First Full-term Pregnancy Research Articles

Epigenetic marks in estrogen receptor alpha CpG island correlate with some reproductive risk factors in breast cancer.

Reproductive backgrounds, such as age at menarche and menopause, age of first full-term pregnancy (FFTP), number of full-term deliveries and oral contraceptive use are main hormone-related risk factors of breast cancer. It seems that the mentioned factors may affect the risk of breast cancer by enhancing the duration of exposure to estrogen as a potent carcinogen for breast tissue, but the molecular mechanism which links each risk factor to breast cancer is unclear. Estrogen mainly works via its nuclear receptor (ERα). As epigenetic alterations such as CpG methylation are potential links between endogenous or exogenous exposures and genome, we hypothesized that hormone-related risk factors may correlate with the epigenetic marks of the ERα promoter in breast tumors. In the present study, the CpG methylation status of the ERα gene in 99 samples of breast tumors belonged to women with different reproductive histories was evaluated. The reproductive history data were collected from patients. ERα CpG methylation was investigated by methylation specific PCR in DNA samples were obtained from the breast tumors. We could show that some of the hormone-related risk factors (early FFTP and increased number of pregnancies) were inversely correlated with epigenetic marks in ERα gene in breast tumors. Other hormone-related risk factors such as age of menarche and menopause and oral contraceptive use did not show any association with ERα methylation. It seems that pregnancy-related risk factors in comparison with other hormone-related factors work via different mechanism. As ERα methylation is a poor prognosis marker in breast tumors, its association with some modifiable reproductive risk factors (FFTP age and numbers of pregnancies) reiterates the importance of programming reproductive life style not only for prevention of breast cancer but also in favoring the prognosis of the affected women. The exact molecular mechanisms of the observed correlation need more investigation in the future.

Active and passive cigarette smoking and breast cancer risk: Results from the EPIC cohort

Recent cohort studies suggest that increased breast cancer risks were associated with longer smoking duration, higher pack-years and a dose-response relationship with increasing pack-years of smoking between menarche and first full-term pregnancy (FFTP). Studies with comprehensive quantitative life-time measures of passive smoking suggest an association between passive smoking dose and breast cancer risk. We conducted a study within the European Prospective Investigation into Cancer and Nutrition to examine the association between passive and active smoking and risk of invasive breast cancer and possible effect modification by known breast cancer risk factors. Among the 322,988 women eligible for the study, 9,822 developed breast cancer (183,608 women with passive smoking information including 6,264 cases). When compared to women who never smoked and were not being exposed to passive smoking at home or work at the time of study registration, current, former and currently exposed passive smokers were at increased risk of breast cancer (hazard ratios (HR) [95% confidence interval (CI)] 1.16 [1.05-1.28], 1.14 [1.04-1.25] and 1.10 [1.01-1.20], respectively). Analyses exploring associations in different periods of life showed the most important increase in risk with pack-years from menarche to FFTP (1.73 [1.29-2.32] for every increase of 20 pack-years) while pack-years smoked after menopause were associated with a significant decrease in breast cancer risk (HR = 0.53, 95% CI: 0.34-0.82 for every increase of 20 pack-years). Our results provide an important replication, in the largest cohort to date, that smoking (passively or actively) increases breast cancer risk and that smoking between menarche and FFTP is particularly deleterious.

Abstract P3-06-13: Transient increase in breast cancer risk after a full term pregnancy among African women

Abstract Background African women affected by breast cancer (BC) have high parity with five children or more, are relatively young at first full term pregnancy (FFTP), are diagnosed at a young age and are often premenopausal at diagnosis. While several studies have assessed the role of reproductive factors for BC risk among African women, none of them have assessed whether there is dual effect of age at full term pregnancy (FTP). In this communications, using a large dataset from an on-going hospital-based case-control study, we examine the role of age at full term pregnancy on breast cancer risk among African women. Methods The study includes sites in Nigeria (University College Hospital, Ibadan), Cameroon (Yaoundé General Hospital) and Uganda (Breast Clinic of Mulago Hospital of Kampala). It was initiated in 1998 in Nigeria and extended to Cameroon and Uganda in 2011. Cases were consecutive females diagnosed with invasive BC. Controls were recruited from the community or within the hospital and have never being diagnosed with any cancer. Cases and controls were aged 18 years or more and gave informed consent. Full term pregnancy was defined as a pregnancy that lasted at least 7 months and included both live birth and stillbirth. Logistic regression models were used to assess the effects of age at first and second FTP, and their interaction with current age on BC risk. Age at menarche, parity, body mass index and hormone contraception use were included in the models. Results The study includes 1668 cases and 2399 controls recruited between 1998 and May 2013. Mean duration of live birth was 9 months (SD±0.52) and 8.8 months (SD±0.66) for a stillbirth. Overall, the mean age at FFTP was 23 years (SD±4.91) for both cases and controls. Compared to nulliparous women, parous women who had FFTP at 20 years have increased risk (OR = 1.59, CI 95%, 1.16-2.21) to develop BC in the year following the pregnancy. Up to 5 years following the FFTP, this OR is 1.38 (CI 95%, 1.06-1.80) while it is 0.77 (CI 95%, 0.62-0.95) 25 years later. This observation was also true for parous women who have had their FFTP at 25, 30, or 35 years. Moreover, a similar pattern was observed when comparing uniparous women to women with 2 or more children. Conclusion Our results show a transient increase in risk of BC after a full term pregnancy which declined and became protective over time. This observation is consistent with the effect of pregnancy on BC that has been described in other populations and may partially explain the current profile of breast cancer among African women. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-06-13.

Association between chronological change of reproductive factors and breast cancer risk defined by hormone receptor status: results from the Seoul Breast Cancer Study

Lifestyle factors have been chronologically changed into western style ones, which could result in the rapid increase of breast cancer incidence in Korea. It is plausible that reproductive factors through hormonal mechanisms are differentially related to the risk of breast cancer subtypes. We investigated the association of reproductive risk factors on breast cancer by birth year groups and also evaluated the differential associations on the hormone receptor-defined subtypes. Using the data from the Seoul Breast Cancer Study (SeBCS), a multicenter case-control study, 3,332 breast cancer patients and 3,620 control subjects were analyzed. The distribution of subtypes among cases was as follows: 61.0% estrogen receptor (ER)-positive, 51.9% progesterone receptor (PR)-positive, and 43.4% both ER/PR-positive status, respectively. Polytomous logistic regression and Wald tests for heterogeneity have been used across the subtypes. The frequencies of reproductive-related risk factors including early age at menarche, nulligravid, age at first full-term pregnancy (FFTP), duration of estrogen exposure before FFTP (EEBF), less number of children, never breastfeeding, and short duration of breastfeeding has increased as women were born later in both cases and controls, respectively (p trend<0.0001. Among breast cancer patients, either ER- or PR-positive subtypes were increased in women born in 1960s compared to women born in 1940s. Early age at menarche increased the risk of breast cancer regardless of the subtypes while nulligravid, late age at FFTP, and longer duration of EEBP were associated with hormone receptor-positive cancer risk only (p heterogeneity<0.05), which associations were stronger among women born later. Our results suggest that the associations of age at menarche, parity, age at FFTP, and duration of EEBF with breast cancer risk were different based on the hormone receptor status and birth year groups in Korea.

Association of CYP1A1 A4889G and T6235C polymorphisms with the risk of breast cancer in Brazilian women.

e11551 Background: Estrogen, activated by cytochrome P450 enzymes (CYP1A1), participates in the breast cancer (BC) development. G and C variant alleles of CYP1A1 A4889G and T6235C polymorphisms encode enzymes with increased activity in activation of this compound when compared with the respective wild alleles. This study aimed to clarify the roles of the polymorphisms in the risk of BC. Methods: CYP1A1 A4889G and T6235C genotypes of 742 sporadic breast cancer (SBC) patients (median age: 52 years, 638 Caucasians, 104 non-Caucasians) and 742 healthy women (median age: 40 years, 638 Caucasians, 104 non-Caucasians) were obtained in genomic DNA by PCR and enzymatic digestion. Results: Patient’s and control’s samples were in HW equilibrium at CYP1A1 A4889G (χ2= 0.15, P= 0.70; χ2= 1.15, P= 0.28) and T6235C (χ2= 2.65, P= 0.10; χ2= 1.93, P= 0.16) loci. The frequency of CYP1A1 4889AG+GG genotypes was higher in patients than in controls (29.0% versus 23.2%, P= 0.004). Carriers of the G allele were under a 1.50 (95% CI: 1.14-1.97)-fold increased risk for SBC than those with the wild AA genotype. The frequencies of 4889AG+GG genotypes in Caucasian SBC patients were higher than those found in Non-Caucasian (30.4% vs 20.2%, P= 0.03), and also in controls (30.4% vs 23.2%, P= 0.002). Carriers of G allele were under a 1.61 (95% CI: 1.20-2.15)-fold increased risk for SBC than others. A higher frequency of the CYP1A1 4889AG+GG genotypes was also seen in patients with an earlier median age at first full-term pregnancy (FFTP), compared to those who had the first pregnancy with a later medium age (33.8% vs 26.1%, P=0.03), and also when compared to controls (33.8% vs 23.2%, P= 0.001). Women with the CYP1A1 4889AG+GG genotypes and with earlier FFTP were under a 1.87 (95% CI: 1.32-2.67)-fold increased risk for SBC than others. The CYP1A1 6235CC genotype was more common in pre-obese or obese SBC patients than in underweight or normal SBC patients (6.8% vs 4.0%, P= 0.04). Conclusions: Our data suggest that CYP1A1 A4889G and T6235C polymorphisms alter BC risk in Brazilian women. We believe that women with variant alleles of the referred polymorphisms should receive additional medical attention for disease prevention and early diagnosis.

Factors influencing breast changes after pregnancy

Pregnancy and breastfeeding are major factors reducing breast cancer (BC) risk. A potential mechanism for this effect might be changes in mammographic density, but other factors might be involved. The aim of this study was to investigate factors influencing changes in breast size and breast stiffness after pregnancy. Of a consecutive cohort of 5991 women who gave birth between 1996 and 1999, 559 replied to a questionnaire including questions about breast changes. The women completed their own assessments of changes in breast size and stiffness since their last pregnancy. Factors being investigated regarding their predictive value for these changes were: BMI before pregnancy, weight gain, age at first full-term pregnancy (FFTP), number of pregnancies, breastfeeding, and BMI of the children's fathers. A decrease in breast size was reported in 21.8% of the participants and an increase in 35.1%. With regard to the breast stiffness, 66.4% reported a decrease and only 5% reported an increase. Independent predictors for increased breast size were age at FFTP, increase in BMI since last pregnancy, BMI before pregnancy, and time since FFTP. Factors predictive of greater breast stiffness included age at FFTP, BMI before FFTP, time since FFTP, breastfeeding status, and number of pregnancies. Breast changes after pregnancy depend on several variables, which are described as BC-risk factors. Individual reaction of the female breast to a pregnancy leads to different outcomes with regard to breast size and stiffness. Further studies are needed to clarify whether these individual responses interact with the effect of pregnancy on the BC risk.

THE PECULIARITIES OF CHANGES IN THE STRUCTURE OF PSYCHOEMOTIONAL SPHERE IN WOMEN DURING THE GESTATION FLAVORS OF PREGNANCY

We examined the structure of psychoemotional sphere of 153 pregnant patients in different terms of pregnancy and 48 non-pregnant women. Our data demonstrated that first-term pregnancy is accompanied by a significant emotional stress. In second-term pregnancy those changes are more positive, at third-term pregnancy the level of the patients feels is significantly increased and the psychoemotional sphere is stabilized. Thereby the specific features of nervous system are influence the status of the pregnant women. Evidently pregnant patients with the high level of anxiety, introversion, psychotic and nevrotic characteristics are in need of the increased attention of the obstetric-gynecologic specialists, anaesthesiologists and psychologists to make correction of the psychoemotional sphere when preventive preparation of birth and the choice of anesthesia delivery.

Pregnancy-Induced Changes in Breast Cancer Risk

Breast cancer is the malignant disease most frequently diagnosed in women of all races and nationalities. Since the 1970s the worldwide incidence of this disease has increased 30-40% in postmenopausal women, in whom, paradoxically, the risk of developing breast cancer is significantly reduced by an early first full term pregnancy (FTP) as compared to nulliparous and late parous women. Although the cause of breast cancer is not known, the mechanisms mediating the protection conferred by an early FTP have been identified to reside in the breast itself, and to be modulated by endogenous and environmental exposures that might negatively affect this organ during specific windows in its development that extend from prenatal life until the first pregnancy. Soon after conception the embryo initiates the production of human chorionic gonadotropin (hCG), the glycoprotein hormone that is diagnostic of pregnancy. HCG in conjunction with ovarian steroid hormones primes the hypothalamic neuroendocrine system for maintaining the pregnancy. Higher levels of hCG during the first trimester of pregnancy have been associated with a reduction in maternal breast cancer incidence after age 50. In preclinical studies it has been demonstrated that both FTP and hCG treatment of virgin rats prevent the development of chemically-induced mammary tumors, a phenomenon mediated by the differentiation of the mammary gland epithelial cells prior to carcinogen exposure. Complete differentiation proceeds through complex morphological, physiological and molecular changes that occur during pregnancy and lactation, that ultimately result in increased DNA repair capabilities of the mammary epithelium, activation of genes controlling differentiation and programmed cell death and imprinting in the breast epithelium a specific and permanent genomic signature of pregnancy. This signature is indicative of a reduced breast cancer risk and serves as a molecular biomarker of differentiation for evaluating the potential use of chemopreventive agents.

Breast Cancer among Pakistani Women in Referral Hospitals: An Overview of Risk Factors

The aim of this study was to determine the significance of various reproductive risk factors amongstPakistani women suffering from breast carcinoma. This observational study was carried out fromMarch 2007 to February 2009 at three hospitals. The women who presented with breast swellingwith or without discharge from nipple were included in the study. The diagnosis of breast cancer wasconfirmed by histopathological examination. A questionnaire included history and various reproductiverisk factors. The study patients were divided into two groups by their menopausal history – premenopausaland post-menopausal as ‘group A’ and ‘group B’, respectively. A total of 70 patients hadthe diagnosis of breast cancer. Of them, 32 were in group A and 38 in group B. Regarding agedistribution, 49% were found in ≥51 years of age and 29% in the age group 30 – 40 years. The meanage at menarche was 13.3 years in group A and 12.4 years in group B. Nulliparity was seen in12.5% cases in group A and 5.26% in group B. History of first full term pregnancy (FFTP) belowthe age of 20 was present in majority of cases in both groups though higher in group B. Breast cancerin post-menopausal women was exclusively found among those who had early menarche (&lt;=11years) and was more frequent among those who had FFTP below 20 years of age compared with thepre-menopausal group (88% vs. 66%). The study showed higher frequency of breast cancer in postmenopausalwomen having early menarche and also more frequent among those with early FFTP.Parity, breast feeding, oral contraceptive pill use were not related to breast cancer.Ibrahim Med. Coll. J. 2010; 4(1): 1-3Indexing Words: Breast carcinoma; risk factors; genetics.DOI: 10.3329/imcj.v4i1.5926

Mimicking Pregnancy To Reduce Breast Cancer Risk

Women who have a full-term pregnancy before their mid-20s substantially reduce their lifetime risk of breast cancer, compared with women who either have children later in life or do not have children, according to many epidemiological studies. Women who breastfeed their babies further reduce that risk. Now breast cancer researchers are asking whether those observations can be transformed into a feasible breast cancer prevention strategy. Some investigators contend that the goal should be at the forefront of breast cancer research, whereas others express concern that pregnancy is too complex to mimic. Despite the challenges, several research groups are trying to tackle the question, and a few are even starting to test their hypotheses in women at high risk for breast cancer. Scientists once believed that a woman’s age at her fi rst full-term pregnancy is the most important factor, in terms of pregnancy’s role in breast cancer risk. But recent studies have shown that it plays less of a role than the number of births and duration of breast-feeding, said Valeria Beral, M.D., director of the cancer epidemiology unit at the University of Oxford, during her presentation at the San Antonio Breast Cancer Symposium in December. The role of multiple pregnancies became clear in 2002 when the Collaborative Group on Hormonal Factors in Breast Cancer, an international research group based at the University of Oxford, published a pooled analysis of 47 studies that included approximately 50,000 breast cancer patients and 96,000 healthy women. The team, of which Beral is a member, reported that when they held the age at fi rst birth constant, each birth was associated with a 7% lower relative risk of breast cancer and each 12 months of breastfeeding was associated with a 4.3% lower risk. One can see the association of lower risk and early, multiple pregnancies by comparing the rate of breast cancer in developed and developing countries. The incidence of breast cancer in the United States and Europe is 6.3% among women up to age 70 years. By contrast, the rate is 1.2% in rural Africa and Asia. Although diet and environment may account for some of that difference, the Collaborative Group estimates that the incidence in developed countries could theoretically drop to 2.7% if women adopted the same reproductive patterns as women in developing countries have. Beral is careful to emphasize that no one is

Biology, Metastatic Patterns, and Treatment of Patients with Triple-Negative Breast Cancer

Of the estimated 1 million cases of breast cancer diagnosed annually worldwide, it is estimated that over 170,000 will harbor the triple-negative (estrogen receptor/progesterone receptor/HER2—negative) phenotype. Most, though not all, triple-negative breast cancers will be basal-like on gene expression micorarrays. The basal-like molecular subtype exhibits a unique molecular profile and set of risk factors, aggressive and early pattern of metastasis, limited treatment options, and poor prognosis. Large population-based studies have identified a higher proportion of triple-negative breast tumors among premenopausal African American women, and a suggestion that increased parity, younger age at first-term pregnancy, shorter duration of breast feeding, and elevated hip-to-waist ratio might be particular risk factors. When BRCA1 mutation carriers develop breast cancer, it is usually basal-like; given the central role of BRCA1 in DNA repair, this could have profound therapeutic implications. When diagnosed, triple-negative breast cancers illustrate preferential relapse in visceral organs, including the central nervous system. Although initial response to chemotherapy might be more profound, relapse is early and common among triple-negative breast cancers compared with luminal breast cancers. The armamentarium of “targeted therapeutics” for triple-negative breast cancer is evolving and includes strategies to inhibit angiogenesis, epidermal growth factor receptor, and other kinases. Finally, the positive association between triple-negative breast cancer and BRCA mutations makes inhibition of poly(adenosine diphosphate-ribose) polymerase—1 an attractive therapeutic strategy that is in active study.

Heightened Risk of Breast Cancer Following Pregnancy: Could Lasting Systemic Immune Alterations Contribute?

The protective effect of having a first full-term pregnancy (FFTP) at a younger age on women's lifetime risk of breast cancer is well known. Less appreciated is the increased risk seen in the years immediately following pregnancy. This adverse effect is more pronounced and more prolonged in women with later age at FFTP. The mechanisms responsible for this increased risk are still poorly understood. In the present paper, we put forward the hypothesis that the marked peripheral immune changes induced by pregnancy may account for these effects. We highlight immune changes that characterize the unique immune state of pregnancy (a combination of cellular immunosuppression and enhanced inflammatory response), note the resemblance of these changes to cancer escape mechanisms, and discuss why such immune changes may be critical for the development of breast cancer following pregnancy. We further support this idea by initial findings from our own laboratory that the age at FFTP is negatively related to natural killer cell cytotoxicity many years later and propose possible models for the kinetics of the immune changes during and following pregnancy. The effect of age at FFTP on the immune function is currently understudied. Its potential relevance to the development of breast cancer stresses the need for further research.

Reproductive Factors, Oral Contraceptive Use, and Human Papillomavirus Infection: Pooled Analysis of the IARC HPV Prevalence Surveys

High parity, early age at first full-term pregnancy (FTP), and long-term oral contraceptive (OC) use increase cervical cancer risk, but it is unclear whether these variables are also associated with increased risk of acquisition and persistence of human papillomavirus (HPV) infection, the main cause of cervical cancer. Information on reproductive and menstrual characteristics and OC use were collected from 14 areas worldwide, among population-based, age-stratified random samples of women aged 15 years or older. HPV testing was done using PCR-based enzyme immunoassay. Unconditional logistic regression was used to estimate the odds ratios (OR) of being HPV-positive according to reproductive and menstrual factors and corresponding 95% confidence intervals (CI). When more than two groups were compared, floating CIs (FCI) were estimated. A total of 15,145 women (mean age, 40.9 years) were analyzed. Women with >or=5 FTPs (OR, 0.90; 95% FCI, 0.76-1.06) showed a similar risk of being HPV-positive compared with women with only one FTP (OR, 1.00; 95% FCI, 0.86-1.16). However, nulliparous women showed an OR of 1.40 (95% CI, 1.16-1.69) compared with parous women. Early age at first FTP was not significantly related to HPV positivity. HPV positivity was similar for women who reported >or=10 years of use of OCs (OR, 1.16; 95% FCI, 0.85-1.58) and never users of OCs (OR, 1.00; 95% FCI, 0.90-1.12). Our study suggests, therefore, that high parity, early age at first FTP, and long-term OC use are not associated with HPV prevalence, but rather these factors might be involved in the transition from HPV infection to neoplastic cervical lesions.

Oral Contraceptive Use as a Risk Factor for Premenopausal Breast Cancer: A Meta-analysis

To perform a meta-analysis of case-control studies that addressed whether prior oral contraceptive (OC) use is associated with premenopausal breast cancer. We searched the MEDLINE and PubMed databases and bibliography reviews to identify case-control studies of OCs and premenopausal breast cancer published in or after 1980. Search terms used included breast neoplasms, oral contraceptives, contraceptive agents, and case-control studies. Studies reported in all languages were included. Thirty-four studies were identified that met inclusion criteria. Two reviewers extracted data from original research articles or additional data provided by study authors. We used the DerSimonian-Laird method to compute pooled odds ratios (ORs) and confidence intervals (CIs) and the Mantel-Haenszel test to assess association between OC use and cancer. Use of OCs was associated with an increased risk of premenopausal breast cancer in general (OR, 1.19; 95% CI, 1.09-1.29) and across various patterns of OC use. Among studies that provided data on nulliparous and parous women separately, OC use was associated with breast cancer risk in both parous (OR, 1.29; 95% CI, 1.20-1.40) and nulliparous (OR, 1.24; 95% CI, 0.92-1.67) women. Longer duration of use did not substantially alter risk in nulliparous women (OR, 1.29; 95% CI, 0.85-1.96). Among parous women, the association was stronger when OCs were used before first full-term pregnancy (FFTP) (OR, 1.44; 95% CI, 1.28-1.62) than after FFTP (OR, 1.15; 95% CI, 1.06-1.26). The association between OC use and breast cancer risk was greatest for parous women who used OCs 4 or more years before FFTP (OR, 1.52; 95% CI, 1.26-1.82). Use of OCs is associated with an increased risk of premenopausal breast cancer, especially with use before FFTP in parous women.

Case–control study of risk factors for breast cancer in Nigerian women

This study evaluated the potential risk factors for breast cancer in Nigerian women using a case-control design of 250 women with breast cancer and their age-matched female controls. Both cases and controls were recruited from 4 University Teaching Hospitals in Midwestern and Southeastern Nigeria. Data on the clinical and epidemiological characteristics were collected using interviewer-administered structured questionnaires. The mean age of the cases and controls were 46.1 and 47.1 years, respectively. Fifty-seven percent of the cases were premenopausal while 43% were postmenopausal. The association of risk factors with breast cancer was assessed using conditional logistic regression. Positive family history of breast cancer in first- and second-degree relatives (Odds ratio [OR] = 8.07, 95% confidence interval [CI], 1.003, 64.95, p = 0.04), education of high school level and above (OR = 1.35, 95% CI 1.04, 1.74, p = 0.0205), age at first fullterm pregnancy (FFTP) greater than 20 years (OR = 1.32 95% CI 1.01, 1.71, p = 0.0413) and waist/hip ratio (WHR) (OR = 1.98, 95% CI 1.27, 3.10, p = 0.0026) were associated with increased risk of breast cancer in the final multiple conditional logistic regression model. The findings from this study have shown that sociodemographic characteristics, reproductive variables and anthropometric measures are significant predictors of breast cancer risk in Nigerian women.

Maternal Demographic and Psychosocial Factors Associated with Low Birth Weight in Eastern Taiwan

The relationship between birth weight and maternal sociodemographic characteristics was examined in a sample from two teaching hospitals in eastern Taiwan. Using a structured questionnaire, we conducted face-to-face interviews with women at antenatal clinics between 1998 and 1999 in Hualien City. One year later, we took the outcome of pregnancy from medical records and birth certificates from the Public Health Bureau of Hualien County. Of the 1,128 single live births, 6.8% had low birth weight (LBW) using the World Health Organization cut-off of 2,500 g. LBW was more common in teenage (< 20 years), older (> 30 years), first-time, and unmarried mothers; those with basic/intermediate educational attainment; and residents of aboriginal districts. Teenage pregnancies were more likely than those in adults to be unplanned, and such mothers had smoking or alcohol-drinking behavior. Prevention of teenage pregnancy is crucial to lower LBW rates in eastern Taiwan. For adult mothers, basic or intermediate educational attainment, residence in an aboriginal district, and first-term pregnancy were significant factors associated with LBW, after adjustment for other psychosocial attributes, such as psychologic distress and poor family support. Thus, we should pay more attention when caring for pregnant women with such sociodemographic characteristics, and ensure that they have adequate prenatal care and can adopt a healthy lifestyle.

Prophylaxis approach to a-symptomatic post-menopausal women: Breast cancer

Breast cancer is the most common cancer of women worldwide. Its frequency increases throughout the female lifespan. Epidemiological research has clearly identified important reproductive risk factors for breast cancer, including age at menarche, age at menopause, age at first-term pregnancy and nulliparity, which provide important clues to the hormonal origin of this disease. The widespread use of exogenous sex steroids as contraceptive agents and as hormonal replacement therapy has been a source of concern and generates discussion about their effects on breast health. Lifestyle changes, exercise or diet could play a role in primary prevention of breast cancer. Regular exercise, ingestion of adequate amounts of fruit and vegetables, limiting alcohol consumption, avoidance of obesity in post-menopausal women, and perhaps the use of olive oil, may all have a protective effect and should be considered by women. There is insufficient scientific evidence of the role played by phyto-oestrogens on breast cancer risk. Other preventive measures that include the use of drugs such as statins or aspirin should not be recommended until we have more information about their effects on the breast. Especially for high-risk women, all the aforementioned measures may be not enough, and chemo-prevention should be considered. The use of selective oestrogen receptor modulators (SERMs) to reduce breast cancer risk is still being evaluated. Tamoxifen was the first SERM approved for the reduction of breast cancer incidence in women at high risk. However its use has limitations, due to significant side effects. Raloxifene has been approved for the prevention and treatment of post-menopausal osteoporosis and has provided excellent indications of breast cancer risk reduction, with a more favourable profile than tamoxifen.

Hormonal and Body-Size Factors in Relation to Breast Cancer Risk: A Prospective Study of 11,889 Women in a Low-Incidence Area

This prospective cohort study of 11,889 women was conducted to determine significant factors associated with the risk of breast cancer among Chinese women in Taiwan, a low-incidence area. In-person interviews were completed for subjects to solicit information on hormonal factors. Measurements of height, weight, and waist-and- hip circumferences were performed by well-trained assistants using standardized techniques. Cox proportional hazards models were employed to estimate relative risks (RRs) and 95% confidence intervals (CIs). During an average follow-up time of 10.3 years (range: 1 to 11 years) with an accumulation of 134,063 person-years, 104 incident breast cancer cases were identified through data linkage with national cancer registry profile. There was a significant elevation in breast-cancer risk with increasing duration of the interval between age at menarche and age at first full-term pregnancy (FFTP). Additionally, central adiposity reflected by hip circumference was a significant predictor of breast cancer in this Chinese female population. The findings of this study indicated common mechanisms responsible for the higher incidence of breast cancer in Western populations may also explain the risk of breast cancer development in Taiwan, a low-incidence area.

Postmenopausal Breast Cancer Risk and Cumulative Number of Menstrual Cycles

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. 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. 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. 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.

Different gene expression in the breast after pregnancy

1019 Background: The protective effect of an early first full-term pregnancy (FFTP) in relation to breast cancer risk is well known, but the molecular and cell-specific mechanisms involved remain unclear. Methods: We analysed the global gene expression profiles of normal mammary tissues taken from a matched multiparous and nulliparous woman using Serial analysis of Gene Expression (SAGE) and Generation of longer cDNA fragments from SAGE tags for Gene Identification. Results: The differentiation markers such as caseinκ, caseinβ, keratin14 en CCAAT/enhancer binding protein β and δ are increased after pregnancy. Genes like bullous pemphigoïd antigen 1, decorin, vimentin, retinoid acid receptor responder, and the transcription factor early growth response 1 are also candidate markers for a pregnancy-induced differentiation. Histon deacetylase 2, Calpain, CAXII, collagen 1, osteonectin and connective tissue growth factor are decreased after pregnancy. Several of the genes that are lost after pregnancy encoded cytoskeletal and extra cellular matrix proteins. One of such genes, the small breast epithelial mucin (SBEM), consists most probably of a secreted sialoglycoprotein and may show a cancer-associated expression. SBEM is almost completely down regulated upon a FTTP but is expressed in 96 % of breast tumor cells. At least three tags corresponding to new genes show expression differences similar to SBEM. Conclusions: Our SAGE data found a different gene expression profile after pregnancy. Some of these genes might be useful in breast cancer risk assessment. No significant financial relationships to disclose.