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.     

The associations between a polygenic score, reproductive and menstrual risk factors and breast cancer risk

We evaluated whether 13 single nucleotide polymorphisms (SNPs) identified in genome-wide association studies interact with one another and with reproductive and menstrual risk factors in association with breast cancer risk. DNA samples and information on parity, breastfeeding, age at menarche, age at first birth, and age at menopause were collected through structured interviews from 1,484 breast cancer cases and 1,307 controls who participated in a population-based case–control study conducted in three US states. A polygenic score was created as the sum of risk allele copies multiplied by the corresponding log odds estimate. Logistic regression was used to test the associations between SNPs, the score, reproductive and menstrual factors, and breast cancer risk. Nonlinearity of the score was assessed by the inclusion of a quadratic term for polygenic score. Interactions between the aforementioned variables were tested by including a cross-product term in models. We confirmed associations between rs13387042 (2q35), rs4973768 (SLC4A7), rs10941679 (5p12), rs2981582 (FGFR2), rs3817198 (LSP1), rs3803662 (TOX3), and rs6504950 (STXBP4) with breast cancer. Women in the score’s highest quintile had 2.2-fold increased risk when compared to women in the lowest quintile (95 % confidence interval: 1.67–2.88). The quadratic polygenic score term was not significant in the model (p = 0.85), suggesting that the established breast cancer loci are not associated with increased risk more than the sum of risk alleles. Modifications of menstrual and reproductive risk factors associations with breast cancer risk by polygenic score were not observed. Our results suggest that the interactions between breast cancer susceptibility loci and reproductive factors are not strong contributors to breast cancer risk.     

Long-term impact of reproductive factors on cancer risk

The relationship between reproductive variables (parity, age at first birth, number of induced and spontaneous abortions) and cancer risk has been analysed using data from an integrated series of case-control studies conducted in northern Italy between 1983 and 1992. The overall data-set included women below age 75 with histologically confirmed cancers of the following sites: oesophagus, 58; stomach, 280; colon, 405; rectum, 210; liver, 82; gall-bladder, 29; pancreas, 129; breast, 3,415; cervix, 742; endometrium, 725; ovary, 953; bladder, 68; kidney, 56; thyroid, 180; lymphomas, 80; myelomas, 57; and a total of 5,619 controls admitted to hospital for acute non-neoplastic, non-gynaecological, non-hormone-related conditions. Multivariate odds ratios, as estimators of relative risks (RR), were obtained after allowance for age, education, use of oral contraceptives and oestrogen replacement treatments, plus various reproductive factors. Direct significant trends with parity were observed for cancer of the liver (RR for women with ≥4 births vs. nulliparae = 3.3) and cervix uteri (RR = 4.1). The risk of gall-bladder cancer was also elevated for multiparae (RR = 1.9). No significant inverse trend in risk emerged. However, the RRs in multiparae were significantly below unity for breast (RR = 0.8), endometrium (RR = 0.7), and ovary (RR = 0.8). With reference to age at first birth, a significant trend in risk was observed for breast cancer (RR = 1.4 for 25 to 29 and 1.5 for ≥30 vs. ≤ 25 years). In contrast, the risk of cervical cancer was inversely related to age at first birth. For spontaneous abortions, the only significant inverse trend was for ovarian cancer (RR = 0.7 for ≥2 vs. 0 abortions), but also the point estimate for endometrial cancer in women with ≥2 abortions was below unity. For induced abortions, there was a strong inverse trend in risk for endometrial cancer (RR = 0.5), and the RRs were below unity also for colon and breast cancer. In contrast, cervical cancer was directly associated with the number of spontaneous abortions. Although the underlying aetiological interpretations are different for various cancer sites, this study provides, in a large and uniform data-set, quantitative information on the long-term impact of reproductive factors on cancer risk.     

Analysis of menstrual, reproductive, and life-style factors for breast cancer risk in Turkish women

The aim of this study was to investigate the association between menstrual, reproductive, and life-style factors and breast cancer in Turkish women. In a hospital-based case-control study in Ankara, 622 patients with histologically confirmed breast cancer were compared with 622 age-matched controls, admitted to the same hospital for acute and non-neoplastic diseases. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) related to risk factors. Overall, menopausal status and age at menopause were found to be significantly associated with breast cancer. Having a full-term pregnancy and early age at first birth were associated with decreased breast cancer risk (OR=0.45, 95% CI=0.30–0.66; OR=0.34, 95% CI=0.22–0.53, respectively). Postmenopausal women with lactation longer than 48 mo had reduced risk of breast cancer (OR=0.36, 95% CI=0.14–0.93). In conclusion, decreased parity, late age at first birth, early menopause, and shorter duration of lactation were the most important determinants of breast cancer risk in Turkish women.     

Lifestyle, parity, menstrual and reproductive factors and risk of gallbladder cancer.

Together with thyroid cancer, cancer of the gallbladder is the only non-sex hormone-related cancer displaying a female preponderance, with incidence being 3-4 times more common among women. We carried out this study to evaluate the role of menstrual, reproductive and lifestyle factors in gallbladder carcinogenesis. A case-control study involving 64 newly diagnosed cases of gallbladder cancer and 101 cases of cholelithiasis was carried out. A detailed menstrual and reproductive history was illustrated beside detailed lifestyle history, in particular consumption of betel nut, tobacco and alcohol and smoking, odds ratio was calculated. Mean age of the patients with cancer was 51+/-1.2 years while it was 40.9+/-1.2 years for gallstones; 69% of cancer patients and 90% of gallstones patients were females. More than half of the cancer patients (53%) and 43% of the gallstone patients were illiterate. A past history of typhoid was present in 22% of cancer patients and 13% of gallstone patients, while 35% of cancer and 25% of gallstone patients were chewers, 18.1 and 9.9% were smokers, and 10% of cancer and 2% of gallstone patients consumed alcohol. Mean age of menarche was 13.4+/-1.2 years among female patients with cancer while it was 14.0+/-1.4 years for gallstone patients. Higher age at menarche (>13 years, OR 2.48, 95% confidence interval (CI) 1.16-5.3), higher number of childbirths(>3 births, OR 3.92; 95% CI 1.4-10.3), higher number of pregnancies (>3 pregnancies, OR 6.66, 95% CI 1.8-23.4), and higher age at last childbirth (>25 years, OR 2.97, 95% CI 1.04-8.5) were found to have significantly higher risk of developing gallbladder cancer. In conclusion, tobacco chewing and smoking are associated with increased odds of gallbladder cancer. Similarly early menarche, late menopause, multiple pregnancies and childbirth increased the risk of gallbladder cancer.     

Menstrual and reproductive factors and risk of breast cancer in Asian-Americans.

We conducted a population-based case-control study of breast cancer among Chinese-, Japanese- and Filipino-American women in Los Angeles County Metropolitan Statistical Area (MSA), San Francisco-Oakland MSA and Oahu, Hawaii. One objective of the study was to quantify breast cancer risks in relation to menstrual and reproductive histories in migrant and US-born Asian-Americans and to establish whether the gradient of risk in Asian-Americans can be explained by these factors. Using a common study design and questionnaire in the three study areas, we successfully conducted in-person interviews with 597 Asian-American women diagnosed with incident, primary breast cancer during the period 1983-87 (70% of those eligible) and 966 population-based controls (75% of those eligible). Controls were matched to cases on age, ethnicity and area of residence. In the present analysis, which included 492 cases and 768 controls, we observed a statistically non-significant 4% reduction in risk of breast cancer with each year delay in onset of menstruation. Independent of age at menarche risk of breast cancer was lower (odds ratio; OR=0.77) among women with menstrual cycles greater than 29 days. Parous Asian-American women showed a significantly lower risk of breast cancer then nulliparous women (OR=0.54). An increasing number of livebirths and a decreasing age at first livebirth were both associated with a lower risk of breast cancer, although the effect of number of livebirths was no longer significant after adjustment for age at first livebirth. Women with a pregnancy (spontaneous or induced abortions) but no livebirth had a statistically non-significant increased risk (OR=1.84), but there was no evidence that one type of abortion was particularly harmful. A positive history of breastfeeding was associated with non-significantly lower risk of breast cancer (OR=.78). There are several notable differences in the menstrual and reproductive factors between Asian-Americans in this study and published data on US whites. US-born Asian Americans had an average age at menarche of 12.12 years-no older than has been found in comparable studies of US whites, but 1.4 years earlier than Asian women who migrated to the US. Asian-American women, particularly those born in the US and those who migrated before age 36, also had a later age at first birth and fewer livebirths than US whites. A slightly higher proportion of Asian-American women breastfed, compared with US whites. The duration of breastfeeding was similar in US-born Asians and US whites, but was longer in Asian migrants, especially those who migrated at a later age. Menstrual and reproductive factors in Asian-American women are consistent with their breast cancer rates being at least as high as in US whites, and they are. However, the effects of these menstrual and reproductive factors were small and the ORs for migration variables changed only slightly after adjustment for these menstrual and reproductive factors. These results suggest that the lower rates of breast cancer in Asians must be largely as a result of other environmental/lifestyle factors.     

Role of reproductive factors on the risk of endometrial cancer

We analyzed the role of reproductive factors on the risk of endometrial cancer using data from a case-control study conducted in Italy. Cases were 752 women with histologically confirmed endometrial cancer <75 years of age. Controls were 2,606 patients <75 years of age admitted for acute, non-gynecological non-hormone-related, non-neoplastic conditions to the same network of hospitals where cases had been identified. In comparison with nulliparae, the risk of endometrial cancer tended to be lower in parous women, and the estimated multivariate odds ratios (ORs) were 0.9, 0.8 and 0.7, respectively, for women reporting 1, 2 and 3 or more births (χ₁² trend 10.21). In comparison with women reporting no induced abortion, the ORs of endometrial cancer were 0.6 in women reporting 1 and 0.4 in those reporting 2 or more induced abortions. When considering parous women only, in comparison with women reporting their last birth 20 years before or longer, the ORs of endometrial cancer were 0.6 in those reporting their last birth 10–19 years before and 0.3 in those reporting their last birth <10 years before. Our results confirm and further quantify a protective role of pregnancy on the risk of endometrial cancer and provide insights on the time-risk relationship between pregnancy and cancer of corpus uteri. Int. J. Cancer 76:784–786, 1998.© 1998 Wiley-Liss, Inc.     

Association of menstrual and reproductive factors with breast cancer risk: results from the Shanghai Breast Cancer Study

The incidence of breast cancer among women in Shanghai, a traditionally low-risk population, has increased substantially over the past 20 years. To evaluate the association of menstrual and reproductive factors with breast cancer risk and the influence of these factors on the temporal trend of breast cancer incidence, we analyzed data from the Shanghai Breast Cancer Study, a population-based case-control study of breast cancer recently completed among Chinese women in urban Shanghai. In-person interviews were completed for 1,459 women newly diagnosed with breast cancer between ages 25 and 64 and for 1,556 controls frequency-matched to cases by age. Unconditional logistic regression was employed to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) related to menstrual and reproductive factors. Earlier menarcheal age, nulliparity, and later age at first live birth were associated with increased risk of breast cancer among both pre- and post-menopausal women, while never having breast-fed and later age at menopause were associated with elevated risk only among post-menopausal women. Among controls, 32% of younger women (40 years) reported starting menarche at age of 13 or younger, and this factor contributed to 44% of cases diagnosed among younger women and 26% to 28% of cases in older women. Older age at first live birth or at menopause explained a considerable portion of cases diagnosed in older, but not younger, women. Our study suggests that the changes in menstrual and reproductive patterns among women in Shanghai have contributed to the recent increase in breast cancer incidence, particularly among younger women.     

Long-term impact of reproductive factors on the risk of cervical, endometrial, ovarian and breast cancer

The influence of maternal age, parity, low or high birthweight, multiple births, and pre-eclampsia on the risk of cervical, endometrial, ovarian and breast cancers was studied. Data on 40 951 women and the outcomes of their deliveries between 1955 and 1995 were obtained from birth registers. For the mothers, data from the Swedish Cancer Registry and the Cause of Death Register were added. The sample was evaluated using Cox's regression in univariate and bivariate analyses where the relative risk and its 95% confidence interval were calculated. Increasing maternal age at first birth was associated with an increasing relative risk of endometrial, ovarian, and breast cancers, and with a decreased risk of cervical cancer. Multiparity was a protective factor for all gynaecological cancers, including cervical and breast cancers. Multiple births were associated with an increased risk of endometrial cancer.     

Breast cancer risk following Hodgkin lymphoma radiotherapy in relation to menstrual and reproductive factors

Background:

Women treated with supradiaphragmatic radiotherapy (sRT) for Hodgkin lymphoma (HL) at young ages have a substantially increased breast cancer risk. Little is known about how menarcheal and reproductive factors modify this risk.

Methods:

We examined the effects of menarcheal age, pregnancy, and menopausal age on breast cancer risk following sRT in case–control data from questionnaires completed by 2497 women from a cohort of 5002 treated with sRT for HL at ages <36 during 1956–2003.

Results:

Two-hundred and sixty women had been diagnosed with breast cancer. Breast cancer risk was significantly increased in patients treated within 6 months of menarche (odds ratio (OR) 5.52, 95% confidence interval (CI) (1.97–15.46)), and increased significantly with proximity of sRT to menarche (P_trend<0.001). It was greatest when sRT was close to a late menarche, but based on small numbers and needing reexamination elsewhere. Risk was not significantly affected by full-term pregnancies before or after treatment. Risk was significantly reduced by early menopause (OR 0.55, 95% CI (0.35–0.85)), and increased with number of premenopausal years after treatment (P_trend=0.003).

Conclusion:

In summary, this paper shows for the first time that sRT close to menarche substantially increases breast cancer risk. Careful consideration should be given to follow-up of these women, and to measures that might reduce their future breast cancer risk.     

Analysis of menstrual, reproductive, and life-style factors for breast cancer risk in Turkish women: a case-control study

The aim of this study was to investigate the association between menstrual, reproductive, and life-style factors and breast cancer in Turkish women. In a hospital-based case-control study in Ankara, 622 patients with histologically confirmed breast cancer were compared with 622 age-matched controls, admitted to the same hospital for acute and non-neoplastic diseases. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) related to risk factors. Overall, menopausal status and age at menopause were found to be significantly associated with breast cancer. Having a full-term pregnancy and early age at first birth were associated with decreased breast cancer risk (OR = 0.45, 95% CI = 0.30-0.66; OR = 0.34, 95% CI = 0.22-0.53, respectively). Postmenopausal women with lactation longer than 48 mo had reduced risk of breast cancer (OR = 0.36, 95% CI = 0.14-0.93). In conclusion, decreased parity, late age at first birth, early menopause, and shorter duration of lactation were the most important determinants of breast cancer risk in Turkish women.     

Combined effect of family history and reproductive factors on breast cancer risk

This study evaluated the combined effect of a family history of breast cancer and each of three reproductive factors on breast cancer risk in the sisters of 404 breast cancer patients. The patients had a family history of breast cancer in a sister and mother or in two sisters. Risks were highest in sisters who had menarche at an early age or who first gave birth at a late age whether the patient had unilateral or bilateral disease, and with low parity only when the patient had bilateral disease. The bilateral group may have included a higher fraction of hereditary forms of breast cancer than the unilateral group. Because similar findings have been reported previously for breast cancer patients in general, the current results suggest that these reproductive factors have an effect on breast cancer risk independent of a family history of the disease. It is important, therefore, that the combined effects of these risk factors be taken into account when counseling women about their breast cancer risks.     

The influence of menstrual risk factors on tumor characteristics and survival in postmenopausal breast cancer

Introduction  

Hormonal factors are implicated in tumor progression and it is possible that factors influencing breast cancer induction could affect prognosis. Our study investigated the effects of menstrual risk factors on tumor characteristics and survival in postmenopausal breast cancer.     

Association between lifestyle,menstrual/reproductive history,and histological factors and risk of breast cancer in women biopsied for benign breast disease

Purpose

Women with benign breast disease (BBD) have an increased risk of subsequent breast cancer. However, whether conventional breast cancer risk factors influence risk of breast cancer among women with BBD is unclear. In this study, we investigated the associations of lifestyle, menstrual/reproductive, and histological factors with risk of breast cancer among women biopsied for BBD.

Methods

We conducted a case–control study, nested within a cohort of 15,395 women biopsied for BBD at Kaiser Permanente Northwest between 1971 and 2006. Cases were women who developed a subsequent invasive breast cancer during follow-up; controls were individually matched to cases on age at BBD diagnosis. A total of 526 case–control pairs were included in the study. We calculated crude and multivariable OR and 95% CI for the associations between lifestyle, menstrual/reproductive, and histological factors and breast cancer risk using conditional logistic regression.

Results

Compared to premenopausal women, postmenopausal women had reduced risk of subsequent breast cancer (OR 0.60; 95% CI 0.39–0.94), whereas women who ever used hormone replacement therapy (HRT) had increased risk (OR 3.61; 95% CI 1.68–7.75), as did women whose BBD lesion showed atypical hyperplasia (OR 5.56; 95% CI 2.05–15.06). Smoking, BMI, early menarche, multiparity (≥4), history of oophorectomy, and extent of lobular involution were not associated with risk of breast cancer.

Conclusion

This study suggests that use of HRT and having atypical hyperplasia are associated with increased risk of breast cancer among women with BBD, while postmenopausal women with BBD have a reduced risk.

     

Ages at different reproductive events, numbers of menstrual cycles in between and breast cancer risk

One hundred and seventy-five pathologically confirmed new cases of female breast cancer in National Taiwan University Hospital were selected as the case group. Four hundred and fifty-seven inpatient controls were individually matched for each case by age and date of admission. Information of reproductive factors and potential confounders were collected from questionnaire interview and medical records. Menstrual cycles before and after first fuIl-term pregnancy were estimated from the questionnaire. Conditional logistic regression was used to estimate the effects of reproductive risk factors and numbers of menstrual cycles before and after first full-term pregnancy. After adjusting for educational level, body mass index, family history of breast cancer and oral contraceptive use, age at menarche and menopause only showed borderline significance. Age at first full-term birth predicted breast cancer risk better. Parity was the most important protective factor. Number of menstrual cycles before first full-term pregnancy was also positively associated with breast cancer risk with linear trends.     

Postmenopausal breast cancer risk and cumulative number of menstrual cycles.

OBJECTIVE: To explore whether the lifetime cumulative number of menstrual cycles, as an index for total exposure to endogenous estrogens, and the number of menstrual cycles until a first full-term pregnancy (FFTP), are associated with breast cancer risk in postmenopausal women. METHODS: Population-based study with data from the Prospect-European Prospective Investigation into Cancer and Nutrition study. Naturally menopausal participants were eligible (n = 6,718). The cumulative number of menstrual cycles was computed in 6,031 (90%) women. We calculated the number of cycles until FFTP among parous participants. The number of menstrual cycles was impossible to compute in women who reported to be always irregular; therefore, we added the "always irregular" category in the analysis. During the 46,746 person-years of follow-up, 168 breast cancer cases were identified. Cox regression models were used and adjustments were made to account for potential confounders. RESULTS: Even when our data does not show a clear linear gradient, we observed an increased breast cancer risk in women with a higher number of cumulative menstrual cycles in their lifetime. Using < or = 415 cycles as reference, the hazard ratio for the irregular group, 416-453, 454-490, and > or = 491 cycles was 1.11 (.56, 2.19), 1.88 (1.14, 3.12), 1.74 (1.05, 2.87), and 1.80 (1.09, 2.96), respectively. Although not statistically significant, and of less magnitude, the risk estimates for the number of cycles before FFTP showed the same tendency. CONCLUSION: Among women who underwent natural menopause, a higher number of menstrual cycles in lifetime, reflecting a longer exposure to endogenous estrogens, is associated with an increased breast cancer risk.     

BRCA2 mutation carriers,reproductive factors and breast cancer risk

Background

Germline mutations in the BRCA genes dramatically increase the risk of breast cancer. In the general population, breast cancer risk is affected by age at menarche, by age at first birth, by the number of births and by the duration of breast feeding. Whether this is true for mutation carriers is not clear.

Methods

In a case–control study, nested in a population-based cohort of the Icelandic Cancer Detection Clinic, two groups of cases were defined, matched on year of birth, on age at diagnosis and on age when giving information on reproductive factors: 100 carriers of the Icelandic founder BRCA2 mutation 999del5, and 361 BRCA2-negative cases. The mean age at diagnosis was 48 years. There were 1000 women in a matched group of unaffected controls. Conditional logistic regression was used for the analysis.

Results

An increased number of births was associated with a decreased risk of breast cancer in BRCA2-negative cases but not in BRCA2-positive cases. A negative association between risk and duration of breast feeding was observed only in the mutation carriers. These associations were not statistically significant, but the effects of the two variables differed significantly according to mutation status (P = 0.007 and P = 0.045 for interaction with number of births and with duration of breast feeding, respectively). This was maintained when limiting the analysis to women diagnosed older than the age of 40 years.

Conclusion

The association between breast cancer and the number of pregnancies and between breast cancer and the duration of breast feeding was not the same for carriers and noncarriers of a detrimental BRCA2 mutation. In the context of other epidemiological and laboratory studies, this may indicate that the product of the BRCA2 gene has a function relating to the differentiation of epithelial tissue in the breast.     

Family history of breast cancer and breast cancer risk in Japan

We studied 132 families with a family history of breast cancer (familial aggregation cases, FA cases) to assess the breast cancer risk presented by such a family history. For comparison with these FA cases, we randomly selected 132 control families of sporadic cases (SP controls) by adjusting for the age of the proband at surgery. Information on family history was collected for all first-degree female relatives and maternal and paternal grandmothers. Japanese women with a first-degree relative affected by breast cancer were found to have an increased risk of the disease. The odds ratio (OR) for women with a family history of breast cancer was 1.99 (95% confidence interval [ CI ], 1.48-2.66). The OR for FA-case doughters of women with breast cancer was 1.54 (95% CI, 0.91-2.63). A higher risk was not observed if a woman's mother had breast cancer. If the proband had a sister with breast cancer, a slightly increased risk of other cancers of the proband was observed (OR, 1.85 [ 0.87-3.92]). These results suggest that a family history of breast cancer in Japanese women may affect their risk of developing cancer of the breast and other organs.     

Nutrition and breast cancer risk in Japan

The present study investigated the problem of whether or not the intake of an Western-style diet will induce within the host a specified hormonal change that increases the risk for breast cancer (BC). The key observations obtained are as follows: 1) The risk for BC in Japan has been increasing for the last 20 years in parallel with the Westernization of dietary habits (increase of fat and animal protein in the diet). 2) A Japanese BC patient is distinguishable from a corresponding normal control by (a) an increase of waist/hip ratio (more specifically, an increase of abdominal fat) and (b) a decrease in the number of live births (relative infertility). Height, weight and height-adjusted weight all cannot distinguish the former from the latter. 3) The former is also distinguishable from the latter by dual steroidal disorders of ovarian dysfunction (progesterone depression) and hypercorticoidism, as revealed by a case control comparison of urinary steroid excretions. 4) The long-term maintenance of an experimental mouse on a fat-rich diet increased abdominal fat weight at an adult age, but not at a young age. 5) In the same experiment, the fat-rich diet produced a reduction of plasma progesterone at an early stage, and also produced dual changes of progesterone depression and corticosterone stimulation at a late stage of experiment. Plasma estradiol was little affected by an excess of dietary fat. 6) In an adult mouse, the weight of abdominal fat was increased by corticosterone treatment and was decreased by estradiol treatment. The suppressive effect of estradiol on abdominal fat weight was dose-dependent. In conclusion, our findings seem to suggest the possibility that a fat rich diet may produce dual steroidal disorders of ovarian dysfunction and hypercorticoidism which in turn will open the way to breast carcinogenesis by activating 2 proto-oncogens at the initiation and promotion steps.     

Role of reproductive factors in breast cancer in a low-risk area: a case-control study.

A case-control study of 689 breast cancer patients seen at Tata Memorial Hospital during the period 1980-84 was carried out. During the same period 711 females who attended the hospital without a history of benign breast lesions or gynaecological complaints were selected as controls. Patients were interviewed by trained investigators to collect data on reproductive factors, menstrual history, tobacco smoking and chewing habit, dietary practices (vegetarian and non-vegetarian diet) and alcohol consumption. Cases and controls were stratified into four age groups (< 35 years, 35-44, 45-54 and 55+ years) and three places of residence (Bombay, Maharashtra, others). The adjusted relative risk (RR) for unmarried women compared with married women was 2.3. Nulliparous women had a 2.2-fold higher risk than parous women. Late age at marriage (30 years and above) and late age at first pregnancy (30 years and above) showed excess risks of 2.5 and 5.4 compared with women married at the age of 14 years and age at first pregnancy of < or = 14 years. Three or more pregnancies was associated with a 40-50% reduction in risk (P < 0.01). Non-vegetarian diet, literacy status and a history of stillbirth and abortion did not emerge as significant risk factors for breast cancer in our study. These findings, in a low-risk population, were consistent with those reported from high-risk populations.