Role and impact of menstrual and reproductive factors on breast cancer risk in Japan.

The aim of this study was to clarify the role and impact of menstrual and reproductive factors in relation to breast cancer and its hormone receptor-defined subtype, overall and separately among premenopausal and postmenopausal women in a low-risk population, using data from the Japan Public Health Center-based Prospective study. A total of 55 537 women aged 40-69 years completed a self-administered questionnaire, which included items about menstrual and reproductive history. During 1990-2002, 441 newly diagnosed cases of breast cancer were identified. Early age at menarche for premenopausal women, late age at natural menopause, nulliparity and low parity for both premenopausal and postmenopausal women, and late age at first birth for postmenopausal women were significantly associated with an increased risk of breast cancer. No overall significant associations were seen between the use of exogenous female hormones or breast feeding and breast cancer risk. Age at menarche and age at natural menopause were somewhat more closely associated with the risk of progesterone receptor-negative than positive breast cancer although no difference was observed for estrogen receptor status. Risks associated with parity, number of births and age at first birth did not significantly differ by hormone receptor-defined breast cancer. Our findings suggest that menstrual and reproductive factors may play an important role in the development of breast cancer among low-risk populations, similarly as they do in Western populations, and that risk factors might differ by hormone receptor status.     

Previous oral contraceptive use and breast cancer risk according to hormone replacement therapy use among postmenopausal women

Objective To assess postmenopausal breast cancer risk in relation to particular patterns of oral contraceptive (OC) use according to hormone replacement therapy (HRT) exposure.Methods Time-dependent Cox regression models were used to analyse information on postmenopausal women from a large-scale French cohort. Among a total of 68,670 women born between 1925 and 1950, 1405 primary invasive postmenopausal breast cancer cases were identified from 1992 to 2000.Results A non-significant decrease in risk of around 10% was associated with ever OC use as compared to never OC use in postmenopausal women. No significant interaction was found between OC and HRT use on postmenopausal breast cancer risk. Breast cancer risk decreased significantly with increasing time since first OC use (test for trend: p=0.01); this was consistent after adjustment for duration of use or for time since last use.Conclusion No increase in breast cancer risk was associated with previous OC exposure among postmenopausal women, probably because the induction window had closed. Some women may develop breast cancer soon after exposure to OCs, leading to a deficit of cases of older women. Further investigation is therefore required to identify young women at high risk.* Address correspondence to: F. Clavel-Chapelon, Equipe E3N-EPIC, INSERM “Nutrition, Hormones, Cancer”, Institut Gustave-Roussy, 94805 – Villejuif, France.     

Breast cancer in premenopausal and postmenopausal women

In the effort to determine if the risk factors for breast cancer differed between premenopausal and postmenopausal women, a case control study was conducted. The study sample included 95 premenopausal and 278 postmenopausal women with breast cancer admitted to the Ontario Cancer Foundation Clinic in London, Canada during the June 1967 to February 1971 period. The controls were 106 premenopausal and 480 postmenopausal women with benign and malignant diseases of sites other than breast admitted to the same clinic during the same period. The breast cancer risk increased with increasing age at 1st pregnancy among postmenopausal women only. Among the prememopausal women, increased breast cancer was associated with early menarche. Late age at natural menopause was an important risk factor for postmenopausal women. The risk in women experiencing natural menopause over the age of 55 was 2.5 times as great as that of women undergoing menopause before age 40. A longer interval between age at menarche and age at 1st pregnancy increased the risk in both groups. Oral contraceptive use, or duration of use, did not increase the risk of breast cancer. Among oral contraceptive users, there was a trend toward greater risk with increasing age at 1st use of OCs.     

Exogenous hormone use and the risk of postmenopausal breast cancer: results from the Netherlands Cohort Study

The association between the use of exogenous hormones as either oral contraceptives (OC) or hormone replacement therapy (HRT) in relation to postmenopausal breast cancer incidence was examined in the Netherlands Cohort Study (NLCS) among 62,573 women aged 55 to 69 years. Information on these types of exogenous hormone use and other risk factors was collected by mailed questionnaire. During 3.3 years of follow-up, 471 incident breast cancer cases were identified. After adjustment for traditional breast cancer risk factors, the relative risk (RR) of breast cancer was 1.09 (95 percent confidence interval [CI]=0.79–1.48) for women who ever used OCs cf women who never used OCs. The relative rates (with CIs) for women who used OCs for a period < 5 years, 5–9 years, 10–14 years, and 15+ years were 0.97 (0.61–1.55), 1.20 (0.69–2.07), 1.03 (0.60–1.77), and 1.96 (0.99–3.89), respectively. The test for trend was not significant (P=0.13). There was no evidence of any association between the number of years between the first and the last use of OCs and breast cancer incidence. In the subgroup of women with first-degree relatives with breast cancer, the RR for breast cancer associated with ever use of OCs was 1.51 (CI=0.67–3.41), whereas in the remaining women, the RR was 0.97 (CI=0.73–1.27). Ever-use of HRT compared with never-use was not associated with an increase in breast cancer risk in the multivariate analysis (RR=0.99, CI=0.68–1.43). Also, the number of years of HRT use was not associated with an increased breast cancer risk (trend P=0.83), nor was the number of years between the first and the last use of HRT and breast cancer incidence. One subgroup of women in which the use of HRT seemed associated (but not significantly) with an increase in breast cancer risk was women with an induced menopause (RR=1.72, CI=0.95–3.12). The RR of breast cancer for women who had ever used both OCs and HRT, compared with women who never used these exogenous hormones was 1.00 (CI=0.51–1.94). From this study, it cannot be concluded that the use of exogenous hormones is a strong risk factor for the development of postmenopausal breast cancer.Since the acceptance of this paper, two other papers have been published on HRT and breast cancer. For HRT (estrogen alone), one supports our finding of no association (Stanford et al, JAMA 1995; 274: 137–42) and one did find a positive association for current use (Colditz et al, New Engl J Med 1995; 332: 1589–93), most pronounced in older women with longer durations of use. With regard to use of combined estrogen-progestin HRT, the results in both papers were comparable to those for estrogen alone. More research on (combinations of) types of hormones is needed.This work was supported by the Dutch Cancer Society.     

Early oral contraceptive use and breast cancer among premenopausal women: final report from a study in southern Sweden

In southern Sweden during the 1960s, women began to use oral contraceptives (OCs) extensively at a young age. This case-control study investigates the relationship between the use of OCs and breast cancer development in women in southern Sweden diagnosed in the early 1980s. The risk for breast cancer after OC use among premenopausal women was modeled, after adjustment was made for age, age at menarche, and age at first full-term pregnancy or parity. Both the duration of OC use before 25 years of age and commencement of OC use at a young age were associated with a significant increase in the risk of breast cancer as well as a significant trend. The duration of OC use before the first full-term pregnancy was associated with an increased risk of breast cancer, but it did not show a significant trend. The total duration of OC use was weakly, but not significantly, associated with breast cancer development. The odds ratio for women starting OC use before 20 years of age was 5.8 [95% confidence interval (CI), 2.6-12.8]; for women using OCs for greater than 5 years before age 25, it was 5.3 (95% CI, 2.1-13.2); and for women using OCs for greater than or equal to 8 years before first full-term pregnancy, it was 2.0 (95% CI, 0.8-4.7). In multivariate analyses including the different measurements of OC use, only starting age of OC use was significantly associated with breast cancer. The exposure-response relationship between duration of OC use and risk of breast cancer depended on the age at first use of OCs. Given a fixed duration of OC use, the risk increased with younger starting age of OC use. The findings point to the importance of the early reproductive years as risk determinants for breast cancer after OC use.     

Mammographic density, parity and age at first birth, and risk of breast cancer: an analysis of four case–control studies

Mammographic density is strongly and consistently associated with breast cancer risk. To determine if this association was modified by reproductive factors (parity and age at first birth), data were combined from four case–control studies conducted in the United States and Japan. To overcome the issue of variation in mammographic density assessment among the studies, a single observer re-read all the mammograms using one type of interactive thresholding software. Logistic regression was used to estimate odds ratios (OR) while adjusting for other known breast cancer risk factors. Included were 1,699 breast cancer cases and 2,422 controls, 74% of whom were postmenopausal. A positive association between mammographic density and breast cancer risk was evident in every group defined by parity and age at first birth (OR per doubling of percent mammographic density ranged between 1.20 and 1.39). Nonetheless, the association appeared to be stronger among nulliparous than parous women (OR per doubling of percent mammographic density = 1.39 vs. 1.24; P interaction = 0.054). However, when examined by study location, the effect modification by parity was apparent only in women from Hawaii and when examined by menopausal status, it was apparent in postmenopausal, but not premenopausal, women. Effect modification by parity was not significant in subgroups defined by body mass index or ethnicity. Adjusting for mammographic density did not attenuate the OR for the association between parity and breast cancer risk by more than 16.4%, suggesting that mammographic density explains only a small proportion of the reduction in breast cancer risk associated with parity. In conclusion, this study did not support the hypothesis that parity modifies the breast cancer risk attributed to mammographic density. Even though an effect modification was found in Hawaiian women, no such thing was found in women from the other three locations.     

Joint effects of nulliparity and other breast cancer risk factors

Background:

Pregnancy may reduce breast cancer risk through induction of persistent changes of the mammary gland that make the breast less susceptible to carcinogenic factors. It is not known to what extent the effects of parity are independent of other breast cancer risk factors.

Methods:

In a Norwegian cohort of 58 191 women (2890 breast cancers), we assessed whether the effects of parity on postmenopausal breast cancer risk may be modified by menstrual and anthropometric factors. We calculated attributable proportions due to interaction as a measure of synergism.

Results:

Parity, height, body mass index (BMI), age at menarche and menopause were all associated with breast cancer risk in the expected directions. For BMI, follow-up was stratified into two age groups because of non-proportional hazards. We found that nulliparity and overweight may amplify each other''s effect on breast cancer risk among women after 70 years of age (attributable proportion 0.21, 95% confidence interval 0.04–0.39). There was some indication that parity and age at menopause may antagonise each other''s effect. Effects of parity were largely unaffected by age at menarche and height.

Conclusion:

Nulliparity and overweight may have a synergistic effect on breast cancer risk in elderly women. If confirmed by others, the findings may help disentangle the interplay of different causes of breast cancer.     

Breast cancer risk factors and mammographic breast density in women over age 70

SummaryBackground Breast density is a strong risk factor for breast cancer, but little is known about factors associated with breast density in women over 70.Methods Percent breast density, sex hormone levels and breast cancer risk factor data were obtained on 239 women ages 70–92 recruited from 1986 to 1988 in the United States. Multivariable linear regression was used to develop a model to describe factors associated with percent density.Results Median (range) percent density among women was 23.7% (0–85%). Body mass index (β= −0.345, p<0.001 adjusted for age and parity) and parity (β= −0.277, p<0.001 adjusted for age and BMI) were significantly and inversely associated with percent breast density. After adjusting for parity and BMI, age was not associated with breast density (β=0.05, p=0.45). Parous women had lower percent density than nulliparous women (23.7 versus 34.7%, p=0.005). Women who had undergone surgical menopause had greater breast density than those who had had a natural menopause (33.4 versus 24.8%, p=0.048), as did women who were not current smokers (26.0 versus 17.3% for smokers, p=0.02). Breast density was not associated with age at menarche, age at menopause, age at first birth, breastfeeding, estrogen levels or androgen levels. In a multivariable model, 24% of the variance in percent breast density was explained by BMI (β= −0.35), parity (β=−0.29), surgical menopause (β=0.13) and current smoking (β= −0.12).Conclusion Factors associated with breast density in older, post-menopausal women differ from traditional breast cancer risk factors and from factors associated with breast density in pre-menopausal and younger post-menopausal women.     

Correlates of mammogram density in southwestern Native-American women

Little is known about the breast cancer risk factors or mammogram characteristics among Native-American women. Southwestern Native-American women have a low risk of breast cancer and a high risk of diabetes. Our purpose was to determine the prevalence of known clinical risk factors for breast cancer and their association with mammogram density in a sample of Southwestern Native-American women undergoing breast cancer screening. A retrospective review was performed of screening mammogram examinations in 455 women. Density was classified by American College of Radiology Breast Imaging Reporting and Data System (BIRADS) density patterns 1 to 4 (fat to dense). Clinical data including patient age, weight, body mass index, parity, lactation, age at first birth, menopause status, hormone replacement therapy, diabetes status, and family history of breast cancer were obtained. Multivariate analyses were performed. Among the entire group, 152 women (33.4%) had diabetes. Patient age (P = 0.0012), weight (P < 0.0001), menopause status (P = 0.0134), estrogen use (P = 0.0311), age at first birth (P = 0.0035), and diabetes (P = 0.0015) were associated with mammogram density. Diabetes was associated with mammogram density in premenopausal women (P = 0.0032) but not in postmenopausal women (P = 0.3178) in stratified analyses. Diabetes, hormone replacement therapy, age, weight, menopause status, parity, and age at first birth were significantly associated with mammogram density. The association of mammogram density with diabetes varied by menopause status and was significant only for premenopausal women.     

Effects of Menstrual and Reproductive Factors on the Risk of Breast Cancer: Meta-analysis of the Case-Control Studies in Japan

To elucidate the magnitude of the effect of menstrual and reproductive factors on breast cancer occurrence among Japanese women, we reviewed eight case-control studies previously conducted in Japan and used a quantitative method (meta-analysis) to summarize the data. While individual studies have different methods and populations, the estimated odds ratios (ORs) in the studies were statistically homogeneous for all study variables. It was confirmed that early age at menarche, late age at first birth, and premenopausal status are significantly associated with risk of breast cancer; an estimated combined OR of 0.68 (95% confidence interval (CI): 0.59-0.77) was obtained for women with onset of menstruation after age 16 compared to those before age 14. Nulliparous women had higher risk than women with first birth before age 25 (OR=1.56 95%, CI: 1.27-1.91). The OR for women with first birth after age 35 was 2.26 (95% CI: 1.85-2.77) compared to women at first birth before age 25. Premenopausal women had a higher risk than women with menopause before age 50 (OR=2.21, 95% CI: 1.53-3.20). We also found a significant protective effect of high parity after controlling for age at first birth and the other menstrual factors. The OR estimate for 3 or more births compared to nulliparity was 0.68 (95% CI: 0.54-0.86). The meta-analysis provided quantitative estimates of breast cancer risk among Japanese women with improved precision.     

The association of reproductive factors and breastfeeding with long term survival from breast cancer

Reproductive factors that influence breast cancer risk may also have an impact on survival, once the disease is diagnosed. In this study, 2,640 women were diagnosed with invasive breast cancer during follow-up after a breast cancer screening that took place in 1956–1959. Survival was assessed in relation to age at menarche, age at first birth, parity, history of breastfeeding, age at menopause, and the effect of BMI was assessed in a subset of patients. It is a special feature that the patients of this study have not been subjected to organized mammography screening and their use of exogenous hormones has been negligible. By the end of follow-up (2008), 2,301 (87%) of the patients had died and 1,022 (44%) of the deaths were caused by breast cancer. Breast cancer survival was not associated with age at menarche, parity or time since last birth, but survival was consistently poorer with increasing age at first birth (P for trend 0.03): comparing a first birth after 35 years with 25–29 years, the hazard ratio was 1.32 (95% CI 1.02–1.72). There was no evidence for a dose-related effect of breastfeeding, but BMI measured many years prior to diagnosis was inversely associated with survival (P for trend <0.01). The main finding was that reproductive factors, including breastfeeding, appear to have little influence on the survival of breast cancer patients. Age at first birth may be an exception to this, since we found a gradually poorer survival with increasing age at first birth. We also found that overweight and obesity, as measured many years prior to diagnosis, were associated with poorer survival.     

UICC Multidisciplinary Project on Breast Cancer: the epidemiology, aetiology and prevention of breast cancer

This report summarizes the conclusions of the 2nd conference of the Multidisciplinary Project on Breast Cancer of the International Union Against Cancer held in 1985. The incidence of breast cancer is rising all over the world and ranges from 0.2-8%/year. There were an estimated 541,000 cases of breast cancer diagnosed in 1975 and over 800,000/year are expected by the year 2000. The increased risk associated with early age at menarche, late age at menopause, late age at 1st birth, and nulliparity suggests the overwhelming importance of ovarian activity in the etiology of breast cancer. No consistent and coherent pattern of endocrine abnormalities associated with breast cancer has been identified, but there is considerable doubt concerning the validity of the concept that estrogen action on the breast is modulated by variations is progesterone secretion. Dietary factors, especially animal fat or meat consumption, are receiving attention. If diet is important, it has to act in childhood or adolescence. The increased risk of breast cancer in women with benign breast disease appears to be restricted to a small proportion of women whose biopsies show atypical hyperplasia. Evidence from a number of recent studies suggests that oral contraceptives (OCs) do not increase the overall risk of breast cancer, although concern has been expressed about numerous subgroups of OC users: women who continue taking OCs around the time of menopause, those who use OCs to delay their 1st pregnancy, and women exposed to prolonged use before age 25 years. Studies of noncontraceptive hormones suggest increased risk occurs only after 10 years or more of use. The prevention of breast cancer was considered in relation to specific agents used as prophylactics in high risk groups and life-style changes. For example, the antiestrogen tamoxifen could be considered for an interventive trial in high-risk women, although problems of toxicity must be considered. Reduction in obesity, especially in postmenopausal women, and a relatively low fat intake are 2 life-style alterations that seem feasible.     

Reproductive factors and breast cancer risk among older women

Reproductive factors have been shown to affect pre- and postmenopausal breast cancer risk differently, but whether there are additional age-specific differences among menopausal women as they age has not been clarified. We analyzed data from a large population-based case–control study that included 1,508 breast cancer cases and 1,556 controls, aged 20–98 years, who completed an in-home interviewer-administered questionnaire. The following subgroups were created to examine if the associations between reproductive factors and breast cancer risk varied by age- and menopausal-status: premenopausal (n = 968), postmenopausal <65 years (n = 1,045), postmenopausal ≥65 years (n = 958). Among postmenopausal women ≥65 years, ever having breastfed decreased risk (odds ratio (OR) = 0.67, 95% confidence interval (CI) = 0.48, 0.92), and a strong dose–response relationship was observed for longer durations of breastfeeding (P trend = 0.02), with the most pronounced protective effect observed for ≥14 months of breastfeeding (OR = 0.40, 95% CI = 0.21,0.76). Late age at first birth (AFB) and older age at last birth (ALB) were associated with non-statistically significant increases in breast cancer risk in this older group, while late age at menarche and surgical menopause decreased risk. ORs for multiparity were close to the null. Among premenopausal women and postmenopausal women <65 years, multiparity significantly decreased risk, and older AFB nonsignificantly increased risk. Our findings suggest that the well-known protective effect of multiparity attenuates with older age. Moreover, breastfeeding, one of the few potentially modifiable risk factors for breast cancer, was an important factor in decreasing risk among older parous postmenopausal women.     

Parity,Other Reproductive Factors,and Risk of Pancreatic Cancer Mortality in a Large Cohort of U.S. Women (United States)

Several studies have found an inverse relationship between parity and risk of pancreatic cancer. However, most of the studies of pancreatic cancer in relation to parity and other reproductive factors have been small and the results inconsistent. Most recently, a well-conducted, prospective cohort study found a linear inverse association between parity and pancreatic cancer. To clarify the relationship between parity and other reproductive factors and risk of pancreatic mortality, we examined these associations among 387,981 postmenopausal U.S. women in the Cancer Prevention Study (CPS)-II cohort. CPS-II participants completed a self-administered questionnaire in 1982 and were followed for mortality through 2000. During follow-up, 1959 pancreatic cancer deaths occurred. Using Cox proportional hazards modeling, we calculated rate ratios (RR) adjusted for age, race, education, personal history of diabetes, body mass index, height, exercise, family history of pancreatic cancer, and cigarette smoking status, frequency, and duration. Overall, we did not observe a significant association between parity and pancreatic cancer mortality (trend p = 0.07). However, women who had five or more births had lower death rates from pancreatic cancer than nulliparous women (RR = 0.80, 95% CI = 0.66–0.96). We observed no association between any other reproductive factors examined (age at first birth, menarche, or menopause; type of menopause; diethylstilbestrol (DES) use; or duration of oral contraceptive or estrogen replacement therapy use) and pancreatic cancer mortality. In summary, our results support the observation that high parity is associated with lower risk of pancreatic cancer but do not show a linear trend with increasing parity. Furthermore, we find no evidence that other reproductive factors are associated with pancreatic cancer mortality.     

Reproductive variables and risk of breast malignant and benign tumours in Yunnan province, China

Introduction and aim: To compare reproductive factor influence on patients with pathological diagnosedmalignant and benign tumor in the Breast Department, The First Peoples’ Hospital of Kunming in Yunnanprovince, China. Methods: A hospital-based case-control study was conducted on 263 breast cancer (BC) casesand 457 non-breast cancer controls from 2009 to 2011. The cases and controls information on demographics,medical history, and reproductive characteristics variables were collected using a self-administered questionnaireand routine medical records. Histology of breast cancer tissue and benign breast lesion were documented bypathology reports. Since some variables in data analysis had zero count in at least one category, binomial-responseGLM using the bias-reduction method was applied to estimate OR’s and their 95% confidence intervals (95%CI). To adjust for age and menopause status, a compound variable comprising age and menopausal status wasretained in the statistical models. Results: multivariate model analysis revealed significant independent positiveassociations of BC with short menstrual cycle, old age at first live birth, never breastfeeding, history of oralcontraception experience, increased number of abortion, postmenopausal status, and nulliparity. Categorisedby age and menopausal status, perimenopausal women had about 3-fold and postmenopausal women had morethan 5-fold increased risk of BC compared to premenopausal women. Discussion and Conclusion: This study hasconfirmed the significant association of BC and estrogen related risk factors of breast cancer including longermenstrual cycle, older age of first live birth, never breastfeeding, nulliparity, and number of abortions morethan one. The findings suggest that female hormonal factors, especially the trend of menopause status play asignificant role in the development of BC in Yunnan women     

Insulin-like growth factor and mammographic density in postmenopausal Norwegian women.

Insulin-like growth factor-I (IGF-I) is associated with breast cancer risk among premenopausal women but rarely among postmenopausal women. Recent data from two European studies suggested an increased risk of breast cancer with increasing levels of IGF-I among women >50 years old or among postmenopausal hormone therapy users >or=55 years old. Mammographic density is one of the strongest risk factors, and possibly an intermediate marker, for breast cancer. We examined the relationship between IGF and mammographic density among postmenopausal women overall and according to hormone therapy use. Altogether, 977 postmenopausal participants in the Norwegian governmental mammographic screening program had IGF concentrations measured by ELISA. Mammograms were classified according to percent and absolute mammographic densities using a previously validated computer-assisted method. After adjustment for age, number of children, age at menopause, body mass index, and hormone therapy use, both plasma IGF-I concentration (P(trend) = 0.02) and IGF-I/IGF binding protein 3 ratio (P(trend) = 0.02) were positively associated with percent mammographic density. The magnitudes of differences in percent mammographic density between women in the lowest and highest quartiles of IGF-I concentrations were 1.5% absolute difference and 21% relative difference. These associations were similar with absolute mammographic density as the outcome variable. When the analyses were stratified according to hormone therapy use, the associations between IGF-I and mammographic density were significant among noncurrent users (P(trend) = 0.03). In conclusion, we found a positive but weak association between plasma IGF-I concentrations and both percent and absolute mammographic densities among postmenopausal women. These associations were found among noncurrent hormone therapy users but not among current users.     

FGFR2 intronic polymorphisms interact with reproductive risk factors of breast cancer: Results of a case control study in Japan

Recently, 2 genome‐wide association studies demonstrated that single nucleotide polymorphisms (SNPs) of the fibroblast growth factor receptor 2 (FGFR2) gene at intron 2 are significantly associated with the risk of female breast cancer. As the next step, it is necessary to evaluate the interaction between these SNPs and known risk factors of breast cancer because such an evaluation could elucidate mechanisms of carcinogenesis and lead to preventive advances. We conducted a case‐control study of 456 newly and histologically diagnosed breast cancer cases and 912 age‐ and menopausal status‐matched noncancer controls. The impact of 5 FGFR2 intronic SNPs on the risk of breast cancer and the interactions between these SNPs and various known risk factors of breast cancer were evaluated in both pre and postmenopausal women. We observed a statistically significant association between 4 SNPs and breast cancer risk and these 4 SNPs were in strong linkage disequilibrium in the Japanese population. rs2420946 was associated with a population‐attributable risk of 17.7%. We found that FGFR2 polymorphisms interact with family history of breast cancer (interaction p = 0.003) and reproductive risk factors, namely, age at menarche (interaction p = 0.019) and parity (interaction p = 0.026). Of note, a significant association between body mass index (BMI) ≥ 25 and FGFR2 polymorphism was observed among postmenopausal women (trend p = 0.012), but not among premenopausal women. In contrast, BMI < 25 had no significant association with this polymorphism regardless of menopausal status. These findings suggest that FGFR2 intronic SNPs affect the reproductive hormone‐related pathway and contribute to the development of female breast cancer in the Japanese population. © 2009 UICC     

Risk factors for breast cancer in black women

Risk factors for breast cancer were examined in black women in a hospital-based case-control study of 529 black women with breast cancer and 589 controls. Late age at menarche was associated with a reduced risk of breast cancer. Women having 5 or more children had a reduced risk relative to that of women with fewer or no children. Late age at first birth was associated with an elevated risk of breast cancer. Among postmenopausal black women, obesity [as measured by body mass index (BMI)] was associated with an increased risk; among premenopausal women, there was no association of breast cancer with BMI. Women whose menopause occurred at or after age 50 were at increased risk relative to those whose menopause occurred earlier. There was no association between number of years of education and breast cancer in black women. History of benign breast disease and history of breast cancer in mother or sisters both were risk factors. The risk factor profile for breast cancer in black women was similar to that observed in whites.     

Impact of menstrual and reproductive factors on breast cancer risk in Japan: results of the JACC study

The incidence of breast cancer among Japanese women, a traditionally low-risk population, has increased substantially. To evaluate the association of reproductive factors with breast cancer risk, we examined 38,159 Japanese women, aged 40-79 years, who responded to a questionnaire on reproductive and other lifestyle factors from 1988 to 1990 in the Japan Collaborative Cohort Study. During an average 7.6 years of follow-up, we documented 151 incidents of breast cancers. Cox proportional hazards modeling was employed to estimate relative risks (RR) and 95% confidence intervals (CI). There was a significant decline in the risk of breast cancer with increasing parity among parous women (trend P=0.01). Women with four or more parities had a 69% lower risk than uniparous women, a reduced risk was also evident among menopausal women. Breast cancer risk tended to rise with increasing age at first delivery (trend P=0.05), the association being very apparent among menopausal women (trend P=0.02). Compared to the women who had their first delivery before age 25, those who delayed this event until after age 34 had an RR of 2.12 (95% CI: 0.72-6.21) and 3.33 (1.07-10.3) among the overall subjects and the menopausal, respectively. There was no apparent association of breast cancer risk with age at menarche or menopause. Our study concerning reproductive risk factors suggests that breast cancer in Japan is similar to that in Western countries, and that reproductive factors, particularly the number of parity and age at first delivery, might be important in the etiology of breast cancer among Japanese women.     

Circulating levels of sex hormones and their relation to risk factors for breast cancer: a cross-sectional study in 1092 pre- and postmenopausal women (United Kingdom)

Objective: To investigate the relationships between plasma concentrations of sex hormones and risk factors for breast cancer. Methods: We investigated the relationship of plasma concentrations of estradiol, progesterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and sex hormone-binding globulin (SHBG) with breast cancer risk factors in 636 premenopausal and 456 postmenopausal women. Risk factor data were obtained from questionnaires and hormone concentrations measured by immunoassays; variations in geometric means were compared using analysis of covariance. Results: SHBG decreased with increasing body mass index and increasing waist–hip ratio both in pre- and postmenopausal women. In postmenopausal women only, estradiol increased with increasing body mass index. In premenopausal women, estradiol decreased with increasing physical activity, estradiol was higher in current than in ex- and non-smokers, and FSH decreased with increasing alcohol intake. No associations were observed between sex hormones and age at menarche, parity, age at menopause, and previous use of oral contraceptives in either pre- or postmenopausal women. Conclusions: Certain factors such as obesity and perhaps waist–hip ratio, physical activity and alcohol consumption, but probably not age at menarche and parity, may mediate their effects on breast cancer risk by changing circulating concentrations of sex hormones.