Breast cancer in relation to the occurrence and time of induced and spontaneous abortion

The authors evaluated whether an induced or spontaneous abortion during the first six months of gestation, particularly if it occurs before the first term pregnancy, increases the risk of breast cancer. Data from a case-control study of women under 70 years of age were used: 3,200 cases of breast cancer were compared with 4,844 controls with nonmalignant nongynecologic conditions. Among both nulliparous and parous women, the risk of breast cancer was not related to the number of induced or spontaneous abortions. After allowance for all identified potential confounding factors, the estimated relative risk for nulliparous women with an induced abortion relative to those who had never been pregnant was 1.3 (95% confidence interval (CI) 0.8-2.2), and for spontaneous abortion, the corresponding estimate was 0.9 (95% CI 0.5-1.5). Among parous women, the estimated relative risks were 1.2 (95% CI 0.9-1.6) for an induced abortion and 0.9 (95% CI 0.8-1.0) for a spontaneous abortion, relative to never having had an abortion of any type. The time of the abortion had little effect: The relative risk estimates were 0.9 (95% CI 0.5-1.4) for induced abortion before the first term birth, 1.4 (95% CI 1.0-1.9) for induced abortion first occurring after the first term birth, 0.9 (95% CI 0.7-1.2) for spontaneous abortion before the first term birth, and 0.9 (95% CI 0.7-1.0) for spontaneous abortion first occurring after the first term birth. Similar results were evident for women under age 40, among whom the frequency of induced abortion was relatively high. These data suggest that the risk of breast cancer is not materially affected by abortion, regardless of whether it occurs before or after the first term birth.     

Induced abortion in relation to breast cancer among parous women: a birth certificate registry study

We wished to assess the relation of induced abortion to the subsequent incidence of breast cancer among parous women, using a design that would prevent the possibility of differentially complete reporting of abortion history by women with breast cancer and controls. Our study was conducted within a cohort of women who gave birth to a child during 1984-1994 while residing in 13 counties of western Washington. Cases were women from the cohort diagnosed with breast cancer between 1984 and 1994. From the remaining cohort members, five controls were matched to each woman with breast cancer by year of index birth (ie, the last child born before breast cancer diagnosis) and by age at delivery. We categorized 463 cases and 2,201 controls according to history of induced abortion as recorded on the index birth certificate. The risk of breast cancer was not found to be associated with a prior induced abortion (estimated relative risk (RR) = 0.9, 95% confidence interval (CI) 0.7-1.2). These results suggest that an induced abortion, if followed at some later time by pregnancy and childbirth, does not increase a woman's risk of breast cancer.     

Case-control differences in the reliability of reporting a history of induced abortion

The authors investigated the possibility that, in interview-based case-control studies, controls are more likely than cases to underreport a history of induced abortion. A case-control study was conducted in White women under 45 years of age who had given birth in Washington State during 1984-1994. The cases were women in three metropolitan counties of Washington State diagnosed with invasive breast cancer during 1984-1994; controls were selected through random digit dialing. A history of induced abortion among study participants was compared between interview data and information collected on the birth record of the last child to whom they gave birth (225 cases, 303 controls). Among women with a prior induced abortion recorded on the birth record, 14.0% of the 43 cases and 14.9% of the 47 controls did not report an induced abortion at interview (difference = -0.9%, 95% confidence interval of the difference: -15, 14). The authors' data do not suggest that controls are more reluctant to report a history of induced abortion than are women with breast cancer.     

Association of parity and ovarian cancer risk by family history of breast or ovarian cancer in a population-based study of postmenopausal women.

Although parity is associated with a decreased risk of ovarian cancer in the general population, this association among women with a family history is less clear. We examined this question in a prospective cohort of 31,377 Iowa women 55-69 years of age at baseline. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated through Cox regression. We identified 181 incident epithelial ovarian cancers through 13 years of follow-up. At baseline, 14% of the women reported breast or ovarian cancer in a first-degree relative, and an additional 12% reported a family history in a second-degree relative. Among women without a family history of breast or ovarian cancer in a first-degree relative, nulliparous women were at slightly increased risk of ovarian cancer (RR = 1.4, 95% CI = 0.9-2.4) compared with parous women, whereas among women with a family history, nulliparous women were at a much higher risk (RR = 2.7, 95% CI = 1.1-6.6) than parous women. Similar results were seen when family history included first- or second-degree relatives with breast or ovarian cancer or a first- or second-degree relative with ovarian cancer only. Nulliparity may be more strongly associated with an increased risk of ovarian cancer among women with a family history of breast or ovarian cancer, compared with women who do not have a family history of those cancers.     

Induced abortion as an independent risk factor for breast cancer: a comprehensive review and meta-analysis.

STUDY OBJECTIVE: To ascertain, from the published reports to date, whether or not a significantly increased risk of breast cancer is specifically attributable to a history of induced abortion, independent of spontaneous abortion and age at first full term pregnancy (or first live birth); to establish the relative magnitude of such risk increase as may be found, and to ascertain and quantify such risk increases as may pertain to particular subpopulations of women exposed to induced abortion; in particular, nulliparous women and parous women exposed before compared with after the first full term pregnancy. INCLUDED STUDIES: The meta-analysis includes all 28 published reports which include specific data on induced abortion and breast cancer incidence. Since some study data are presented in more than one report, the 28 reports were determined to constitute 23 independent studies. Overall induced abortion odds ratios and odds ratios for the different subpopulations were calculated using an average weighted according to the inverse of the variance. An overall unweighted average was also computed for comparison. No quality criteria were imposed, but a narrative review of all included studies is presented for the reader's use in assessing the quality of individual studies. EXCLUDED STUDIES: All 33 published reports including data on abortion and breast cancer incidence but either pertaining only to spontaneous abortion or to abortion without specification as to whether it was induced or spontaneous. These studies are listed for the reader's information. RESULTS: The overall odds ratio (for any induced abortion exposure; n = 21 studies) was 1.3 (95% confidence interval of 1.2, 1.4). For comparison, the unweighted overall odds ratio was 1.4 (1.3,1.6). The odds ratio for nulliparous women was 1.3 (1.0,1.6), that for abortion before the first term pregnancy in parous women was 1.5 (1.2,1.8), and that for abortion after the first term pregnancy was 1.3 (1.1,1.5). CONCLUSIONS: The results support the inclusion of induced abortion among significant independent risk factors for breast cancer, regardless of parity or timing of abortion relative to the first term pregnancy. Although the increase in risk was relatively low, the high incidence of both breast cancer and induced abortion suggest a substantial impact of thousands of excess cases per year currently, and a potentially much greater impact in the next century, as the first cohort of women exposed to legal induced abortion continues to age.     

Incomplete pregnancy is not associated with breast cancer risk: the California Teachers Study

BACKGROUND: Early studies of incomplete pregnancy and development of breast cancer suggested that induced abortion might increase risk. Several large prospective studies, which eliminate recall bias, did not detect associations, but this relationship continues to be debated. STUDY DESIGN: To further inform this important question, we examined invasive breast cancer as it relates to incomplete pregnancy, including total number of induced abortions, age at first induced abortion and total number of miscarriages among women participating in the ongoing California Teachers Study (CTS) cohort. Incomplete pregnancy was self-reported on the CTS baseline questionnaire in 1995-1996. Incident breast cancers were ascertained in 3324 women through 2004 via linkage with the California Cancer Registry. RESULTS: Using Cox multivariable regression, we found no statistically significant association between any measure of incomplete pregnancy and breast cancer risk among nulliparous or parous women. CONCLUSION: These results provide strong evidence that there is no relationship between incomplete pregnancy and breast cancer risk.     

A prospective study of reproductive factors and breast cancer. II. Age at first and last birth

The relations between age at first and last full-term pregnancy and breast cancer risk were investigated after 20 years of follow-up of 63,090 Norwegian women, among whom 1,565 breast cancer cases occurred. An association seen in preliminary analyses between early age at first birth and low risk of breast cancer was removed after adjustment for parity and age at last birth. Age at last birth showed initially no association with breast cancer. After adjustment for parity, however, a significant positive association emerged. The authors' observations suggest that the relation between age when a pregnancy occurs and breast cancer risk may be more complex than previously believed. Despite the overall association between increasing parity and lower risk, the women with many late pregnancies and those with few, widely spaced pregnancies had higher risk than nulliparous women, indicating that both the age when pregnancy occurs and the length of intervals between successive births may modify the protective effect. The findings are consistent with a dual effect of a pregnancy, causing a transient increase followed by a subsequent strong and long-lasting decrease in risk of breast cancer.     

A prospective study of reproductive, familial and socioeconomic risk factors for breast cancer using NHANES I data

Risk factors for breast cancer in a cohort of women who participated in the first National Health and Nutrition Examination Survey (NHANES) and its followup epidemiologic survey were examined. The analytic cohort consisted of 122 breast cancer cases and 7,304 noncases, with a median followup time of 10 years. We found no appreciable increase in risk among women who reported their onset of menarche as occurring before the age of 13 compared with those reporting onset at ages 13 and older. Breast cancer risk was progressively elevated with increasing age at first live birth (test for trend, P less than 0.007). The number of children born to a woman did not influence risk, but the data suggested an increased risk for nulliparous women. A family history of breast cancer in a first-degree relative was the strongest predictor of risk for this cohort of women, with relative risks of 2.2 and 2.4 associated with a mother or sister affected with breast cancer, compared with women having no family history. The age of natural menopause had little influence on breast cancer risk, and the data suggested a slight protective effect of early surgical menopause. Higher education (compared with less than a high school education) was associated with an increased risk in this cohort of women (relative risk (RR) = 2.1; 95 percent confidence interval (CI) = 0.9-5.1). These results (a) confirm the importance of some well-recognized risk factors for breast cancer in a cohort of women, followed prospectively for 10 years, and perhaps more importantly, (b) uniquely provide risk estimates on a probability sample of women in the United States.     

Early abortion and breast cancer risk among women under age 40

In New York State, incidence of cancer and fetal death are reportable health events mandated by state law. These data enabled a population-based record linkage study of the effect of early pregnancy termination on breast cancer risk to be conducted. In upstate New York 1451 cases under age 40 were reported to the Cancer Registry during 1976-1980. Cases were matched with 1451 population controls by year of birth and by residence using zip codes. All names including those changed by marriage were matched with the reports of fetal deaths occurring between 1971 and 1980. Matched pairs analyses revealed an excess of early pregnancy terminations among cases in all categories. Odds ratios (OR) were significantly elevated among those with an induced abortion (OR = 1.9) and a spontaneous abortion (OR = 1.5). Elevated risks were also noted for consecutive abortion events without intervening livebirths.     

Occupation and breast cancer risk among Shanghai women in a population-based cohort study

INTRODUCTION: A total of 74,942 female subjects were recruited in a population-based cohort study in Shanghai, China between 1997 and 2000. We examined the relationship between occupation and breast cancer risk. METHODS: Cases were 586 women previously diagnosed with breast cancer at baseline and 438 women newly diagnosed with breast cancer during follow-up through December 2004. Eight controls were randomly selected for each case from cancer-free cohort members and frequency-matched to the cases by year of birth and age at diagnosis. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of breast cancer risk associated with occupations, adjusting for established breast cancer risk factors. RESULTS: In the prevalent breast cancer data analysis, increased risks of breast cancer were associated with technicians in engineering/agriculture/forestry (OR = 1.6, CI: 1.0-2.4), teaching personnel (OR = 1.5, CI:1.1-2.0), tailoring/sewing workers (OR = 1.6, CI:1.0-2.7), and examiners/measurers/testers (OR = 1.5, CI:1.1-2.1) among those who started the jobs at least 20 years ago. Among incident breast cancer cases, significantly increased risks were associated with medical/health care workers (OR = 1.4, CI:1.0-2.0), administrative clerical workers (OR = 1.5, CI:1.0-2.4), postal/telecommunication workers (OR = 2.2, CI:1.0-5.5), and odd-job workers (OR = 1.7, CI:1.1-2.8) among those who started the jobs at least 20 years ago. The excess risks were found in both prevalent and incident cases for postal/telecommunication workers and purchasing/marketing personnel, although ORs reached only marginal significance. CONCLUSIONS: This study suggests that white-collar professionals and several production occupations may be associated with an increased risk of breast cancer.     

Timing of menarche and first full-term birth in relation to breast cancer risk

Ages at menarche and first birth are established risk factors for breast cancer. The interval between these ages may also affect risk, since the breast is more susceptible to carcinogenic insults during this period than during the parous period. However, few investigators have studied this relation. Using logistic regression, the authors evaluated associations between the timing of reproductive events and breast cancer risk among 4,013 cases and 4,069 controls enrolled in a multicenter, population-based US case-control study of White and African-American women (1994-1998). For White, parous premenopausal and postmenopausal women, those who had an interval of > or =16 years between the ages of menarche and first birth had 1.5-fold (95% confidence interval (CI): 1.0, 2.2) and 1.4-fold (95% CI: 1.1, 1.8) increased risks of breast cancer, respectively, in comparison with those who had < or =5 years between these ages. Adjusting for age at first birth altered these risk estimates somewhat, to odds ratios of 1.5 (95% CI: 0.8, 2.9) and 1.0 (95% CI: 0.6, 1.5), respectively. These associations were stronger for lobular and hormone-receptor-positive tumors but were absent among premenopausal African-American women. The authors conclude that the interval between age at menarche and age at first birth is associated with the risk of hormonally sensitive types of breast cancer, particularly among White women.     

General epidemiology of breast cancer in northern Italy

The role of the major identified risk factors for breast cancer was assessed using data from a hospital-based case-control study conducted in Northern Italy on 1108 women with histologically confirmed breast cancer and 1281 control subjects with a spectrum of acute conditions unrelated to any of the established or potential risk factors for breast disease. With reference to nulliparous women, the risk of breast cancer was below unity for those who first gave birth below age 25, and above unity for those with later first full-term pregnancy. However, in each stratum of age at first birth, the point estimate was below unity for women with five or more births. The relative risk for greater than or equal to 5 births compared with 1 or 2 was 0.6 (95% confidence interval = 0.4-0.9) when allowance was made for age at first birth. Likewise, there was a significant and independent effect of age at last birth which was evident in various strata of parity and age at first birth. The overall relative risk for last birth at 30 years or over compared with under 30 was 1.4 (95% confidence interval = 1.1-1.8). There was little relation of breast cancer risk with abortions or miscarriages. Breast cancer cases reported earlier menarche and later menopause; further, lifelong irregularities in menstrual pattern were less common among the cases (relative risk = 0.6, 95% confidence interval = 0.5-0.8). The risk estimates were elevated in women with positive history of benign breast disease, family history of breast cancer and greater body mass index.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hormonal and body-size factors in relation to breast cancer risk: a prospective study of 11,889 women in a low-incidence area

PURPOSE: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.     

Joint effects on cancer risk of age at childbirth, time since birth and attained age: circumventing the problem of collinearity.

In previous studies of female cancer risk, we introduced a new method for circumventing the problem of collinearity in age-adjusted analysis of the joint effects of age at birth and time since birth. The basic idea was to estimate the pure age effect considering nulliparous women, assuming that the age effect is common to all women. However, risk estimates for attained age obtained in this manner may suffer from bias, in particular in small data sets, which may in turn influence risk estimates for reproductive factors among parous women. Certain factors possibly affecting cancer risk among nulliparous women only, for instance biological infertility, might also introduce bias. The purpose of this paper is to investigate the accuracy of risk estimates obtained by the joint approach, and to reveal the extent of bias in traditional separate age-adjusted analyses of age at birth or time since birth among parous women. Results are based on analyses of simulated data sets reflecting reproductive and demographic characteristics of a cohort of 1.1 million Norwegian women. Incidence rate ratios are calculated in Poisson regression analyses of person-years at risk. Our simulations show that the joint analysis in general yields unbiased risk estimates, but the number of cases must be rather high to achieve reliable results. Risk estimates from separate analyses can be seriously biased, although the amount of bias depends on the strength and direction of associations with cancer risk. With a total of 5500 cancer cases, the estimators for age at last birth and time since last birth were 13-78 per cent and 5-66 per cent more efficient in the joint than in the separate analysis, respectively. Significance levels were close to the nominal 5 per cent in the joint analysis, but about twice as high in the separate analysis. Adding an effect of biological infertility on cancer risk among nulliparous women, without taking it into account in the analyses, did not seriously affect risk estimates in the joint model.     

Nulliparity, decade of first birth, and breast cancer in Connecticut cohorts, 1855 to 1945: an ecological study.

Risk of breast cancer increases with age at first birth, and is lower in women who bear their first children while young than in nulliparous women. While previous studies have investigated risk of breast cancer in birth cohorts by examining partial aspects of cohort childbearing, the present ecological study assesses total cohort childbearing risk in Connecticut women born between 1855 and 1945. In each cohort, the proportion of women nulliparous and first bearing children in their twenties, thirties, and forties are weighted by relative risks associated with these events as ascertained in previous studies. Summed cohort childbearing risks are compared to the incidence of breast cancer in women 40 years of age and older in the same cohorts. Changes in decade of first birth and nulliparity do not explain the changes in breast cancer incidence observed: while cohort childbearing risk has declined over the period examined, breast cancer incidence has increased in the same cohorts. Alternative explanations for cohort increases in breast cancer incidence are reviewed.     

Maternal risk of breast cancer and birth characteristics of offspring by time since birth.

We examined the association between birth characteristics of offspring and the subsequent maternal risk of breast cancer in a population-based cohort of 998,499 women, 13 to 48 years of age at entry. There were 9,495 incident cases of breast cancer during 12.8 million person-years of follow-up among these women. Compared with mothers of singleton infants, mothers having a multiple birth had an increased risk of breast cancer in the first 5 years after a birth (relative risk (RR) = 1.8; 95% confidence interval (CI) = 1.1-2.8). The risk for mothers having a heavy-weighted child (>3.75 kg), as compared with a child of light weight (< or =3 kg), was also slightly increased (RR = 1.2; 95% CI = 0.9-1.5). This latter effect was primarily due to an increased incidence of tumors larger than 2 cm at diagnosis (RR = 1.4; 95% CI = 0.9-1.9). Our findings are compatible with the hypothesis that the hormonal level during pregnancy influences the risk of breast cancer in the early years after delivery.     

中国五城市流动育龄妇女人工流产风险因素研究

目的了解流动育龄妇女人工流产现状段危险周素,为有针对性的改善流动育龄妇女人工流产服务及利用提供借鉴。方法利用2005年中同5城市流动人口生殖健康调查数据,对4687例流动育龄妇女的人口学特征、外出工作生活特征和避孕情况进行描述分析,采用多因素logistic回归模型分析人口学特征、外出工作生活特征和避孕情况与流动育龄妇女人工流产风险暴露的关联。结果<30岁和30～39岁年龄组人工流产发生风险分别是40,49岁组的2.2I倍(95CI：1.47—3J34)和2.38倍(95%CI,：1.53—3.70);受教育程度越高,其发生人工流产的风险越高,小学、初中、高中/中专及以上的流动育龄妇女发生人工流产的风险分别是未上学者的2.15倍(95%CI：1.15—4.03)、2.47倍(95%CI：1.33—4.57)、2.6I倍(95%CI：1.34—5.11)。流入地打工年数在2—4年及≥5年组人工流产发生风险分别是<2年组的2.62倍(95%C!：1,83.3.76)和7.78倍(95%CI：5.63,10.75)：流动育龄妇女与配偶共同居住的人工流产风险是不与配偶共同居住者的1.49倍(95qoCI：1.05～2.11);从事家政保洁业.餐饮娱乐业和批发零售业者人工流产风险分别是从事办公室文员的5.82倍(95%C,：1.73一t9 59)、5.07倍(95%Ch l 59—16.ts)和4.37倍(95%d：1.37-13.92)。结论流动育龄妇女的人口学特征、外出工作生活特征等均可增加人工流产风险,血有针对性开展对流动育龄妇女健康教育。     

身体测量指标与女性乳腺癌关系的前瞻性队列研究

目的研究上海女性身体测量指标与绝经前后乳腺癌之间的关系.方法采用前瞻性队列研究方法.1997-2000年在上海市区建立一个73 461人年龄40～70岁的女性队列.每2年随访一次,至2004年6月共收集乳腺癌新发病例432例.用Cox回归模型估计身体测量指标与女性乳腺癌发生的相对危险度（RR）和95%可信区间（CI）.结果调整年龄、文化程度、能量摄入、月经、生育等混杂因素后,基线调查时体重、体重指数（BMI）、腰臀围比例（WHR）和20岁后体重增加与绝经后女性乳腺癌危险性呈正相关,与绝经前女性乳腺癌发生无关.身高与乳腺癌危险的显著正相关关系仅在绝经前女性中发现,20岁时身高在161 cm以上者发生乳腺癌的危险是157.1 cm以下者的1.84倍（95%CI：1.30～2.61）.20岁时BMI处于平均水平者绝经前患乳腺癌的危险性显著高于其他两组.BMI和WHR互相调整后,WHR独立于BMI的作用接近显著性水平.调整BMI后,20岁后体重增加会显著增加绝经后乳腺癌危险（RR=1.61,95%CI：1.09～2.37）.结论对于绝经后女性,成年后体重增加和中心性肥胖都是预测乳腺癌危险的指标.因此控制成年后体重、减少腹部脂肪堆积是预防绝经后乳腺癌发生的有效措施.身高可能是影响绝经前女性乳腺癌发生的危险因素.     

Increased risk of breast cancer with alcohol consumption in postmenopausal women.

The association between breast cancer incidence and alcohol consumption among postmenopausal women was examined in the Iowa Women's Health Study. In January 1986, a cohort of 41,837 postmenopausal women, aged 55-69 years, completed a questionnaire that included alcohol intake and other information. Through December 1989, 493 incident breast cancer cases were identified. Age-adjusted relative risks of consumption of less than 1.5, 1.5-4.9, 5.0-14.9, and 15.0 g or more of alcohol per day compared with abstention were 1.08, 1.10, 1.08, and 1.28, respectively (p for trend = 0.11). After controlling for age, body mass index, age at first livebirth, age at menarche, and family history of breast cancer, the relative risks were 1.18, 1.20, 1.25, and 1.46 (p for trend = 0.04). Multivariate modeling, using Cox proportional hazards regression, revealed a significant multiplicative interaction between alcohol intake and noncontraceptive estrogen use. The relative risks of breast cancer associated with average daily alcohol consumption of 5.0-14.9 and 15.0 g or more were 1.88 (95% confidence interval 1.30-2.72) and 1.83 (95% confidence interval 1.18-2.85), respectively, among ever-users of estrogen; no association between alcohol and breast cancer was observed among never-users of estrogen.     

Risk of breast cancer after miscarriage or induced abortion: a Scottish record linkage case-control study

STUDY OBJECTIVE: To assess the risk of breast cancer in patients with a previous history of miscarriage or induced abortion. DESIGN: Case-control study relating "exposure" to outcome by linkage of national hospital discharge and maternity records, the national cancer registry, and death records. SETTING: Scotland. PARTICIPANTS: Miscarriage analysis-2828 women with breast cancer and 9781 matched controls; induced abortion analysis-2833 women with breast cancer and 9888 matched controls. MAIN RESULTS: After stratification for age at diagnosis, parity, and age at first birth, the odds ratio (95% confidence intervals) of breast cancer was 1.02 (0.88 to 1.18) in women with a previous miscarriage, and 0.80 (0.72 to 0.89) in women with a previous induced abortion. Further adjustments for age at bilateral oophorectomy, socioeconomic status (based on small area of residence), and health board area of residence had only minor effects on these odds ratios. CONCLUSION: These data do not support the hypothesis that miscarriage or induced abortion represent substantive risk factors for the future development of breast cancer.