Oral contraceptive agents and breast cancer: a population-based case-control study

In this population-based case-control study that was conducted in Adelaide, South Australia, and which involved 395 case subjects and 386 control subjects who were aged 20 years to 69 years, the adjusted relative risk of breast cancer for women who had ever used oral contraceptive agents was 1.06 (95% confidence interval [CI], 0.70-1.60). Relative risks that were associated with use of oral contraceptive agents for one month to 18 months and for 19 months or more before a first pregnancy were 1.09 (95% CI, 0.45-2.62) and 1.67 (95% CI, 0.63-4.42), respectively, but the trend was not statistically significant. Relatively-little variation in risk was found in association with the total duration of the use of oral contraceptive agents and with years since the first and the last use of oral contraceptive agents. When the risk of breast cancer in association with the use of oral contraceptive agents was examined across levels of risk factors of breast cancer (history of benign breast disease, family history of breast cancer and parity), the only relative risk which deviated markedly from unity was that which was associated with use of oral contraceptive agents in women with a history of benign breast disease; however, the relative risk of 1.77 (95% CI, 0.35-8.97) was not statistically significant. In conclusion, the results of this study support those of the majority of previous studies in showing no overall relationship between the use of oral contraceptive agents and the risk of breast cancer.     

Hormone replacement therapy after a diagnosis of breast cancer: cancer recurrence and mortality

OBJECTIVE: To determine whether hormone replacement therapy (HRT) after treatment for breast cancer is associated with increased risk of recurrence and mortality. DESIGN: Retrospective observational study. PARTICIPANTS AND SETTING: Postmenopausal women diagnosed with breast cancer and treated by five Sydney doctors between 1964 and 1999. OUTCOME MEASURES: Times from diagnosis to cancer recurrence or new breast cancer, to death from all causes and to death from primary tumour were compared between women who used HRT for menopausal symptoms after diagnosis and those who did not. Relative risks (RRs) were determined from Cox regression analyses, adjusted for patient and tumour characteristics. RESULTS: 1122 women were followed up for 0-36 years (median, 6.08 years); 154 were lost to follow-up. 286 women used HRT for menopausal symptoms for up to 26 years (median, 1.75 years). Compared with non-users, HRT users had reduced risk of cancer recurrence (adjusted relative risk [RR], 0.62; 95% CI, 0.43-0.87), all-cause mortality (RR, 0.34; 95% CI, 0.19-0.59) and death from primary tumour (RR, 0.40; 95% CI, 0.22-0.72). Continuous combined HRT was associated with a reduced risk of death from primary tumour (RR, 0.32; 95% CI, 0.12-0.88) and all-cause mortality (RR, 0.27; 95% CI, 0.10-0.73). CONCLUSION: HRT use for menopausal symptoms by women treated for primary invasive breast cancer is not associated with an increased risk of breast cancer recurrence or shortened life expectancy.     

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.     

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.     

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).     

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.     

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.     

乳腺疾病血清催乳素测定的临床意义

用放射免疫法测定184例正常乳腺、良性乳腺疾病和乳腺癌患者血清催乳素浓度。结果显示:3组良性乳腺疾病血清催乳素含量无差别;乳腺癌及良性乳腺疾病均高于正常人;乳腺癌组明显高于良性乳腺疾病组;乳腺癌术后血中催乳素含量恢复正常。提示:循环血中催乳素异常升高可能是良性乳腺疾病发病原因之一,并与乳腺癌的发生、发展有密切关系。测定催乳素有助于乳腺良、恶性疾病的诊断及鉴别诊断,可作为乳腺癌预后的随访指标。     

Association between the T29-->C polymorphism in the transforming growth factor beta1 gene and breast cancer among elderly white women: The Study of Osteoporotic Fractures

CONTEXT: Transgenic animal experiments suggest that increased expression of transforming growth factor beta1 (TGF-beta1) is protective against early tumor development, particularly in breast cancer. A T-->C (thymine to cytosine) transition in the 29th nucleotide in the coding sequence results in a leucine to proline substitution at the 10th amino acid and is associated with increased serum levels of TGF-beta1. OBJECTIVE: To determine whether an association exists between this TGF-beta1 polymorphism and breast cancer risk. DESIGN, SETTING, AND PARTICIPANTS: The Study of Osteoporotic Fractures, a prospective cohort study of white, community-dwelling women aged 65 years or older who were recruited at 4 US centers between 1986 and 1988. Three thousand seventy-five women who provided sufficient clinical information, buffy coat samples, and adequate consent for genotyping are included in this analysis. MAIN OUTCOME MEASURE: Breast cancer cases during a mean (SD) follow-up of 9.3 (1.9) years, verified by medical chart review and compared by genotype. RESULTS: Risk of breast cancer was similar in the 1124 women with the T/T genotype (56 cases; 5.4 per 1000 person-years) and the 1493 women with the T/C genotype (80 cases; 5.8 per 1000 person-years) but was significantly lower (P =.01) in the 458 women with the C/C genotype (10 cases; 2.3 per 1000 person-years). In analyses that adjusted for age, age at menarche, age at menopause, estrogen use, parity, body mass index, and bone mineral density, women with the C/C genotype had a significantly lower risk of developing breast cancer compared with women with the T/T or T/C genotype (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.17-0.75). There was no significant difference between the risk for women with the T/C genotype compared with women with the T/T genotype (adjusted HR, 1.04; 95% CI, 0.73-1.48). CONCLUSIONS: Our findings suggest that TGF-beta1 genotype is associated with risk of breast cancer in white women aged 65 years or older. Because the T allele is the common variant and confers an increased risk, it may be associated with a large proportion of breast cancer cases.     

血清缬氨酸、甲硫氨酸浓度水平与乳腺癌临床特征及风险的相关性

  目的  比较健康人群、乳腺良性肿瘤患者和乳腺癌患者的血清Val、Met浓度差异,探究血清缬氨酸和甲硫氨酸与乳腺癌临床特征及风险的关系。  方法  采用液相色谱-串联质谱法测定38名乳腺良性肿瘤患者,87名乳腺癌患者的血清Val、Met浓度,同时选择91名健康人群作为对照组。经Kruskal-Wallis H检验比较不同分组间的血清Val、Met浓度差异,分析不同化疗方案及手术方式对乳腺癌患者血清Val、Met浓度的影响。再通过二元Logistic回归分析、计算优势比和95%置信区间（CI）来评估血清Val、Met与乳腺癌的风险关系并绘制ROC曲线评估血清Val及Met对乳腺癌的诊断效能。  结果  与健康对照组相比,乳腺癌（BC）组的血清Val浓度水平高于乳腺良性肿瘤（BE）组和健康对照组,BC组和BE组的Met水平都高于健康对照组,差异有统计学意义（P < 0.05）。不同TNM分期及接受不同化疗方案的乳腺癌患者血清Val、Met浓度,差异无统计学意义（P > 0.05）,但不同分子分型组间乳腺癌患者的血清Val浓度,差异有统计学意义（P < 0.05）。另外,血清Val浓度水平和乳腺癌风险无明显关系,但血清Met会显著影响乳腺癌的发生（P < 0.001）,血清Met的浓度越高,乳腺癌的患病风险就越高,并且Met的浓度水平每增加一个单位,乳腺癌患病风险就增加24%（OR = 1.24 95% CI:1.15～1.34）。并且血清Met（P < 0.001）对乳腺癌的诊断具有统计学意义。其AUC为0.83、敏感度及特异性分别为69%和90.1%,临界值为19.76 μmol/L。  结论  乳腺癌患者的血清Val浓度高于乳腺良性肿瘤患者及健康人群;与健康人群相比,乳腺癌患者及乳腺良性肿瘤患者的血清Met浓度水平也有所升高。血清Val浓度水平和乳腺癌风险无明显关系,但血清Met与乳腺癌风险呈负相关,并且血清Met对乳腺癌诊断具有一定的诊断效能。     

A prospective study of folate intake and the risk of breast cancer

CONTEXT: Folate is involved in DNA synthesis and methylation and may reduce breast cancer risk, particularly among women with greater alcohol consumption. OBJECTIVES: To assess the association between folate intake and risk of breast cancer and whether higher folate intake may reduce excess risk among women who consume alcohol. DESIGN: Prospective cohort study performed in 1980, with 16 years of follow-up. SETTING AND PARTICIPANTS: A total of 88818 women who completed the dietary questionnaire section of the Nurses' Health Study in 1980. MAIN OUTCOME MEASURE: Incidence of invasive breast cancer by levels of folate and alcohol intake. RESULTS: A total of 3483 cases of breast cancer were documented. Total folate intake was not associated with overall risk of breast cancer. However, among women who consumed at least 15 g/d of alcohol, the risk of breast cancer was highest among those with low folate intake. For total folate intake of at least 600 microg/d compared with 150 to 299 microg/d, the multivariate relative risk (RR) was 0.55 (95% confidence interval [CI], 0.39-0.76; P for trend = .001). This association was only slightly attenuated after additional adjustment for intake of beta carotene, lutein/zeaxanthin, preformed vitamin A, and total vitamins C and E. The risk of breast cancer associated with alcohol intake was strongest among women with total folate intake of less than 300 microg/d (for alcohol intake > or =15 g/d vs <15 g/d, multivariate RR, 1.32; 95% CI, 1.15-1.50). For women who consumed at least 300 microg/d of total folate, the multivariate RR for intake of at least 15 g/d of alcohol vs less than 15 g/d was 1.05 (95% CI, 0.92-1.20). Current use of multivitamin supplements, the major source of folate, was associated with lower breast cancer risk among women who consumed at least 15 g/d of alcohol (for current users of supplements vs never users, RR, 0.74; 95% CI, 0.59-0.93). CONCLUSIONS: Our findings suggest that the excess risk of breast cancer associated with alcohol consumption may be reduced by adequate folate intake.     

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.     

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。     

Sex steroid hormones and breast cancer: is there a link with oral contraceptives and hormone replacement therapy?

OBJECTIVE: To determine whether use of sex steroid hormones for contraception and hormone replacement therapy alters the risk of breast cancer, and whether the risk varies with their composition, duration of use, the period of a woman's life when the hormones are used, and after successful treatment for breast cancer. DATA SOURCES: The results of important epidemiological reports, readily available from the English literature and published since 1981, were evaluated, using reports of basic scientific work as a background to the problem. STUDY SELECTION: An attempt was made to obtain most of the relevant reports. Twenty case-control and seven cohort studies were available on the oral contraceptive pill (OCP) and eleven case-control and five cohort studies on hormone replacement therapy (HRT). DATA EXTRACTION: The relative risk estimates for breast cancer (and their 95% confidence intervals) determined by each report were tabulated according to the specific conditions of analysis, for example users under age 25, duration of use. Results by meta-analysis from previous studies were also used to determine risk. A significant positive association was present when the risk estimate exceeded 1.0 and the 95% confidence interval did not cross 1.0. DATA SYNTHESIS: Among OCP users, the vast majority of reports showed no significant risk of breast cancer--overall, longest duration of use, and use before first full-term pregnancy. However, a positive association between breast cancer and users under age 25 was found in three of eight reports. Similarly, the majority of reports showed no significant risk of breast cancer among HRT users, overall as well as in relation to duration of use and interval since first use. There was no increased risk with additional progestogen; it may be protective. An improved prognosis was found in users who developed breast cancer. On the limited data, use of hormones for postmenopausal symptoms did not appear to be harmful to women who had been successfully treated for breast cancer. CONCLUSIONS: The review revealed good evidence that use of sex steroid hormones had no significant effect on the risk of breast cancer, whether given for contraception or hormone replacement. There was some concern about increased risk with prolonged use of the OCP, especially in younger women. At present, use of these hormones is a matter of informed choice, with individual considerations of the risk-benefit ratio.     

Dietary fat and fiber in relation to risk of breast cancer. An 8-year follow-up.

OBJECTIVE--To address the hypotheses that dietary fat increases and fiber decreases the risk of breast cancer. DESIGN--Prospective cohort study with dietary assessment at baseline, using a validated, self-administered food frequency questionnaire. SETTING/PARTICIPANTS--89,494 women in the Nurses' Health Study who were 34 through 59 years of age in 1980 and who were followed up for 8 years (> 95% complete). RESULTS--1439 incident cases of breast cancer were diagnosed, including 774 among postmenopausal women. After adjustment for age, established risk factors, and total energy intake, we observed no evidence of any positive association between total fat intake and breast cancer incidence (relative risks [RRs] for increasing quintiles of fat intake were 1.0, 0.85, 0.96, 0.91, and 0.90; 95% confidence interval for highest vs lowest quintile, 0.77 to 1.07). Among postmenopausal women alone, corresponding RRs were 1.0, 0.89, 1.00, 0.95, and 0.91. Comparing extreme deciles of total fat intake (> or = 49% vs < 29% of total energy intake), the RR was 0.86 (95% confidence interval, 0.67 to 1.08). A similar absence of any positive association was observed without adjustment for energy intake; for tumors less than 2 cm as well as 2 cm or greater in diameter; for saturated, monounsaturated, and polyunsaturated fat; and after excluding the first 4 years of follow-up. Also, we found no suggestion of any positive association when using a more detailed and precise dietary questionnaire completed in 1984 (666 subsequent cases), even when women consuming less than 25% of energy from fat were used as the comparison group. No suggestion of a protective effect of dietary fiber was observed (RRs for increasing quintiles were 1.0, 0.95, 0.93, 1.02, and 1.02). CONCLUSIONS--These data provide evidence against both an adverse influence of fat intake and a protective effect of fiber consumption by middle-aged women on breast cancer incidence over 8 years. Nevertheless, the positive association between intake of animal fat and risk of colon cancer observed in many studies provides ample reason to limit this source of energy.     

Oral contraceptives and breast cancer: a national study

In a population based case-control study 433 New Zealand women aged 25-54 with newly diagnosed breast cancer were compared with 897 women selected at random from the electoral rolls. The relative risk of breast cancer in women who had ever used oral contraceptives was 0.94 (95% confidence interval 0.70 to 1.25). The relative risk in women aged 25-34 at diagnosis was estimated to be 2.2 (95% confidence interval 0.47 to 9.9) and in older women less than 1. Analyses of risk by duration of use of oral contraceptives, age at first use, and time since first use showed no adverse effect of the pill. In particular, there was no increased risk in women who had used oral contraceptives before the age of 25 or before their first pregnancy, even for prolonged periods. Given the high prevalence of use in New Zealand, this study provides strong evidence against the hypothesis that use of oral contraceptives at young ages increases the risk of breast cancer.     

中国汉族女性血清脂联素水平与乳腺癌关系的Meta分析

目的：综合评价中国汉族女性血清脂联素水平与乳腺癌的关系。方法：收集1995年1月至2012年11月国内公开发表的有关文献进行评述,提取信息,并进行Meta分析。结果： 最终有8篇文献纳入本研究,乳腺癌组481例,正常对照组346例。对纳入研究数据进行Meta分析,结果显示:① 与健康对照组相比,乳腺癌血清脂联素水平显著降低［P<0.01,加权均数差(WMD)=-2.412,95％CI为-3.173～-1.651］。绝经前乳腺癌患者血清脂联素水平显著低于绝经前健康女性(P<0.01,WMD=-1.884,95％CI为-2.770 ～-0.998)。② 与淋巴结未转移组相比,乳腺癌淋巴结转移组血清脂联素水平也显著降低(P=0.002,WMD=-1.981,95％CI为-3.238～-0.724)。结论：中国汉族女性低脂联素血症可能是乳腺癌发病危险因素,且与乳腺癌预后不良相关。     

Breast cancer and oral contraceptives: findings in Oxford-Family Planning Association contraceptive study

Among the 17 032 women taking part in the Oxford-Family Planning Association contraceptive study, 72 were first diagnosed as having breast cancer between the date they were admitted to the study and 1 September 1980. The relative risk of developing the disease in women who had used oral contraceptives in comparison with those who had never used them was estimated to be 0.96 (95% confidence limits 0.59 to 1.63). Among women aged under 35 years, the corresponding relative risk (based on only 14 women with breast cancer) was estimated to be 0.61. No relation was apparent between the risk of developing breast cancer and duration of oral-contraceptive use or interval since first oral-contraceptive use in any age group. The data in this study are thus reassuring; but observations based on women with long-term use of oral contraceptives, especially those starting to use the preparations at an early age, are few.     

Serum Estradiol Level and Risk of Breast Cancer During Treatment With Raloxifene

Context  As endogenous estradiol increases, risk of breast cancer increases. Raloxifene competes with endogenous estrogen for binding to estrogen receptors in breast tissue. A woman's estradiol level may alter the effects of raloxifene on breast cancer and other outcomes. Objective  To test the hypothesis that raloxifene reduces breast cancer risk more in women with relatively high estradiol levels than in women with very low estradiol levels. Design  Analysis of the Multiple Outcomes of Raloxifene Evaluation, a randomized, double-blind, placebo-controlled trial conducted from 1994 to 1999. Setting  One hundred eighty community settings and medical practices in 25 countries including the United States. Participants  A total of 7290 postmenopausal women aged 80 years or younger with osteoporosis who had baseline serum estradiol concentrations measured by a central laboratory using a sensitive assay. Women with a history of breast cancer or estrogen use were excluded. Intervention  Participants were randomly assigned to receive 60 mg/d or 120 mg/d of raloxifene (n = 4843) or matching placebo (n = 2447) for 4 years. Main Outcome Measure  New cases of histopathologically confirmed breast cancer in the treatment and placebo groups, stratified by estradiol levels. Results  In the placebo group, women with estradiol levels greater than 10 pmol/L (2.7 pg/mL) had a 6.8-fold higher rate of breast cancer (3.0% per 4 years; 95% confidence interval [CI], 1.8%-4.1%) than that of women with undetectable estradiol levels (0.6% per 4 years; 95% CI, 0%-1.1%; P = .005 for trend). Women with estradiol levels greater than 10 pmol/L in the raloxifene group had a rate of breast cancer that was 76% (95% CI, 53%-88%) lower than that of women with estradiol levels greater than 10 pmol/L in the placebo group (absolute rate reduction, 2.2% [95% CI, 1.0%-3.5%; number needed to treat = 45]). In contrast, women with undetectable estradiol levels had similar breast cancer risk whether or not they were treated with raloxifene (risk difference, -0.1%; 95% CI, -0.8% to 0.6%; P = .02 for the interaction). In this cohort, treating women with estradiol levels greater than 10 pmol/L with raloxifene for 4 years would have avoided 47% of breast cancer cases. Conclusions  Measurement of estradiol level by sensitive assay in postmenopausal women identifies those at high risk of breast cancer who may benefit most from raloxifene. If confirmed, this suggests that measuring estradiol and treating women with high estradiol levels could substantially reduce the rate of breast cancer among postmenopausal women.      

胰岛素样生长因子-1在妇科疾病中的作用

在许多组织增生过程中，通过内分泌、旁分泌和自分泌会产生胰岛素样生长因子-1(IGF-1)。最近的研究发现，IGF-1存在于各种增生组织，如子宫内膜和卵巢组织。患有严重子宫内膜异位症时，血清中IGF-1水平较高，而子宫内膜局部的：IGF-1水平减低，这可能是导致不孕的原因，多囊性卵巢综合征(PCOS)患者卵巢局部的IGF-1活性增强，与患者肥胖、高雄激素水平等一系列临床症状有关。IGF-1在良、恶性肿瘤中也起着重要的作用，IGF-1能刺激子宫肌瘤细胞的生长。围绝经期妇女若存在高IGF-1和低IGF-1结合蛋白-3(IGFBP-3)水平，则患乳腺癌的风险增大。绝经前后女性的高IGF-1水平与宫颈癌、卵巢癌和子宫内膜癌的发病率存在相关性。