Oral contraceptives and breast cancer. A prospective cohort study

In 1976, information on oral contraceptive (OC) use as well as numerous risk factors for breast cancer was provided by 121,964 married female registered nurses aged 30 to 55 years. Ninety-two percent of women in the cohort completed follow-up questionnaires, and vital records were systematically searched to ascertain deaths among nonrespondents. After four years of follow-up, 592 incident cases of breast cancer were identified. Compared with never users, the age-adjusted relative risk (RR) of breast cancer, regardless of menopausal status, among all women who had ever used OCs was 1.0. Among premenopausal women compared with those who had never used OCs, the RR of breast cancer was 1.5 for current use of OCs in 1976 and 1.0 for past use. Among postmenopausal women, the RR for past use of OCs was 1.0. These estimates were essentially unaltered after controlling for other known risk factors for breast cancer in multiple logistic regression analysis. Furthermore, there was no modification of these effects by family history of breast cancer, age at first use, timing of the first birth, or other breast cancer risk factors. Data on past use of OCs provide substantial reassuring evidence that there is no large excess risk of breast cancer within a few years of cessation of pill use. The observed moderate elevation of breast cancer risk with current use was of borderline statistical significance. However, the observation was based on 29 cases and may reflect the effect of sampling variability, as most other studies have not observed a relationship between current use of OCs and breast cancer in women of this age.     

Prospective study of estrogen replacement therapy and risk of breast cancer in postmenopausal women

We prospectively examined the use of estrogen replacement therapy in relation to breast cancer incidence in a cohort of women 30 to 55 years of age in 1976. During 367 187 person-years of follow-up among postmenopausal women, 722 incident cases of breast cancer were documented. Overall, past users of replacement estrogen were not at increased risk (relative risk, 0.98; 95% confidence interval, 0.81 to 1.18), including even those with more than 10 years since last [corrected] use (relative risk after adjustment for established risk factors, 0.70; 95% confidence interval, 0.45 to 1.10). However, the risk of breast cancer was significantly elevated among current users (relative risk, 1.36; 95% confidence interval, 1.11 to 1.67). Among current users, a stronger relationship was observed with increasing age but not with increasing duration of use. These data suggest that long-term past use of estrogen replacement therapy is not related to risk of breast cancer but that current use may modestly increase risk.     

Adult weight change and risk of postmenopausal breast cancer

Context  Endogenous hormones are a primary cause of breast cancer. Adiposity affects circulating hormones, particularly in postmenopausal women, and may be a modifiable risk factor for breast cancer. Objective  To assess the associations of adult weight change since age 18 years and since menopause with the risk of breast cancer among postmenopausal women. Design, Setting, and Participants  Prospective cohort study within the Nurses' Health Study. A total of 87 143 postmenopausal women, aged 30 to 55 years and free of cancer, were followed up for up to 26 years (1976-2002) to assess weight change since age 18 years. Weight change since menopause was assessed among 49 514 women who were followed up for up to 24 years. Main Outcome Measure  Incidence of invasive breast cancer. Results  Overall, 4393 cases of invasive breast cancer were documented. Compared with those who maintained weight, women who gained 25.0 kg or more since age 18 years were at an increased risk of breast cancer (relative risk [RR], 1.45; 95% confidence interval [CI], 1.27-1.66; P<.001 for trend), with a stronger association among women who have never taken postmenopausal hormones (RR,1.98; 95% CI, 1.55-2.53). Compared with weight maintenance, women who gained 10.0 kg or more since menopause were at an increased risk of breast cancer (RR, 1.18; 95% CI, 1.03-1.35; P  = .002 for trend). Women who had never used postmenopausal hormones, lost 10.0 kg or more since menopause, and kept the weight off were at a lower risk than those who maintained weight (RR, 0.43; 95% CI, 0.21-0.86; P = .01 for weight loss trend). Overall, 15.0% (95% CI, 12.8%-17.4%) of breast cancer cases in this population may be attributable to weight gain of 2.0 kg or more since age 18 years and 4.4% (95% CI, 3.6%-5.5%) attributable to weight gain of 2.0 kg or more since menopause. Among those who did not use postmenopausal hormones, the population attributable risks are 24.2% (95% CI, 19.8%-29.1%) for a weight gain since age 18 years and 7.6% (95% CI, 5.9%-9.7%) for weight gain since menopause. Conclusions  These data suggest that weight gain during adult life, specifically since menopause, increases the risk of breast cancer among postmenopausal women, whereas weight loss after menopause is associated with a decreased risk of breast cancer. Thus, in addition to other known benefits of healthy weight, our results provide another reason for women approaching menopause to maintain or lose weight, as appropriate.      

脂联素、瘦素及可溶性瘦素受体对乳腺癌发病风险影响的人群研究

  目的  探讨脂联素、瘦素、可溶性瘦素受体（soluble leptin receptor,sOB-R）对女性绝经前后乳腺癌的单独或联合效应,为揭示肥胖与乳腺癌之间的分子机制提供证据。  方法  序贯纳入乳腺癌新发患者469例及同期按1∶1年龄频数匹配的469例健康女性为研究对象。采用问卷收集研究对象基线信息,并采用ELISA法检测血浆中脂联素、瘦素、sOB-R水平。采用多因素非条件logistic回归,并进一步按照腰臀比（waist-to-hip ratio,WHR）和体质量指数（body mass index,BMI）分层,分析观察指标对绝经前后乳腺癌发生风险的影响。  结果  本研究共纳入480例绝经前和458例绝经后女性。绝经前病例组249例,对照组231例,中位BMI分别为22.9 kg/m2、23.2 kg/m2,中位WHR分别为0.80、0.83。绝经后病例组220例,对照组238例,中位BMI分别为23.4 kg/m2、23.7 kg/m2;中位WHR分别为0.82、0.86。多因素logistics回归发现,模型校正前后,sOB-R、脂联素的升高与绝经前后的乳腺癌风险降低相关（P<0.05）,而瘦素/可溶性瘦素受体比值（FLI） 、瘦素/脂联素比值（leptin/adiponectin,L/A）仅与绝经后乳腺癌的发生风险升高有关。进一步按WHR和BMI分层,脂联素、FLI与绝经后乳腺癌的关联在所有亚组仍有统计学意义。在体质量正常的中心型肥胖（18.5 kg/m2≤BMI<24 kg/m2且WHR≥0.85）妇女中,高L/A比值与绝经后乳腺癌风险增加有关。未发现瘦素与绝经前后乳腺癌的关联。  结论  sOB-R、脂联素水平降低,FLI、L/A升高的绝经后女性,sOB-R、脂联素水平降低的绝经前女性,乳腺癌的发生风险高。     

女性癌症发病率和病死率与体重指数的关系：百万妇女队列研究

目的 检测体重指数（BMI）与癌症发病率和病死率的关系。设计前瞻性队列研究。研究对象1996年至2001年间,年龄50～64岁的120万英国女性;对其随访,对发病率平均随访5．4年,对病死率平均随访7．0年。主要检测结果发病率和病死率的相对危险度（RR）;对于17种类型的肿瘤,分析其BMI、校正年龄、地理区域、社会阶层、初产年龄、孕产次、吸烟情况、饮酒情况、活动能力,绝经期及激素替代治疗情况。结果 随访期间45037例患癌,17203例死亡。发病率随BMI增大而增高的有：子宫内膜癌（RR=2．89,95％可信区间2．62～3．18）,食管腺癌（2．38,1．59～3．56）,肾癌（1．52,1．27～1．84）,白血病（1．50,1．23～1．83）,多发性骨髓瘤（1．31,1．04～1．65）,胰腺癌（1．24,1．03～1．48）,非霍奇金淋巴瘤（1．17,1．03～1．34）,卵巢癌（1．14,1．03～1．27）,所有癌症合并（1．12,1．09～1．14）,绝经后女性乳腺癌（1．40,1．31～1．49）,绝经前女性结直肠癌（1．61,1．05～2．48）;简言之。病死率与BMI的关系与发病率类似。而结肠癌、恶性黑色素瘤、乳腺癌和子宫内膜癌的发病风险,根据是否绝经有明显不同。结论 在检测的17种癌症中,10种癌症随着BMI增大发病风险明显增加。对于英国绝经后妇女,5％（每年约6000例）的癌症与超重或肥胖相关。对于子宫内膜癌和食管腺癌,BMI是独立风险因素,绝经后妇女约有半数病例与超重和肥胖有关。     

The contribution of reproductive factors and family history towards premenopausal breast cancer risk in Kuala Lumpur, Malaysia

Breast cancer is the most common cancer among Malaysian women. This study aimed to determine the reproductive for premenopausal breast cancer risk in Kuala Lumpur, Malaysia. A case-control study was conducted in 216 histopathologically confirmed cases of premenopausal breast cancer and 216 community-based controls that were matched by age within a 5-year period and ethnicity. The results of this study showed that premenopausal breast cancer risks were strongly related to parity, number of live births and family history of breast cancer. Premenopausal women with these known reproductive and family history risk factors should take extra measures to undergo appropriate screening method for early detection of breast cancer.     

The risk of breast cancer in postmenopausal women who have used estrogen replacement therapy

We studied the association between estrogen replacement therapy (ERT) and the risk of breast cancer as part of the Cancer and Steroid Hormone Study. All subjects in the analysis were postmenopausal women enrolled from eight geographic areas. Women 25 to 54 years old with newly diagnosed breast cancer were identified through population-based tumor registries and diagnosed between Dec 1, 1980, and Dec 31, 1982. Controls were selected from the same eight geographic areas by the random digit dialing of residential telephone numbers. Analyses included 1369 cases and 1645 controls. Among women with bilateral oophorectomy, the relative risk of breast cancer for women who had ever used ERT was 1.3, compared with women who had never used ERT. Among women who had undergone hysterectomy but who still had at least one ovary, the relative risk was 1.1; among women who reported a natural menopause, the relative risk was 0.8. Overall, the risk of breast cancer did not appear to increase appreciably with increasing ERT duration or latency, even for durations and latencies of 20 years or longer.     

血浆类固醇性激素水平与女性乳腺癌危险性的关系

目的 :评价绝经前后血浆类固醇性激素水平与汉族女性乳腺癌危险性的关系。方法 :采用放射免疫法检测原发性乳腺癌病例 90例和 116例匹配对照组血浆雌二醇 (E2 )、睾酮 (T)及孕酮 (P)水平 ,并应用条件Logistic回归等方法分析绝经前后血浆E2 、T、P水平 ,以及体质指数 (BMI)和腰臀围比 (WHR)对乳腺癌的危险度 (OR)及 95 %可信限(CI)。结果 :①绝经前 ,病例组血浆P水平显著低于对照组 ;绝经后血浆T、E2 水平、BMI和WHR ,病例组均显著高于对照组 ;②以下四分位 (P2 5)为非暴露参考 ,绝经前 ,血浆P上四分位 (P75)水平调整OR(95 %CI)为 0 .2 1(0 .11～0 .6 0 ) ,趋势P =0 .19;绝经后 ,血浆E2 P75水平OR为 3.74 (1.17～ 11.96 ) ,调整OR为 2 .98(0 .84～ 7.96 ) ,趋势P =0 .0 3;③BMI和WHR与绝经后乳腺癌有正性联系 ,OR分别为 4 .97(2 .0 9～ 11.79)和 2 .80 (1.2 7～ 6 .17)。结论 :血浆性激素水平与乳腺癌的危险性相关。血浆P水平对绝经前乳腺癌有保护作用 ;血浆E2 为绝经后乳腺癌的危险因素 ,且存在剂量反应暴露效应 ;BMI和WHR与血浆E2 呈正相关且为绝经后乳腺癌的危险因素。     

广东地区妇女乳腺癌高危因素分析与对策

目的 分析广东地区妇女乳腺癌的危险因素,为建立乳腺癌风险模型,有针对性地筛查高危人群进行早期干预提供依据.方法 采用成组配对的病例对照研究,对绝经前和绝经后妇女分别进行乳腺癌人群和非乳腺癌人群危险因素的单因素分析和Logistic多元回归分析.结果 绝经前妇女中,服用避孕药、亲属中有乳腺癌患者、有不良情绪、有不良事件、劳动强度大等因素是乳腺癌的危险因素;有乳腺增生病史、有乳腺组织活检史、有相对剧烈的运动等因素可能是乳腺癌的保护因素.绝经后妇女中,亲属中有乳腺癌患者是危险因素,情绪调节能力强是保护因素.结论 绝经前后乳腺癌的危险因素和保护因素不完全相同,根据不同的影响因素,建立绝经前后不同的乳腺癌预报模型,更有针对性地进行乳腺癌的早期干预应是今后工作的重点.

Abstract：

Objective To screen high-risk population of breast cancer by analyzing the risk factors of breast cancer in Guangdong Province.Methods A case-control study was performed to identify the risk factors of breast cancer between premenopausal women and postmenopausal women. Chi-square test and unconditional logistic regression were used to analyze the data. Results In premenopansal women,prophylactic, family history of breast cancer, bad mood, bad life incidence and work load were the risk factors,and breast hyperplasia history,breast tissue examination history,regular exercise and sleeping without bm were the protective factors.In postmenopausal women,family history of breast cancer was the risk factor, and breast hyperplasia history and mood adjustment were the protective factors. Conclusion The risk and protective factors of breast cancer differ between premenopausal and postmenopausal women,which highlights the importance of using different risk models to screen the high-risk populations.     

A prospective study of selenium status and breast cancer risk

Low dietary intake of selenium has been proposed as a risk factor for breast cancer. To address this hypothesis, we collected toenail clippings from 62,641 women in the Nurses' Health Study cohort who were free from cancer (other than nonmelanoma skin cancer) in 1982 and 1983. The selenium concentration in nails has been shown to reflect dietary intake of selenium. During 53 months of follow-up, 434 cases of breast cancer were diagnosed among women who had submitted a set of toenail clippings, and we matched one control free from breast and other cancers to each case. The mean selenium level in toenails in the cases (0.823 microgram/g; SD, 0.197) was almost identical to that of the controls (0.821 microgram/g; SD, 0.174). After controlling for known breast cancer risk factors, the relative risk for women in the highest quintile of selenium as compared with the lowest quintile was 1.10 (95% confidence interval, 0.70 to 1.72) and there was no trend across quintiles. Results were similar for both premenopausal and postmenopausal women. Although these data do not exclude a possible influence of selenium intake before adulthood on subsequent risk of breast cancer, selenium intake later in life is not likely to be an important factor in the etiology of breast cancer.     

A meta-analysis of the effect of estrogen replacement therapy on the risk of breast cancer

To quantify the effect of estrogen replacement therapy on breast cancer risk, we combined dose-response slopes of the relative risk of breast cancer against the duration of estrogen use across 16 studies. Using this summary dose-response slope, we calculated the proportional increase in risk of breast cancer for each year of estrogen use. For women who experienced any type of menopause, risk did not appear to increase until after at least 5 years of estrogen use. After 15 years of estrogen use, we found a 30% increase in the risk of breast cancer (relative risk, 1.3; 95% confidence interval [CI], 1.2 to 1.6). The increase in risk was largely due to results of studies that included premenopausal women or women using estradiol (with or without progestin), studies for which the estimated relative risk was 2.2 (CI, 1.4 to 3.4) after 15 years. Among women with a family history of breast cancer, those who had ever used estrogen replacement had a significantly higher risk (3.4; CI, 2.0 to 6.0) than those who had not (1.5; CI, 1.2 to 1.7).     

Risk of coronary heart disease in women after menopause

An increase in the incidence of coronary heart disease risk has commonly been reported in postmenopausal women. The study population comprised 263 adult healthy men and 237 women (104 premenopausal and 133 postmenopausal) ranging in age group of 21-70 years who were examined for coronary heart disease risk factors from Nellore district in Andhra Pradesh. Anthropometric measurements, blood pressure and serum lipids were analysed using standard procedures. There were no significant differences for anthropometric variables between postmenopausal and premenopausal women. Postmenopausal women had significantly higher levels of blood pressure, pulse rate, serum total cholesterol, triglycerides, low-density lipoprotein cholesterol and ratios of total cholesterol:high-density lipoprotein cholesterol and low-density lipoprotein cholesterol:high-density lipoprotein cholesterol as atherogenic indices than premenopausal women and the corresponding age group of male counterparts. However, the variation of high-density lipoprotein cholesterol levels between these groups were not statistically significant. The prevalence of hypertension, hypercholesterolaemia, hypertriglyceridaemia and atherogenic indices was significantly greater in postmenopausal women than in premenopausal women. This study confirms a higher prevalence of risk factors for coronary heart disease among women in older age group and suggests that when oestrogen production ceases in menopausal women, the risk of coronary heart disease increases.     

Menopausal estrogen and estrogen-progestin replacement therapy and breast cancer risk

CONTEXT: Whether menopausal hormone replacement therapy using a combined estrogen-progestin regimen increases risk of breast cancer beyond that associated with estrogen alone is unknown. OBJECTIVE: To determine whether increases in risk associated with the estrogen-progestin regimen are greater than those associated with estrogen alone. DESIGN: Cohort study of follow-up data for 1980-1995 from the Breast Cancer Detection Demonstration Project, a nationwide breast cancer screening program. SETTING: Twenty-nine screening centers throughout the United States. PARTICIPANTS: A total of 46355 postmenopausal women (mean age at start of follow-up, 58 years). MAIN OUTCOME MEASURE: Incident breast cancers by recency, duration, and type of hormone use. RESULTS: During follow-up, 2082 cases of breast cancer were identified. Increases in risk with estrogen only and estrogen-progestin only were restricted to use within the previous 4 years (relative risk [RR], 1.2 [95% confidence interval [CI], 1.0-1.4] and 1.4 [95% CI, 1.1-1.8], respectively); the relative risk increased by 0.01 (95% CI, 0.002-0.03) with each year of estrogen-only use and by 0.08 (95% CI, 0.02-0.16) with each year of estrogen-progestin-only use among recent users, after adjustment for mammographic screening, age at menopause, body mass index (BMI), education, and age. The P value associated with the test of homogeneity of these estimates was .02. Among women with a BMI of 24.4 kg/m2 or less, increases in RR with each year of estrogen-only use and estrogen-progestin-only use among recent users were 0.03 (95% CI, 0.01-0.06) and 0.12 (95% CI, 0.02-0.25), respectively. These associations were evident for the majority of invasive tumors with ductal histology and regardless of extent of invasive disease. Risk in heavier women did not increase with use of estrogen only or estrogen-progestin only. CONCLUSION: Our data suggest that the estrogen-progestin regimen increases breast cancer risk beyond that associated with estrogen alone.     

Ovarian irradiation and prednisone therapy following surgery and radiotherapy for carcinoma of the breast.

Following mastectomy, patients with operable breast cancer underwent postoperative irradiation of the chest wall and regional lymph nodes. They were then assigned at random to receive no further therapy, ovarian irradiation (2000 rads in 5 days) or ovarian irradiation in the same dosage plus prednisone, 7.5 mg daily. A total of 705 patients received the randomly assigned treatment and were followed for up to 10 years. In premenopausal patients who received ovarian irradiation the recurrence of breast cancer was delayed and survival prolonged, but not significantly. In premenopausal women aged 45 years or more ovarian irradiation plus prednisone therapy significantly delayed the recurrence of breast cancer (P = 0.02) and prolonged survival (P = 0.02); the survival expectancy of these patients was similar to that of the general population of the same age from the third year after the cancer operation. No value was demonstrated for ovarian irradiation with or without prednisone therapy in postmenopausal patients.     

Risk of breast cancer with oral contraceptive use in women with a family history of breast cancer

CONTEXT: Oral contraceptive (OC) use is weakly associated with breast cancer risk in the general population, but the association among women with a familial predisposition to breast cancer is less clear. OBJECTIVE: To determine whether the association between OC use and risk of breast cancer is influenced by family history of the disease. DESIGN AND SETTING: Historical cohort study of 426 families of breast cancer probands diagnosed between 1944 and 1952 at the Tumor Clinic of the University of Minnesota Hospital. Follow-up data on families were collected by telephone interview between 1991 and 1996. PARTICIPANTS: A total of 394 sisters and daughters of the probands, 3002 granddaughters and nieces, and 2754 women who married into the families. MAIN OUTCOME MEASURE: Relative risk (RR) of breast cancer associated with history of OC use by relationship to proband. RESULTS: After accounting for age and birth cohort, ever having used OCs was associated with significantly increased risk of breast cancer among sisters and daughters of the probands (RR, 3.3; 95% confidence interval [CI], 1.6-6.7), but not among granddaughters and nieces of the probands (RR, 1.2; 95% CI, 0.8-2.0) or among marry-ins (RR, 1.2; 95% CI, 0.8-1.9). Results were essentially unchanged after adjustment for parity, age at first birth, age at menarche, age at menopause, oophorectomy, smoking, and education. The elevated risk among women with a first-degree family history of breast cancer was most evident for OC use during or prior to 1975, when formulations were likely to contain higher dosages of estrogen and progestins (RR, 3.3; 95% CI, 1.5-7.2). A small number of breast cancer cases (n = 2) limited the statistical power to detect risk among women with a first-degree relative with breast cancer and OC use after 1975. CONCLUSIONS: These results suggest that women who have ever used earlier formulations of OCs and who also have a first-degree relative with breast cancer may be at particularly high risk for breast cancer. Further studies of women with a strong family history who have used more recent lower-dosage formulations of OCs are needed to determine how women with a familial predisposition to breast cancer should be advised regarding OC use today. JAMA. 2000;284:1791-1798.     

Concurrent or sequential use of cytotoxic chemotherapy and hormone treatment in advanced breast cancer: report of the Swiss Group for Clinical Cancer Research

In a trial of combined hormone treatment and cytotoxic chemotherapy 464 patients with advanced breast cancer were randomly allocated to either concurrent or sequential treatment. Cytotoxic drugs were given only if the antitumour activity of the hormone treatment was inadequate. Hormone treatment consisted of oophorectomy for premenopausal and tamoxifen administration for postmenopausal patients. Length of survival was better, though not significantly, in premenopausal patients (p = 0.29) treated concurrently and in postmenopausal women (p = 0.17) treated sequentially; the difference was highly significant (p = 0.003) only for postmenopausal women in the low-risk category. The findings suggest that postmenopausal women with metastatic breast cancer should probably be treated primarily by carefully monitored hormone treatment.     

Cigarette smoking and the risk of endometrial cancer:A meta-analysis

OBJECTIVE:Epidemiologic findings are inconsistent concerning the association of endometrial cancer risk with cigarette smoking.We conducted a meta-analysis of epidemiologic studies to examine this relation.METHODS:A systematic literature search up to June of 2007 was performed in MEDLINE and EMBASE.Study-specific risk estimates were pooled using a random-effects model.RESULTS:Ten prospective and 24 case-control studies were included in the analysis of the effect of ever smoking.Ever smoking was statistically significantly associated with a reduced risk of endometrial cancer among prospective studies(relative risk 0.81;95% confidence interval[CI],0.74-0.88) and case-control studies(odds ratio 0.72;95% CI,0.66-0.79).The inverse association was significant among current and former smokers.Six prospective and 6 case-control studies were included in the quantitative analysis.We noted that an increase in smoking of 20 cigarettes per day was statistically significantly associated with 16% and 27% reduced risks of endometrial cancer in prospective and case-control studies,respectively.We also found that cigarette smoking was significantly associated with a decreased risk of endometrial cancer among postmenopausal women(relative risk 0.71;95% CI,0.65-0.78) but not among premenopausal women.In addition,the risk reduction seemed to be stronger among hormone replacement therapy users than nonusers.CONCLUSION:Cigarette smoking was found to be significantly associated with a reduced risk of endometrial cancer,especially among postmenopausal women.(C) 2008 Elsevier Inc.All rights reserved.     

血浆催乳素水平与绝经前乳腺癌危险性的关系评估

目的:评估血浆催乳素(PRL)水平与绝经前女性乳腺癌危险性的关系.方法:采用放射免疫法测定65例绝经前女性乳腺癌患者(病例组)和65例匹配对照者(对照组)的血浆PRL水平,条件logistic回归分析血浆PRL水平与绝经前乳腺癌危险性的关系.根据肿瘤的临床病理特征对病例组再进行分组,评价血浆PRL水平与乳腺癌各亚组危险性的关系.结果:病例组血浆PRL水平显著高于对照组(P < 0.01).血浆PRL水平上四分位数相比下四分位数的调整OR(95%CI)为1.54(0.84～4.07),趋势P=0.031;PRL与绝经前乳腺癌危险性的关系在雌激素受体阳性的肿瘤中稍增强,但不随肿瘤大小、病理类型、肿瘤分级、淋巴结转移情况而变化.结论:血浆PRL水平与绝经前女性乳腺癌的危险性呈正相关,尤其是雌激素受体阳性的乳腺癌患者.     

Prolactin and breast cancer risk

A study of 424 women was undertaken to determine whether there was an association between serum prolactin levels and breast cancer; whether prolactin levels would reflect degrees of risk of developing breast cancer; and whether associations between known risk factors for breast cancer and serum prolactin concentrations could be demonstrated. Prolactin levels higher than the median value in control subjects were found to be associated with a more than two-fold increase in the risk of breast cancer (relative risk, 2.1; confidence interval [CI], 1.0-4.5). Moreover, a relative risk of 1.7 (CI, 0.9-3.3) for a group of women with benign epithelial hyperplasia (high risk of developing breast cancer), and a relative risk of 1.0 (CI, 0.6-1.8) for a group with benign fibrocystic disease (low risk of developing breast cancer), provided supportive evidence that prolactin plays a role in the development of breast cancer. A considerable fall in the concentration of prolactin at menopause was noted, so those women who have an early menopause have a reduced period of exposure to high concentrations of prolactin. Similarly, there was a considerable reduction in prolactin concentration after the first pregnancy. Finally, our results showed that, in premenopausal women, a high intake of saturated fats was associated with a high prolactin concentration. Our study supports the concept that parity, menstrual status, and saturated fat consumption influence a woman's exposure to prolactin and therefore the risk of developing breast cancer.     

Family history and the risk of breast cancer

To investigate whether a family history of breast cancer increases a woman's risk of developing breast cancer, we analyzed data from the Centers for Disease Control's Cancer and Steroid Hormone Study. The 4,735 cases were women 20 to 54 years old with a first diagnosis of breast cancer ascertained from eight population-based cancer registries; the 4,688 controls were women selected at random from the general population of these eight areas. Compared with women without a family history of breast cancer, women who had an affected first-degree relative had a relative risk of 2.3; women with an affected second-degree relative had a relative risk of 1.5; and women with both an affected mother and sister had a relative risk of 14. The risk of breast cancer for a woman was higher if her first-degree relative had unilateral rather than bilateral breast cancer or had breast cancer detected at a younger rather than older age. For women aged 20 to 39, 40 to 44, and 45 to 54 years, the estimated annual incidence of breast cancer per 100,000 women attributable to a first-degree family history of breast cancer was 51.9, 115.1, and 138.6, respectively, and that attributable to a second-degree family history of breast cancer was 12.1, 19.2, and 92.4, respectively.