Epidemiological evidence on meat intake and breast cancer is inconsistent, with little research on potentially carcinogenic meat-related exposures. We investigated meat subtypes, cooking practices, meat mutagens, iron, and subsequent breast cancer risk.Among 52 158 women (aged 55–74 years) in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, who completed a food frequency questionnaire, 1205 invasive breast cancer cases were identified. We estimated meat mutagen and haem iron intake with databases accounting for cooking practices. Using Cox proportional hazards regression, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) within quintiles of intake.P trend=0.22), the heterocyclic amine (HCA), 2-amino-3,8-dimethylimidazoquinoxaline (MeIQx), , and dietary iron  were positively associated with breast cancer. We observed elevated, though not statistically significant, risks with processed meat, the HCA 2-amino-3,4,8-trimethylimidazoquinoxaline (DiMeIQx), mutagenic activity, iron from meat, and haem iron from meat.Comparing the fifth to the first quintile, red meat (HR=1.23; 95% CI=1.00–1.51, In this prospective study, red meat, MeIQx, and dietary iron elevated the risk of invasive breast cancer, but there was no linear trend in the association except for dietary iron. Evidence of the role of meat intake in breast cancer is mixed. There are conflicting findings from a pooled analysis of cohort studies  and polycyclic aromatic hydrocarbons (PAHs), are formed in meat cooked to well done at high temperatures . Meat muWe used unique databases and a detailed meat questionnaire to comprehensively assess meat intake and potentially carcinogenic meat-related exposures in relation to postmenopausal invasive breast cancer in the prospective Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.http://riskfactor.cancer.gov/DHQ/), the National Cancer Institute's (NCI) self-administered validated food frequency questionnaire (FFQ)  or the DHQ (n=16 886); missed more than seven food items on the DHG (n=1563); reported energy intake in the top or bottom 1% of women (n=1226); had a history of cancer other than non-melanoma skin cancer before dietary assessment (n=6819); or no follow-up time (n=1110). After exclusions, with some subjects meeting multiple criteria, our analytic cohort consisted of 52 158 women. The vast majority of the cohort was postmenopausal based on self-reported age at last period and reason for last period. Menopausal status was ambiguous for 1.7%, but 89.1% of the women with ambiguous data were 57 or older, so the cohort was assumed to be postmenopausal.Women were excluded from this analysis if they lacked the baseline questionnaire  and progesterone receptor (PR) data collection is ongoing; we had receptor status for 388 of our cases. Entry date for the analytic cohort was the latest of the following: randomisation, completion of baseline questionnaire, or completion of the DHQ. Follow-up ended on 31 December 2006, with breast cancer cases exiting at the date of diagnosis and non-cases exiting at the date of the most recent annual study update questionnaire without a report of breast cancer.*Calc Analysis Program . Red meat (g per day) included bacon, beef, cheeseburgers, cold cuts, ham, hamburgers, hot dogs, liver, pork, sausage, veal, venison, and red meat from mixed dishes. White meat included chicken, fish, and turkey. Processed meat included bacon, cold cuts, ham, hot dogs, and sausage.The DHQ assessed usual intake (frequency and portion size) of 124 food items over the past year. Nutrient intake was estimated using the Diethttp://www.charred.cancer.gov) software application and data from a detailed meat-cooking module included in the DHQ, we generated intake estimates of three HCAs (ng per day): 2-amino-3,4,8-trimethylimidazoquinoxaline (DiMeIQx), 2-amino-3,8-dimethylimidazoquinoxaline (MeIQx), and 2-amino-1-methyl-6-phenyl-imidazopyridine (PhIP), as well as benzo[a]pyrene (B[a]P), a marker of total PAH exposure, and mutagenic activity in meat (revertant colonies per day) (With the Computerised Heterocyclic Amines Resource for Research in Epidemiology of Disease (CHARRED) (per day)  Survey NP-values are two-sided and analyses were conducted using SAS .Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression with age at baseline as the underlying time metric; proportional hazards assumptions were not violated. Quintile cut points for the dietary exposures were based on intake in the analytic cohort, with the lowest quintile as referent. Dietary variables, except the meat mutagens, were energy adjusted using the multivariate nutrient density method; residual adjustment did not alter our findings . Tests fMultivariate models were adjusted for the following potential confounders, which were selected because inclusion in the age-adjusted model resulted in a 10% change in risk estimates, they were associated with breast cancer in this dataset, or are established breast cancer risk factors: age, race, education, study centre, randomisation group, family history of breast cancer, age at menarche, age at menopause , age at first birth and number of live births, history of benign breast disease, number of mammograms during past 3 years, menopausal hormone therapy, body mass index (BMI), and intakes of alcohol, total fat, and total energy. We included cross product terms in the multivariate models to assess effect modification by alcohol intake, parity, family history of breast cancer, BMI, menopausal hormone therapy, and number of mammograms.During a mean follow-up of 5.5 years, we identified 1205 invasive breast cancer cases. Mean total meat intake was 62.9 g per 1000 kcal, with 29.5 g per 1000 kcal from red meat and 33.4 g per 1 000 kcal from white meat. Women in the highest quintile of red meat intake were slightly younger, less educated, and were less likely to have a family history of breast cancer or more than one mammogram in the past 3 years than those in the lowest quintile . FurtherP trend=0.22), consistent with a potential threshold effect (n=259) to non-cases, the effect of red meat seemed to be stronger . There were no statistically significant associations with processed meat, white meat, or individual meat items.We observed statistically significant or borderline-positive associations between red meat and breast cancer starting in the second quintile, and there was no evidence for a dose–response effect , PhIP (0.014), mutagenic activity (0.010), and haem iron (0.016) on breast cancer risk in women with BMI <25 (469 cases) as opposed to those who were overweight  or obese  (data not shown). There was no effect modification by alcohol intake, parity, family history of breast cancer, menopausal hormone therapy, or number of mammograms.We found some evidence of a stronger effect of red meat  they cannot be evaluated in the same model, making it difficult to determine whether the risk can be attributed to this individual component. However, individuals were not always ranked in the same quintile of the two exposures (weighted Kappa=0.59), indicating that haem iron may not just be a surrogate for red meat.Our results for haem iron may vary from earlier research (Strengths of this analysis include the detailed prospective data and investigation of specific meat-related exposures with separate, plausible pathways for influencing breast carcinogenesis. Although there is inherent measurement error in FFQs, this typically results in attenuation of risks. To minimise this error, our models included total energy intake. However, our ability to detect small associations may still be limited. The diet was assessed only once and this may not have been the time period most relevant to neoplasia. We also had limited ability to evaluate tumour sub-types, as our results were based on ongoing and therefore incomplete ascertainment. Finally, the observed associations could be due to unmeasured confounding, although we investigated many potential confounders.Overall, the epidemiological evidence for meat in relation to breast cancer remains inconclusive; however, with few known modifiable risk factors, this dietary component should be further investigated. Our results regarding meat mutagens and haem iron indicate a need to evaluate multiple meat-related exposures in relation to breast carcinogenesis.


By inhibiting cyclooxygenase-2, nonsteroidal anti-inflammatory drugs (NSAIDs) decrease aromatase activity and might reduce breast cancer risk by suppressing estrogen synthesis. Epidemiologic evidence for a protective role of NSAIDs in breast cancer, however, is equivocal.We tested NSAID use for its association with breast cancer incidence in the National Institutes of Health–AARP Diet and Health Study, where 127,383 female AARP (formerly known as the American Association of Retired Persons) members with no history of cancer, aged 51 to 72 years, completed a mailed questionnaire (1996 to 1997). We estimated relative risks of breast cancer for NSAID exposures using multivariate Cox proportional hazards regression models. The state cancer registry and mortality index linkage identified 4,501 primary incident breast cancers through 31 December 2003, including 1,439 estrogen receptor (ER)-positive cancers and 280 ER-negative cancers.Proportional hazards models revealed no statistically significant association between overall NSAIDs and total breast cancer. As cyclooxygenase inhibition by aspirin (but not other NSAIDs) is irreversible, we tested associations by NSAID type. Although we observed no significant differences in risk for daily use (versus nonuse) of aspirin  or nonaspirin NSAIDS , risk of ER-positive breast cancer was significantly reduced with daily aspirin use  – a relationship not observed for nonaspirin NSAIDS. Neither aspirin nor nonaspirin NSAIDs were associated with risk of ER-negative breast cancer.Breast cancer risk was not significantly associated with NSAID use, but daily aspirin use was associated with a modest reduction in ER-positive breast cancer. Our results provide support for further evaluating relationships by NSAID type and breast cancer subtype. Numerous epidemiologic studies have examined the association between nonsteroidal anti-inflammatory drugs (NSAIDs) and breast cancer, with equivocal results. Most, but not all, case–control studies have found relative risk reductions from 20% to 40% -3 -1 and COX-2, which cyclize and oxygenate arachidonic acid, eventually producing prostaglandins [A protective role of NSAIDs in breast carcinogenesis is biologically plausible. glandins . While iglandins , inactivglandins .Since aspirin and nonaspirin NSAIDs have different biologic effects (aspirin permanently inactivates COX-2 ), separaThe NIH–AARP Diet and Health Study design and methodology have been described in detail . BrieflyThe study was initiated in 1995 and 1996 when a questionnaire was mailed to 3.5 million members of the AARP (formerly known as the American Association of Retired Persons) aged 50 to 71 years, who resided in one of six states  or two metropolitan areas  that have large AARP membership, large minority populations, and high-quality cancer registries. The questionnaire captured diet history, demographic characteristics, reproductive history, menopausal status, and family history of cancer. Of the 617,119 men and women (17.6%) who returned the questionnaire, 567,169 satisfactorily completed it.In 1996 and 1997 a second questionnaire was sent to collect additional information on family history of cancer, anthropometry, and use of menopausal hormone therapy (HT) and other medications, including NSAIDs. A total of 337,074 men and women completed this questionnaire.n = 2,166), excluding proxy respondents to the baseline  or second  questionnaires, and excluding 188,117 men, the study population included 136,408 potentially eligible womenAfter excluding individuals who died or moved out of the cancer registry ascertainment area before their second questionnaire was received and scanned  and nonaspirin NSAIDs  had been used in the past 12 months. As acetaminophen is an analgesic with weak anti-inflammatory activity , particiWhile the demographic characteristics, lifestyle, and reproductive history were largely obtained through the first questionnaire, the second questionnaire ascertained a self-reported history of hypertension, mammogram screening, and vigorous physical activity. Menopausal hormone therapy use and history of breast cancer in a first-degree relative were derived from information collected on both the first and second questionnaires.Cohort members were followed annually for mailing address changes and vital status. Address changes were identified through linkage to the US Postal Service's National Change of Address database, through US Postal Service updates received with undeliverable mail, through use of other address change update services, and through participants' notifications. Vital status was updated through linkage to the Social Security Administration Death Master File and was verified by the National Death Index.in situ breast cancers and invasive breast cancers were initially identified through probabilistic linkage to eight state cancer registries using first and last name, address, sex, date of birth, and Social Security Number from the baseline questionnaire. The cancer registry ascertainment area was recently expanded to include three additional states  to capture cancer occurring among participants who moved to those states during follow-up. Each registry has been certified by the North American Association of Central Cancer Registries for meeting the highest standards of data quality.Incident Breast cancer estrogen receptor (ER) status was coded as described in the American Joint Committee on Cancer's Collaborative Staging Site-Specific Factors Manual, with a threshold of >10 fmol cytosol protein per milligram for a positive tumor; however, the ER status was not reported by the Florida, Michigan, and Pennsylvania cancer registries. Histology was defined using the International Classification of Diseases for Oncology codes, third edition . A previBecause information regarding NSAID use was not collected on the baseline questionnaire, we limited analyses to the 136,408 women who completed the second questionnaire. We excluded 9,022 women who reported a personal cancer history other than nonmelanoma skin cancer on either questionnaire (including 942 breast cancers), 1,259 women who were missing information on NSAID use (including 52 breast cancers), and three women with no follow-up. Thus, 126,124 women were included in the present analyses.in situ, 3,703 invasive, and 17 missing stage). Among the 2,282 invasive breast cancer cases from states that collected the ER status, 1,439 were coded as ER-positive and 280 as ER-negative (the ER status was unavailable for the remaining 563 invasive cases). There were no substantial risk factor differences between women from states where ER information was available and states where it was unavailable. The majority of invasive breast cancers were ductal carcinomas , followed by lobular (n = 400), mixed (n = 310), and other (n = 584) histologic types.Through 31 December 2003, 4,501 women developed breast cancer  for breast cancer associated with NSAID use; age was the time scale , and tievice versa. Tests for linear trends across the NSAID exposure categories were calculated by treating these categorical variables as ordinal variables.Multivariate models were used to control for age at entry (years), race/ethnicity (white versus other/unknown), age at first birth , HT use , number of breast biopsies , alcoholic drinks per day , history of hypertension , and family history of breast cancer in a first-degree relative . Models examining frequency of aspirin use and breast cancer risk also included terms for frequency of nonaspirin NSAID use and In subsequent models, we adjusted for calendar time and several additional factors, including ages at menarche and menopause, mammogram in the past 3 years, self-reported heart disease, self-rated health quality, physical activity, and body mass index (BMI). The results were essentially the same and are not shown here.2, 25 to 29 kg/m2, ≥30 kg/m2, or unknown), and smoking status . In addition, we examined whether the relationship between NSAIDs and breast cancer incidence differed by ER status (positive or negative), by stage at diagnosis (in situ or invasive disease), and by histologic type .We used a likelihood ratio test, comparing models with and without the interaction terms, to separately examine effect modification by age at entry , HT use , BMI .Among the 126,124 mostly white, postmenopausal women in this report, 65.6% reported ever-use of aspirin in the past 12 months. Among all women, 31.8% took aspirin less than once per week, 16.1% used aspirin one to six times per week, and 17.7% were daily aspirin users. Slightly fewer women reported ever-use of nonaspirin NSAIDs: 31.5% took nonaspirin NSAIDs less than once per week, 15.2% used nonaspirin NSAIDs one to six times per week, and 13.3% were daily nonaspirin NSAID users. Nearly 85% of women in our study reported any NSAID use within the past 12 months.2), and to have a history of breast biopsy.In general, aspirin and nonaspirin NSAID users shared similar characteristics Tables  and 2. CThe 126,124 women accrued 836,863 person-years during an average follow-up of 3.43 years for cases  and of 6.75 years for noncases . The mean (standard deviation) ages for entry and exit were 63.1 (5.2) years and 66.5 (5.6) years for cases and were 62.6 (5.4) years and 69.3 (5.4) years for noncases, respectively. Breast cancer risk factors in this population were generally consistent with established associations with age, BMI, ages at menarche, first birth and menopause, parity, estrogen–progestin therapy use, number of breast biopsies, and family history of breast cancer.Because NSAID exposure was collected on the second questionnaire, and the response rate for this questionnaire was ~60%, we also examined the association between breast cancer risk factors captured on the first questionnaire and breast cancer risk among the entire cohort. The associations between risk factors and breast cancer in the entire cohort were comparable with those observed in the subcohort of respondents to the second questionnaire (data not shown).P = 0.08). Compared with nonuse, daily use of nonaspirin NSAIDs was not associated with breast cancer risk . The association between NSAID use and breast cancer risk was not modified by age, HT use, BMI, or smoking (data not shown).In multivariate proportional hazards models, there was no statistically significant association between ever-use of NSAIDs in the past 12 months and total breast cancer Table . Comparein situ disease (Table in situ breast cancers were 0.95 (95% CI = 0.85 to 1.06) and 0.75 (95% CI = 0.59 to 0.95), respectively , which permanently inactivates COX-2 , potentiA US hospital-based study – the Case–Control Surveillance Study – reported a 26% nonsignificant reduction (95% CI = 0.44 to 1.26) in HR-positive breast cancer associated with regular (versus <4 times/week) aspirin use . More rein situ breast cancer than invasive breast cancer. Among the few prior studies that have reported results separately for in situ breast cancer and invasive breast cancer, two case–control studies reported decreased risks of both in situ and invasive breast cancers associated with aspirin [in situ breast cancer were not statistically significant in either study. The Iowa Women's Health cohort study reported a reduction in breast cancer risk with increased frequency of aspirin, but not with nonaspirin NSAIDs, for both in situ and invasive disease [in situ and invasive breast tumors express COX-2 [in situ compared with invasive tumors have led investigators to suggest that the potential therapeutic impact of COX-2 inhibition may be more relevant for in situ breast cancer than invasive breast cancer . The inP = 0.09) [We observed no variation in risk with HT, smoking status, or BMI, and our findings are generally consistent with previous investigations. For the most part, tests for interactions between HT and NSAID use have been statistically nonsignificant across case–control studies ,33 and c = 0.09) . We, alo = 0.09) ,33 and s = 0.09) ,22,24,25In summary, our results do not support an important influence of NSAIDs on total breast cancer risk. Daily aspirin use, however, appeared to offer some protection for ER-positive breast cancer in this population. In addition, our findings suggest that the associations for aspirin use may vary by tumor stage. Our results provide support for further evaluating relationships in prospective studies with well-defined measures of NSAID use by NSAID type, by breast cancer stage, and by ER status.BMI = body mass index; CI = confidence interval; COX = cyclooxygenase; ER = estrogen receptor; HR = hormone receptor; HT = hormone therapy; NIH = National Institutes of Health; NSAID = nonsteroidal anti-inflammatory drug; RR = relative risk.The authors declare that they have no competing interests.AS, ARH, and MFL participated in the acquisition of data. GLG, LAB, JVL Jr, AS, and MFL were involved with the study concept and design. GLG, JVL Jr, MFL, DR, and LAB contributed to the statistical analyses. GLG, JVL Jr, and LAB participated in manuscript preparation. All authors participated in the interpretation of results and critical revision of the manuscript for important intellectual content. All authors read and approved the final manuscript.


Independent, strong and unequivocal evidence suggests that life style factors such as obesity and lack of physical activity along with certain reproductive choices can increase the risk of breast cancer. There are no studies measuring the effectiveness of guidelines from the Department of Health regarding life style choices made by women presenting to breast clinics. The aim of this audit was to study the prevalence of obesity, physical activity and reproductive factors in women referred to breast clinic.All patients attending the Breast clinic as new referrals were invited to complete a life style questionnaire. The data was analysed for prevalence of various risk factors for breast cancer. Three hundred and 73 patients completed the questionnaire.2. The median age of menarche was 13 and 18% of women started their period below the age 12. Twenty one percent of women were nulliparous and 14% had their first live birth after the age of 30. Fourteen percent of patients were on the hormone replacement therapy of which 57% have used hormones for more than 5 years. Twenty two percent of women smoked and 9% of women consumed alcohol 5 days a week of which 13% had more than 4 glasses of alcohol in a day.Final analyses of 373 patients demonstrated that 42% of women performed no exercise and only 24% of patients met Department of Health guideline of 30 minutes of exercise for 5 days a week. Overall 50% of patients were either obese or overweight and 22% of patients had BMI of > 30 kg/mThere is preponderance of high risk life style choices in women attending breast clinic. If these life style options are not modified, there could potentially be a significant rise in the number of breast cancer in West Midlands. Breast cancer is the most common cancer in women in the UK and is twice as frequent as any other female cancer. There has been a significant rise in the incidence of breast cancer in the last 20 years, as number of newly diagnosed breast cancer has increased from approximately 20,000 in 1988 to 45,000 in 2004. There is an understandable need to investigate and manage the cause of this rise in the incidence of breast cancer. The life style in women has significantly deteriorated in last 20 years [The evidence that obesity contributes to the development of breast cancer in postmenopausal women is overwhelming and indisputable ,3. ObesiRecently, evidence has emerged which indicates a dose response between alcohol consumption and increased risk of developing breast cancer -13. A meThe aim of this study is to identify the life style choices being made by a cohort of women attending as a new patient to a Breast clinic in a large teaching Hospital.All new patients attending breast clinic were invited to take part in this cross-sectional survey of life style and breast cancer at a large teaching hospital in the West Midlands, England between July 2008 to December 2008. The questionnaires were in SP15 format. Patients who were unable to read English were excluded. All male patients and follow up patients were excluded.The patients were handed questionnaires at the visit before clinical consultation. The health care professional recorded the height, weight and BMI. The obesity was defined as WHO criteria. Women were questioned on their lifestyle choices such as smoking habits (cigarettes per day), alcohol intake (units per week) and level of physical activity (hours per week). For the purpose of this study, post-menopausal status was defined as 50 years of age or above. Women who had previously had a hysterectomy were categorised as post-menopausal.The questionnaire was adopted from the clinical information that is collected as a part of new patient consultation. Because of the factual and basic nature of the information in the questionnaire, no formal validation was carried out.Statistical methods Responses were analysed with frequencies, single variable and multiple response analyses using SPSS software programme™. Frequency table analysis and percentage distribution was carried out.Over the 6 month period, 381 consecutive women Breast clinic as a new patients were invited to complete the questionnaire. One patient declined to complete the questionnaire and one did have her reading glasses. Three men were given the questionnaire and were not eligible for the study and four follow up patients completed the questionnaire. These patients were excluded from the study. Data presented here is for 373 patients.Median age of the patients was 43 years and 34% of patients were postmenopausal. The median age of Menache was 13 (range 9–18) in this cohort of patients and 18% of women has their first period below the age of 12. One-fifth (19%) of women were nulliparous and median age of birth of first child was 25 years (range 17- over 30 years of age). Almost one in six (14%) of women had first live birth after the age of 30. Over one third of women (38%) had a miscarriage or abortion. Fourteen percent of women took HRT, of whom 39% were on HRT for more than 5 and 18% took HRT for more then 10 years.In this cohort of patients, half the women had unhealthy weight. Almost 22% were obese and 28% were overweight Figure The most frequent response among patients was that they did not consume alcohol at all (37%), while 22% of patients reported drinking on one day per week and 16% reported drinking on two days per week. Of the patients who reported consuming alcohol, 23% reported drinking one glasses, 41% reported drinking 2 glasses and 22% reported drinking three glasses. Wine was the most frequently reported type of alcohol consumed (64%) Figure Of the study cohort 5% were diagnosed with breast cancer. The numbers are too small for statistical analyses.The risk factors for breast cancer can be divided into several main groups. Genetic or familial, reproductive or hormonal factors, lifestyle factors and environmental factors. The reproductive and life style factors are considered to be the modifiable risk factors for the development of breast cancer. The present study found that an alarming number of women attending for consultation as new patients were obese or overweight, about one third smoked and one in six were taking exogenous hormones. It was also found that a vast majority of women was not achieving the exercise guidelines set by the department of health. The Chief Medical Officer recommended a total of at least 30 minutes a day of at least moderate intensity physical activity on five or more days of the week for general health. . The NatThe data that physical activity and maintaining a healthy weight improves the incidence of breast cancer is very powerful and supported by most long term, large cohort and Epidemiological studies. A systematic review of literature including 19 cohort studies and 29 case-control studies concluded that there was strong evidence for an inverse association between physical activity and postmenopausal breast cancer with risk reductions ranging from 20% to 80% . A revieAmong postmenopausal women in the UK, 5% of all cancers  are attributable to being overweight or obese . Almost Epidemiological data suggest that increasing alcohol consumption by one unit of alcohol per day increases the relative risk of developing breast cancer by 7%. There was considerable diversity in the number of days women drank in a week, though there was a downward trend from the highest number reporting drinking on zero days per week, through to the lowest number reporting drinking on six or seven days per week. Most of this sample of women appear to be consuming alcohol at safe levels, with few women drinking daily and most women consuming little alcohol when they do drink. This pattern of alcohol consumption is unlikely to increase their risk of developing breast cancer, however it must be acknowledged that the responses were only collected on one occasion, and there may be variation in alcohol consumption that we have not accounted for. However, a vast majority (64%) of women who reported drinking, reported drinking wine, and this could be a cause for concern. Research by Gill and Colleagues ,20 showsThese data provide a snap shot of the life style behaviour of women presenting to breast clinic in Dudley and provide a clear idea of the extent of the modifiable risk factors in patients attending breast clinic. The weaknesses of this study are a relatively small sample size and potential for confounding variables. This is an observational study and relied on self-reporting. Nevertheless, these data suggest that women may be exposing themselves to increased risk of breast cancer by life style choices.In Dudley population, there is a preponderance of life style related risk factors that increase the risk of developing breast cancer. The health education message about physical activity and healthy weight is clearly not reaching this cohort of patients. These data point to trend that it is possible that patients in Dudley could be exposing themselves to higher breast cancer risk based upon our current understanding of the risk factors associated with the disease. More research is needed to investigate this life style behaviour in order to design effective interventions for life style modifications. These alarming statistics are likely to have significant impact on the incidence of breast cancer in women in West Midlands. If further rise in incidence of breast cancer is to be prevented then a more robust system of education is needed.The authors declare that they have no competing interests.ARC conceived the idea, designed the questionnaire and recruited the patients, LH collated and analysed the data and RC advised about alcohol intake data collection and wrote the section of the paper about alcohol intake.


The period at risk started in 1978 and continued until a breast cancer diagnosis, death, emigration, or 31 December, 1992, whichever occurred first. After adjusting for attained age, parity, age at first birth and calendar period, we observed the following relative risks of breast cancer for different lengths of the pregnancy: < 29 gestational weeks = 2.11 ; 29–31 weeks = 2.08 (1.20–3.60); 32–33 weeks = 1.12 (0.62–2.04); 34–35 weeks = 1.08 (0.71–1.66); 36–37 weeks = 1.04 (0.83–1.32); 38–39 weeks = 1.02 (0.89–1.17); 40 weeks = 1 (reference). Parous women who had a preterm delivery below 32 weeks gestation had a 1.72-fold (1.14–2.59) increased risk of breast cancer compared with other parous women. In conclusion, a preterm delivery of 32+ weeks gestation did not significantly increase a woman's risk of contracting breast cancer. Only for the very small group of women with preterm deliveries of less than 32 weeks gestation did we observe an increased risk. © 1999 Cancer Research CampaignTo explore the risk of breast cancer in relation to the length of a pregnancy we tested whether a preterm delivery carries a higher risk of breast cancer than does a full-term delivery. Based on information from the Civil Registration System, and the National Birth Registry in Denmark, we established a population-based cohort of 474 156 women born since April 1935, with vital status and detailed parity information, including the gestational age of liveborn children and stillbirths. Information on spontaneous and induced abortions was obtained from the National Hospital Discharge Registry and the National Registry of Induced Abortions. Incident cases of breast cancer in the cohort (


The absence of effects on risk of later ages at, or short intervals since, a last birth fails to support the view that endometrial cancer is influenced by mechanical clearance of initiated cells. Alternative explanations for reproductive effects should be sought, including alterations in endogenous hormones.We conducted a population-based case–control study of reproductive factors in Warsaw and Ló∂ź, Poland, in 551 incident endometrial cancer cases and 1925 controls. The reproductive variable most strongly related to risk was multiparity, with subjects with three or more births having a 70% lower risk than the nulliparous women. The reduced risk was particularly strong below 55 years of age. Subjects with older ages at a first birth were also at reduced risk even after adjustment for number of births. Ages at last birth or intervals since last birth were not strongly related to risk. Spontaneous abortions were unrelated to risk, but induced abortions were associated with slight risk increases (odds ratios=1.28, 95% confidence intervals 0.8–2.1 for 3+  Nulliparous women are known to be at an increased risk of endometrial cancer, but effects of other reproductive factors remain less defined. Inverse associations with later ages at a first birth have been demonstrated in some studies , a database with demographic information from all residents of Poland, was used to select controls. A complementary breast cancer study, initiated in January 2000, in which controls were randomly selected according to the anticipated age distribution (in 5 year categories) of breast cancer cases in each city provided a source for controls from the beginning of the endometrial cancer study until the end of the breast study . These controls were supplemented with additional subjects who were specifically selected for the endometrial cancer cases. One control per cancer case was selected during the breast cancer study, with two controls per case after this time. Eligible controls had neither a history of breast or endometrial cancer at enrolment.After obtaining signed informed consent forms approved by the National Cancer Institute and local Institutional Review Boards (IRB), personal interviews were conducted using a questionnaire on demographic and reproductive factors, contraceptive behaviour, use of exogenous hormones, physical activity, passive and active cigarette smoking, occupational history, diet, alcohol use, first-degree family history of breast and ovarian cancer, medical and screening history, prenatal exposures and developmental history.Of the 694 eligible cases and 2843 eligible controls, 551 (79.4%) and 1925 (67.7%), respectively, agreed to complete an interview. The primary reason for non-response was refusal, relevant to 106 (15.3%) of the eligible cases and 705 (24.8%) of the controls. The median length of the interview was 85 min, and the overall quality as rated by the interviewers was identical for the cases and controls, with 48.1% rated high quality, 49.1% generally reliable, 2.3% unreliable, and 0.5% unrated. The median time from case diagnosis to interview was 69.0 days and the median time from control selection to interview was 19.0 days. Medical records of endometrial cancer patients were reviewed for diagnostic and treatment details.Information on all prior pregnancies was collected, including outcomes , gestational lengths (in weeks or months), and dates each pregnancy ended. For livebirths, subjects were asked whether they had breastfed the baby and for how long. Subjects were also asked if they had ever tried to become pregnant for two straight years without successful conception and whether they had ever visited a doctor, clinic or hospital because of difficulty in becoming pregnant. If relevant, they were asked when they first sought advice and whether they were given any medication or hormones to help in getting pregnant.Unconditional logistic regression analysis was used to estimate adjusted odds ratios (OR) and associated 95% confidence intervals (CI). In order to examine the independent effects of correlated reproductive factors, we used the approach described by Heuch and others  , although subsequent births were associated with continued reductions in risk .A significantly decreased risk was associated with parity (OR0.4–0.7) . In addiAmong gravid women, a history of any spontaneous abortion was unrelated to risk, but there was a slightly increased risk for women who reported an induced abortion. However, there was no evidence that risk increased linearly with number of induced abortions, the risk for those with three or more induced abortions being similar to that with only one abortion (respective ORs of 1.28 (0.8–2.1) and 1.31 (1.0–1.7)). The risks associated with a history of induced abortion did not differ significantly by whether women were parous or nulliparous.In contrast to the other reproductive parameters, a history of infertility (defined as the inability to get pregnant after trying to conceive for 2 years or longer) was only marginally related to risk and this association entirely disappeared after adjustment for other risk factors. A history of infertility was also not related to risk when defined more specifically according to whether physician advice had ever been sought or treatment received. Using various definitions, infertility was also not associated with risk when examined specifically among nulliparous women.vs within 15 years, there were discrepant risks, being, respectively, 1.78 (0.9–3.4) vs 0.81 (0.3–2.0). However, this latter risk was based on only 10 cases and 220 controls. Among parous women, extended breastfeeding (24 or more months) appeared initially to be associated with a significant decrease in risk, but this relationship was attenuated after adjustment for a variety of other factors, including parity.For consistency with most previous published analyses that have attempted to distinguish effects of correlated reproductive risk factors, further analyses focused on parous women . In initvs <20), whereas age at last birth was unrelated to risk. However, in contrast to our previous analyses, which suggested a possible increase in risk with years since last birth, these additional analyses showed no association with risk.We also used a modelling approach . DespiteWe also examined risks according to varying ages at diagnosis . As trends were very similar for the women 55–65 and those over 65, we combined these two groups for presentation . The invSimilar to previous investigations (We were particularly interested in following up the observations of an inverse relationship of endometrial cancer risk with ages at (It is important to note that several studies that have emphasised the importance of timing of the last birth have been unable to fully account for other predictors of endometrial cancer (first birth were associated with some risk reductions. This factor has not generally been regarded as a predictor of endometrial cancer risk (In contrast to the lack of association with ages at or intervals since a last birth, we observed that late ages at a The effects of infertility on endometrial cancer risk have been of considerable interest given that anovulatory menstrual cycles often reflect high exposure to oestrogens in the absence of sufficient progesterone. Elevated risks have been associated with delays in conception (Our investigation also enabled evaluation of effects of short-term pregnancies, including spontaneous and induced abortions. Although several studies have noted either reduced (Several investigations have suggested that women with extensive breastfeeding histories may be at reduced endometrial cancer risk (In sum, this study confirmed that endometrial cancer is strongly related to parity. Using analytic techniques which overcome previous difficulties in assessing correlated reproductive variables, we found that late ages at a first birth also appeared to reduce risk, but that late ages at a last birth or extended intervals since a last birth were unrelated. Endometrial cancer risk did not appear to be substantially influenced by incomplete pregnancies, histories of infertility, or years of breastfeeding. Future investigations should focus on hormonal alterations underlying multiparity and late ages at a first birth in order to clarify processes involved in endometrial carcinogenesis.


BRCA1 or BRCA2 genes are at an increased risk of developing breast, ovarian and peritoneal cancer. Primary peritoneal carcinoma is a rare tumour histologically identical to papillary serous ovarian carcinoma. Risk-reducing surgery in the form of mastectomy and oophorectomy in premenopausal women has been recommended to prevent breast and ovarian cancer occurrence and decrease the risk of developing primary peritoneal cancer.Women that carry germ-line mutations for BRCA1 mutation, a prophylactic left-sided mastectomy was performed. After remaining well for twenty-seven years, she presented with rectal bleeding and altered bowel habit, and was found to have a secondary cancer of the sigmoid colon. She was finally diagnosed with primary papillary serous carcinoma of the peritoneum (PSCP).We present a case report of a woman with a strong family history of breast cancer who underwent risk-reducing surgery in the form of bilateral salpingo-oophorectomy following a mastectomy for a right-sided breast tumour. Following the finding of a BRCA mutations.PSCP can present many years after risk-reducing surgery and be difficult to detect. Surveillance remains the best course of management for patients with known  BRCA1 or BRCA2 germ-line mutations are at an increased risk of developing tumours of the breast, ovary and peritoneum. The cumulative lifetime risk of invasive breast cancer for women with either mutation is between 60–85% whereas this is between 15–65% for epithelial ovarian cancer [Women with n cancer . ManagemPrimary papillary serous carcinoma of the peritoneum (PSCP) is a rare tumour found predominantly in elderly and post-menopausal women . It sharBRCA1 mutation in the context of breast disease management. Following investigation for bowel related symptoms, she was found to have a secondary sigmoid cancer of indeterminate origin. After undergoing a laparotomy and resection of this lesion, a diagnosis of PSCP was reached.The authors present an interesting case of primary peritoneal cancer. This was diagnosed twenty-seven years after risk-reducing surgery (ovarian ablation and mastectomy) for a A 33-year old Caucasian woman was diagnosed with adenocarcinoma of the right breast in 1976 following the discovery of a breast lump. She underwent a right-sided mastectomy without adjuvant therapy. Two years later at age 35, back pain prompted a bone scan which revealed a 'hot spot' in the region of the lumbar spine. This was thought to represent spinal metastases and the patient received local radiotherapy. After counselling for risk-reducing surgery, the patient chose to undergo a bilateral salpingo-oophorectomy, but declined a proposed hysterectomy.BRCA1 mutation (185delAG). A prophylactic left-sided mastectomy was subsequently performed.There was a strong family history of breast disease with both her mother and maternal grandmother diagnosed with breast cancer at 34 years and 41 years, respectively. There were no other known cancers in her family. In 2004, aged 62 years, the patient underwent genetic testing, which uncovered a Aged 64 years, the patient presented complaining of change in bowel habit, faecal leakage, urgency and left-sided abdominal discomfort. Examination revealed a tender, palpable fullness in the left iliac fossa. Initial routine blood tests showed haemoglobin of 11.7 g/dl with a normal mean cell volume and no abnormalities of electrolytes, liver or kidney function. Tumour markers revealed carcinoembryonic antigen (CEA) 3 ug/L and CA125 3 Ku/L . At colonoscopy, a necrotic lesion was seen in the proximal sigmoid colon. Biopsies confirmed a very poorly differentiated papillary adenocarcinoma of the sigmoid, the immunoprofile of which favoured ovarian origin rather than colonic; being highly positive to CK7, while negative to CK20 Figures  and 1b. Laparotomy findings included a bulky tumour adherent to the left pelvic brim and pelvic side-wall, as well as two separate peritoneal deposits, one within the pelvis and one at the terminal ileum. There was no further pathology noted. The patient underwent an en bloc resection of sigmoid colon, bladder, omentum, left pelvic side wall and uterus. The histology of the surgical specimens revealed peritoneal nodules of poorly differentiated papillary adenocarcinoma Figures  and 2b, BRCA1 gene (and BRCA2) are associated with inherited breast and ovarian cancer, although the exact nature of this tissue specificity is incompletely understood. The prevalence of mutations of BRCA1 gene in the general population is between 0.07% and 0.24% and between 0.14% and 0.22% for BRCA2 although this is higher in Ashkenazi Jews [BRCA1 (and BRCA2) mutations with a cumulative lifetime risk of between 1.3–20% [Mutations in azi Jews . The ris 1.3–20% ,9,10. ThThe development of PSCP is thought to originate de novo from the peritoneal lining of the pelvis and abdomen. However, it is histologically indistinguishable from its ovarian analogue and may develop in women years after a prophylactic oophorectomy . Two theDiagnosing PSCP can be particularly challenging as most peritoneal carcinomas present late and are difficult to detect both clinically and radiologically. There are certain CT features which are specific to peritoneal disease, but these are subtle and may only help in differentiating from other similar lesions such as mesothelioma and metastatic disease . There iIn the case report the patient had undergone ovarian ablation as a form of risk-reduction surgery during the management of breast cancer. The genetic associations were not known at the time but the surgery acted indirectly as prophylaxis for future ovarian and peritoneal cancer. The initial dilemmas with this patient were in understanding the origin of the sigmoid tumour. The clinical picture, colonoscopy findings and CT images suggested a primary colonic pathology which was in contrast to the histology results favouring an ovarian origin. This was made all the more confusing as the patient had previously undergone a bilateral salpingo-oophorectomy and serum CA125 titres were normal. The fact that the sigmoid colon had become a site of tumour spread was not surprising due to the intimate anatomical relationship of peritoneum and sigmoid colon.BRCA mutations as they are at an increased risk of cancer from several sources. In addition to the risks of those cancers which make up the HBOC syndrome, there have been lower but significant risks reported for other cancers, including pancreas and stomach [This case highlights the difficulties faced by patients with  stomach ,16. When stomach . The est stomach ,18. It i stomach .This is the first described case of primary peritoneal carcinoma presenting as a secondary colonic malignancy many years after risk-reducing surgery. This diagnosis was reached following investigation and surgical resection for symptoms related to the lower gastrointestinal tract. Despite risk-reducing surgery in the form of prophylactic mastectomy and bilateral oopherectomy, albeit in the context of breast cancer, a primary peritoneal serous carcinoma developed many years later. The authors emphasise that although risk-reducing surgery has been shown to confer a clear reduction in risk of developing breast, ovarian and peritoneal carcinoma, the possibility of a late presentation of peritoneal carcinoma remains.The author(s) declare that they have no competing interests.MC – literature review; writing of manuscript and revisions; covering letters and addressing reviewers' comments. PJM – case-note review. GFN – conceived study, manuscript revision with particular reference to language and style. ADC – conceived study and helped review manuscript, TH – review of manuscript.All authors read and approved the manuscript.


P-value for trend = 0.001) compared to those in the lowest quartile. Relative to women with a waist to hip ratio (WHR) of less than 0.75, the OR of having a high-risk pattern in women with a WHR greater than 0.80 was 0.30 (95% CI 0.14–0.63). Breast size as measured by cup size was significantly and negatively related to high-risk pattern. Our study indicates that both BMI and WHR are negatively associated with high-risk patterns. However, both phenomena are associated with increased risk of breast cancer in post-menopausal women. This negative confounding of two positive risk factors means that the effect of parenchymal patterns on risk will tend to be underestimated when not adjusted for BMI and WHR and vice versa. Thus we may have underestimated the importance of BMI and mammographic parenchymal patterns in the past. Further studies are needed to determine a measure of parenchymal density that is independent of anthropometric measures and breast size. © 1999 Cancer Research CampaignMammographic parenchymal patterns are related to breast cancer risk and are also affected by anthropometric measure. We carried out a case–control study comprising 200 cases with high-risk (P2 and DY) mammographic parenchymal pattern and 200 controls with low-risk (N1 and P1) patterns in order to investigate the effect of body size and shape and breast size on mammographic patterns. Women in the highest quartile of body mass index (BMI) distribution were significantly less likely to have a high-risk pattern (odds ratio (OR) = 0.21, 95% confidence interval (CI) 0.08–0.52,


Although a key function of cancer genetics services is to provide risk information, to date there has been little consistency in the way in which breast cancer risk perception has been measured. The aims of the study were to measure estimates of (i) population risk, (ii) absolute risk and (iii) comparative risk of developing breast cancer for Ashkenazi Jewish women, and to determine predictors of breast cancer risk perception. Of 152 women, 107 (70%) completed all questions. The mean (s.d.) estimates for population risk, absolute risk and comparative risk were 22.7% (15.9), 31.8% (20.6) and 1.9-fold (1.9), respectively. Most women overestimated population risk. Women at population risk generally overestimated the population risk and their own absolute risk, yet understood they are at the same risk as the population. Those with a family history understood that they are at increased risk, but underestimated the extent to which their familial risk is increased. Anxiety, high estimation of population risk and lesser family history predicted overestimation of absolute risk, whereas high estimation of population risk and a strong family history predicted underestimation of comparative risk. A key function of cancer genetics services is to provide clients with cancer and genetic risk information, for the purpose of informing clients, aiding decision-making, reducing anxiety and possibly improving adherence to appropriate screening practices. In the context of breast cancer, this includes discussion of both the woman's risk of developing breast cancer and of the major factors contributing to this risk, in particular her family cancer history. These services may further try to identify clients’ misconceptions about breast cancer risk and modify their beliefs so as to provide clients with a more realistic view of their own breast cancer risk.An accurate and reliable measure of women's breast cancer perception is required to assess whether women accurately estimate their breast cancer risk before genetic counselling, and if not, to assess to what extent cancer genetics services are successful in modifying inaccurate breast cancer risk perceptions. However, after more than a decade of literature, there is little consensus on how risk perception should be measured.It has previously been recognised that risk perception measurement may depend on both the statistical measure and the population studied . Risk peWith regard to the population studied, if estimates are pooled for women of differing actual risk categories , important issues may be masked. This is because risk perception and its determinants may differ by actual risk. More recent publications have compared, rather than pooled, women from different absolute risk categories or limited their study to women from a specific absolute risk category  the population risk of breast cancer, (ii) their absolute risk of breast cancer and (iii) their comparative risk of breast cancer to determine predictors of breast cancer risk perception as a function of women's family histories and their actual absolute and comparative risks.In this study, we asked Ashkenazi Jewish women participating in a study of the breast cancer susceptibility genes The study was approved by the Human Research Ethics Committees of the Peter MacCallum Cancer Institute (Melbourne), The Prince of Wales Hospital (Sydney) and The University of Melbourne. Written informed consent was obtained from all participants.Participants of the Australian Jewish Breast Cancer Study (AJBCS) were self-identified as being of Ashkenazi Jewish descent, living in Melbourne or Sydney, and reported having (a) had an earlier diagnosis of breast or ovarian cancer themselves or (b) a first- or second-degree male or female relative who had been diagnosed with breast or ovarian cancer  after their enrolment. For women who learnt their genetic test result, an average of 39 months (5–57 months) had elapsed since their attendance at a cancer family genetics clinic. The follow-up questionnaire included a genetic knowledge instrument consisting of nine true–false questions. This instrument was developed specifically for knowledge about breast cancer and the A2 genes .‘What percentage (number from 0 to 100) of women in the population do you think will get breast cancer in their lifetime?’ (2) Choose an option to describe their comparative risk. ‘Do you think YOUR chance of getting breast cancer is higher or lower than this, or about the same? Please tick the box to indicate your response’  (3) Provide a numeric value for their perception of their own absolute risk of developing breast cancer. ‘In your opinion, what percentage (number from 0 to 100) reflects your chance of getting breast cancer in the future?’The follow-up questionnaire included questions on risk perception that were developed for this study. These questions asked participants to (1) Provide a numeric value for their perception of population risk; The participants’ numeric value for their perception of their comparative risk was then derived by dividing their perception of their absolute risk by their perception of the population risk. For example, a woman who responded that the population risk was 25%, and her absolute risk was 50%, would have a numeric perceived comparative risk of 50/25=2.0.Participants received a genetic information session at the time of enrolment. Those who wished to receive their genetic test result also attended a cancer family genetics clinic to receive further genetic counselling and later attended a genetics clinic for a result disclosure appointment. The genetic information sessions were conducted by the researchers and the clinic appointments were conducted by 14 genetic counsellors and clinic geneticists, based at six clinics. Risk counselling was provided during the genetic information session and at each of the clinic appointments, so that all participants in this study received risk counselling on at least one occasion and most received it on at least two or three occasions.guide  using the guide . That isFor this study, we used the risk figures provided by the researchers and genetic counsellors to the participants as estimates of the actual risk. For population risk, participants were told the figure of a 9% lifetime risk, and so responses within a range of 7–12% were coded as ‘correct’. Participants who estimated the population risk to be above 12% were coded as having overestimated, and those selecting less than 7% were coded as having underestimated.guide, we used the categories of the guide as an estimate of the participant's actual risk. The family history categories are: Family History Category 1, 2 and 3. Individuals in Family History Category 1 are those at population risk of developing breast cancer, and women in this category were informed that they were at the same risk as the general population, which is 9%. Responses in the range of 7–12% were therefore coded as correct (as for the estimate of the population risk), corresponding to a comparative risk of 0.8- to 1.3-fold. Participants in Family History Category 2 and 3 are those at estimated risks (as per NBCC guide) of 13–25% and 26–49%, respectively, corresponding to comparative risks of 1.4- to 2.8-fold and 2.9- to 5.4-fold, respectively. Participants’ estimates of their own absolute risk, and the calculated comparative risk, were coded as having being estimated correctly if they were within the stated ranges; overestimated if above the upper limit of those ranges; and underestimated if below the lower limit of those ranges.Given that all participants were counselled with estimates of their absolute risk and comparative risk of developing breast cancer determined from the NBCC BRCA1 or BRCA2. These women were provided with different risk information from those who did not carry these mutations. Available data on the penetrance of these mutations changed over the course of this study, and so women who received their results in 1996 or early in 1997 were counselled that a mutation conferred an 85–90% risk of developing breast cancer, whereas those who received their result later were counselled that this conferred a risk of ‘about 50%’. For mutation carriers, we therefore coded any responses for absolute risk between 50 and 90% and comparative risk between 5.5- and 10-fold as having been estimated correctly; those above these ranges were coded as having overestimated; and those below these ranges were coded as having underestimated.In addition, a number of women in this study learnt that they carry an ancestral mutation in For the question asking women to select a response that best describes their comparative risk in words, women in any family history category who selected ‘a little lower’ or ‘much lower’ were coded as underestimated.Those in Family History Category 1 who selected ‘same’ were coded as correctly estimated, and those who selected ‘a little higher’ or ‘much higher’ were coded as overestimated.Those in Family History Category 2 who selected ‘same’ were coded as underestimated, those who selected ‘a little higher’ as correctly estimated and those who selected ‘much higher’ were coded as overestimated.Those in either Family History Category 3 or the Mutation Carrier Category who selected ‘same’ or ‘a little higher’ were coded as underestimated, and those who selected ‘much higher’ were coded as correctly estimated. For these two categories, a woman was only coded as overestimated if she selected ‘definitely will get breast cancer’.Regression analysis was performed to identify predictors of women's risk estimates. Five analyses were conducted with the dependent variables on the log odds of women's estimates of: (i) population risk, (ii) absolute risk, (iii) comparative risk, (iv) overestimation of absolute risk and (v) underestimation of comparative risk. Independent variables were indicators of respondents’ personal characteristics. Analyses were preformed using Stata v8.2.Of the 339 AJBCS participants who were sent the follow-up questionnaire (average 44 months after enrolment in the study), 256 (76%) returned them. However, 100 women with breast cancer and 4 unaffected women who had had prophylactic bilateral mastectomy were excluded. Of the remaining 152 women eligible for this study, 109 (72%), 144 (95%) and 128 (84%) gave a response for the numeric estimate of population risk of breast cancer, their own absolute risk of developing breast cancer and their comparative risk of developing breast cancer, respectively. Complete personal characteristic data, family cancer history data and risk question data were available for 107 participants (70%).P<0.05), whereas younger women were more likely to have a university degree (P<0.01) and had better genetic knowledge (P<0.05). The mean STAI score was 37.7 (1.5). Recent cancer diagnosis in the family was associated with being a carrier of an ancestral mutation (P<0.01).From Multivariate regression was performed on the log odds of participants’ estimates of population risk, their own absolute risk and their calculated comparative risk (their estimate of their own absolute risk divided by their estimate of the comparative risk). Results are reported in Genetic knowledge and anxiety scores were significantly associated with estimated population risk. An increase in genetic knowledge score was significantly associated with a decrease in the estimate of the population risk, whereas an increase in anxiety score was significantly associated with an increase in estimate of the population risk.Genetic knowledge score was significantly associated with an increase in the estimated absolute risk. Further, having a strong family cancer history (Family History Category 3) and being a mutation carrier (Family History Category Carrier) were also significantly associated with an increase in the estimated absolute risk. There were no statistically significant independent associations between genetic knowledge scores and family history.Family history and mutation carrier status were significantly associated with increasing estimates of comparative risk. That is, having a moderate (Family History Category 2) or strong (Family History Category 3) family cancer history and being a mutation carrier (Family History Category Carrier) were associated with higher estimates of their comparative risk compared with women at population risk (Family History Category 1).Finally, regression analysis was used to identify predictors of overestimation of absolute risk and predictors of underestimation of comparative risk see . Those wThe only variables significantly associated with underestimation of comparative risk were the estimates of population risk and the family history category variables. Higher estimates of population risk and higher family history category  were associated with greater underestimation of comparative risk.In this study, we used a novel approach to determine Ashkenazi Jewish women's estimates of their risk of developing breast cancer. Women were asked their numeric estimates of the population risk and their own absolute risk of developing breast cancer. Their responses were used to calculate their numeric estimate of their comparative risk of developing breast cancer. Further, a comparative risk question, asking the women to choose a category that describes their comparative risk in words, was included to determine whether the numeric values provided by the women reflected their understanding.We have shown that the response in words selected by these women to describe their comparative risk of developing breast cancer was remarkably consistent with the numeric comparative risk calculated by dividing their percentage estimate of the population risk with their percentage estimate of their own absolute risk.We have further shown that women's estimates of the population risk were far higher than the actual population risk of 9%. Overall, participants estimated that more than one in five Australian women will develop breast cancer, when in reality less than half that number will be diagnosed with the disease in their lifetime. Although higher anxiety scores and lower genetic knowledge scores were associated with higher estimates of population risk, the variables included in regression analysis accounted for only a small amount of variation in the data. That is, the number selected for the population risk was for the most part random. This finding is consistent with the economics and psychology literature on risk perception, and suggests that the population risk estimate may be an anchor point upon which other estimates are made , given their high estimate for the population risk. There is a possibility, therefore, that the underestimation of comparative risk in these women could be because they have reached a ceiling or upper limit.The economics of safety literature provides some insight into this issue. Data have been collected where one half of the study participants were asked to estimate the risk of three events , and the other half were provided with the actual risk figure for the first event (death in a car crash) and asked to estimate the risk of the second and third events (death in a motorcycle and bus crash). This study showed that in the first instance all three scenarios were highly overestimated, but once an anchor point had been placed for the first, the estimate of the second and third scenario came much closer to the actual absolute risk and also much closer to the actual comparative risk , then the data in this study showed a ceiling effect, and women have in fact correctly understood the degree to which their family history increases their risk. However, if the women provide lower estimates of their absolute risk, then they have not understood the extent to which their family history increases their own risk.For women in the lowest family history category (those at population risk), the estimate of their absolute risk was generally far too high, but once their estimate of the population risk  was taken into account, their comparative risk estimate was generally correct. That is, these women have placed their anchor point too high but it seems that they understood that they are at the same risk as other women in the general population.BRCA1 and BRCA2 genes. It is not known to what extent these findings may be applicable to other groups. The principles and questions used in this study could easily be applied to other populations to determine whether findings in this study apply to those groups.Participants in the study were drawn from a cohort of Ashkenazi Jewish women participating in a study of the In this study of Ashkenazi Jewish women we have shown that population risk is substantially overestimated. Although significant predictors were found, we were unable to explain most of the variation in the population risk estimate, and we suggest that it may be simply an anchor point upon which women base their other risk estimates. We also found that absolute risk estimates are substantially overestimated by women at population risk, but that this overestimation decreases with increasing family history. Related to this, estimated comparative risk was correct for about half of women at population risk, but substantial underestimation occurs with increasing family history.These findings suggest that women at population risk generally understand their risk, and may be able to provide a better estimate of their absolute risk with better education about the population risk. These findings also suggest that women with a stronger family history understand that their risk is higher due to their family cancer history, but may not understand the full extent to which their risk is higher due to this risk factor. However, the possibility that the underestimation of comparative risk in these women was due to a ceiling effect should be examined in further studies.


Several diseases are known or suspected to be associated with altered levels of hormones and growth factors that may influence breast cancer risk. To elucidate this possibility, we studied the relationship between 23 medical conditions or procedures and breast cancer risk by means of data from a multicentric case-control study conducted between 1991 and 1994 in six Italian areas. The study included 2569 histologically confirmed incident cases of breast cancer  and 2588 control women  admitted to the same hospitals as cases for a variety of acute conditions unrelated to known or suspected risk factors for breast cancer. After allowance for education, parity and body mass index, elevated odds ratios (ORs) emerged for history of diabetes mellitus in post-menopausal women , hypertension in pregnancy  and breast nodules . Risk decreases were associated with ovarian ablation for ovarian cysts  and with thyroid nodules  but not with the combination of any type of benign thyroid disease. While most examined conditions seemed unrelated to breast cancer risk, the association with late-onset diabetes is of special interest as it suggests a role of hyperinsulinaemia and insulin resistance in breast cancer promotion. It also points to preventive lifestyle modifications.


Hyperemesis, a severe nausea combined with vomiting during pregnancy, is associated with increased levels of human chorionic gonadotropin. We investigated the possible relationship between hyperemesis and subsequent breast cancer risk in a case–control study based on registry data. Among 13 079 breast cancer cases and 34 348 individually matched controls we found 148 cases and 405 controls who had been hospitalised for hyperemesis. Hyperemesis was not associated with breast cancer risk , and similar risks were observed regardless of age at diagnosis, number of hospitalisations for hyperemesis or time of follow-up. Our results do not support the hypothesis that human chorionic gonadotropin is responsible for the protective effect of pregnancies upon breast cancer risk.Both parity and a young age at first pregnancy are associated with a reduction in breast cancer risk. The hormones involved in this process are not fully investigated. Human chorionic gonadotropin is a placental hormone, which in rats and in human breast cells British Journal of Cancer (2002) 87, 974–976. doi:10.1038/sj.bjc.6600605www.bjcancer.comCancer Research UK© 2002  In animal models, hCG has been shown both to prevent and to inhibit growth of breast cancer induced by 7,12-dimethylbenz-e (DMBA) . Likewisin vitro .Observational data on exposure to hCG and subsequent breast cancer risk are sparse. One study found a significant decrease in breast cancer risk among women who had been administrated hCG as part of an infertility treatment or as a weight-loss regimen  with 95% confidence intervals (95% CI) using conditional logistic regression for matched case–control studies.To evaluate differences in effect on pre- and post-menopausal breast cancer, we made sub-set analyses of cases with an age at diagnosis of above and below 50 years. To reveal potential long-term effects of hyperemesis we also made subset analyses by time since hyperemesis.Height was evaluated as a potential confounder in a subset analysis consisting of all risk-sets where height was available for the case and at least one control .Mean age at diagnosis of breast cancer was 45 years. Of the cases, 67% were below 50 years of age at diagnosis and were in the analysis considered as pre-menopausal. Compared with controls, cases had on average fewer births, a higher age at first birth, and were taller. There were no differences in offspring gender or proportion of multiple births among cases and controls. The characteristics of cases and controls are shown in Table 1A diagnosis of hyperemesis during at least one pregnancy was reported for 148 cases and 405 controls, resulting in an odds ratio of 1.05 (95% CI 0.86–1.27) after adjustment for parity, age at first birth and the number of pregnancies within a region covered by the in-patient registry (Table 2There was no trend in breast cancer risk with number of pregnancies with hyperemesis. Equally, no trend in risk was observed depending on time between hyperemesis and diagnosis of breast cancer (Table 3We found no altered risk of breast cancer following one or more diagnoses of hyperemesis. The lack of association was independent of length of follow-up. We found no decrease in risk, either for premenopausal or for postmenopausal breast cancer. A slight but not significantly increased risk was observed for postmenopausal breast cancer.At least two previous studies have examined possible associations between nausea during pregnancy and subsequent risk of developing breast cancer. One (Only a little more than 1% of subjects had received inpatient care for hyperemesis. However, the study was large enough to provide reasonably large numbers of cases and controls exposed to hyperemesis. Levels of hCG increase with severity of nausea (Parity and young age at first birth are strong protective factors against breast cancer . It remaOur results suggest that pregnancies do not protect against breast cancer through hCG, at least not in a dose-dependent manner. As women with hyperemesis are exposed to high levels of hCG, they provide one of the few human populations in which to study effects of this hormone. Apart from increases in serum hCG, hyperemesis has also been linked to raised levels of circulating oestrogens, particularly oestradiol (Only the long-term breast cancer risk is reduced by pregnancies (in vitro studies, confirmation is required before hCG can be tested as a preventive agent against breast cancer.In conclusion, we found no association between hyperemesis and subsequent breast cancer risk, and therefore no support for a protective effect of hCG. In spite of the promising results from animal and


Women whose first tumour was c-erbB-2 positive had a 1.7-fold (95% CI: 1.0–3.0) excess CBC risk. Body mass index and c-erbB-2 expression may be risk factors for CBC in young women. Further observational studies are needed to confirm these findings and to evaluate whether testing for c-erbB-2 in this population may help identify those at high risk for CBC.Women diagnosed with a first breast cancer before the age of 45 years have a greater than 5.0-fold risk of developing a second primary contralateral breast cancer (CBC) than women in the general population have of developing a first breast cancer. Identifying epidemiologic or molecular factors that influence CBC risk could aid in the development of new strategies for the management of these patients. A total of 1285 participants in two case–control studies conducted in Seattle, Washington, who were 21–44 years of age when diagnosed with a first invasive breast carcinoma from 1983 to 1992, were followed through December 2001. Of them, 77 were diagnosed with CBC and 907 tumour tissues from first cancers were analysed. Women with body mass indices (BMIs) ⩾30 kg m The strongest identified risk factor for second primary contralateral breast cancer (CBC) is the age at diagnosis of a woman's first primary breast cancer . SmallerA family history of breast cancer and having a first breast tumour with a lobular histology have also been shown to increase CBC risk, while treatment of a first primary breast cancer with chemotherapy or tamoxifen has each been shown to decrease CBC risk  were excluded from our study, and the remaining 1285 women with invasive breast cancer formed our cohort. Both methods of case–control studies were essentially the same and have been described previously (in situ or invasive primary breast cancers among non-Hispanic white women who were diagnosed from 1 January 1983 through 30 April 1990 at 45 years of age or younger and who were born after 1944. Interviews were completed on 845 cases (83.3% of eligible cases). The second study ascertained all incident first in situ and invasive primary breast cancer cases of any race who were diagnosed from 1 May 1990 through 31 December 1992 at age less than 45 years. Interviews were completed on 643 (83.9%) of all eligible cases.The 1488 breast carcinoma patients eligible for this study were women who had previously been interviewed in two population-based case–control studies. Women with −2 are considered underweight, 20.0–24.9 kg m−2 as normal weight, 25.0–29.9 kg m−2 as overweight, and ⩾30.0 kg m−2 as obese) and into quartiles. Information on ever use of treatments for the subjects' first breast cancer, including chemotherapy, radiation, and tamoxifen, was subsequently obtained from three sources: (1) medical record abstractions, (2) telephone and written contacts with subjects or their proxies, and (3) CSS. Informed consent was obtained from all subjects prior to participation.Participants in both studies were interviewed in their homes by a trained interviewer. Respondents were asked about their reproductive history, family history of breast cancer, and their body size history. Weight 1 year prior to diagnosis was used to determine body mass index (BMI) for this study. In our analyses, BMI was grouped using Bray's criteria  , whichever occurred first. Women were considered to have developed CBC if their second breast tumour was: (1) diagnosed greater than 6 months after their first breast cancer was diagnosed; (2) was diagnosed in the opposite breast; and (3) was invasive. All participants had a follow-up time of 6 months or greater. The registry annually contacts the hospital tumour registrar for information on the disease status and vital status of each patient. The tumour registrar then contacts the physician following each patient for an updated determination of vital status. If there is no physician who has had sufficiently recent contact with the patient, then the registrar sends a letter to the patient. This follow-up for both disease status and vital status is performed for cases, regardless of whether or not they currently reside in the CSS catchment area. In addition, passive surveillance through routine computer linkage of patients with Washington State death certificates, the National Death Index, and Health Care Finance Administration tapes is conducted. The status of greater than 85% of the cohort was known within 2 years of December 2001.Data on tumour stage, histology, and size were obtained from CSS. Tumour specimens were requested from hospital and commercial pathology laboratories. We were unable to obtain permission to request tumour tissue from 4.1% of the women. In addition, 25.3% of the tumour blocks were not available or had been discarded by the pathology laboratories.Tumour tissue sufficient for immunoperoxidase assays was available for 907 (70.6%) of the study participants. The study pathologist  conducted a complete histopathologic review for all the tumours collected. The CBC status and clinical and personal characteristics of the women were unknown at the time of review. Expression of oestrogen receptor (ER), progesterone receptor (PR), p53 tumour suppression gene protein, Ki-67 proliferation-related antigen, c-erbB-2 oncogene protein, apoptosis regulatory protein bcl-2, and cell cycle proteins cyclin E and p27 were evaluated on sections from a single tumour block as described previously .Antibodies were scored using a subjective interpretation of staining intensity and/or the percentage of tumour cells positive. Categories of intensity and/or percent cells positive were collapsed into positive/high or negative/low categories as follows: for ER and PR, any nuclear staining was considered positive; the percentage of Ki-67 positive tumour cells was averaged over four high-powered fields and converted to quartiles; the nuclear staining of >10% tumour cells for p53 was considered positive; a distinct membranous staining pattern of 1–3+ was considered positive for c-erbB-2. The antibody staining for c-erbB-2 was carried out using the AO485 antibody from DAKO and was initiated prior to the acceptance of the DAKO's Herceptest kit as the FDA-approved technique for the evaluation of c-erbB-2 expression. The clinical use of this marker to determine therapy was not the objective of this study and as such, we assigned tumours that demonstrated a clear positive membranous stain over that of normal breast epithelium to the positive category. The intensity of bcl-2 stains was categorised as negative, low, intermediate, and high. Expression of cyclin E and p27 was scored as a value from 1 (negative) to 7 (highest intensity). Low intensity included all values of 1–4 and high intensity included values from 5 to 7.Bivariate flow cytometric analysis of DNA content and S-phase fraction was completed for 694 (59%) of the tumours, as described previously  (Table 1−2) when diagnosed with their first breast cancer also had an increased risk of CBC compared to women with a BMI ⩽19.9 kg m−2. When assessed as quartiles, women in the upper two quartiles of BMI had a greater risk of CBC compared to women in the lowest quartile . With respect to weight, women who were in the upper two quartiles of weight had a greater risk of CBC compared to women in the lowest quartile. Alcohol use was not associated with an increased risk of CBC. Finally, a first-degree family history increased CBC risk 1.5-fold, although this increase was within the limits of chance.Multivariable-adjusted estimates of risk for CBC in relation to various patient characteristics are presented in Table 2criteria , women wNeither stage, histology, nor tumour size of the first tumour appeared to alter CBC risk  and a total body weight in the upper two quartiles at the time women were diagnosed with their first breast were associated with increases in CBC risk. The relation of BMI to breast cancer risk and mortality is complex. A high BMI is protective of premenopausal breast cancer, but increases a woman's risk of postmenopausal breast cancer. However, BMI is also positively correlated with risk of mortality among both premenopausal , since participants in research studies may underestimate their weight. This issue has been addressed to some extent since women in the second case–control study who formed our cohort were weighed and measured at the time of their interview. It has been shown that the correlation between self-reported weight 1 year before diagnosis and weight measured at the interview for these women was With respect to molecular markers that are related to CBC risk, we found that expression of c-erbB-2 was associated with an increased CBC risk in our cohort. Given that c-erbB-2 is a potent oncogene and a strong predictor of prognosis, this finding is not surprising, although it needs to be verified by others. While we did not find that any of the other markers we evaluated significantly altered CBC risk, this study was limited by a relatively small number of CBC cases and thus may have lacked sufficient power to detect these associations. Furthermore, this study is largely hypothesis generating and therefore these associations need to be viewed tentatively. Additional insight into the molecular aetiology of CBC is needed and could be gained by the assessment of these and other markers in the contralateral tumours themselves and by comparing them to those expressed by first primary breast tumours.In summary, we present the first data from a large group of young women with breast cancer and find that high BMI at the time of a first breast cancer diagnosis and c-erbB-2 expression by this tumour, both appear to be important risk factors for CBC. If these associations are borne out in future studies, the subgroups of women who either have a high BMI or whose first tumours overexpress c-erbB-2 may warrant closer screening for CBC. Additionally, it will be important to establish whether interventions such as treatment with c-erbB-2-targeted therapies, such as trastuzumab, after diagnosis with breast cancer alter the incidence of CBC in young women.


It has been suggested that World War II influenced breast cancer risk among Norwegian women by affecting adolescent growth. Diet changed substantially during the war, and the reduction in energy intake was assumed to be larger in non-food- producing than in food-producing municipalities. In the present study, we have looked at the influence of residential history in areas with and without food production on the incidence of breast cancer in a population-based cohort study consisting of 597 906 women aged between 30 and 64 years. The study included 7311 cases of breast cancer, diagnosed between 1964 and 1992. The risk estimates were calculated using a Poisson regression model. The results suggest that residential history may influence the risk of breast cancer, where the suggested advantageous effect of World War II seems to be larger in non-food-producing than in food-producing areas. Breast cancer incidence was observed to decline for the post-war cohorts, which is discussed in relation to diet.British Journal of Cancer (2002) 86, 362–366. DOI: 10.1038/sj/bjc/6600084www.bjcancer.comThe Cancer Research Campaign© 2002  It has been suggested that breast cancer incidence is particularly sensitive to influences early in life. Associations have been observed between birth weight  and otheIn Norway, there has for a long time been a contrast between the incidence of breast cancer in urban and that in rural areas. During World War II the Norwegian population experienced food restriction, as well as changes in the foods consumed. These changes were more pronounced in towns and in areas that did not produce food .The present study aimed, therefore, to examine the influence of residential history, in areas with and without food production, on breast cancer incidence in relation to the dietary effects of World War II.Statistics Norway conducted a national population census in 1960, which consisted of all inhabitants living in Norway at this time. Based on this census, all inhabitants were assigned an 11-digit personal identification number, which was put into use in 1964; this gave rise to the opportunity to register vital statistics about the Norwegian population. Since 1964 the Central Population Registry has compulsorily registered all migration to or from Norway, and between municipalities within the country. All cancer cases diagnosed since 1953 have been compulsorily reported to the Cancer Registry of Norway.From this census, the following information was used for each person: place of birth, year of birth, vital status, residence data, reproductive data and data about education and occupation. Cancer information was obtained by linkage to the Cancer Registry of Norway using the personal number of every citizen.The median age of a first full-term pregnancy for birth cohorts during the period 1935–1953 was 23 . Hence, The municipalities were classified into areas with (Food) and without food (Non-food) production, according to the main income sources for the municipalities in 1968 . The Foon=740 531), and who fulfilled the criteria of a residence category, were included. This resulted in 597 906 women, including 7311 women with breast cancer. The closing date of follow-up was the date of diagnosis, death, migration from Norway or a cut-off date of 31 December 1992.The study is based on a total of 2 255 814 women registered as living in Norway since 1960. Women born between 1926 and 1960, aged between 30 and 64 years during the observation period 1964–1992 , medium (10–12 years) and high (⩾13 years) educational level. Based on the information from the census, according to International standard classification of occupations 1958 , three lTo investigate the relationship between residential history and the incidence of breast cancer, a model of age, period and cohort was applied, based on the Poisson distribution. Stratified analyzes by residence category were performed. Estimation and testing were carried out using the EPICURE statistical program , with 95% confidence intervals (95% CI). The effects of potentially confounding variables, available in this study, were evaluated by including age at first birth, and level of education and occupational activity in the analyses.To illustrate the pattern of breast cancer incidence in Norway during the twentieth century and for comparison with results obtained previously  the inciTable 1Table 2Figure 1nd III-5 . The sugIt is notable, from Table 3In Norway, there has been an increasing incidence of breast cancer over time, however, the incidence seems to have levelled off for women who were teenagers during the World War II . The maiOf course, the residential areas are different in many aspects. The child-bearing pattern has been different, as well as the educational levels and occupational possibilities. From previous studies, it is known that these factors may also influence breast cancer risk (The level of physical activity increased during the war . A higheThe present results may support the hypothesis that energy deprivation at certain ages is a determinant of breast cancer. A reduced stature as a result of energy restriction early in life may explain the reduced incidence of cancer in Non-food relative to Food areas. Energy restriction during the growth years is associated with reduced adult stature and a reduced number of breast tissue cells, which affects the risk of breast cancer . Lund NiThe age at menarche was not substantially changed during the war ; hence tThe tendency for a decline in incidence in post-war cohorts corresponds to the observation by During World War II, In conclusion, the results indicate that residential history may influence the risk of breast cancer. The suggestion that World War II had a beneficial influence on breast cancer risk seems to be evident more in Non-food than in Food areas, which supports the influence of nutrition during the growth years on breast cancer risk. Furthermore, breast cancer incidence appears to decline in post-war cohorts, and later on in Food areas. In discussion about future studies of diet and breast cancer, energy restriction and patterns of exposure to myocardial infarction risk factors could be taken into account.