in postmenopausal women. These data suggested that mammographic density was associated with the risk of breast cancer in Japanese women as is the case in Caucasian women. However, the associations of the risk of breast cancer with breast size and a high breast density greater than 75%, needs to be confirmed in future studies. It has long been indicated that the appearance of breast parenchyma on mammograms is a marker of breast cancer risk . HistoriThe methods of measuring mammographic density are still being refined, especially with the development of digital mammography. Two of the present authors, Fujita and Matsubara, developed an automated method for detecting mammographic mass based on an adaptive thresholding technique  view were not obtained from 32 cases. Therefore, the remaining 146 women comprised the cases for the present analysis.This particular hospital has been conducting mass screening campaigns for breast cancer since the early 1980s. Women residing near the hospital were invited by the city to take part in the screening. From 2000 to 2002, the women attending the breast cancer screening at the hospital were recruited for a study of mammographic breast density. The main purpose of the study was to identify the determinants of mammographic breast density. A total of 1430 women participated in the study. The participation rate was estimated to be 70.3%. Details of the study have been described elsewhere  answered the questionnaire 3–12 months after the diagnosis. As their exclusion from the analysis did not essentially alter the results, we kept them in the present study.n=59 for left and n=87 for right. For the controls, the mammogram side used for the present analysis was selected at random according to the distribution among the cases because the percentage of high-density area was somewhat higher in the left than in the right breast. Informed consent was obtained from each woman. This study was approved by the institutional review board.Mammograms of the MLO view were taken using a Senographe DMR and read and recorded using a FCR AC-3CS and a CR-LP415. For the cases, the mammogram of the breast that would remain cancer-free was selected; The assessment of mammographic density consists of seven stages: (1) image digitalisation (0.05 mm sampling pitch and 12-bit density resolution); (2) the extraction of the breast border; (3) reduction of the image matrix; (4) the extraction of the pectoralis muscle region; (5) determination of the breast area; (6) determination of the threshold; and (7) extraction of the dense area. The details of this procedure have been described elsewhere . In postmenopausal women, the total breast area was significantly greater in the cases.The unadjusted means and 95% CIs of mammographic measures are shown in Significantly increased ORs of breast cancer were observed for breast densities of 25–49 and 50–74% in premenopausal women after controlling for age, body mass index (BMI), years of education, parity, age at menarche, lactation (yes or no), age at first birth, smoking status, alcohol intake, use of hormone replacement therapy, and family history of breast cancer among first-degree relatives . An incrP=0.004.) The ORs were 1.63, 3.22, and 3.43 for the second to the fourth quartile of total breast area, respectively (P for trend=0.005) after controlling for the percent density.Odds ratios were significantly increased for breast densities of 25–49 and 50–100% in postmenopausal women after controlling for the covariates including age at menopause and type of menopause. The linear trend for the risk increase with increasing percent of density was statistically significant. Dense area was significantly and positively associated with the risk of breast cancer. Increasing total breast area was also significantly associated with the risk of breast cancer. Total breast area and the percent of density were independently significantly associated with the risk of breast cancer after mutual adjustment; the ORs were 1.09, 3.37, and 4.21 for breast densities of 0, 1–25, 25–49, and ⩾50% respectively, after controlling for total breast area.  and unchanged in postmenopausal women  after controlling for the covariates. We also analysed data restricting cases to those who were detected by the screening or who had attended a mammographic screening before (n=55). The risk increase for every 1% increase of percent density was somewhat increased in premenopausal women  and unchanged in postmenopausal women . The association of total breast area with risk of breast cancer in postmenopausal women was unchanged; the OR for the highest vs the lowest quartile was 4.52.We reanalysed data after excluding 20 cases detected by the screening. The risk increase for every 1% increase of percent density was slightly decreased in premenopausal women  was observed for Asian women including Chinese, Filipinos, and Japanese, but a similarly low OR (=1.8) was also noted for Caucasian women in their study.Most of the previous studies in which quantitative methods were used to assess the breast density showed ORs of 4.0 or greater for the densest categories compared with the least dense categories . The resPotential sources of bias must be considered when evaluating the findings of the present study. The cases and the controls were not retrieved from the same population in the current study; therefore, selection bias may have affected the results. The controls were selected from participants in a mammographic screening. The use of cases who were detected by the same screening system was desirable, but such subjects were few. It is likely that the characteristics of the participants in the screening differ from those of the general population. If the participants in the screening were more likely to have a lower percent density than nonparticipants, the observed ORs would be overestimated. We tried to evaluate the effect of this selection bias. The use of information about the history of participation in mammographic screenings revealed that the amount of previous participation was unrelated to the breast density among the controls. We also reanalysed the data after excluding the cases detected by the screening or restricting cases to those who had previously attended mammograhic screenings. The results were not changed greatly in the reanalyses.We observed a significant positive association between total breast area and breast cancer risk among postmenopausal women. It is not likely that the control women attended the breast cancer screening because of their small breast size. Large breast size has been suggested to be associated with the risk of breast cancer but has never been confirmed . ObesityIn this conventional case–control study, the effects of masking  are diffWe used mammograms taken in the MLO direction because the screening system in Japan has adopted the MLO view. Most of the previous studies conducted in other countries have used the cranio caudal (CC) direction. A high correlation between the MLO and CC views for dense area was reported by We used analog films instead of digital films for 12 cases. Exclusion of these cases did not alter the results substantially; the risk increases were 0.5 and 2.1% for every 1% increase of percent density for pre- and postmenopausal women, respectively. As is the nature of retrospective design, the mammograms used in this present study were taken at the time of diagnosis. Although we used mammograms of the contra lateral breast, an underlying illness may have affected the density of the lateral breast.The present results show that the mammographic density measured by a quantitative assessment method was associated with the risk of breast cancer in Japanese women. The possibility of risk increase in those with a larger breast size or with a high percent of density, such as >75%, should be examined in future studies.


For a difference of 20 cm (about two standard deviations) in waist circumference, the multivariate RRs were 1.32 (95% CI: 0.73–2.37) among women and 1.74 (95% CI: 1.00–3.01) among men. Pancreatic cancer risk was associated with history of diabetes  and cigarette smoking . Current smokers of ⩾40 pack-years had a five-fold elevated risk compared with never smokers. Risk among past smokers approached the RR for never smokers within 5–10 years following smoking cessation. Findings from this prospective study support positive relationships of overall obesity, abdominal adiposity, diabetes and smoking with risk of pancreatic cancer.We examined the associations of body mass index (BMI), waist circumference, a history of diabetes, and cigarette smoking with risk of pancreatic cancer among 37 147 women and 45 906 men followed up during 560 666 person-years in the Swedish Mammography Cohort and the Cohort of Swedish Men; 136 incident cases of pancreatic cancer were diagnosed. The multivariate rate ratio (RR) of pancreatic cancer for obese women and men (BMI ⩾30 kg/m Cancer of the pancreas, the sixth leading cause of cancer death in the European Union , is a rain vitro, animal and human studies indicates that insulin, insulin resistance and abnormal glucose metabolism may play a role in pancreatic cancer etiology  and abdominal adiposity (waist circumference) and the risk of pancreatic cancer. In addition, we report findings for diabetes, cigarette smoking and smoking cessation on pancreatic cancer risk.Two population-based prospective cohort studies provided data for the present analyses: the Swedish Mammography Cohort (SMC) and the Cohort of Swedish Men (COSM). The SMC was established between 1987 and 1990, when all women born between 1914 and 1948 and living in central Sweden  received a mailed questionnaire that elicited information on diet, weight, height and education; 66 651 women (74% of the source population) returned a completed questionnaire. In the autumn of 1997, an expanded questionnaire that included data on various lifestyle factors and medical history was mailed to women who were still alive and residing in the study area; 39 227 women (70%) completed the questionnaire. In the autumn of 1997, 48 850 men born between 1918 and 1952 and residing in central Sweden (Västmanland and Örebro counties) were enrolled in the COSM by return of a mailed questionnaire that was identical to the 1997 SMC questionnaire (except for some sex-specific questions).Eligible participants for the present study were women and men who completed the 1997 questionnaire (information on cigarette smoking and diabetes was first obtained in 1997). After excluding participants with erroneous or missing national registration number and those with a cancer diagnosis (except nonmelanoma skin cancer) before baseline, a total of 37 147 women and 45 906 men were eligible for follow-up. The study was approved by the Regional Ethical Review Board in Stockholm.2) as a measure of overall obesity. High validity has been observed for self-reported height (r=0.9) and weight (r=0.9) compared with actual measurement among Swedish women and men (r=0.8)  code 157]. We excluded islet-cell carcinomas (ICD-9 code 157.4) because the etiology of these tumors may be different from that of the exocrine pancreas. Information on dates of death and dates of moving out of the study area was obtained from the Swedish Death and Population registries.Incident cases of pancreatic cancer were identified by computerised record linkage of the study population to the National Swedish Cancer Register and the Regional Cancer Register covering the study area, both of which have been estimated to be nearly 100% complete . Pancrea2) corresponding to <20.0, 20.0–24.9 (reference group), 25.0–29.9 and ⩾30.0. Participants with a BMI below 15 or above 60 kg/m2 were excluded in the BMI analyses. For waist circumference, we used quartiles based on the distribution among women and men separately.Person-years of follow-up for each participant were computed as the time from baseline to the date of diagnosis of pancreatic cancer, death from any cause, emigration, or until December 31, 2004. Participants were categorized into four groups with BMI (kg/m2), physical activity (four categories), history of diabetes (yes or no), cigarette smoking  and alcohol consumption (quartiles). Multivariate analyses of waist circumference were further controlled for height (quartiles). Trends tests for BMI and waist circumference were performed by scoring the categories and entering the score as a continuous term in the regression model. Statistical interaction between BMI and cigarette smoking in relation to pancreatic cancer risk was tested using the likelihood ratio test. We used the SAS statistical package  for all analyses. All statistical tests are two-sided.Cox proportional hazards models  were use2 among women and 25.8 (3.4) kg/m2 among men. In all, 34% percent of the women and 46% of the men were overweight (BMI 25–29.9 kg/m2); 11% percent of the women and 10% of the men were obese (BMI ⩾30 kg/m2). Compared with women and men with a BMI of 20–25 kg/m2, obese women and men were less likely to have a post-secondary education and to be current smokers, but were more likely to have diabetes; they also exercised less and had lower alcohol consumption. BMI was strongly correlated with waist circumference . The proportions of never, past and current smokers, respectively, at baseline were 54, 27 and 19% among women and 36, 46 and 18% among men.A total of 136 incident cases  of pancreatic cancer were diagnosed during 560 666 person-years of follow-up, yielding a crude incidence rate of 24.3 per 100 000 person-years. The incidence rate was similar among women (24.1 per 100 000 person-years) and men (24.4 per 100 000 person-years). The mean (±s.d.) age of the participants at baseline in 1997 was 62 (9.3) years for women and 60 (9.7) years for men. The mean (±s.d.) age of the participants at time of diagnosis of pancreatic cancer was 72 (8.5) years for female cases and 72 (8.0) years for male cases. 2 or higher had an 81% increased risk compared with those with a BMI of 20–25 kg/m2. When analysed as a continuous variable, an increment of 1 BMI unit (kg/m2) was related to a 5% increased risk of pancreatic cancer among women and men combined , a 4% increased risk among women , and a 6% increased risk among men . The findings for BMI did not change appreciably after excluding cases that occurred within the first year of follow-up. Waist circumference was also positively associated with risk of pancreatic cancer, and similar to the observed association for BMI; the risk was greater among men (We observed a positive association between BMI and risk of pancreatic cancer . After cmong men . For a dn=5).A history of diabetes was associated with a statistically significant 1.9-fold elevated risk of pancreatic cancer . This asP value for trend=0.0003).Women and men who were current smokers at baseline had a significantly higher risk of pancreatic cancer compared with never smokers . Past smWe also assessed the association between smoking cessation and risk of pancreatic cancer . CompareP for interaction=0.74). Compared with nonsmokers (never and past) with a BMI of less than 25 kg/m2, current smokers with a BMI of 30 kg/m2 or more, had a multivariate RR of 5.07 (CI: 1.93–13.30).2) compared with those with a normal weight (BMI 20–25 kg/m2). We also confirmed associations between history of diabetes and cigarette smoking and increased risk of pancreatic cancer. In addition, we found that smokers who had quit smoking for 5–10 years had a risk of developing pancreatic cancer similar to that of never smokers.In this prospective analysis, we observed approximately a doubling of the risk of pancreatic cancer for obese women and men  and risk of pancreatic cancer. We found that waist circumference was positively associated with pancreatic cancer risk, particularly among men. A previous cohort study found that women and men who reported ‘central’ weight gain had increased relative risk of pancreatic cancer compared with women and men who reported peripheral weight gain; the association was stronger among men (vs 22 kg/m2)  to a greater extent than those who are lean, and shorter individuals tend to overestimate their height (In summary, results from this population-based prospective study suggest that obesity may increase the risk for pancreatic cancer. Findings from this study also provide further support for associations of history of diabetes and cigarette smoking with pancreatic cancer risk.


The aim of this study was to describe breast tumor subtypes by common breast cancer risk factors and to determine correlates of subtypes using baseline data from two pooled prospective breast cancer studies within a large health maintenance organization.Tumor data on 2544 invasive breast cancer cases subtyped by estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (Her2) status were obtained . Demographic, reproductive and lifestyle information was collected either in person or by mailed questionnaires. Case-only odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression, adjusting for age at diagnosis, race/ethnicity, and study origin.P = 0.0001) and were less likely to consume alcohol , use hormone replacement therapy (HRT) , and oral contraceptives . Compared with luminal A cases, triple-negative cases tended to be younger at diagnosis (P ≤ 0.0001) and African American , were more likely to have not breastfed if they had parity greater than or equal to three , and were more likely to be overweight  or obese  if premenopausal. Her2-overexpressing cases were more likely to be younger at diagnosis (P = 0.03) and Hispanic  or Asian , and less likely to use HRT .Compared with luminal A cases, luminal B cases were more likely to be younger at diagnosis (These observations suggest that investigators should consider tumor heterogeneity in associations with traditional breast cancer risk factors. Important modifiable lifestyle factors that may be related to the development of a specific tumor subtype, but not all subtypes, include obesity, breastfeeding, and alcohol consumption. Future work that will further categorize triple-negative cases into basal and non-basal tumors may help to elucidate these associations further. Among women in the USA, breast cancer remains the most commonly diagnosed cancer, excluding skin cancers, and the second leading cause of cancer-related death . Breast Luminal tumors have been associated with the most favorable prognoses, while Her2-overexpressing and basal-like tumors, or their surrogate triple negative tumors, have been associated with the worst prognoses ,6,10-18.Although many studies have examined associations between common breast cancer risk factors, race -36 and hThe Life After Cancer Epidemiology (LACE) Study consists of 2280 women diagnosed with invasive breast cancer between 1997 and 2000 and recruited primarily from the Kaiser Permanente Northern California (KPNC) Cancer Registry (82%) and the Utah Cancer Registry (12%). Further details on the LACE cohort have been previously reported . BrieflyThe Pathways Study is a prospective cohort study actively recruiting women diagnosed with invasive breast cancer from the KPNC patient population since January 2006. Women are recruited as soon after diagnosis as possible , as described elsewhere . Briefly2). Any missing values were supplemented by concurrent information from KPNC electronic medical records.In the mailed baseline questionnaire of the LACE Study and during the in-person baseline interview of the Pathways Study, participants were asked detailed information on family history of cancer and reproductive history, including age at first full-term pregnancy, number of biological children, breastfeeding, and menopausal status. Additional information was collected on smoking, alcohol use, hormone use , hormone replacement therapy (HRT)), and demographics . Self-reported height and weight one year before diagnosis (LACE) and around diagnosis (Pathways) was obtained to calculate body mass index  at the KPNC regional cytogenetics laboratory. If the FISH score (Her2: 17 cen) is less than 2.0 [Data on ER and PR status and Her2 expression were obtained from medical record review and the KPNC Cancer Registry  for LACEthan 2.0 , then th2).Demographic, reproductive, and lifestyle covariates of interest were classified as follows: age at diagnosis , race/ethnicity , menopausal status , family history of breast cancer , parity , age at first full-term pregnancy , lifetime duration of lactation , alcohol use , smoking duration , hormone replacement therapy (HRT) among post-menopausal women , OC use , and BMI  and 95% confidence intervals (CIs) were estimated using logistic regression. The luminal A group was selected as the referent because the majority of invasive breast cancer cases are of this subtype. All models were adjusted for age at diagnosis, race/ethnicity, and Pathways/LACE study origin except when these covariates were the predictors of interest. We also examined whether the associations between parity and tumor subtype varied by breastfeeding and whether BMI and tumor subtype varied by menopausal status by first generating strata-specific estimates and then including an interaction term in the model to test for statistical significance. CIs not overlapping with 1.00 or Demographic, reproductive, and lifestyle factors varied significantly by race/ethnicity in the combined studies Table . DemograP < 0.05). The majority of the whites (75.3%), Asians (71.4%), Hispanics (68.5%), other (68.5%), and African Americans (59.4%) had the luminal A tumor subtype. The Her2-overexpressing subtype was least common among all races/ethnicities . African Americans had the highest prevalence of the triple negative subtype (28.4%) compared with the other races/ethnicities .The distribution of breast cancer subtypes by race/ethnicity in the combined studies is presented in Table P = 0.0001) and were less likely to consume alcohol , use HRT , and OC . Compared with luminal A cases, triple negative cases tended to be younger at diagnosis  and African American . Breastfeeding for at least four months was associated with being less likely to have a triple negative tumor, yet this association was of borderline significance . Compared with luminal A cases, Her2-overexpressing cases were more likely to be younger at diagnosis (P = 0.03), similar to luminal B and triple negative cases, and less likely to use HRT , similar to luminal B cases. Furthermore, Her2-overexpressing cases were more likely to be Hispanic  and Asian . The associations between the risk factors and tumor subtypes for the individual studies are presented in Additional data files The associations between various demographic, reproductive, and lifestyle factors within each subtype  compared with luminal A are shown in Tables P values for interaction of parity by breastfeeding were not statistically significant. As for the effect of BMI by menopausal status, premenopausal triple-negative and Her2-overexpressing cases were more likely to be overweight  or obese  at diagnosis, yet the effect measures for Her2-overexpressing tumors were not statistically significant. Among luminal A cases, these associations were not observed. All P values for interaction of BMI by menopausal status were not statistically significant.For the subgroup analyses, among non-breastfeeding cases, parity of at least three children was associated with a statistically significant increased likelihood of having a triple-negative tumor  and a Her2-overexpressing tumor  compared with luminal A. In contrast, no differential associations of breastfeeding and parity were observed among luminal B cases. All In a pooled analysis of 2544 breast cancer cases using data from two prospective cohort studies housed within a large health maintenance organization, associations between breast cancer subtypes and various demographic, reproductive, and lifestyle factors were examined. In case-case analyses with the luminal A cases as the reference group, luminal B cases were more likely to be younger at diagnosis and were less likely to consume alcohol, use HRT, and OCs. Triple-negative cases tended to be younger at diagnosis and African American, and were more likely to be overweight and/or obese at diagnosis if premenopausal. Women with triple-negative tumors were also less likely to breastfeed for longer periods, and were more likely to not breastfeed if they had at least three children. Her2-overexpressing cases were more likely to be younger at diagnosis and Hispanic or Asian, and less likely to use HRT. We also found that these cases were more likely to be women with at least three children and no history of breastfeeding. These case-case observations suggest that heterogeneity in associations with traditional breast cancer risk factors exists by tumor subtype.in situ and invasive cases) [Several studies have assessed risk factor profiles of tumor subtypes, including the Carolina Breast Cancer Study  , the Pole cases) , and a pe cases)  [see Adde cases) . SimilarAs for luminal B and Her2-overexpressing cases, our results are in agreement with those of the CBCS that luminal B and Her2-overexpressing cases tended to be younger than luminal A cases. In contrast to the CBCS results, we observed that these cases were less likely to use HRT although luminal B cases were less likely to consume alcohol. No associations with these factors were observed in the PBCS, and the WS study did not examine luminal tumors separately by luminal A and luminal B subtype. We found that Her2-overexpressing cases were more likely to be Hispanic or Asian, but not African American, an observation which was not seen in any of the other studies. In fact, the CBCS, comprised of only whites and African Americans, reported that Her2-overexpressing cases were slightly more likely to be African American. Finally, we observed that Her2-overexpressing cases were more likely to be women who had at least three children and had not breastfed, an association not seen in the CBCS.Although our results tend to be in agreement with those of other studies, limitations of our study should be discussed. Only case-case comparisons were conducted, and it must be emphasized that the associations reported here are all in reference to risk of having a luminal A tumor subtype and should not be extended to risk of having invasive breast cancer. Case-case analyses among tumor subtypes are a useful exploratory tool to examine etiologic heterogeneity between the subtypes . As prevIn summary, using a case-case analysis to assess the associations between traditional breast cancer risk factors and breast cancer subtypes , we observed significant heterogeneity of associations by tumor subtype. These varying associations by subtype lend further support to the growing evidence base that breast cancer is a heterogeneous disease defined by ER, PR, and Her2 expression with distinct etiologic pathways and prognoses. Future research should focus on refinement of tumor subtypes into more homogenous subgroups in order to best elucidate how risk factors may vary by subtype. Important modifiable factors that may be related to the development of specific tumor subtypes include obesity and possibly breastfeeding (triple negative) and alcohol consumption , yet no clear modifiable risk factor profile was apparent for Her2-overexpressing subtypes due to a limited sample size. Given this information, public health programs aimed towards achieving a healthy weight and promoting breastfeeding might reduce the number of poor prognostic triple negative tumors among all breast cancer cases, especially the high-risk African American group.in situ hybridization; Her2: human epidermal growth factor receptor 2; HRT: hormone replacement therapy; IHC: immunohistochemical; IRB: institutional review board; KPNC: Kaiser Permanente Northern California; LACE: Life After Cancer Epidemiology; OC: oral contraceptive; OR: odds ratio; PBCS: Polish Breast Cancer Study; PR: progesterone receptor; WS: Washington State.BMI: body mass index; CBCS: Carolina Breast Cancer Study; CI: confidence interval; CK: cytokeratin; EGFR: epidermal growth factor receptor; ER: estrogen receptor; FISH: fluorescence The authors declare that they have no competing interests.MLK contributed to study conception and design, and acquisition, analysis, and interpretation of data; and drafted and revised the manuscript critically for important intellectual content. LHK and BJC contributed to study conception and design, and acquisition, analysis, and interpretation of data; and revised the manuscript critically for important intellectual content. EW contributed to analysis and interpretation of data; and revised the manuscript critically for important intellectual content. BM contributed to study conception and design; and revised the manuscript critically for important intellectual content. SEK contributed to analysis and interpretation of data; and revised the manuscript critically for important intellectual content. RSF contributed to acquisition of data; and revised the manuscript critically for important intellectual content. MML contributed to analysis and interpretation of data; and revised the manuscript critically for important intellectual content. CBA contributed to analysis and interpretation of data; and revised the manuscript critically for important intellectual content. All authors read and approved the final manuscript.A word file containing a table that lists previous studies that have examined associations between common breast cancer risk factors and breast cancer tumor subtypes.Click here for fileA word file containing a table that lists the distribution of demographic, reproductive, and lifestyle risk factors in the LACE and Pathways studies individually and combined (n = 2544).Click here for fileA word file containing a table that lists case-only odds ratios and 95% confidence intervals from logistic regression models of associations between breast cancer tumor subtypes and demographic, reproductive, and lifestyle risk factors, LACE study (n = 1821).Click here for fileA word file containing a table that shows case-only odds ratios and 95% confidence intervals from logistic regression models of associations between breast cancer tumor subtypes and demographic, reproductive, and lifestyle risk factors, Pathways study (n = 723).Click here for file


Exposure of the breast to ionising radiation increases the risk of breast cancer, especially among young women. However, some issues remain controversial, for instance the shape of the dose-response curve and the expression of time-related excess. The main purpose of this report was to examine the dose-response curves for radiation-induced breast cancer formulated according to radiobiological target theories. Another purpose was to analyse the time-related excess of breast cancer risk after exposure when dose and age at first exposure were held constant. Breast cancer incidence was analysed in a cohort of 3090 women diagnosed with benign breast disease during 1925-61 (median age 37 years). Of these, 1216 were treated with radiation therapy. The dose range was 0-50 Gy (mean 5.8 Gy). The incidence rate as function of dose was analysed using a linear-quadratic Poisson regression model. Cell-killing effects and other modifying effects were incorporated through additional log-linear terms. Additive and multiplicative models were compared in estimating the time-related excess. The analysis, which was based on 278 breast cancer cases, showed a linear dose-response relationship at low to medium dose levels with a cell-killing effect of 5% Gy-1 . For a given absorbed dose and age at first exposure the time-related excess was proportional to the background rates with a suggestion that the excess remains throughout life.


Hormonal factors are implicated in tumor progression and it is possible that factors influencing breast cancer induction could affect prognosis. Our study investigated the effects of menstrual risk factors on tumor characteristics and survival in postmenopausal breast cancer.We used a nationwide, population-based, case-case design of 2,640 Swedish women who were 50 to 74 years old and had postmenopausal breast cancer during 1993 to 1995. Follow-up was conducted until 31 December 2000. We used polytomous multiple logistic regression to investigate the relationships between menstrual factors , tumor characteristics , and Cox proportional hazards modeling for 5-year survival.Younger ages at menarche were significantly associated with grade and lymph node involvement. Women with an age at menarche of 11 years or younger had a more than twofold excess risk of medium-grade  and high-grade  tumors. Early menarche significantly increased the risk of lymph node metastases. Survival was poorest in women with the earliest age at menarche, with a 72% increased risk of dying within 5 years after diagnosis . No significant associations were observed for other menstrual factors with tumor characteristics or survival.Age at menarche has a significant impact on breast cancer prognosis and survival. It remains to be established whether the associations are attributable to age at menarche directly or are associated with the early-life physiological events of breast development and carcinogenesis also taking place during childhood and puberty, as menarche is only the culmination of this series of events. Haenszel  hypothesSeveral studies have generated support for Haenszel's hypothesis, with the confirmed association between obesity and poorer breast cancer prognosis -9. To daThe question of whether menstrual risk factors influence breast cancer prognosis is timely due to the decreasing age at menarche , with chThis study is an extension of a population-based case-control study among all women who were born in Sweden and who were 50 to 74 years of age between 1 October 1993 and 31 March 1995 and is described in detail elsewhere ,24. We uWomen with incident primary invasive breast cancer were identified through the six Swedish Regional Cancer Registries and contacted by their doctors. Out of 3,979 women with a primary diagnosis of invasive breast cancer, 3,345 women (84%) participated in the study. The primary reason for nonparticipation was patient's or doctor's refusal due to patient ill health. Excluded patients had previous or other tumors (151 cases), noninvasive breast cancer according to patient records from the regional cancer registry (58 cases), a diagnosis outside the study period (19 cases), lack of patient consent (58 cases), premenopausal status (198 cases), being younger than 55 years with an unknown age at menopause (202 cases), missing age at first birth (5 cases), and missing height or recent weight (14 cases). The study included 2,640 eligible postmenopausal breast cancer patients of European descent.The ethical review board at the Karolinska Institute  and the six ethical review boards in other regions of Sweden approved the study. Prior to participation via a mailed questionnaire, written consent was obtained from all patients. The mean interval between diagnosis and data collection was 4.3 months (standard deviation of 1.5 months).With the exception of clinical data on tumor characteristics and follow-up data for survival outcomes, exposure and covariate data used in this study were derived from the case-control study questionnaire. In brief, data on sociodemographic, anthropometric, reproductive, and menstrual factors, use of oral contraceptives, and medical history (1 year prior to data collection) were collected by means of a postal questionnaire. Detailed information pertaining to the use of menopausal hormone therapy (MHT), including timing and type of hormones for each treatment episode, was requested along with a color chart that displayed all preparations ever marketed in Sweden and that was included with the questionnaire to facilitate recall. Additionally, approximately 50% of cases were contacted by telephone to complete missing or ambiguous responses, mainly on the use of MHT.Menstrual factors assessed were age at menarche, age at menopause, irregular menstruation, cycle length, and lifetime number of menstrual cycles. Age at menarche was classified as not older than 11 years, older than 11 but not older than 13 years, older than 13 but not older than 14 years, and older than 14 years. Menopause was defined as the age at last menstrual period or age at bilateral oophorectomy if at least 1 year prior to data collection. To ensure an accurate classification of the true age at menopause, analyses for age at menopause were firstly restricted to women with known natural or surgical age at menopause who had not used MHT prior to menopause. Due to the large percentage of women with a missing true age at menopause (39%), we decided to use all women with an age at menopause and adjust our analyses for use and type of MHT. Age at menopause was grouped as younger than 50 years, 50 to 55 years, and older than 55 years. Irregular menstruation was either absent or present during the lifetime. Cycle length was classified as not more than 27.5 days per cycle, 28 days per cycle, or more than 28 days per cycle. Lifetime number of menstrual cycles was a created variable derived from all women with known values for age at menarche, age at menopause, parity, and cycle length and did not include those women with irregular menstruation or miscarriages and/or abortions. Lifetime number of menstrual cycles was classified as not more than 423 cycles per lifetime, more than 423 but not more than 500 cycles, and more than 500 cycles.Information regarding tumor characteristics was retrieved from the medical records of all participants from surgical and oncological units throughout Sweden. Data pertaining to tumor characteristics included tumor size, grade , estrogen receptor (ER) and progesterone receptor (PR) status, and lymph node involvement. Information on grade was not in routine use in Sweden during the study period and is therefore missing in 33% of patients.The Swedish National Registration Number, a unique 10-digit number for each Swedish resident, was used to link the cohort with the Swedish National Population Register and the Swedish Cause of Death Register to obtain data on emigrations and on the dates and causes of death, respectively. The latter register covers all residents in Sweden and has been shown to accurately classify 98% of all breast cancer deaths .P less than 0.05 were considered significant. ORs with 95% confidence intervals (CIs) were calculated using polytomous multiple logistic regression [The significance of differences between tumor characteristics and menstrual factors was evaluated using frequencies with chi-square tests of association. All probability values of gression , with tuFollow-up time began on the date of breast cancer diagnosis and ended on the date of death, date of emigration, or date of study truncation or 5 years after the date of diagnosis, whichever occurred earlier. The outcome was breast cancer-specific deaths . One woman emigrated, 264 died from breast cancer, and 383 died from other causes during 12,290 person-years of follow-up.Breast cancer mortality rates were calculated by menstrual factors as the number of breast cancer deaths per 100 person-years. Cumulative 5-year survival rates were calculated using the Kaplan-Meier method, and the significance of differences in survival was evaluated using the log-rank test. The Cox proportional hazards regression model was used to quantify the effects of menstrual factors on 5-year survival. The covariates chosen for multivariate analysis adjustments were based on biological associations deemed important in assessing menstrual factors and survival.® version 9.2  was used for data analyses.The menstrual prognostic factors in our study all occurred prior to the diagnosis of breast cancer. Therefore, any effects on tumor progression would have been mediated through the biological characteristics of the tumor itself. Hence, adjusting for any tumor characteristic variables in the Cox regression model would be incorrect as they did not confound the association between menstrual factors and breast cancer survival but rather acted as intermediates in the causal pathway. STATAAll menstrual factors were analyzed in relation to tumor characteristics and 5-year survival. Cycle length, total lifetime number of menstrual cycles, irregular menstruation, and age at menopause showed no significant trends, with most estimates close to unity. Therefore, only the results of survival analyses will be presented for these menstrual factors.Background reproductive and menstrual factors of all cases in relation to age at menarche are summarized in Table The associations of age at menarche and tumor characteristics of breast cancer patients are summarized in Table P value for log-rank test = 0.0466). As determined using a Cox model  at 18 years of age as BMI could be a confounder in the association of age at menarche and tumor characteristics and survival. Strictly speaking, BMI at 18 years is chronologically after menarche. However, in our study, we used this BMI as a proxy for childhood obesity. Thus, our results assume that no drastic changes in BMI occurred between childhood and 18 years of age. The timing of menarche is known to be affected by BMI as ovulation and menstruation require a threshold weight . An incrOur study was population-based with a high response rate among cases (84%). Detailed information was available on menstrual risk factors in addition to other breast cancer risk factors. Sound information on tumor characteristics was collected, with only 2% and 3% of participants missing data on tumor size and lymph node involvement, respectively.However, one limitation of our study was that nonparticipants had somewhat larger tumors on average and therefore these tumors were more likely to be receptor-negative with a higher proportion of lymph node involvement. We lacked information on tumor grade in 33% of cases. However, as all menstrual exposures assessed occurred well before the diagnosis of breast cancer, this would have had a negligible effect on our estimates. Similarly, receptor status was missing for 30% of cases, with estimates similar to those risks for developing ER-negative and PR-negative tumors. Receptor status was assessed at seven different laboratories, and several pathologists classified tumor size, lymph node involvement, and grade of differentiation. However, misclassification due to the nonstandardized analyses, together with the distribution of missing information, was certainly unlikely to be related to menstrual risk factors and is therefore nondifferential. For our analyses into lifetime number of menstrual cycles, we were not able to assess the effects of exclusivity of breastfeeding on breast cancer prognosis. In our study, we cannot exclude the possibility that our results are due to chance. However, we feel that this is unlikely since our findings were significant only for one menstrual factor (age at menarche) as we clearly showed significant findings, using two different methodologies and outcomes , of poorer tumors and survival, and this is consistent with the interpretation of a poorer prognosis. All other menstrual factors addressed showed no significant finding for tumor characteristics or survival, with most estimated being around unity. Finally, we did not have childhood, pubertal, and adolescent somatic and anthropometric data to be able to disentangle whether the worse tumor characteristics observed in our study were due to these somatic and anthropometric factors themselves, or whether age at menarche, serves only as a proxy for these somatic and anthropometric factors: of which, these may be even more critical to breast cancer etiology.We found age at menarche to be significantly associated with grade and lymph node involvement and we found survival to be poorest in women with the earliest age at menarche. The finding of our study is timely due to the decreasing age at menarche in most developed countries and emphasizes the importance of potential early-life influences on breast tumor characteristics and survival.BMI: body mass index; CI: confidence interval; ER: estrogen receptor; HR: hazard ratio; ICD: International Classification of Diseases; MHT: menopausal hormone therapy; OR: odds ratio; PR: progesterone receptor.The authors declare that they have no competing interests.CCO conducted all data management and statistical analyses, interpreted the data, and wrote the manuscript. PH revised the manuscript critically for important intellectual content and interpreted the data. LUR contributed to the acquisition of data and revised the manuscript critically for important intellectual content. KC conceptualized and designed the study, interpreted the data, and revised the manuscript critically for important intellectual content. All authors read and approved the final manuscript.


Previous research demonstrated increased risk of breast cancer associated with higher socioeconomic status (SES) measured at both the individual and community levels. However, little attention has been paid to simultaneously examining both measures.We evaluated the independent influences of individual and community SES on the risk of breast cancer using case–control data. Because our previous work suggests that associations may be stronger after including a latency period, we also assessed the effect of community-level SES assuming a 10-year latency period.We obtained individual education for cases and matched controls diagnosed between 1987 and 1993 on Cape Cod, Massachusetts (USA). We acquired community-level SES from census data for 1980 and 1990. Using SES data at diagnosis and 10 years earlier, we constructed models for breast cancer risk using individual-level SES only, community-level SES only, and a multilevel analysis including both. We adjusted models for other individual-level risk factors.Women with the highest education were at greater risk of developing breast cancer in both 1980 and 1990 . Similarly, women living in the highest-SES communities in 1990 had greater risk (OR = 1.30). Results were stronger in the analyses considering a latency period (OR = 1.69). Adjusting for intragroup correlation had little effect on the analyses.Models including individual- or community-level measures of SES produced associations similar to those observed in previous research. Results for models including both measures are consistent with a contextual effect of SES on risk of breast cancer independent of individual SES. Over the course of her lifetime, approximately one woman out of every eight will develop invasive breast cancer. Breast cancer remains the most commonly diagnosed non-skin cancer and is the second leading cause of cancer death in women . BecauseOverall, community-level SES is also associated with breast cancer incidence. Similar to the results of studies that examine individual SES, higher educational attainment and income as measured at the community level are also associated with higher incidence of breast cancer .Although previous research has provided much information about these separate associations, few prior studies examined individual and community SES simultaneously. As a result, it is unclear whether the greater breast cancer incidence in high-SES communities is attributable to a greater number of high-SES women living in an area—that is, the composition of the areas—or to some aspect of high-SES communities that confers a greater risk of being diagnosed to all residents, regardless of their SES, that is, a contextual effect. For example, communities with higher SES may have greater access to screening mammography and diagnose more cases of breast cancer, even if the true incidence rates are otherwise similar.Community-level variables commonly used in ecologic analyses, such as census data, are the aggregate of individual-level observations. It remains unclear whether health risks observed in ecologic studies are compositional, attributable to the risk in the individual components, or contextual, related to some characteristic of place. Ecologic studies are limited by their inability to control for individual-level confounders. Because individuals group themselves by social constructs, the distribution of confounders is not random and may result in biased group-level effect estimates . ExaminiTo the best of our knowledge, only one prior study has attempted to distinguish the impact of individual and community SES measures on breast cancer incidence . The resWe previously studied the spatial epidemiology of breast cancer on Cape Cod, Massachusetts (USA), using case–control data and 40-year residential histories, and analyzed individual-level risk factors for the development of breast cancer e.g., . We founa) random digit dialing for living controls < 65 years of age, b) Centers for Medicare and Medicaid Services  for the living population 65 or more years of age, and c) death certificates for controls who had died from 1983 onward. We assigned an index year to all controls based on the diagnosis year of the matched cases. Interviews collected information on numerous established and hypothesized individual-level risk factors, including age, race, height, weight, physical activity, alcohol use, educational attainment, personal and family history of breast cancer , menstrual and reproductive history, history of mammography, oral contraceptive use, pharmaceutical hormone use, and exposure to ionizing radiation. We also collected a 40-year residential history up to the time of diagnosis or index year.We investigated the association between breast cancer and individual- and community-level measures of SES using data from a population-based case–control study of Cape Cod, Massachusetts (USA) . The InsBecause we did not include income data in the original questionnaire, we chose education as the individual-level measure of SES. Although education may be an imperfect measure of SES, it is thought to be a relatively stable indicator because it is generally set early in adulthood. Using a stable measure of individual SES may be advantageous in this population because about half of the study participants were older than retirement age, a point where more variable measures such as income may change rapidly. A single measure of income is less likely than a single measure of education attainment to capture lifetime average financial resources . Becausen = 141) and at the larger census-tract level (n = 34) (n = 167) for 1980 because Cape Cod had not yet been tracted. Enumeration districts were similar in size to the 1990 census block groups but did not encompass identical areas.We linked the addresses of study participants to census data from 1980 and 1990. The 1990 data measured community-level SES for the residence at approximately the time of diagnosis or index year; 1980 data measured community-level SES for the residence 10 years previously. We obtained the 1990 data from the U.S. Census Bureau at the census-block-group level ((n = 34) . We purcWe considered two community-level measures of SES for each year: percentage of population with incomes below the U.S. poverty line , 2003, aWe divided each category into quintiles based on the distribution of the control women in a particular analysis and assigned a score from 1 to 5. We reverse-coded the percentage of adults in poverty and the percentage of unemployment so that larger values represented areas with higher SES. We then summed the four category scores and divided the composite values again into quintiles. In the composite index, possible SES scores range from 1, representing a low SES, to 5, representing high SES relative to other areas.Previous research suggests that the association between community-level SES and breast cancer may be confounded by urbanicity . We calca) individual-level SES only, b) community-level SES only, and c) both individual- and community-level SES. We adjusted all models for age, race, body mass index (BMI), alcohol use, personal and family history of breast cancer , menstrual history, reproductive history , history of mammography (ever/never), oral contraceptive use, pharmaceutical hormone use, and exposure to ionizing radiation. For multilevel  models, we used generalized estimating equations (GEEs) with a logit link function while assuming a compound symmetric correlation structure. The latter allowed us to take into account residual within-group correlation. For nonhierarchical models, we used logistic regression. We report ORs with 95% CIs. Use of generalized linear mixed models gave very similar results. We used GEEs for several reasons, including an interest in population-averaged effects rather than cluster-specific effects.Using census data on SES from the time of diagnosis and 10 years earlier, we constructed several models for the risk of breast cancer: Using the other measure of community-level SES, percentage of the adult population with incomes below the U.S. poverty line, the OR estimates at the block-group level were similar to the results using the SES composite index. Compared with women living in communities with the highest percentages of adults with incomes below the poverty line, women in middle- and low-poverty communities had an increased risk of developing breast cancer, OR = 1.16  and OR = 1.30 , respectively. These estimates were not substantially altered by the inclusion of the individual-level SES measures. The results at the census-tract level were similar, with both low and medium poverty having increased odds of developing breast cancer, OR = 1.28  and OR = 1.07 , respectively.The 1980 analysis using percentage of adults with incomes below the poverty line as the measure of community-level SES produced effect estimates near the null. The percentage of adults with incomes below the poverty line was more variable in 1980 than in 1990, producing quite different cut points for the 20th and 80th percentiles. To determine whether these differences may have contributed to the change in effect size between 1990 and 1980, we conducted a second analysis applying the 1990 cut points to the 1980 data. Again, the results were near the null (data not shown).Because of missing covariate data, we did not use approximately 18% and 15% of the observations in the 1980 and 1990 analyses, respectively. Family history, hormone use, and oral contraceptive use had the largest percentage of missing values, between 5% and 8% each. To determine whether our results were sensitive to missing data, we performed multiple imputation using IVEware . The resThe individual-level results suggest that higher educational attainment is associated with increased breast cancer risk. Although imprecise (with wide CIs encompassing 1), they are consistent with the magnitude of risk observed in other individual-level analyses using education as a measure of SES . The indCommunity-level effects were also similar to those observed in other research . The magThe effect of community-level SES near diagnosis (1990) was similar using both the composite SES measure and the percentage of adults living in poverty. Measured 10 years earlier (1980), the effect of the poverty variable was much smaller than the composite SES index. The difference may be attributable to the inclusion of three additional community-level variables in the composite measure: family income, unemployment, and education. Alternatively, the meaning of poverty may have changed on Cape Cod between 1980 and 1990. The poverty line is set nationally and does not account for regional differences in the cost of living. The 1980 poverty variable may not have captured important differences between the lowest-and highest-SES groups on Cape Cod.Neither individual- nor community-level effects of SES changed substantially when adjusting for the other. This implies that the SES measures on the two levels are not highly correlated. We constructed the community-level SES measures from census data for all adults , whereas the individual-level measure examines highest education achieved in a predominantly older female group. Our results are consistent with a contextual effect of SES on the risk of breast cancer independent of individual-level SES. They suggest there is something about living in high-SES communities that results in an increased risk of breast cancer independent of individual-level SES. Alternatively, the community-level SES may be capturing an unmeasured aspect of individual-level SES. Individual educational attainment alone may not sufficiently characterize the association between SES and breast cancer; the community-level variables may operate as proxies for residual individual-level information. Our results may be of interest to both social epidemiologists investigating contextual effects and environmental epidemiologists searching for better ways to adjust for SES.The effect of the composite index of community-level SES was somewhat stronger when measured 10 years before diagnosis, suggesting the importance of latency for the contextual effect. This phenomenon had not been previously studied for breast cancer and only rarely examined for other health outcomes. The investigation and meaning of latency in multilevel models deserve more attention; studies that do not consider latency may underestimate contextual effects.Although our results suggest an increased risk of breast cancer in higher-SES communities independent of individual SES, the mechanism of action remains unclear. It has been hypothesized that access to mammography is a possible explanation for the greater risk observed in high-SES communities . AdjustiOur study has several limitations. Although we have 40-year residential histories and have shown elsewhere that spatial variation in breast cancer risk on Cape Cod increased assuming 20 years of latency , we wereWomen living in higher-SES communities had an increased risk of developing breast cancer independent of their own SES. This suggests that a characteristic of high-SES communities may increase the risk of breast cancer apart from individual-level risk factors. Alternatively, the community-level measure may be capturing an unmeasured aspect of individual-level SES. Latency assumptions should also be considered when investigating community-level SES.


Approximately 20–30% of women delay for 12 weeks or more from self-discovery of a breast symptom to presentation to a health care provider, and such delay intervals are associated with poorer survival. Understanding the factors that influence patient delay is important for the development of an effective, targeted health intervention programme to shorten patient delay. The aim of the study was to elicit knowledge and beliefs about breast cancer among a sample of the general female population, and examine age and socio-economic variations in responses. Participants were randomly selected through the Postal Address File, and data were collected through the Office of National Statistics. Geographically distributed throughout the UK, 996 women participated in a short structured interview to elicit their knowledge of breast cancer risk, breast cancer symptoms, and their perceptions of the management and outcomes associated with breast cancer. Women had limited knowledge of their relative risk of developing breast cancer, of associated risk factors and of the diversity of potential breast cancer-related symptoms. Older women were particularly poor at identifying symptoms of breast cancer, risk factors associated with breast cancer and their personal risk of developing the disease. Poorer knowledge of symptoms and risks among older women may help to explain the strong association between older age and delay in help-seeking. If these findings are confirmed they suggest that any intervention programme should target older women in particular, given that advancing age is a risk factor for both developing breast cancer and for subsequent delayed presentation.British Journal of Cancer (2002) 86, 1373–1378. DOI: 10.1038/sj/bjc/6600260www.bjcancer.comCancer Research UK© 2002  Delayed presentation of symptomatic breast cancer of three months or more is associated with lower survival rates . The Department of Health now plans to extend routine breast screening to women up to the age of 70, and the procedure will be available on request to women over 70 . It has Women's knowledge of breast cancer risk factors and of survival have been studied in Scottish, American and Australian populations  as a module of their Omnibus survey. Data collection took place during January and February 2000. Three thousand addresses were selected from the Postal Address File (PAF) and a letter sent to each household outlining the survey. Trained interviewers visited each address and at least three calls were made, at different times of the day and week. The interview schedule was specifically designed for the study, and pilot testing was conducted to ensure the survey was comprehensible to the target group. The questions examined four issues:Knowledge of a woman's lifetime risk of developing breast cancer: Participants were first asked a knowledge question and were required to choose a woman's approximate overall lifetime risk  of developing breast cancer. They were then asked to provide a general estimation of their personal risk in comparison to the general population and were required to state whether they perceived themselves to be more, less, or as likely to develop breast cancer than the rest of the female population as a whole.Knowledge of the risk factors associated with breast cancer: Participants were shown a list of 10 established or probable risk factors and six non-risk factors  and asked to indicate which they thought could be potential symptoms of breast cancer. (The order of the breast changes was randomly assigned.) The percentage of respondents reporting each symptom as a potential symptom of breast cancer is reported. A score was produced of the number of correct potential symptoms identified by each respondent.Perceptions of management and outcomes in breast cancer: Participants were asked to identify methods of treatment used for breast cancer and the responses were categorised according to themes. Participants rated attitudinal statements about the efficacy and consequences of breast cancer treatment on a four-point scale (strongly agree to strongly disagree). The lower the score the more the participant agreed with the statement.From the original 3000 randomly chosen addresses there were 1830 respondents (a response rate of 67%). Nine hundred and ninety-six of these respondents were female  and completed the breast cancer module of the survey. The demographic groupings of the sample can be found in Table 1The data were analysed according to the age and SES groups shown in 2=54.27, df=6, P<0.001) with 35% of over 65-year-olds and 30% of over 75-years-olds reporting reduced personal risk. There was also a relationship between SES and perception of risk , with 32% of professional and intermediate  women reporting reduced risk compared to 10–15% of partly skilled and unskilled women. The explanations for reduced risk (in response to an open-ended question) provided by the women included absent family history (47%), lifestyle factors, such as following a healthy diet and exercise plan (12%) and not smoking (5%). Approximately 25% of the women reporting a belief that they were at reduced risk believed that they were too old to develop breast cancer; the mean age of this sub-sample was 76 years (range 63–91). These participants provided explanations such as: ‘I think if I was going to develop it I would have by now’, ‘At my age I think the danger has passed’, ‘[Because] they stop mammograms at 65’ and ‘I think older people are less likely to have breast cancer problems’.Respondents were overly optimistic regarding a woman's risk of developing breast cancer, with 31% reporting that a woman had a 1 in 1000 chance of developing breast cancer, 35% reporting a one in 100 risk and 23% correctly indicating a 1 in 10 risk. The majority of the sample (76%) reported that they were just as likely to develop breast cancer as the rest of the female population in the UK, while 7% reported a belief that they were at increased risk, and 17% reported that they were less likely to develop breast cancer. However, there was a relationship between age and the perception of risk (χP<0.001). Professional women and women classified as intermediate (SES groups I and II) had a greater knowledge of risk factors than women who were partly skilled, skilled manual workers, or who had never worked =17.50, P<0.001). Women aged 35–59 were perceived, by the sample, to be most at risk of developing breast cancer, and those aged 75–90 years to be at least risk .The most frequently cited treatment method for breast cancer was surgery (87%), followed by chemotherapy 66%) and radiotherapy (49%). Only 5% of the sample spontaneously mentioned hormone therapy as a treatment method. Tables 56% and ra2=31.55, df=6, P<0.001), as were manual and unskilled workers . Professional and intermediate women (SES groups I and II) were more likely to believe that five-year survival following breast cancer was achievable .The results of the survey demonstrated that although British women have good understanding of some aspects of breast cancer there is poor awareness of other important issues, including knowledge of non-lump breast symptoms and lifetime risk of developing the disease. The survey also highlighted important age and SES variations in knowledge of risk and of the range of potential symptoms of breast cancer. These variations may help to explain some of the differences in help-seeking behaviour observed among women with breast cancer symptoms in the UK.Respondents were overly optimistic regarding a woman's risk of developing breast cancer with less than one quarter correctly indicating a 1 in 10 risk. Although health education campaigns have included information about the lifetime risk of breast cancer, it is apparent that the majority of British women have either not accessed this information or have not interpreted it correctly. However, the format of these educational campaigns may also account for the poor awareness observed among these women. It is known that leaflets produce only limited and short-lived changes in knowledge . TherefoThe findings of this study suggest that the importance of advancing age as a risk factor for breast cancer is poorly understood, not only by older women in this country, but by the general female UK population as a whole. This is in line with findings from USA and Australian populations .In our sample, a significant proportion of women aged over 65 perceived themselves to be at less personal risk than the general population, and in a significant proportion of these the explanation for reduced risk related to their advanced age. In the UK, women aged 50–64 are routinely invited for breast cancer screening  and thisIn addition to poor awareness of advancing age as a risk factor, older women demonstrated poorer knowledge of risk factors in general. This lower level of knowledge was also apparent among women in SES groups III and IV. Surveys in the USA and Australia have demonstrated that older women, particularly those classified as lower SES, have poorer knowledge of key risk factors for various cancers . The resOne risk factor that the majority of women recalled was a family history of the disease, and this finding is in agreement with previous research (The majority of the women surveyed recognised a painless breast lump as a symptom of breast cancer. In line with previous findings , less thKnowledge of symptoms was poorer among older women and women who had never been employed. Older women were less likely to perceive nipple eczema, changes in the shape or size of the breast, and nipple retraction as symptoms of breast cancer. It is possible that older women attribute such symptoms to the ageing process, as has been reported previously for other symptoms . FurtherThe majority of participants reported that five-year survival was a common event, which reflects the improvements in five-year survival that have recently been reported (Women generally reported positive beliefs about breast cancer outcomes, however there were aspects of symptomatology and risk that were poorly understood. This poor level of knowledge could potentially contribute to delay in seeking medical help. This is especially true for older women, who have a poor awareness both of the risk factors and of the range of symptoms associated with breast cancer. This poor level of knowledge is of particular concern, given the increased risk of developing breast cancer with advancing age, and may partly explain the increased delay behaviour observed among older women. However, further research is necessary to confirm this. The current study forms part of a larger programme of research examining delay behaviour for breast cancer. This includes work to examine the relationship between the intention to seek help for breast symptoms and knowledge and beliefs about breast cancer in the general female population. A future study is being planned drawing upon these findings with a clinical sample of women who have recently sought medical help for breast cancer symptoms, with the aim of developing a health promotion intervention.


Certain studies suggest that alcohol may reduce the risk of thyroid cancer in women, but the effect in men remains unclear.n=490 159) prospective NIH-AARP Diet and Health Study with self-reported beer, wine, and liquor intakes.We analysed the association between alcohol and thyroid cancer in a large .Over 7.5 years of follow-up (median), 170 men and 200 women developed thyroid cancer. Overall, the thyroid cancer risk decreased with greater alcohol consumption (⩾2 drinks per day These results suggest a potential protective role for alcohol consumption in thyroid cancer. The rapid increase in thyroid cancer incidence in the United States over the past three decades may be related to changes in certain environmental exposures, as well as increased surveillance and more widespread use of sensitive diagnostic tools  and two metropolitan areas , withdrew from the study (n=6), moved outside the study area or died before follow-up (n=617), were proxy respondents (n=15 760), had prevalent cancer except non-melanoma skin cancer (n=51 193) or end-stage renal disease at baseline (n=997), had cancer identified only from death records (n=3876), or had missing or extreme (greater than twice the interquartile range of sex-specific transformed intake above the 75th or below the 25th percentile) caloric intake (n=4 382). The analytic cohort included 490 159 participants (292 101 men and 198 058 women).Among 567 169 questionnaire respondents, we excluded individuals who provided duplicate questionnaires   corresponds to 12 fluid ounces of beer (12.96 g ethanol), 5 fluid ounces of wine (13.72 g ethanol), and 1.5 fluid ounces of 80-proof distilled spirits (13.93 g ethanol).Q statistic  and 95% confidence intervals (CI) for thyroid cancer in all participants and by sex. Models were additionally adjusted for sex, race, smoking status, body mass index (BMI), and family history of cancer. We mutually adjusted for beer, wine, and liquor in models of alcohol type. Medians of each exposure category were modeled as continuous in trend tests. Sub-group analyses were conducted using categories of sex, smoking status, BMI, and thyroid cancer histology. The heterogeneity within sub-groups was assessed using the tatistic . We founThe median alcohol intake among participants reporting any alcohol consumption over the past year was 4.5 g per day, or approximately one-third of the amount of a standard alcoholic drink. Over 11% of the cohort (9574 women and 45 149 men) reported consuming two or more alcoholic drinks daily. There were higher proportions of beer or liquor drinkers among the heavier drinking groups, and of wine drinkers among the more moderate drinking group. Compared with non-drinkers, heavier drinkers were more likely to be male, white non-Hispanic, more educated, and to have ever smoked, and less likely to be obese .P-trend=0.01; P-trend=0.03). No clear dose-response associations with wine were observed, but liquor intake was associated with a nonsignificant decreased risk in women.Over a median 7.5 years of follow-up, 200 women and 170 men were diagnosed with thyroid cancer. Compared with non-drinking, consuming two or more drinks per day was associated with a significantly decreased risk . Although we observed a clearer inverse association for papillary  as compared with follicular cancer , these results were not significantly different (P-heterogeneity=0.36). For every 10 g consumed, the RRs for thyroid cancer were 0.95 (95% CI 0.89–1.01) for men, 0.84 (95% CI 0.71–1.01) for women, and 0.94 (95% CI 0.88–0.99) for men and women combined. The results were not materially altered after excluding the first 2 years of follow-up, when the lightest drinkers were considered as the referent category, or when models were additionally adjusted for smoking intensity (data not shown).The strength of the inverse association with alcohol intake was relatively consistent according to sex, smoking status, and BMI categories, as well as histology . It was vs follicular cancers, this difference was not significant. However, there were only 64 follicular cancers in this study.In this large prospective study, we observed that greater alcohol intake was associated with a reduced risk of thyroid cancer in both men and women, independent of cigarette smoking. The inverse association for beer seemed stronger than for wine or liquor, particularly among men in this cohort. In women, we observed a nonsignificant inverse association for liquor intake, but no clear association for other alcohol types. These differences may reflect the smaller range of alcohol intake in women, residual confounding by socioeconomic status or related factors, drinking patterns , or differences in measurement error by the type of alcohol. Nonetheless, similar dose-response associations with total alcohol intake were observed by sex, and associations by alcohol type were generally in the same inverse direction. Although we observed a clearer reduction in risk for papillary Given the strong, positive correlation between alcohol and smoking, and the evidence linking smoking with a reduced risk of thyroid cancer . Participants reported intake during the past year, which obviously does not cover cumulative lifetime drinking, and our results could be attenuated by the inclusion of recent quitters in the reference category of non-drinkers. However, excluding the first 2 years of follow-up did not materially change the results, and a similar inverse dose-response association was observed when the lightest drinkers were the referent group.vs 25% per 10 g per day; In this large prospective study, we found a reduction in thyroid cancer risk in both men and women with a greater consumption of alcohol. The decrease in risk associated with consuming 10 g per day is reasonably consistent between women in this study and in another large prospective study (16