Across Europe, the outlook for women diagnosed with early breast cancer is likely to be far better now than at the start of my career. Effective screening programmes mean women are being diagnosed earlier, and greatly improved surgical techniques have also made a significant impact. Post-surgery, the evolution of adjuvant therapy has meant that we now have an armoury of effective treatments to stop breast cancer returning, although debate continues on how these treatments should be used for maximum benefit.The greatest concern for doctors, and for women who are being treated for early breast cancer, is that it may return, which ultimately means their disease is incurable. Although all patients are at risk of recurrence, the greatest risk is around 18 months after surgery and a level of risk remains for many years, particularly in hormone receptor positive early disease [Looking back at clinical trials shows how far the oncology world has come. The effect of oestrogen on breast cancer risk was first shown over 100 years ago when researchers found that removing the ovaries of women with breast cancer improved their chances of survival. Following this, the first anti-oestrogens were developed and it is now over 30 years since tamoxifen was found to delay breast cancer recurrence. In 1983, the breakthrough NATO trial confirmed the place of tamoxifen as a gold-standard treatment for post-menopausal women with early breast cancer, by reducing the risk of recurrence by around 50% .Following tamoxifen, aminoglutethimide was investigated as an anti-aromatase adjuvant treatment for early breast cancer, laying the first steps for aromatase inhibitors (AIs)  AIs are Data from the ATAC  trial, one of the world’s largest and longest-running breast cancer trials, comparing five years of upfront anastrozole with tamoxifen, has further confirmed the place of anastrozole as a new gold-standard treatment for early breast cancer. Over a median follow-up of 100 months (>8 years), anastrozole significantly reduces the risk of recurrence compared with tamoxifen by 24% (p<0.0001) and improves disease-free survival by 15% [Other early breast cancer trials that have followed thousands of women over many years have also confirmed the benefits of AI treatment, indicating that five years of treatment with tamoxifen alone may be sub-optimal for all patients other than those at the lowest risk of recurrence. Recent survival data from BIG 1–98, albeit not statistically significant, suggest longer follow-up and meta-analytical approaches may be required in order to determine whether the efficacy advantages of the aromatase inhibitors over tamoxifen, in terms of recurrence risk reduction, will translate into breast cancer survival benefit .The debate still remains, however, around when it is best to introduce an AI into a treatment regimen, that is upfront as initial adjuvant treatment, following 2–3 years of tamoxifen or to extend adjuvant treatment after five years of tamoxifen is completed. The Intergroup Exemestane Study (IES) reported that switching to exemestane after 2–3 years of treatment with tamoxifen significantly improved survival rates for the AI, although it should be remembered that a switching strategy may put patients at risk by starting with the inferior treatment at the time when risk of recurrence is highest and also expose patients to the risk of side effects from two different agents . The BIGTo add to the evidence base, a number of investigations are underway to ascertain the optimal treatment period for adjuvant therapy. There is a clear rationale for continuing to treat with hormonal therapy, given that breast cancer recurrence remains a threat more than ten years after surgery. Preliminary results from the Adjuvant Tamoxifen Longer Against Shorter (ATLAS) study investigated the benefits of using tamoxifen beyond five years, although the accumulation of serious side effects during long-term tamoxifen use has led to questions around the effectiveness of this approach .Ensuring women remain free from breast cancer for many years will continue to be a clinical challenge. In my view, the best chance of protecting against recurrence is to commence treatment with the most effective adjuvant therapy at diagnosis, one that is well tolerated, has a well-understood safety profile, and means that fewer patients have to be told the devastating news that their breast cancer has recurred. Advancements in treatments and ongoing clinical debate will undoubtedly continue, but we can be certain that the evolution of hormonal treatments has secured the place of aromatase inhibitors for many years to come.Tony Howell is a Professor of Medical Oncology in the Cancer Research UK Department of Medical Oncology, University of Manchester, at the Christie Hospital NHS Foundation Trust, Manchester, UK. After training in London and Birmingham and working for the Medical Research Council, he became the Head of the Medical Oncology Breast Service, Christie Hospital. His major interest is in all aspects of breast diseases, having published more than 472 papers in this area. He has received educational and research grants from AstraZeneca.


Previous studies showed that sex hormone might play a role in the development of oesophageal cancer in Western countries. However, evidence from Chinese populations is still lacking.We performed a hospital-based case-control study in Guangzhou, China. From June 2006 to May 2009, face-to-face interviews were conducted on 73 cases and 157 controls. Cases were Chinese females with newly diagnosed primary oesophageal cancer. Controls were hospitalized individuals without cancer and frequency matched by age groups. The interviews included questions about childbearing and menarche history, together with potential confounders. Unconditional logistic regression was used to estimate the risk of factors.Women who had given birth before were not at increased risk compared to childless women . The risk of oesophageal cancer increased with age at first birth: the adjusted OR for women first giving birth at age 25 or later was 2.02 (95% CI: 1.01 ~ 4.04) compared with those reporting their first birth before age 22. History of spontaneous abortion was not significantly associated with increased risk . No significant association was observed between menstrual variables  and risk of oesophageal cancer.Giving birth at later age may increase the risk of oesophageal cancer in women. Further studies in Chinese populations with larger sample sizes are still needed. Worldwide, oesophageal cancer is the eighth most common type of cancer and the sixth most common cause of death from cancer . In ChinOesophageal cancer occurs mainly in two histological types, squamous cell carcinoma and adenocarcinoma. Squamous cell carcinoma has always been the dominant histological type of oesophageal cancer in China. However, the incidence of adenocarcinoma has increased rapidly in some developed countries during the past decades. Meanwhile, the incidence of squamous cell carcinoma has been more stable over time in these countries . Such inOne of the most intriguing observations in the incidence of oesophageal cancer is the male predominance, which has not been well explained. In Western countries, the incidence of oesophageal cancer has a male to female ratio of up to 8:1 ,8. This Although incidence of oesophageal cancer in China is among the highest in the world, no evidence is available on the effect of sex hormone on oesophageal cancer risk among Chinese populations. In addition, squamous cell oesophageal cancer represents the majority of oesophageal cancer cases in China. Thus, previous evidences from Western countries mostly concerning the effect of reproductive factors on the risk of oesophageal adenocarcinoma may not apply to Chinese populations. Therefore, we conducted a case-control study in Guangzhou, China, to investigate the long-term effects of reproductive factors on oesophageal cancer risk in women in a Chinese population.This study was conducted in one large teaching hospital in Guangzhou, China. Guangzhou is a city with moderate incidence rates for oesophageal cancer in China. In 2006, there were totally 257 male and 56 female cases diagnosed with oesophageal cancer in Guangzhou with crude incidence rates of 13.04/100.000 and 2.97/100,000, respectively, showing a male/female incidence ratio of 4.4 . All ChiTrained interviewers conducted face-to-face interviews using a structured questionnaire to collect information on childbearing and menarche history, together with sociodemographic characteristics and potential confounding factors. Collected potential confounders mainly included tobacco smoking, alcohol use, gastroesophageal reflux, anthropometric measures (height and weight), dietary habits, and regular medication. Similar to previous studies ,13, histAll statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS) software 13.0 for windows. Chi square or t tests were used to test differences of sociodemographic factors and potential confounders between the cases and controls. Unconditional logistic regression was used to estimate the odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for each exposure variable. The associations between exposure variables and risk of oesophageal cancer were further examined after adjusting for potential confounders using multivariate logistic regression models. Potential confounders entered into the final model included: age, reflux, smoking, alcohol use, education, employment, body mass index, and intake of fresh vegetables and fruits. We also considered further adjustment for aspirin or nonsteroidal anti-inflammatory drugs (NSAID) use but the estimated ORs did not substantially changed. Also because only a very small proportion of the subjects (lower than 10% for both cases and controls) had regular use of such medicines, aspirin or NSAID use was not included in the final models. The cut-off points for number of children born and age at menarche were predefined based on biological considerations. Age at first birth, age at menopause, and years of menstruation were grouped into quartiles using cut-off points among the controls. To see whether the risk estimates differ by histological type, we also re-analyzed the data after restricting cases to those with diagnosis of squamous cell carcinoma.Squamous cell carcinoma was the most frequent histological type, which comprised 93.2% (68 cases) of all cases. The distribution of demographic characteristics and major risk factors for oesophageal cancer among cases and controls are shown in Table The relationship between oesophageal cancer risk and reproductive factors is presented in Table The present study was the first one that has been performed in a Chinese population to investigate the effects of reproductive factors on oesophageal cancer risk. This study suggested that giving birth at later age might increase the risk of oesophageal cancer in women. Such findings were in line with those of a previous study in Italy that the OR was 2.5 for women first giving birth at age 30 or later compared with those whose first birth occurred before age 25 . We did This study has several major strengths. First, an extensive effort was made to collect information on major risk factors for oesophageal cancer, which was further considered and adjusted throughout the analysis. Second, all cases in this study were histologically confirmed, which minimized misclassification. In addition, in many hospital-based studies, controls were taken from hospitalized individuals with higher chance than the general population to share a common exposure with cases, which may be a threat to the validity of the results. In this study controls were selected from those who came to hospitals for routine health examination, probably making the controls more representative of the general population. However, since it was not a random sample of the general population, there was still a certain risk of selection bias if people seeking routine health examination had any difference in terms of the studied exposures.Because of the rarity of oesophageal cancer in women, we only had limited number of cases. Actually, other similar studies also suffered from this problem with low statistical power . IncreasAs the first study to investigate the effects of reproductive factors on oesophageal cancer risk in a Chinese population, this study found suggestive evidence that giving birth at later age might increase the risk of oesophageal cancer in women though this needed confirmation. Further studies in Chinese populations with larger sample sizes are still warranted.The authors declare that they have no competing interests.All authors read and approved the final study. ZHC designed and coordinated the study, carried out data analysis and wrote the draft. JLS, JRL, and XZ recruited subjects, organized interviews, and participated in data analysis. QC participated in study design and coordination, and edited the manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-230X/11/49/prepub


It is debated whether mammographic density gives rise to more aggressive cancers. We therefore aimed to study the influence of mammographic density on prognosis.n = 1774). Mammographic density of the unaffected breast was assessed using a computer-assisted thresholding technique. The Cox proportional hazards model was used to study recurrence and survival with and without stratification on surgical procedure (breast-conserving surgery vs. mastectomy).This is a case-only study within a population-based case-control study. Cases were all postmenopausal women in Sweden with incident breast cancer, diagnosed 1993-1995, and aged 50-74 years. Women with pre-diagnostic/diagnostic mammograms were included (Percentage density (PD) was associated with both local and locoregional recurrence even after adjustment for established prognosticators; hazards ratio (HR) 1.92, p = 0.039, for local recurrence and HR 1.67, p = 0.033, for locoregional recurrence for women with PD≥25% compared to PD<25%. Stratification on surgical procedure showed that the associations were also present in mastectomized women. PD was neither associated with distant recurrence nor survival.High mammographic density is an independent risk factor of local and locoregional recurrence but is neither associated with distant metastasis nor survival. The relationships with local and locoregional recurrences were also present in women treated with mastectomy, indicating that they are not merely explained by density masking residual disease in women treated with breast-conserving surgery. Rather there appears to be a true association. Thus, mammographic density should possibly influence adjuvant therapy decisions in the future. Mammographic density (MD) is one of the strongest risk factors for breast cancer. Women with highest density (>75%) have a fivefold increased risk compared with women with almost entirely fatty breasts (<5%) . MD refeWhether MD influences prognosis is not known. There are several possible mechanisms by which density could affect prognosis. MD has consistently been shown to be associated with the stromal composition of the breast , which in = 3,979), and 84%  participated. However, 19 cases were diagnosed outside of the study period, one case had a diagnosis other than breast cancer, and 58 cases had non-invasive breast cancer, rendering them ineligible and leaving 3,267 women in the study.This study is an extension of a large case-control study among all Swedish residents who were born in Sweden and who were 50 to 74 years old at the time of enrollment (1 October 1993 to 31 March 1995). Details on data collection and subjects have been provided previously . Women wet al. [For this study, the inclusion criteria were further refined to include only post-menopausal women who had no prior diagnosis of cancer other than non-melanoma skin cancer  for body mass index (BMI), breast cancer heredity, previous benign breast disease, age at menarche, oral contraceptive use, age at first birth, parity, breast feeding, age at menopause, and hormone replacement therapy (HRT) use. However, there was a difference in age at study entrance .Values of descriptive statistics (means and proportions) for women excluded because of the factors above did not differ significantly from those for included women , the Regional Ethical Review Board in Umeå, and the Regional Ethical Review Board in Uppsala. Prior to participation via a mailed questionnaire, written consent was obtained from all patients.Data on sociodemographic, anthropometric, hormonal, and lifestyle factors were collected by means of a postal questionnaire. Because date of mammography was prior to study entrance, the variables of age, menopausal status, and HRT use were reassessed according to date of mammography. This was not possible for BMI as we had information on BMI at study entrance and 1 year prior to study entrance only. However, it has previously been shown that inter-individual variations in BMI are small , and theHRT use was classified as 'current', 'former', or 'never' to indicate how recent it was. Because the influence of HRT on MD is supposed to diminish within 3 weeks of cessation , former We used the national registration numbers to retrieve patient records and register information. Between 2000 and 2002, we collected information on primary surgery, adjuvant treatment , tumor characteristics, possible recurrence, and reason for diagnostic mammography from surgical and oncological patient records throughout Sweden.We collected information on emigrations from the Swedish National Population Register and on the date and cause of death until 31 December 2008 from the Swedish Causes of Death Registry. The latter registry covers all residents in Sweden with essentially no missing deaths and has been shown to correctly classify 98% of breast cancer deaths . The folGrade was classified according to the Nottingham histologic grade or the Bloom-Richardson scale into three groups. Tumors were considered estrogen receptor (ER)-positive or progesterone receptor (PR)-positive if they contained at least 0.05 fmol receptor/μg DNA or at least 10 fmol receptor/mg protein.Type of surgery was classified as breast-conserving surgery or mastectomy independent of axillary surgery because 98% of our study participants had axillary lymph node clearance carried out. Local recurrence included recurrence in the residual ipsilateral breast, scar tissue, or chest wall. Locoregional recurrence included both local recurrences and recurrences in regional lymph nodes. During the collection of follow-up information from clinical records, the study subjects' follow-up period was marked as complete or incomplete depending on whether follow-up information was complete or missing until date of retrieval. The follow-up time for recurrence variables was thus computed as follows: If the specific recurrence occurred, the follow-up time was computed from the date of diagnosis to the date of that specific recurrence; if the specific recurrence did not occur and follow-up information from medical records was considered complete, the follow-up time was computed from the date of diagnosis to the date of medical record retrieval or the date of death, whichever came first; if information on follow-up was considered incomplete, the follow-up time was computed from the date of diagnosis to the last documented date in the medical record or the date of death, whichever came first.2 of 0.92).Film mammograms of the medio-lateral oblique view were digitized by using an Array 2905HD Laser Film Digitizer , which covers a range of 0 to 4.7 optical density. The medio-lateral oblique view was used since this was the routine view used at mammography screening in Sweden. The density resolution was set at 12-bit spatial resolution. We used Cumulus, a computer-assisted thresholding technique, to assess density  of the mAs in the report by Eriksson and colleagues , densityt tests for continuous variables. We also carried out age-adjusted analyses pertaining to the above by using logistic regression.The descriptive characteristics of cases with high density versus cases with lower density were compared by using chi-squared tests for categorical variables and Student The survival analyses were carried out by using the Cox proportional hazards model. We made use of two models. The first model was carried out to attempt to study the association between MD and recurrence and survival variables. We therefore included only age (continuous), BMI (continuous), and HRT use  in this model since these variables are strongly associated with MD and breast cancer risk  and may P <0.0001), BMI (P <0.0001), previous oral contraceptive use (P <0.001), parity and age at first birth (P = 0.005), HRT use (P <0.001), and previous benign breast disease (P <0.001) were all associated with PD (Table P <0.001), parity and age at first birth (P = 0.001), HRT use (P <0.001), and previous benign breast disease (P <0.001) as well as age at menopause (P = 0.046).The mean PD was 18%. Age at mammography (P = 0.011) and tumor size (P = 0.007) as well as a tendency for women with dense breasts to develop locoregional recurrence more often (P = 0.056)  had a threefold higher risk of local recurrence and twofold higher risk of locoregional recurrence compared with women in the lowest PD quartile . Thus, our density measurements should be representative for a post-menopausal cohort. Because the reader was blinded to outcomes, any measurement error would be a non-differential misclassification of exposure and thus would only attenuate results. However, the reader who was trained by Norman Boyd, an expert on MD and one of the developers of Cumulus [2 = 0.92), which should minimize exposure misclassification.The mean density was relatively low in this study population since all women were post-menopausal when the mammograms were taken. The mean age at mammography was thus relatively high (approximately 62 years of age). The study population was originally population-based. Hence, we had information on breast cancer risk factors on 84% of all women who were 50 to 74 years of age and whose invasive breast cancer was diagnosed in Sweden during 1 October 1993 to 31 March 1995, and we were able to compare this information with the women who were not included in the present study. We found that there were no differences in risk factors  except for a difference in age at study entrance of the original study  participated in the study design, interpretation of results, and the revision of the manuscript and read and approved the final manuscript.


Isoflavones, phytoestrogens in soy beans with estrogen-like properties, have been examined for their cancer protective effects. Mammographic density is a strong predictor of breast cancer. This review summarizes studies that have examined the association between isoflavones and breast density. Observational investigations in Hawaii and Singapore suggest slightly lower breast density among women of Asian descent with regular soy intake, but two larger studies from Japan and Singapore did not observe a protective effect. The findings from seven randomized trials with primarily Caucasian women indicate that soy or isoflavones do not modify mammographic density. Soy foods and isoflavone supplements within a nutritional range do not appear to modify breast cancer risk as assessed by mammographic density.  The low breast cancer rates in Japan as compared to Western countries and epidemiologic evidence ,2 offer Soy and soy derived foods are by far the richest source of isoflavones  in the human diet . IsoflavIf isoflavones act on breast cancer risk through an antiestrogenic mechanism, it is possible that isoflavone supplementation in premenopausal women with high circulating estrogen levels is not sufficient to influence breast cancer risk. However, in postmenopausal women with low circulating estrogen levels primarily derived through conversion from androgens in adipose tissue, isoflavones from foods or supplements may be more likely to exert an estrogen-like action on the breast raising some concern about adverse effects . In addiMammographic density, one of the strongest breast cancer risk factors, describes the radiographic appearance of the female breast . Fat, whHormone replacement therapy (HRT), in particular containing progestin, has been shown to increase mammographic densities . As obseIn comparison to HRT, the relation between mammographic density and endogenous sex steroids is less clear . WhereasOur search for studies on isoflavones and breast density identified six reports  from fivThe cross-sectional studies  and the Two reports from the same study population in Singapore indicated possible beneficial effects of soy on breast density ,54. DietDespite three suggestive reports ,53,54, tOf the eight reports describing seven randomized trials , hormonaIn most studies, the mammograms had been obtained as part of regular medical care; the subjects were not exposed to additional radiation as part of the interventions. Therefore, due to current screening recommendations, women under 40 years could not be enrolled into the interventions. All trials except the soy-food based trial  were blivs. −0.5%) and was attenuated after adjustment for baseline percent density (P = 0.06). The OPUS trial had the challenge that some of the mammograms were digital, whereas the majority were regular film mammograms [All but three reports ,61,64 usmmograms . FortunaIn the 2-year nutritional trial, the effects of lifetime soy intake on mammographic density were also explored . Soy intThe eight reports, including the three high-dose trials, were in agreement that isoflavone or soy treatment did not result in statistically significant changes in mammographic densities when compared to the control arm ,63,64,65Soy consumption may have a stronger association with mammographic density in subjects who are able to metabolize the isoflavone daidzein to equol than those who cannot . SeveralAlthough cross-sectional investigations in Hawaii and Singapore suggest slightly lower breast density among women of Asian descent with regular soy intake ,53,54, tThe body of literature discussed here has a number of limitations. Nearly every trial reviewed here administered a different isoflavone containing product  or even Methodological problems in density assessment raise some questions about the validity of the findings. As shown in a comparative report , there wOn the positive side, the lack of an isoflavone treatment effect on breast density offers some reassurance to those who are concerned about the possible risks of soy foods . Concern


Evaluating the cost-effectiveness of breast cancer screening requires estimates of the absolute risk of breast cancer, which is modified by various risk factors. Breast cancer incidence, and thus mortality, is altered by the occurrence of competing events. More accurate estimates of competing risks should improve the estimation of absolute risk of breast cancer and benefit from breast cancer screening, leading to more effective preventive, diagnostic, and treatment policies. We have previously described the effect of breast cancer risk factors on breast cancer incidence in the presence of competing risks. In this study, we investigate the association of the same risk factors with mortality as a competing event with breast cancer incidence.We use data from the Canadian National Breast Screening Study, consisting of two randomized controlled trials, which included data on 39 risk factors for breast cancer. The participants were followed up for the incidence of breast cancer and mortality due to breast cancer and other causes. We stratified all-cause mortality into death from other types of cancer and death from non-cancer causes. We conducted separate analyses for cause-specific mortalities.We found that “age at entry” is a significant factor for all-cause mortality, and cancer-specific and non-cancer mortality. “Menstruation length” and “number of live births” are significant factors for all-cause mortality, and cancer-specific mortality. “Ever noted lumps in right/left breasts” is a factor associated with all-cause mortality, and non-cancer mortality.For proper estimation of absolute risk of the main event of interest common risk factors associated with competing events should be identified and considered. Women in a clinical trial with breast cancer incidence as the endpoint may die due to causes other than breast cancer before the occurrence of the cancer. Competing events should be taken into account in evaluating the efficacy and cost-effectiveness of screening interventions both at the population level and for a given individual . A specific screening intervention may be recommended for a woman based on her age and other characteristics, such as having a family history of breast cancer. However, these characteristics can also affect the occurrence of competing events; so, it is essential to study the effect of risk factors on both breast cancer incidence and its competing events such as mortality due to other causes.Some studies have focused on the main event of interest and considered competing risks. Fang et al. examinedOther studies focused on all competing events and investigated the effect of some risk factors on the main event of interest and its competing risks. Several studies used cohort life tables to derive probability estimates for death due to breast cancer as well as mortality due to other causes. Hence, they were able to estimate reductions in breast cancer mortality,6. LambeIn another study, we haveThe main focus of the current study and of is on brBreast cancer incidence and mortality due to non-breast cancer causes are competing risks and both should be analyzed. The necessity of studying both events is given in detail in Discussion section of the paper. In this paper, we investigate the effect of 39 risk factors on mortality due to causes other than breast cancer. So, the current paper and are compThe Canadian National Breast Screening Study (CNBSS) has been described previously-12. Its Woman in the CNBSS were not pregnant at the time of enrolment, had no history of breast cancer and no mammogram in the past 12 months. At enrolment, they completed enrolment and epidemiology questionnaires which included information on demographics, life style, family history of breast cancer, and personal history of breast disease. Moreover, at enrolment a nurse or physician performed a physical examination of the breasts and recorded information on several risk factors.The CNBSS contains information on breast cancer diagnoses reported for women in the intervention group; these women received up to five mammograms. In addition, breast cancer diagnoses were identified by record linkage with the National Cancer Registry and deaths through linkage with the Canadian Mortality Database at Statistics Canada for both the control and the intervention groups after the annual screenings had ended.For this analysis we consider 1980–1989 as the study period and exclude breast cancers which were diagnosed less than six months after enrolment to eliminate long-term prevalent breast cancers.A total of 89,434 women were considered in our study: of these, 944 were diagnosed with invasive breast cancer, 922 died from causes other than breast cancer  value was less than 0.05.It should be noted that hazard of subdistribution proposed by Fine and Gray is anothWe checked the interaction of the variables with each other and with time to event (time of death or censoring time) to find those variables with a time-varying effect on the risk of mortality. No interaction terms were found to be statistically significant.cuminc in package cmprsk in R (http://cran.r-project.org/web/packages/cmprsk/cmprsk.pdf).In Figure From 89,434 participants in the study, 1.06% (N = 944) were diagnosed with invasive breast cancer, 1.03% (N = 922) died from causes other than breast cancer, and 97.9 %  were alive and not diagnosed with breast cancer by the end of 1989. 58.1% (N = 536) of the deaths were due to other types of cancer, and 41.9% (N = 386) due to causes other than cancer. The mean times from enrolment to cancer diagnosis and to death are 3.52 (SD 2.0) and 4.26 (SD 2.17) years respectively. The median from enrolment to cancer diagnosis and to death are respectively 3.18 and 4.23 years.The mean and median follow-up time of women in the censored group  are 6.72 SD 1.32) and 6.39 years, respectively. Figure 2 and 6.3Figure Table Women who have ever noted lumps in their breasts or have had discharge from their breasts have respectively 1.3 and 1.5 times higher risk of death than those who have not. Having the first child at age 14 to 19 is associated with a 1.4-fold higher risk of death  than having the first child at age 20 to 25.The predictors for mortality due to cancer (excluding breast cancer) are presented in Table Table )”, and “cigarettes smoked per day” are common to the three morality models. If we compare the significant risk factors for mortality with those associated with breast cancer incidence, we find “age at entry” appears in all four models. “Menstruation length” and “number of live births” are statistically significant risk factors for breast cancer incidence, all-cause mortality, and cancer-specific mortality. “Ever noted lumps in breasts” is associated with breast cancer incidence, all-cause mortality, and non-cancer mortality.Table In this study, we identify the predictors for all-cause mortality, cancer-specific mortality , and non-cancer mortality. As previously reported, mortality due to causes other than breast cancer is a competing risk for breast cancer incidence in the data from the Canadian National Breast Screening Study (CNBSS). It should be noted that we investigated the associations for allocation group (no-mammography vs. mammography) to both breast cancer incidence and its competing mortality. We conducted univariate and multivariate analyses, and in none of the models, did this categorical variable reach statistical significance when combined with other risk factors. This does not mean there is no some real difference in breast cancer incidence in these two groups, but the data do not show it statistically. Otherwise, the analysis would have been stratified by allocation group and separate results obtained for each group. Therefore, to make use of a larger sample size for statistical analysis we combined all the data without stratification by allocation group.We found that using estrogen or progesterone supplements for a longer time and longer menstruation are both protective factors against all-cause mortality. These results are consistent with other studies’ findings that mortality among women who use hormones is lower than among nonusers,18, and The all-cause mortality analysis revealed a decrease in mortality with number of live births. In the literature, there is no consistent pattern of mortality with the number of births. Some stSimilar to our result which shows an increase in the risk of mortality when a woman has her first child at a younger age (14–19), Grundy and Kravdal also fouSimilar to the results from all-cause mortality, increase in the number of live-births exhibits a decreasing trend in the risk of cancer-specific mortality, although the nulliparous level does not reach statistical significance. As the number of pregnancies increases the risk of cancer-specific mortality increases as well, although only more than ten times of pregnancy reaches statistical significance. Moreover, increasing age at first child birth shows a clear decreasing trend for risk of cancer-specific mortality; however, only decrease in the risk of women who had their first child-birth at age 20–25 compared to those who had it at age 14–19 is statistically significant.We also found that women who were practicing BSE on enrolment also had lower all-cause mortality. Arguably, women who practice BSE are more likely to have better personal health practices such as exercise, nutrition, etc.Event though we observe no trend in the first three levels of the number of cigarettes smoked per day (i.e. up to 11–25 cigarettes per day), the next three levels clearly show an increasing trend in the risk in all three mortality models.Ever noting lumps in the breasts or having discharge from the breasts are both associated with non-cancer mortality. Although we do not have sufficient data to investigate biological association of these two factors with each cause of mortality, one reason for increased risk of non-cancer mortality could be anxiety caused by discovery of a breast abnormality. Women wBy using the CNBSS, our study takes advantage of a large cohort linked to the Canadian Cancer Registry and the Mortality Database at Statistics Canada and relatively complete data collected at the time of enrolment and the initial physical examination of the breasts. This makes our investigation of the association of 39 different risk factors with breast cancer incidence and its Estimating the absolute risk of an event as accurately as possible is fundamental in clinical decision-making-28. In tMoreover, describing the natural history of cancer and possible pathways that an individual may go through is an essential component of any simulation model which is developed to assess the effectiveness of different intervention policies. In a microsimulation model, the life histories of many individuals are generated, and each history substantially depends on the value of different risk factors for a given individual. For example, a woman who has a relative with breast cancer is at a higher risk of being diagnosed with breast cancer at a younger age. Other competing events, such as death due to different causes can also be influenced by the risk factors. For example, a woman aged 70 or above may die due to heart attack before she is diagnosed with breast cancer. Therefore, the effect of risk factors on all competing events should be studied and described to model realistic life paths of individuals. The simulation models could be either developed for evaluating costs and benefits of cancer interventions at the population level, or for an individual according to her risk factors, as the practice of personalized medicine.A cost-effective breast cancer screening policy relies on knowing the absolute risk of breast cancer, and as discussed, to obtain the absolute risk, competing risks should also be studied and taken into account. The absolute risk can then be used to decide whether a woman is categorized as high risk and whether a specific intervention with higher frequency should be recommended.Gail et al. developeIn this study, we show that some risk factors are statistically significant for both the main event of interest (incidence of invasive breast cancer) and a competing event . In addition, we identify other risk factors associated with all-cause mortality and cause-specific mortality. All these factors must be taken into account in estimating the probability of a competing event. With more accurate estimation of the probability of a competing event, the estimations of absolute risk of the main event of interest can be estimated more precisely. This in turn leads to more robust cost-effective analysis of preventive, diagnosis, and treatment policies which are decided based on the results of the absolute risk prediction model.We used a cause-specific model to conduct regression analysis on our competing risks data. In addition, we fitted the Fine-Gray model and the results were very close to the results of the cause-specific hazard model. The cause-specific model is more clinically and biologically understandable since it directly describes the effect of a covariate on a specific cause and its hazard, regardless the effect of other covariates,30. In oK competing causes, the cause-specific hazard, which is defined as the instantaneous probability of failing from cause k isWhen there are Z is a vector of covariates (risk factors), and the overall hazard isk is defined as follows[where  follows:The authors report no conflicts of interest associated with this work.ST prepared the CNBSS data for analysis, conducted the statistical analysis, and drafted the initial manuscript. JF helped in conducting the statistical analysis and writing the literature review of the manuscript. DB and NM contributed in conducting statistical methods, constructing the models, and interpreting the results. ABM designed, coordinated and directed the Canadian National Breast Screening Study (NBSS), and helped in understanding the data and interpreting the statistical results. BJH assisted in understanding the data and interpreting the statistical results. AJ and BJH are the co-PIs of the project and performed critical revisions of the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/12/299/prepub


Women who receive chemotherapy for a first primary breast cancer have been observed to have a reduced risk of contralateral breast cancer (CBC), however, whether the genetic profile of a patient modifies this protective effect is currently not understood. The purpose of this study is to investigate the impact of germline genetic variation in genes coding for drug metabolizing enzymes, transporters, and targets on the association between chemotherapy and risk of CBC.From the population-based Women’s Environment Cancer and Radiation Epidemiology (WECARE) Study, we included 636 Caucasian women with CBC (cases) and 1,224 women with unilateral breast cancer (controls). The association between common chemotherapeutic regimens, CMF and FAC/FEC, and risk of CBC stratified by genotype of 180 single nucleotide polymorphisms in 14 genes selected for their known involvement in metabolism, action, and transport of breast cancer chemotherapeutic agents, were determined using conditional logistic regression.CMF  and FAC/FEC  are associated with lower CBC risk relative to no chemotherapy in multivariable-adjusted models. Here we show that genotype of selected genes involved in the metabolism and uptake of these therapeutic agents does not significantly alter the protective effect of either CMF or FAC/FEC on risk of CBC.The results of this study show that germline genetic variation in selected gene does not significantly alter the protective effect of CMF, FAC, and FEC on risk of CBC.The online version of this article (doi:10.1007/s10552-013-0237-6) contains supplementary material, which is available to authorized users. Adjuvant chemotherapy is indicated in the clinical management of most premenopausal women and postmenopausal women with ER- tumors, improving disease-free and overall survival –5. StudiGermline genetic variation in drug metabolizing enzymes and transporters is thought to contribute to the observed inter-individual variation in treatment efficacy , 14. TheCYP1A1, CYP1B1, CYP2A6, CYP2B6, CYP2C9, CYP2D6, CYP3A4, CYP3A5, GSTM1, GSTM2, GSTP1), targets , and transporters (ABCB1), known to be involved in the metabolism and action of drugs commonly used in polychemotherapy regimens for breast cancer  . Models were run adjusting for age at first breast cancer diagnosis and included an ‘offset term’ , takingAge and multivariable-adjusted [as described above] analyses were also conducted to confirm the association between chemotherapy and CBC risk in the subgroup of women included in the current analyses .α = 0.0003, obtained from (0.05/180 SNPs) at which results were considered statistically significant. All analyses were conducted using SAS 9.2 . Figures were generated using Microsoft® Excel 2007.A conservative Bonferroni correction was used to determine the multiple comparison cut-point (10(p for heterogeneity) for each SNP, grouped by chromosome, and for CMF and FAC/FEC analyses, respectively. Results showing the association between CMF and FAC/FEC treatments and risk of CBC stratified by genotype for all SNPs did not differ in age and multivariable adjusted models and can be found in Online Resource 2 and Online Resource 3, respectively. Findings from some commonly studied candidate SNPs are reported below.Selected characteristics of the eligible WECARE Study population are shown in Table MTHFR, known to be associated with altered enzyme activity, did not significantly modify the reduction in CBC risk seen with CMF .In multivariable-adjusted models, the variants rs1801133 and rs1801131 in GSTP1 also did not significantly modify the effect of chemotherapy on risk of CBC .Rs1695 in CYP3A4*1B (rs2740574) genotype .Similarly, the association between chemotherapy and risk of CBC did not differ when stratified by Chemotherapy reduces the risk of CBC –12; howeCTX, a widely used nitrogen mustard alkylating agent, is a component of both the CMF and FAC/FEC regimens and the most common agent received by the WECARE Study population. The pharmacokinetics of CTX are highly variable (reviewed in ). CTX isMTHFR has also been shown to increase sensitivity to 5FU and decrease sensitivity to MTX in breast cancer cell lines  have multiple anti-cancer mechanisms including DNA intercalation, generation of free-radicals, and disruption of topoisomerase II-mediated DNA repair . Doxorublele rs27574 had sABCB1 [multi-drug resistance (MDR-1)] gene . Laiewed in  found thotherapy –55. Studen mixed , 57.CYP1A1). It is possible that un-typed variants in these candidate genes and variation in genes not included in the current analysis could modify the effect of treatment on risk of CBC. A further limitation of this study is that for variants with a low minor allele frequency or modest effects on the association between chemotherapy and risk of CBC, our power is reduced.The strengths of this study include the population-based design, the large number of women with CBC, enabling the examination of CBC as an outcome, and the extensive review of patient medical records and questionnaire data, to obtain detailed treatment information. A limitation of the tagSNP approach used here is that it does not address the impact of less common or rare variants (MAF < 5 %), SNPs not in LD with typed variants, insertions/deletions, epigenetic modifications, and copy number variations, on treatment response. Further, complete gene coverage was not achieved for all genes, and in some cases, a candidate SNP approach was used  is associated with a lower risk of CBC regardless of genetic variation in selected genes that code for proteins involved in the metabolism of these commonly used chemotherapeutic agents.Supplementary material 1 (XLS 51 kb)Supplementary material 2 (XLS 166 kb)Supplementary material 3 (XLS 166 kb)Below is the link to the electronic supplementary material.


Purpose. The aim of this paper was to investigate whether cancer genetic counseling could be considered as a stressful event and associated with more anxiety and/or depression compared to other cancer-related events for instance attending mammography screening or receiving a cancer diagnosis. Methods. A total of 4911 individuals from three Scandinavian countries were included in the study. Data was collected from individuals who had attended either cancer genetic counseling (self-referred and physician-referred) or routine mammography screening, were recalled for a second mammograpy due to a suspicious mammogram, had received a cancer diagnosis or had received medical follow-up after a breast cancer-surgery. Data from the genetic counseling group was also compared to normative data. Participants filled in the Hospital Anxiety and Depression Scale twice: prior to a potentially stressful event and 14 days after the event. Results. Pre-counseling cancer genetic counselees reported significant lower level of anxiety compared to the cancer-related group, but higher levels of anxiety compared to the general population. Furthermore, the level of depression observed within the genetic counseling group was lower compared to other participants. Post-event there was no significant difference in anxiety levels between the cancer genetic counselees and all other groups; however, the level of depression reported in the self-referred group was significantly lower than observed in all other groups. Notably, the level of anxiety and depression had decreased significantly from pre-to post-events within the genetic counseling group. In the cancer-related group only the level of anxiety had decreased significantly post-event. Conclusion. Individuals who attend cancer genetic counseling do not suffer more anxiety or depression compared to all other cancer-related groups. However, some counselees might need additional sessions and extended support. Thus, identifying extremely worried individuals who need more support, and allocating further resources to their care, seems to be more sufficient. Modern gene technology has made it possible to identify individuals at an increased risk for genetic diseases. Therefore, since increasing numbers of individuals will now desire access to information about their genetic risk for developing a disease, genetic counseling services have become an integral part of specialized health care system. An implicit assumption has been that receiving information about a potentially life-threatening event, such as a cancer diagnosis, may cause psychological and emotional difficulties, and that genetic counseling may facilitate adjustment to this information . NeverthIt is anticipated that in the near future, extensive information regarding the genetic transmission of a number of diseases will be available and consequently genetic counseling will have a substantial impact on both the structure and the costs of health services. Thus, it seems reasonable that aside from wondering whether genetic counseling actually facilitates an individuals' adjustment and wellbeing, question whether there is evidence to indicate that genetic information may leads to significant increases in personal distress (anxiety and/or depression).During the last decade, several systematic reviews documenting the psychological impact of learning of ones' genetic risk for developing certain illnesses have been performed. One of the main conclusions from these reviews is that genetic counseling does not have any harmful effect on counselees and is effective in reducing pre-counseling levels of anxiety, depression and distress -6. In a The main aim of this paper was to study whether genetic counseling could be considered as a stressful event by the individuals who attend such sessions. An additional aim was to explore whether counselees were more anxious and/or depressed in comparison to other large cancer-related groups within the health care systems .The rationale was that if genetic counseling attendees were found to be more anxious or depressed, then there would be need for psychological interventions to explore these emotions in depth. Such evidence could then be taken into account when planning and allocating resources to the future care of individuals who demand information about their genetic risk for a particular disease.In the current study, comparisons were made between the level of anxiety and depression among individuals who attended genetic counseling due to having an increased risk for developing cancer; individuals who attended mammography screening for non-hereditary cancer; various cancer patients and a random sample of the general population.Data were collected from Sweden, Norway and Denmark, and a total sample of 4911 participants was included in the study. Participants from Norway were “self-referred” to genetic counseling, whilst in Sweden and Denmark participants were referred to genetic counseling by their primary health care physicians. This differences in referral method presented the opportunity to compare individuals who sought genetic counseling in order to receive a risk evaluation as a first step (comparable to primary care), to those individuals who were referred to genetic counseling by a primary health care physician since they were considered to be at an increased risk for developing cancer.In current study, participants attended their first genetic counseling session. During the first counseling session, the counselor usually provides information regarding the differences between sporadic cancer versus hereditary cancer, basic genetics, and the risk of developing cancer as a carrier of a mutated gene. In addition, the geneticist estimates the risk for non-affected counselees' or for affected counselees' close relatives and supplies information about genetic testing and surveillance programs. Counselees who undergo genetic testing will attend an additional session in association with the disclosure of the test results.All participants gave informed consent and the study was approved by the Norwegian and Swedish Ethical Committee, Danish National Board of Health and the Danish Data Protection Agency.The term “stressful events” referred to: attending genetic counseling, attending a routine mammography, being recalled for another mammography appointment due to a previous suspicious mammogram, receiving a cancer diagnosis and going for a medical follow-up following surgery for cancer. The different groups and events are described in more detail both below and in To analyze the data, the sample was divided in three groups; a genetic counseling group, a cancer-related group and the general population group. Data for each group is presented separately. Comparisons were also made between subgroups of genetic counseling and cancer-related groups. Follow-up data (14 days after the event) was not available for all participants.Participants were recruited between September 2003 and September 2004 from four genetic outpatient clinics at University Hospitals throughout Denmark, and one genetic clinic in Sweden over a period of six years (1999 to 2005).The criteria for inclusion in the study were an age above 18 years together with at least one first or second degree relatives having been diagnosed with breast, breast/ovarian or colorectal cancer. Counselees were referred to the genetic counseling by a general physician or a specialist due to being at an increased risk for developing a hereditary cancer. A consecutive sample of 674 counselees was included in this group and this consisted of 431 participants from Denmark and 243 participants from Sweden. In Denmark 76% of counselees who were asked to participate in the study accepted whilst in Sweden 89% of counselees agreed to participate. Follow-up data was only available for the Swedish counselees  were asked to participate in the study during 2003. Inclusion criteria were as described above. A total of 221 counselees (80%) agreed to participate in the study. The majority (65%) had a history of breast- and/or ovarian cancer, 23% had a history of colorectal cancer and 12% had a history of both cancer forms within their families.A total of 689 women attending for routine mammography screening at two hospitals in Denmark throughout 2003 and 2004 were asked to participate in the study. In total, 61% (n = 417) agreed to participate and filled out the questionnaire.In 1997, 26086 women attended a population-based mammography screening program in Uppsala, Sweden. In total, 901 women (3.5%) were then recalled for further investigation due to a suspect result, for instance a lump in the breast. All 901 women were asked to participate in the study, of which 509 (56%) agreed to and were included.Between October 1993 and December 1995, a consecutive group of Swedish patients (n = 729), that were either newly diagnosed or under investigation for breast cancer (n = 331); colorectal cancer (n = 154); gastric cancer (n = 47) or prostate cancer (n = 197), were asked to participate in the study. Seventy-two percent of patients (n = 527) accepted and agreed to participate in the study. A subgroup of breast cancer patients (n = 149) had filled out the questionnaire before their diagnosis was confirmed. This created a unique opportunity whereby the level of anxiety and depression prior to diagnosis could also be assessed. This is often impossible since patients are generally included in studies only after having been diagnosed with cancer.During 2000 and 2001 a group of 72 women diagnosed with breast cancer in Sweden, were asked to participate in the study in association with their first medical follow-up after the cancer surgery. In total, 63% (n = 45) accepted and were included in the study. The only criterion for inclusion was being younger than 50 years of age at the time of diagnosis. This criterion was chosen due to a minor increased risk for hereditary cancer, but not so high a risk level that makes genetic counseling necessary.Normative data on anxiety and depression, using The Hospital Anxiety and Depression Scale (HADS), were obtained from the Nord-Trondelag Health Study (The HUNT-2 Study) . The HUNThe Hospital Anxiety and Depression Scale (HADS)  consistiApproximately half of the sample, 2428/4911 individuals filled out the HADS in connection with a potential stress-full event 14 days before the event and 14 days after the event. This data was compared to the data from a random sample of the general population (n = 2483).The proportion of men (11%) and women (89%) were equal in both samples.Comparisons of the mean values were performed by unpaired two-tailed t-tests. Pre to post-event changes were investigated by paired t-tests. T-tests were used instead of two-way ANOVA due to lack of follow-up data for most participants. Analyses of variance (ANOVA) were used for comparison of three or more groups. Due to unequal sample sizes, post hoc comparisons were performed with the Tukey's Honestly Significantly Different (HSD) Unequal Sample Sizes test. Post hoc test results are reported only for comparisons between genetic counseling group (as a whole or as self-referred and physician-referred subgroups) and each of the other included groups.Prior to the stress-full event, the genetic counseling group reported significantly lower levels of anxiety (M = 5.6), compared to the cancer-related group (M = 6.9), but higher levels of anxiety compared to the general population (M = 4.4)  . HoweverAfter counseling, no differences in anxiety were observed between the genetic counseling group  and the other groups  .cancer-related = 3.8, SD = 3.7, Mgeneral population = 3.5, SD = 3.1)   compared to both the cancer-related group and general population . There was no corresponding difference for depression between the two groups , and after  the counseling session compared to the physician-referred counselees  = 57.3, p < 0.001]. No significant differences in anxiety were observed between the genetic counseling and the other included groups post-counseling   and b.The genetic counseling subgroups separately reported significantly lower levels of depression both pre  and post-counseling  compared to most other groups  and b. Tpre-event = 5.5, Mpost-evem = 5.0, ], and the cancer-related group  (Anxiety levels decreased significantly from pre-to-post-event measurement in both the genetic counseling group [M 0.001)] .pre-event = 2.9, MPost-event = 2.6, ]. However, no significant decrease in the level of depression was observed in the cancer-related group  ] .pre-event = 6.0, Mpost-event = 5.4, t = 3.6, p < 0.001] and depression  over time ] ] .Based on the results of this study, before attending counseling, individuals within the genetic counseling group, reported significantly lower level of anxiety and depression compared to those in the cancer-related group and higher levels of anxiety and lower level of depression compared to the general population. Post-event, there was no difference in the level of anxiety between the genetic counseling group and the cancer-related group, but the level of depression was still lower than both the cancer-related group and the general population.Compared to the general population, the cancer-related group still reported a higher level of anxiety and depression post-event.The level of anxiety and depression had decreased significantly in the genetic counseling group from pre-to-post-event measurement. However, this lower level of anxiety and depression was only observed in the counselees who were referred to the genetic counseling by a physician. The other group who reported a significant decrease in anxiety post-event was the cancer diagnosis group.The significantly lower level of anxiety and depression reported by the physician-referred counselees post-counseling supports the important role played by genetic counseling.Individuals probably experienced high levels of unnecessary distress prior to counseling, and attendance at the counseling session may have helped them to realize the actual risk and the possibility of receiving further help.It was not surprising that the women who were recalled for further mammography reported the highest levels of anxiety, since uncertainty and being at risk of receiving a cancer diagnosis may be considered as a very stressful event .Depending on whether genetic counseling is primarily considered as a session for delivering precise information regarding the genetic risk for a given illness , or is cGenetic counseling is considered as a psycho-educative process due to the notion that genetic information might give rise to a substantial amount of psychological distress ,26,27, aIn line with previous studies ,29,30, oAs mentioned earlier, anxiety levels in counselees who seek genetic counseling on their own initiative was, pre-counseling, significantly lower than counselees referred to the genetic counseling by a physician, and compared to most other studied events. This is not unexpected since having a suspicious mammogram, receiving a cancer diagnosis or being operated for breast cancer might be associated with higher level of anxiety. Nevertheless, it is possible that the lack of significance in the group of self-referred counselees could be due to the smaller size of this group or because physicians refer individuals who have higher risk of developing cancer and are more anxious to the counseling to help them to receive realistic risk estimation.It is noteworthy that at the time of collecting data for the current study, genetic counseling was a relatively new activity. It seems reasonable to speculate that this first wave of individuals who sought counseling on their own probably were more motivated, had more information about cancer and perhaps were not as anxious or depressed as individuals who are referred by another person. As the genetic risk evaluation will be used more widely it is reasonable to assume that individuals who seek genetic counseling might not have the same characteristics and will require a different type of care.In accordance with an earlier report , our resOne of the most important strengths of the current study is that the results are based on a very large sample from different clinics from three Scandinavian countries. Furthermore, the study had two unique advantages. The first was the possibility to compare self-referred counselees, who probably have different characteristics, to individuals who are referred to genetic counseling by a physician due to being at an increased risk for developing cancer. The second was the opportunity of having access to data for a subgroup of breast cancer patients before their diagnosis was confirmed. This made it possible to assess the level of anxiety and depression pre-diagnosis possible; a variable which is often impossible to measure since patients are usually included in studies only after having been diagnosed by cancer.In addition, psychological distress was assessed with a well established instrument proven to have good psychometric properties.However, the study is not without limitations and the results need to be considered in the light of these short-comings. For instance, the homogeneity of the groups was not optimal and the date of measurement was different for various subgroups. However, the time points of pre to post-measurements had been the same for all groups.The representativeness of women recalled for further examination (response rate 56%) may be doubtful and generalization of these results should be done with caution due to the selectiveness of the sample. The lack of follow-up data is also an undesirable fact which may have affected the results.Genetic counseling can give rise to some distress, though it does not seem to be a more stressful event compared to other events within the health care service. On the contrary, genetic counseling may be associated with some transient elevations of anxiety that for most individuals will be handled without the requirements for any specific intervention.Considering these results and the findings of previous studies indicating that the level of distress in genetic counseling counselees decreases over time, one plausible conclusion might be that genetic counseling probably helps counselees to cope with their cancer or cancer susceptibility over the long term. However, some counselees might need additional sessions and extended support. Thus, it seems that identifying individuals who are extremely worried and need more support, and allocating additional resources to the care of them, is more important.


Hormonal factors may influence risk for upper gastrointestinal cancers in women. We examined risk of oesophageal and gastric cancers in relation to reproductive factors in a large UK cohort, the Million Women Study.Among 1 319 409 women aged on average 56 years at recruitment, 1186 incident cancers of the oesophagus and 1194 of the stomach were registered during 11.9 million person-years’ observation. Adjusted relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models.P⩽0.01 for both); and, among postmenopausal women, risk was higher the younger women were at menopause . For factors relating to childbearing, including women's age at first birth, their number of children, and breastfeeding history, the only significant association was a higher risk of oesophageal cancer in nulliparous, compared with parous, women . When risks for squamous cell and adenocarcinomas of the oesophagus were compared, most did not differ significantly, but statistical power was limited.Risks of both oesophageal and gastric cancer were significantly higher in postmenopausal than in pre- or peri-menopausal women (RRs 1.46, 1.07–2.00 and 1.59, 1.15–2.20, respectively; Both oesophageal and gastric cancer risks appeared to be related to menopausal status and age at menopause, but there was little consistent evidence for associations with factors related to childbearing. Cancers of the upper gastrointestinal tract are associated with significant morbidity and mortality. Cancers of the oesophagus and of the stomach are both more common in men than in women and it has been suggested that this may reflect protection offered by exposure to high levels of oestrogens  number, and are followed via record linkage  to the NHS Central Registers, so that cancer registrations and deaths are routinely notified to the study investigators. The Central Registers provide information on the date of each such event and code the cancer site and cancer morphology using the 10th revision of the WHO International Classification of Diseases (ICD10). Register follow-up is over 99% complete. All participants gave their written consent to take part in the study and ethical approval was provided by the Oxford and Anglia Multi-Centre Research Ethics Committee.A total of 1.3 million women aged 50–64 were recruited into the Million Women Study in 1996–2001, completing a recruitment questionnaire about reproductive factors , sociodemographic factors and other personal characteristics, including use of hormone therapy for the menopause (HT) and of hormonal contraceptives. Details of the study design and methods are described elsewhere  and gastric cancer (ICD-10 C16). Cases of oesophageal cancer were further classed, where possible, as adenocarcinoma (ICD-O morphology codes 8140–8573) or squamous cell carcinoma (ICD-O 8050–8082). Adenocarcinomas of the stomach were classed, where possible, as cancers of the gastric cardia (C16.0) and of specified non-cardia sites (C16.1–16.5). Exposure and adjustment variables for the analyses were derived from information provided at baseline. Women were classed as pre/peri-menopausal if they reported still having periods at the time of recruitment, and as postmenopausal if they reported having had either a natural menopause, or a bilateral oophorectomy. Women who reported having had a hysterectomy were excluded from analyses of menopausal factors; and, in order to study the effect of menopause without additional exogenous hormones, all analyses of menopausal factors were further restricted to never users of HT . Analyses of age at menopause were restricted to women with known age at natural menopause.Women diagnosed with any invasive cancer other than non-melanoma skin cancer (ICD10 C44) before recruitment were excluded from the analyses. For the remaining women, person-years were contributed from recruitment until the earliest of date of diagnosis with oesophageal or gastric cancer, date of death, end of follow-up  and West Midlands (30 June 2008) and East Anglia and Scotland (31 December 2008)), or diagnosis with any cancer other than oesophageal or gastric cancer (or non-melanoma skin cancer) during the follow-up period.−2), strenuous physical activity , smoking status , alcohol intake , use of oral contraceptives  and, where appropriate, use of hormone therapy for the menopause . All analyses were mutually adjusted for reproductive factors.Cox proportional hazards models with attained age as the underlying time variable were used to estimate the relative risks (RRs) of developing oesophageal or gastric cancer in relation to age at menarche , menopausal status , age at natural menopause , type of menopause , parity  and, within parous women, by number of full-term pregancies , age at first birth , and breastfeeding of at least one child . Women with missing data for an exposure of interest were excluded from the relevant analyses. Within the analyses, adjustment for region of residence (10 cancer registry areas in the UK) and quintiles of socio-economic status  years, were included in the analyses. During a total of 11.9 million woman-years of observation (mean 9.1 years per woman), 1186 incident cancers of the oesophagus and 1194 incident cancers of the stomach were reported, with an average age at diagnosis of about 59 years. Of the oesophageal cancers, 49% (578/1186) were specified as squamous cell carcinoma and 34% (399/1186) as adenocarcinoma, with the remaining 17% (209/1186) not specified histologically. The majority of cancers of the stomach were specified as adenocarcinomas (81% 971/1194), with most of the remaining 233 cancers being of unspecified histology. Of gastric adenocarcinomas, 29% (283/971) were coded to the cardia and 26% (249/971) to specified non-cardia sites, with no site within the stomach specified for 44% (430/971: 9 stomach cancers were of overlapping sites).vs 61% for nulliparous and parous, respectively).vs pre- or peri-menopausal women: 2.44, 1.11–5.28 for oesophageal cancer (29 cases) and 1.61, 0.75–3.44 for gastric cancer (27 cases)). For both cancers, risk in postmenopausal women was higher, the younger women were at menopause . No difference in risk was seen for either cancer between women with natural menopause and those with bilateral oophorectomy. For childbearing factors, only one significant association was observed. Risk of oesophageal, but not of gastric, cancer was significantly higher in nulliparous than in parous women . Within parous women, neither cancer was associated with number of full-term pregnancies, age at first birth nor with breastfeeding history.P for difference in trend, 0.003); and for parity, where the increase in risk in nulliparous compared with parous women was shown to be confined to squamous cell carcinoma . An association with age at menopause was seen for squamous cell carcinoma  but not for adenocarcinoma ; the difference between the 2 types was of borderline statistical significance .For gastric cancer, no substantial differences were seen in relation to reproductive factors between specified cardia and non-cardia cancers, although numbers were limited .There were no material differences between the results presented here and those for sensitivity analyses restricted to women with known values for all adjustment variables; nor, for the non-menopause exposures, between results for all women and those from analyses restricted to never users of HT.In this large prospective analysis, risks of both oesophageal and gastric cancers were higher in postmenopausal than in pre- or peri-menopausal women of a similar age, and, among postmenopausal women, higher for women with an earlier age at menopause. Risk of oesophageal cancer was higher in nulliparous than in parous women, but no other significant associations were seen between risk of either cancer and factors related to childbearing.Few differences in risk were seen for oesophageal cancers with different histology or for gastric cancers at different subsites. The association between parity and risk of oesophageal cancer was greater for squamous cell than for adenocarcinoma; and age at menarche was significantly associated with adenocarcinoma, but not squamous cell carcinoma, of the oesophagus. No significant differences in risk associated with reproductive factors were seen between adenocarcinomas of the gastric cardia and of non-cardia sites.Previous epidemiological studies have provided little evidence for strong or consistent relationships between menstrual and reproductive factors and upper gastrointestinal tract cancers. No consistent associations have been found between age at menarche and risk of oesophageal cancer (case–control studies, Some previous studies have found, as we did, significant trends toward lower risk of oesophageal (Published evidence is insufficient to draw conclusions about risk of oesophageal cancer in relation to menstrual factors by histological type. We found a lower risk associated with older age at menarche for adenocarcinoma but not for squamous cell carcinoma of the oesophagus. A similar pattern of risk was seen in the NIH-AARP cohort (For factors related to childbearing, published studies have found no consistent associations with parity for either oesophageal (Strengths of the present study include its large size; the prospective determination of exposure and of adjustment factors, minimising risk of recall bias; and full follow-up through reliable disease registries for incident cancers. There is increasing evidence for differences between squamous cell and adenocarcinoma in relation to some risk factors (The strongest and most consistent associations with cancer risk in our study were with menopausal status and age at menopause. Risks of both oesophageal and gastric cancers were higher in postmenopausal than in pre- or peri-menopausal women, and, among postmenopausal women, risks were higher the younger the women were at menopause. The association between menopause and upper gastrointestinal cancer risk may be related to endogenous sex hormone levels, particularly because postmenopausal women taking hormone therapy for the menopause have lower risk of these cancers than women who are not (


This association was particularly evident for multiple miscarriages , with no significant association for multiple induced abortions . Our findings suggest that multiple miscarriages are associated with an increased risk of epithelial ovarian cancer, possibly through a shared cluster of etiological factors or a common underlying pathology. These findings should be interpreted with caution as this is the first study to show this association and given the small number of cases in the highest exposure categories.While the risk of ovarian cancer clearly reduces with each full-term pregnancy, the effect of incomplete pregnancies is unclear. We investigated whether incomplete pregnancies (miscarriages and induced abortions) are associated with risk of epithelial ovarian cancer. This observational study was carried out in female participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). A total of 274,442 women were followed from 1992 until 2010. The baseline questionnaire elicited information on miscarriages and induced abortions, reproductive history, and lifestyle-related factors. During a median follow-up of 11.5 years, 1,035 women were diagnosed with incident epithelial ovarian cancer. Despite the lack of an overall association (ever vs. never), risk of ovarian cancer was higher among women with multiple incomplete pregnancies (HR Increasing parity reduces the risk of ovarian cancer Incomplete pregnancies include miscarriages (spontaneous losses) and induced abortions , which have diverse aetiologies and, therefore, their association with ovarian cancer risk might differ. Of particular interest are women who have multiple incomplete pregnancies, as the effect of a single event may be too small to detect and/or the risk may not change in a linear manner with each additional incomplete pregnancy.The aim of the current analysis was to explore the association of multiple miscarriages and induced abortions with risk of epithelial ovarian cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC).All participants signed an informed written consent. The present study was approved by the Institutional Review Board of the International Agency for Research on Cancer (IARC) and local institutional review boards in participating centres.EPIC is a prospective cohort study initiated in 1992 in 10 European countries: Denmark, France, Germany, Greece, Italy, the Netherlands, Norway, Spain, Sweden, and the United Kingdom. Between 1992 and 2000, a total of 519,978 men and women were recruited. Of these, most were aged 25–70 years and recruited from the general population. Exceptions were the Oxford cohort, UK , the Utrecht cohort, The Netherlands (based on women attending breast cancer screening), the French cohort , and components of the Italian and Spanish cohorts . A full description of the study design and cohort has been published elsewhere a priori exclusion of women with prevalent malignancy  or bilateral oophorectomy  at baseline, incomplete follow-up , missing lifestyle data (n = 526), and women from centres with missing information on miscarriages and induced abortions . For the analysis on induced abortions, we additionally excluded women from Malmo as information on induced abortions was not available for this centre.Our analysis is based on data from all 274,442 female participants after Eligible subjects who decided to participate signed an informed consent form and completed diet and lifestyle questionnaires, which were either interviewer-administered  or mailed self-administered . In most countries, participants were invited to a centre for blood collection and anthropometric measurements. Through the baseline questionnaire, women were asked whether they had ever had a miscarriage or an induced abortion, and if so, how many miscarriages and/or induced abortions they have had, as well as the age at first and last abortion. The structure and availability of the questions varied by center. For that reason, all variables were standardized centrally. If a participant recorded either a number of miscarriages/induced abortions or their age at a miscarriage, then, it was assumed that they had experienced a miscarriage. Number of miscarriages/induced abortions have been transformed into 1, 2, 3, 4, and 5 or more. Questions on miscarriages and induced abortions were missing for Bilthoven, Umea, and Norway, while, questions on abortions only were missing for Malmo. Therefore, these centres have been excluded from the specific analyses on miscarriages and/or abortions."Women were considered as premenopausal at baseline when they reported having had regular menses over the past 12 months or if they were less than 46 years of age. Women were considered postmenopausal when they reported not having had any menses over the past 12 months, or when they were older than 55 years. Women who were between 46 and 55 years of age and who had missing or incomplete questionnaire data for menopausal status were classified as perimenopausal/unknown.Participants were followed up from study entry and until diagnosis of any cancer (except non-melanoma skin cancer), death, emigration, or until the end of the follow-up period, whichever occurred first. Incident epithelial ovarian cancer was defined as ovarian, fallopian tube and primary peritoneal cancer . Incident cancer cases were identified through either population-based cancer registries or a combination of methods including health insurance records, cancer and pathology registries, and active follow-up through study participants and their next-of-kin. Mortality data were also obtained from either the cancer registry or mortality registries at the regional or national level. The end of the follow-up period was different for different centres and ranged between December 2004 and June 2010.Person-years at risk were calculated from the start of the study until censoring at the date of diagnosis of any ovarian cancer, death, emigration, other loss to follow-up or the date at which follow-up ended, defined as the last date at which follow-up data were judged to be complete or the last date of contact in the centers that used active follow-up.Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models with age as the underlying time variable and stratified by centre and age. Multivariate models were adjusted for parity (number of full-term pregnancies), duration of oral contraceptive use (continuous), body mass index (continuous), menopausal status , education , and age at menarche (continuous). Missing covariate values were imputed using mean substitution We performed a sensitivity analysis restricted to postmenopausal women as these women had complete information on number of miscarriages and induced abortions since they were at the end of their fertile life. In this sensitivity analysis we additionally adjusted for age at menopause (continuous) and duration of hormone therapy (continuous).An additional sensitivity analysis was performed by excluding the first 5 years of follow-up.All statistical analyses were carried out using SAS 9.2 .During a median follow-up of 11.5 years, 1,035 women were diagnosed with incident epithelial ovarian cancer .Compared with women who never had a miscarriage, women with multiple miscarriages (≥2) were slightly older, had higher body mass index, were more likely to be postmenopausal, less likely to have had a full-term pregnancy, less likely to have used oral contraceptives, and more likely to have used hormonal therapy . These d≥4vs.0: 1.74, 95% CI: 1.20–2.70; number of cases in this category: n = 23). When the number of incomplete pregnancies was divided into miscarriages and induced abortions, women with a history of ≥4 miscarriages had a statistically significant 2-fold increased risk , although this estimate is based on a small number of cases. No association was observed for women who had only one miscarriage. Results were stronger among women who were postmenopausal at baseline . No substantial differences were observed when restricting analyses to ever-pregnant women and when stratifying by age at first pregnancy . To prevent reverse causation we performed an additional sensitivity analysis , for which we excluded the first 5 years of follow-up . This resulted in a stronger association .We observed no association between ever having had an incomplete pregnancy or having had one incomplete pregnancy and risk of ovarian cancer, as compared with never having had an incomplete pregnancy . However≥4vs.0: 1.46, 95% CI: 0.68–3.14; number of cases in this category: n = 7).Multiple induced abortions were not significantly associated with epithelial ovarian cancer risk (In this large prospective cohort study, we observed a 2-fold increased risk of epithelial ovarian cancer among women with 4 of more miscarriages.This is the first prospective study that investigated the association of multiple miscarriages with ovarian cancer. Most case-control studies only investigated ever versus never had a miscarriage and did not observe an association In line with most studies we observed no overall association between induced abortions and ovarian cancer risk, whereas two studies reported a reduced risk Our results suggest that miscarriages and induced abortions may have different effects on ovarian cancer risk and therefore examining the association between incomplete pregnancies and risk of ovarian cancer may obscure any real association.A major strength of this large cohort study is the prospective design, with detailed exposure and covariate assessment prior to diagnosis. A limitation of our study is the relatively small number of cases in the top categories of incomplete pregnancies. In addition, we do not know in which week of the pregnancy the miscarriage or induced abortion occurred. Miscarriages most frequently occur during the 6th to 12th week of pregnancy and our results, therefore, are most likely driven by these early pregnancies. We have not been able to review medical charts to confirm a women’s self-report of miscarriage/induced abortion. However, underreporting seems more likely than over-reporting. If we indeed have missed some miscarriages or induced abortions, this would cause non-differential misclassification since data on pregnancy loss were collected prior to cancer diagnosis. The result would be an attenuation of the risk estimates. An additional limitation of our study is that information about pregnancy loss was collected at baseline only. Among premenopausal women this information might therefore be incomplete, which again may lead to an attenuation of the association. Among postmenopausal women, for whom these data were complete, indeed, we observed a stronger association between multiple miscarriages and ovarian cancer risk.In conclusion, our findings suggest that multiple miscarriages are associated with an increased risk of epithelial ovarian cancer. As this is the first prospective study that observed this association, more studies are needed to confirm or dispute our findings.


Weight gain rather than weight loss often occurs after breast cancer diagnosis despite breast cancer survivors frequently reported making healthful lifestyle changes. This study describes the prevalence and magnitude of changes in weight before and after breast cancer diagnosis and examines lifestyle behaviors of breast cancer survivors with stable weight, weight gain or weight loss.Respondents were 368 women with breast cancer characterized by stages I, II and III. All were recruited from hospitals or breast cancer support groups and had completed conventional treatment. Current weight and height were measured while weight at cancer diagnosis and 1 year before diagnosis were self-reported. Weight change was calculated as the difference between current weight and weight a year preceding breast cancer diagnosis. A 24-hour diet recall and Global Physical Activity Questionnaire assessed dietary intake and physical activity, respectively. Differences in lifestyle behaviors among weight change groups were examined using Analysis of Covariance (ANCOVA).Mean weight change from a year preceding diagnosis to study entry was 2.73 kg (95% CI: 1.90-3.55). Most women (63.3%) experienced weight gain rather than weight loss (36.7%) with a higher percentage (47.8%) having at least 5% weight gain (47.8%) rather than weight loss (22%), respectively. Compared to other weight change groups, women in >10% weight gain group had the lowest fruit and vegetable servings  and highest servings of dairy products .Weight gain was evident in this sample of women after breast cancer diagnosis. Information on magnitude of weight change after breast cancer diagnosis and lifestyle behaviors of breast cancer survivors with varying degrees of weight change could facilitate the development and targeting of effective intervention strategies to achieve healthy weight and optimal health for better survival. Breast cancer is the second most frequent cancer in the world, with an estimated 1.05 million cases in the year 2000 . The 5-yWeight change occurs in most women after breast cancer diagnosis and the amount of weight gain or loss could vary among the survivors . Most caLifestyle change is one of the many possible actions women may take when they have been diagnosed with breast cancer in order to improve breast cancer prognosis and reduce the probability of cancer recurrence. Several studies -15 have As many developing countries, including Malaysia, have disproportionately high rates of breast cancer morbidity and mortality, a comprehensive assessment of lifestyle behaviors after breast cancer is essential as these behaviors may potentially affect prognosis, cancer recurrence, long-term survival and risk of other chronic diseases such as cardiovascular, hypertension and diabetes . To dateThis cross-sectional survey was conducted in eight general hospitals and four breast cancer support groups in seven states of Peninsular Malaysia. These states represented the Northern, Central, Southern and East Coast regions of Peninsular Malaysia. Respondents were recruited from oncology or surgical out-patient clinics of general hospitals and breast cancer support groups over a period of 10 months (February to December 2008). Lists of cancer patients attending the out-patient clinics for medical check-up as well as active members of support groups were provided by the hospitals and support groups, respectively. Out of 615 breast cancer survivors screened, 400 women met the selection criteria and were invited to participate in this study. A total of 368 women voluntarily participated in the study, giving a response rate of 92%.This study employed purposive sampling as the selection of respondents was based on several criteria i.e. women 20-65 years old at the time of diagnosis, diagnosed with cancer of stages 0-III, completed conventional treatments  at least 6 months prior to recruitment, free from cancer recurrence and not currently under any medication  that would affect the study outcome. All respondents were interviewed using a pre-tested questionnaire either at the hospitals or premises of breast cancer support groups. The study protocol was approved by the Medical Research Ethics Committee of the Faculty of Medicine and Health Sciences, Universiti Putra Malaysia and the Medical Research Ethics Committee (MREC), Ministry of Health Malaysia. Prior to data collection, informed consent was obtained from all respondents.A 24-hour recall was used to assess the dietary intakes of the respondents. Portion size, brand names and cooking method were recorded. Standard household measuring cups and spoons were used to assist respondents in portion size estimation. The nutritionist Pro™ software version 2.5  , SingapoThe current physical activity level was measured using the Global Physical Activity Questionnaire (GPAQ) . Women wThe weight a year preceding breast cancer diagnosis, was based on self-reported information. All respondents indicated that the reported weights were stable for at least 6 months prior to diagnosis. Current weight and height were measured to the nearest 0.1 kg and 0.1 cm, respectively using TANITA digital weighing scale  and SECA body meter . Body mass index (BMI) was calculated and classified according to the World Health Organization classification . Waist cWeight change was defined as the difference between the present weight and the weight a year preceding breast cancer diagnosis. Percent of weight change was calculated as = [present weight (kg) - weight a year preceding breast cancer diagnosis (kg)]/weight a year preceding breast cancer diagnosis (kg) x100%. The changes in weight for the women were then categorized into >10% weight loss, 5-10% weight loss, no change (<5% weight loss and weight gain), 5-10% weight gain and >10% weight gain groups . These wInformation were also collected on socio-demographic background , reproductive and breast cancer history , family history of breast and other specific cancers.Statistical Package for the Social Sciences for Windows (SPSS version 15) . One way analysis of variance (ANOVA) and Chi-square analysis were used to examine weight change according to selected socio-demographic characteristics. The general linear model of analysis of covariance (ANCOVA) was used to test the differences in dietary intake, and physical activity by weight change groups with household income, years of education, age at diagnosis and time since diagnosis as covariates. The LSD (Least Significant Difference) test was applied to evaluate the statistically significant mean difference among the weight change groups.All data were analyzed using the Table Table Dietary intake and physical activity of women after breast cancer diagnosis are described in Table Among socio-demographic and cancer characteristics of women, only BMI a year before diagnosis was significantly different by weight change groups Table . Women wWeight gain is a common observation among women with breast cancer. This study supports the existing evidence that women tend to gain weight after breast cancer diagnosis. A significant gain in weight amounting to 2-3 kg after diagnosis of breast cancer was found in this study. Although some aspects of weight gain pattern among the breast cancer survivors in our study were similar to those observed in other studies ,27,28, t2 had a risk ratio of recurrence of 1.4 and those who gained more than 2.0 kg/m2 had a risk ratio of 1.53, with both groups having significantly higher all-cause mortality compared to survivors with a stable weight. The clinical significance of weight gain (2.7 kg) observed in the present study is not known, however the calculated increase (1 year before diagnosis to study entry) in body mass index is 1.11 kg/m2 which if based on previous studies could have significant effect on cancer recurrence and survival. About two-thirds of the women (65.8%) in this present study had at risk waist circumference. Having a higher BMI and waist circumference could put these women at risk of cardiovascular diseases, diabetes and cancer recurrence [Overweight and obesity were already prevalent in over 40% of the women prior to diagnosis, however more women were overweight and obese at study entry. Similar to Rock et al. (1999) , we alsocurrence .We found that women who gained weight after breast cancer diagnosis had lower fruit and vegetable intakes compared to those who lost weight. Although the weight loss groups had a higher intake of fruit and vegetables, the number of servings still did not meet the recommendation of 3-5 servings daily. Increasing the consumption of fruits and vegetables may reduce the risk of overweight/obesity as well as facilitate the slowing down of weight gain, especially among overweight and obese adults . HoweverAdequate consumption of dairy products is encouraged because they are rich sources of essential nutrients that are important for bone health. The present study found that women who gained > 10% of weight consumed significantly more servings of dairy products than those who lost > 10% of weight after breast cancer diagnosis; although none of the groups met the recommended intake of 1-3 servings of dairy products. A plausible explanation for the low dairy product intake among these women is that many believed milk and dairy products are high in saturated fat and cholesterol, and contain carcinogens that can cause cancer recurrence. Although we did not examine changes in dietary intake before and after cancer diagnosis, it is possible that these women could have stopped or reduced the intake of dairy products since cancer diagnosis. Skeie et al. (2009)  also repMost of the women (80.4%) in the present study had moderate and high physical activity level. This physical activity pattern is consistent with the findings of a study among United States women that showed 70% of women with breast cancer had moderate-intensity physical activity while 10% had high-intensity physical activity . HoweverThis study has several limitations. The small sample size of this study may not be representative of the population of women with breast cancer in Malaysia. Despite the recruitment of respondents from hospitals and breast cancer support groups throughout the country, there could still be differences in socio-demographic, reproductive and other characteristics. Another limitation is that study participation was voluntary which could result in selection bias in that those who are weight or health conscious would participate in the study. This study used self-reported weight a year preceding breast cancer diagnosis, which is subject to recall error and consequently could affect the calculation and classification of weight change. However, self-reported weight has been shown to be accurate  and mostThe high proportion of breast cancer survivors experiencing weight gain in this study suggests that efforts are needed to encourage breast cancer survivors to achieve or maintain healthy body weight. Understanding lifestyle behaviors i.e. dietary intake and physical activity of women diagnosed with breast cancer and with varying degrees of weight change is essential for the development and targeting of effective strategies to improve health and survival of breast cancer survivors. As the intake of fruits, vegetables and dairy products of women in this study are still below the recommended servings per day, dietary strategies should target all breast cancer survivors, regardless of their weight status. Despite limited evidence on how lifestyle behaviors prevents cancer recurrence or prolongs life, a diagnosis of breast cancer should be a starting point for women to have healthful diets and regular physical activity.The authors declare that they have no competing interests.YHY designed the study, conducted data collection, performed and interpreted the analyses and prepared the manuscript; ZMS designed the study, supervised and assisted data collection, analysed and interpreted of study findings, assisted in the preparation of the manuscript and approved the final manuscript; CYM, ZH, MK, RMY, ZO, NS and YHW supervised and assisted in study design and data collection. All authors read and revised the manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/11/309/prepub