夜间睡眠时间与女性乳腺癌发病风险的前瞻性队列研究

目的 我国女性乳腺癌发病率逐年上升,夜间睡眠时间长短可能与一系列健康效应相关,为探究夜间睡眠时间与乳腺癌发病关联性,本研究以唐山开滦集团前瞻性动态队列中的女性人群为基础进行了相关分析.方法 采用2006-2011年开滦集团体检人群中女性人群资料,收集社会人口学资料、睡眠习惯、身高、体质量等基线信息及乳腺癌发病结局信息.采用Cox比例风险回归模型分析夜间睡眠时间与女性乳腺癌发病风险的关联性.结果 共纳入24 692名女性体检者,总随访108 029.22人年,平均随访时间为4.38年,新发乳腺癌病例107例.以夜间睡眠7h为参比组,单因素分析提示夜间睡眠偏短(≤6h,HR=0.99,95％CI=0.52～1.87)或偏长(≥8h,HR=0.84,95％CI=0.49～1.45)与乳腺癌发病风险无统计学关联.调整年龄、受教育程度、饮酒等混杂因素后,分析仍显示夜间睡眠时间偏短(HR=0.82,95％CI=0.43～1.56)或偏长(HR=0.94,95％CI=0.54～1.64)与女性乳腺癌的发病无统计学关联.按年龄、打鼾情况和BMI分层分析及敏感性分析后,结果仍未发现存在显著性关联.结论 本研究结果尚不支持夜间睡眠时间偏短或偏长与女性乳腺癌的发病风险存在关联性.     

以副肿瘤综合征为表现的急性髓系白血病伴嗜碱性粒细胞增多1例并文献复习

目的提高对以副肿瘤综合征(PS)为表现的急性髓系白血病(AML)伴嗜碱性粒细胞增多的认识。方法回顾性分析河北省石家庄平安医院2021年7月收治的1例以PS为表现的AML[慢性粒细胞白血病(CML)转化]伴嗜碱性粒细胞增多患者的临床资料, 并复习相关文献。结果患者, 女性, 54岁, 诊断为CML 42个月, 反复出现低血压等PS表现, 血常规提示嗜碱性粒细胞增多, 骨髓涂片提示AML, 第2代酪氨酸激酶抑制剂(TKI)联合化疗未缓解, ABL基因检测到T315I突变, 给予第3代TKI联合化疗PS症状改善, 嗜碱性粒细胞数量恢复正常, 骨髓形态学缓解, 最后行异基因造血干细胞移植(allo-HSCT)达到完全缓解, 嗜碱性粒细胞比例及数量均正常。结论以PS为表现的AML患者预后主要与AML预后相关, CML急变为AML发生T315I突变后, 一、二代TKI及化疗效果差, 预后差, 可尝试allo-HSCT改善不良预后。     

中性粒细胞与淋巴细胞比值、癌胚抗原联合凝血指标对直径≤1.0 cm的良恶性乳腺结节鉴别诊断价值研究

目的:探讨中性粒细胞与淋巴细胞比值（NLR）、癌胚抗原（CEA）联合凝血指标凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、凝血酶时间（TT）、纤维蛋白原（FIB）对直径≤1.0 cm的良恶性乳腺结节鉴别诊断的价值。方法:选择2017年1月至2023年3月在新疆医科大学附属肿瘤医院行健康体检的直径≤1.0 cm乳腺结节患者为研究对象,将2017年1月至2020年6月的患者定义为训练集,2020年7月至2023年3月的患者定义为验证集。训练集中,良性乳腺结节患者83例,乳腺癌患者106例;验证集中,良性乳腺结节患者109例,乳腺癌患者136例。采用logistic回归分析乳腺结节良恶性的影响因素,二元logistic回归构建良恶性乳腺结节的诊断预测模型,受试者工作特征（ROC）曲线评价各项指标、诊断预测模型对乳腺结节良恶性的诊断效能。结果:训练集与验证集中,良性乳腺结节患者与乳腺癌患者的中性粒细胞（ t=6.76, P<0.001;t=9.14, P<0.001）、淋巴细胞（ t=7.67, P<0.001;t=17.00, P<0.001）、NLR（ t=13.97, P<0.001;t=17.41, P<0.001）、CEA（ t=33.44, P<0.001;t=8.15, P<0.001）、PT（ t=15.81, P<0.001;t=60.15, P<0.001）、APTT（ t=39.50, P<0.001;t=16.34, P<0.001）、TT（ t=13.34, P<0.001;t=14.37, P<0.001）、FIB（ t=16.66, P<0.001;t=20.30, P<0.001）相比,差异均有统计学意义。单因素分析显示,中性粒细胞（ OR=3.52,95% CI为1.26~5.37, P=0.036）、淋巴细胞（ OR=2.64,95% CI为1.52~3.72, P=0.033）、NLR（ OR=1.96,95% CI为1.15~3.42, P<0.001）、CEA（ OR=2.16,95% CI为1.29~3.05, P<0.001）、PT（ OR=1.75,95% CI为1.17~2.69, P<0.001）、APTT（ OR=3.11,95% CI为1.55~5.38, P<0.001）、TT（ OR=2.59,95% CI为1.38~4.11, P<0.001）、FIB（ OR=2.89,95% CI为1.36~4.55, P<0.001）均是直径≤1.0 cm乳腺结节良恶性的影响因素。多因素分析显示,NLR（ OR=2.06,95% CI为1.32~2.76, P<0.001）、CEA（ OR=1.19,95% CI为1.09~1.37, P=0.008）、PT（ OR=1.63,95% CI为1.05~2.11, P<0.001）、APTT（ OR=1.52,95% CI为1.13~2.34, P<0.001）、TT（ OR=1.64,95% CI为1.14~2.74, P<0.001）、FIB（ OR=1.42,95% CI为1.11~1.89, P<0.001）均是直径≤1.0 cm乳腺结节良恶性的独立影响因素。ROC曲线分析显示,在训练集中,NLR、CEA、PT、APTT、TT、FIB诊断乳腺癌的曲线下面积（AUC）分别为0.83、0.65、0.69、0.72、0.73、0.70,NLR诊断乳腺癌的敏感性为76%,特异性为69%。将多因素分析中有统计学意义的指标建立诊断预测模型,logit（ P）=1.76×NLR+21.42×CEA+5.14×PT+5.34×APTT+5.78×TT+6.52×FIB。ROC曲线分析显示,诊断预测模型用于训练集与验证集患者鉴别诊断的AUC分别为0.81、0.80。诊断预测模型对≤60岁及>60岁乳腺癌诊断的AUC分别为0.79、0.77,敏感性分别为82%、80%,特异性分别为75%、83%。诊断预测模型对肿瘤直径<0.3 cm、0.3~0.6 cm、0.7~1.0 cm乳腺癌诊断的AUC分别为0.63、0.74、0.91,敏感性分别为68%、73%、81%,特异性分别为72%、77%、84%。 结论:NLR、CEA、PT、APTT、TT、FIB均是直径≤1.0 cm乳腺结节良恶性的独立影响因素,利用NLR、CEA联合凝血指标PT、APTT、TT、FIB构建的预测模型对直径≤1.0 cm的良恶性乳腺结节具有较高的诊断效能。     

他汀类药物与前列腺癌发生风险:一项基于人群的纵向队列研究北大核心CSCD

目的：探讨他汀类药物与前列腺癌发生风险的相关性。方法：选择2008年1月-2010年12月在福建医科大学附属漳州市医院体检中心接受体检的符合纳入标准的50～75岁的男性作为研究对象,随访5年。通过比较非他汀类药物组和他汀类药物组的血清前列腺特异性抗原水平、前列腺穿刺活检率、前列腺癌发生率、Gleason评分和5年生存率,探讨他汀类药物与前列腺癌发生风险之间的相关性。结果：共1391例老年男性符合研究对象选择标准。其中,非他汀类药物组717例,平均年龄为（60．1±4．1）岁;他汀类药物组674例,平均年龄为（60．4±4．2）岁。2组的年龄、合并疾病、前列腺癌家族史和基线期血清前列腺特异性抗原水平的差异均无统计学意义（P值均〉0．05）。非他汀类药物组有15例（2．1％）失访,他汀类药物组有13例（1．9％）失访。5年随访期间,非他汀类药物组和他汀类药物组血清总的前列腺特异性抗原水平、前列腺穿刺率和前列腺癌发生率均逐渐升高,且非他汀类药物组总的升高趋势较他汀类药物组更明显（P〈0．05）。他汀类药物组中,不同药物亚组之间上述观察指标的差异均无统计学意义（P值均〉0．05）。他汀类药物组中确诊为前列腺癌患者的比例低于非他汀类药物组（P〈0．001）,患者年龄高于非他汀类药物组（P〈0．001）,高组织学分级（Gleason评分≥7）前列腺癌的比例低于非他汀类药物组（P〈0．001）。结论：他汀类药物可能降低前列腺癌发生风险,长期用药的效果更为显著。     

Cumulative number of menstrual cycles and breast cancer risk: results from the E3N cohort study of French women

Objective: To examine the relationship between breast cancer risk and the cumulative number of cycles before a first full-term pregnancy (FTP) and lifetime, taking age at menarche and at onset of regular cycling, periodicity and regularity of cycles, duration of periods of pregnancy, and lactation, oral contraceptive (OC) use, and age at menopause into account. Methods: The data were taken from the E3N prospective cohort study of women aged 40–65 years in 1990. A total of 1718 breast cancer cases were identified during the 579,525 person-years of follow-up. Results: There was a highly significant linear relationship between breast cancer risk and both the cumulative number of cycles before a first FTP (p for trend < 0.0001) and lifetime (p for trend < 0.001), with multivariate relative risk (RR) of a similar magnitude for both variables. Compared to women with a lifetime number of cycles 402 ( 30 years), the RR for those with a lifetime total of 403–441, 442–480, 481–520, and 521 cycles were 0.95 (0.75–1.21), 1.21 (0.97–1.52), 1.23 (0.96–1.58), and 1.60 (1.25–2.04), respectively. Results restricted to never OC users were similar. Conclusions: Further investigation is needed to clarify whether the underlying factor is repeated exposure to fluctuating hormones, the number of anovular/ovular cycles, or the relative importance of the follicular and luteal phases.     

Association between ambient air pollution and breast cancer risk: The multiethnic cohort study

Previous studies using different exposure methods to assess air pollution and breast cancer risk among primarily whites have been inconclusive. Air pollutant exposures of particulate matter and oxides of nitrogen were estimated by kriging (NO_x, NO₂, PM₁₀, PM_2.5), land use regression (LUR, NO_x, NO₂) and California Line Source Dispersion model (CALINE4, NO_x, PM_2.5) for 57,589 females from the Multiethnic Cohort, residing largely in Los Angeles County from recruitment (1993–1996) through 2010. Cox proportional hazards models were used to examine the associations between time-varying air pollution and breast cancer incidence adjusting for confounding factors. Stratified analyses were conducted by race/ethnicity and distance to major roads. Among all women, breast cancer risk was positively but not significantly associated with NO_x (per 50 parts per billion [ppb]) and NO₂ (per 20 ppb) determined by kriging and LUR and with PM_2.5 and PM₁₀ (per 10 μg/m³) determined by kriging. However, among women who lived within 500 m of major roads, significantly increased risks were observed with NO_x (hazard ratio [HR] = 1.35, 95% confidence interval [95% CI]: 1.02–1.79), NO₂ (HR = 1.44, 95% CI: 1.04–1.99), PM₁₀ (HR = 1.29, 95% CI: 1.07–1.55) and PM_2.5 (HR = 1.85, 95% CI: 1.15–2.99) determined by kriging and NO_x (HR = 1.21, 95% CI:1.01–1.45) and NO₂ (HR = 1.26, 95% CI: 1.00–1.59) determined by LUR. No overall associations were observed with exposures assessed by CALINE4. Subgroup analyses suggested stronger associations of NO_x and NO₂ among African Americans and Japanese Americans. Further studies of multiethnic populations to confirm the effects of air pollution, particularly near-roadway exposures, on the risk of breast cancer is warranted.     

Serum lipids and breast cancer risk: a cohort study of 5,207 Danish women

The association between serum lipids and breast cancer risk was investigated in a cohort of 5,207 Danish women, who participated in The Glostrup Population Studies between 1964 and 1986. During four to 26 years of follow-up, 51 incident cases of breast cancer were identified by linkage to the Danish Cancer Registry. At the time of lipid measurement, the women were between 30 and 80 years of age. An inverse association was found between serum high-density lipoprotein (HDL) cholesterol and risk of breast cancer, which was not changed by adjustment for potential confounders such as social class, age at menarche and menopause, number of full-term pregnancies, body mass index, or alcohol and coffee consumption. The relative risk was 0.3 (95 percent confidence interval = 0,1–0.8) for women in the highest quartile of serum HDL-cholesterol compared with women in the lowest quartile and the relation displayed a significant negative trend (P = 0.01). For serum triglycerides there was a suggestion of a positive association with breast cancer incidence, but the trend was not significant (P = 0.06). No relationship between total serum cholesterol or low-density lipoprotein cholesterol and risk of breast cancer was observed. Risk estimates for well known breast cancer risk factors such as social class, age at menopause, number of full-term pregnancies, and obesity were in the directions expected.Dr Høyer and Ms Engholm are with the Danish Cancer Registry, Copenhagen, Denmark; Dr Høyer is also with The Glostrup Population Studies, Glostrup, Denmark. Address correspondence to Dr Høyer at The Danish Cancer Registry, Institute of Cancer Epidemiology, Danish Cancer Society, Rosenvangets Hovedvej 35, DK-2100 Copenhagen Ø, Denmark. This study was funded by Sygekassernes Helsefond DK, Sundhedspuljen DK and the Danish Cancer Society.     

Effect of lifetime lactation on breast cancer risk: a Korean women's cohort study

The objective of our study was to examine the effect of lifetime lactation on breast cancer risk among premenopausal women. The data were from a prospective cohort study with a follow-up period of 6 years in Korea (1995-2000). The cohort was composed of 110,604 premenopausal parous Korean women, aged 20 years and older, who received health insurance from the Korea Medical Insurance Corporation and who had medical evaluations in 1992 and 1994. Multivariate Cox proportional hazard models were tested, controlling for age, age at menarche, number of children, age at first pregnancy, oral contraceptive use, smoking, exercise and obesity. At baseline, 57,440 (51.9%) reported breastfeeding and 4,584 (4.1%) reported breastfeeding more than 24 months. From 1995-2000, 360 incident cases of breast cancer (61.8/100,000 person-years) occurred. Compared to parous women who had no history of lactation, a period of lactation of 13-24 months decreased the risk of breast cancer (RR, 0.7; 95% CI, 0.5-1.1), and this risk was decreased even further for those who breastfed for more than 24 months (RR, 0.6; 95% CI, 0.3-1.0). There was a clear trend of decreasing breast cancer risk with the duration of lactation (p for trend <0.001). In conclusion, our study of a large Korean cohort provides additional empirical evidence to current theoretical conjecture that lactation decreases the risk of breast cancer among premenopausal women.     

Cancer risk among Danish women with cosmetic breast implants

The available epidemiologic evidence does not support a carcinogenic effect of silicone breast implants on breast or other cancers. Data on cancer risk other than breast cancer are limited and few studies have assessed cancer risk beyond 10-15 years after breast implantation. We extended follow-up of our earlier cohort study of Danish women with cosmetic breast implants by 7 years, yielding 30 years of follow-up for women with longest implant duration. The study population consisted of women who underwent cosmetic breast implant surgery at private clinics of plastic surgery (n = 1,653) or public hospitals (n = 1,110), and a control group of women who attended private clinics for other plastic surgery (n = 1,736), between 1973-95. Cancer incidence through 2002 was ascertained using the Danish Cancer Registry. Risk evaluation was based on computation of standardized incidence ratios (SIR) and Cox proportional hazards models, adjusting for age, calendar period and reproductive history. We observed 163 cancers among women with breast implants compared to 136.7 expected based on general population rates (SIR = 1.2; 95% confidence interval [CI] = 1.0-1.4), during a mean follow-up period of 14.4 years (range = 0-30 years). Women with breast implants experienced a reduced risk of breast cancer (SIR = 0.7; 95% CI = 0.5-1.0), and an increased risk of non-melanoma skin cancer (SIR = 2.1; 95% CI = 1.5-2.7). Stratification by age at implantation, calendar year at implantation and time since implantation showed no clear trends, however, the statistical precision was limited in these analyses. When excluding non-melanoma skin cancer, the SIR for cancer overall was 1.0 (95% CI = 0.8-1.2). With respect to other site-specific cancers, no significantly increased or decreased SIR were observed. Similar results were found when directly comparing women who had implants at private clinics with women who attended private clinics for other plastic surgery, with rate ratios for cancer overall, breast cancer and non-melanoma skin cancer of 1.1 (95% CI = 0.8-1.6), 0.7 (95% CI = 0.4-1.3) and 1.5 (95% CI = 0.8-2.7), respectively. In conclusion, our study lends further support to the accumulating evidence that silicone breast implants are not carcinogenic. Reasons for the consistently reported deficit of breast cancer among women with breast implants remain unclear, whereas increased exposure to sunlight may explain the excess occurrence of non-melanoma skin cancer. We found no indication of delayed diagnosis of breast cancer due to the presence of breast implants.     

Dietary polyunsaturated fatty acids and breast cancer risk in Chinese women: a prospective cohort study

Breast cancer is the most common cancer in women. Controversy exists regarding the role of dietary fat in breast cancer etiology. We investigated the association of dietary polyunsaturated fatty acids (PUFAs) and the ratio of n-6 PUFAs to marine-derived n-3 PUFAs with breast cancer risk in the Shanghai Women's Health Study, a prospective cohort study including 72,571 cancer-free participants at baseline. Dietary fatty acid intake was determined using food frequency questionnaires. We used Cox proportional hazards analysis to estimate the relative risks (RRs) and 95% confidence intervals (CIs) for the association of breast cancer risk with dietary fatty acids consumption. In 583,998 person-years of follow-up, we identified 712 breast cancer cases. We found no association of breast cancer risk to dietary intake of linoleic acid, arachidonic acid, α-linolenic acid or marine-derived n-3 PUFA. We found a statistically significant interaction between n-6 PUFA intake, marine-derived n-3 PUFA intake and breast cancer risk (p = 0.008). Women with lower intake (the lowest tertile) of marine-derived n-3 PUFA and higher intake (the highest tertile) of n-6 PUFA had an increase risk for breast cancer (RR = 2.06; 95% CI = 1.27-3.34) compared to women with higher intake (the highest tertile) of marine-derived n-3 PUFAs and lower intake (the lowest tertile) of n-6 PUFAs after adjusting for potential confounders. The relative amounts of n-6 PUFA to marine-derived n-3 PUFAs may be more important for breast cancer risk than individual dietary amounts of these fatty acids.     

Differential effects of reproductive factors on the risk of pre- and postmenopausal breast cancer. Results from a large cohort of French women

The aim of this study was to obtain a better understanding of the role of hormonal factors in breast cancer risk and to determine whether the effect of reproductive events differs according to age at diagnosis. It analysed the effect of age at menarche, age at first full-term pregnancy, number of full-term pregnancies and number of spontaneous abortions both on the overall risk of breast cancer and on its pre- or postmenopausal onset, using the data on 1718 breast cancer cases, obtained from a large sample of around 100000 French women participating in the E3N cohort study. The results provide further evidence that the overall risk of breast cancer increases with decreasing age at menarche, increasing age at first pregnancy and low parity. No overall effect of spontaneous abortions was observed. The effect of these reproductive factors differed according to menopausal status. Age at menarche had an effect on premenopausal breast cancer risk, with a decrease in risk with increasing age of 7% per year (P<0.05). Compared to those who had their first menstrual periods at 11 or before, women experiencing menarche at 15 or after had an RR of 0.66 (95% CI 0.45-0.97) in the premenopausal group. Age at first full-term pregnancy had an effect on both pre- and postmenopausal breast cancer risk, with significant tests showing increasing risk per year of increasing age (P=0.001 and P<0.05 respectively). A first full-term pregnancy above age 30 conveyed a risk of 1.63 (95% CI 1.12-2.38) and 1.35 (95% CI 1.02-1.78) in the pre- and postmenopausal groups respectively. A protective effect of high parity was observed only for postmenopausal breast cancer risk (P for trend test =0.001), with point estimates of 0.79 (95% CI 0.60-1.04), 0.69 (95% CI 0.54-0.88), 0.66 (95% CI 0.51-0.85) and 0.64 (95% CI 0.48-0.86) associated to a one, two, three and four or more full-term pregnancies. A history of spontaneous abortion had no significant effect on the risk of breast cancer diagnosed before or after menopause. Our results suggest that reproductive events have complex effects on the risk of breast cancer.     

Selenium and the risk of postmenopausal breast cancer in the DOM cohort

Summary Selenium has been claimed to have chemo-preventive properties. However, data showing that in humans selenium levels are already decreased prior to diagnosis of breast cancer were not available. Such information is mandatory before oral selenium supplementation in the primary prevention of (breast) cancer in humans is acceptable. This question of a preventive-potential of selenium was evaluated in a case-control study nested in a cohort, because this design allows determination of the time-order of preceding selenium levels and subsequent cancer risk.The cohort consisted of 5577 women aged 55–70 years from the DOM project, a population based breast cancer screening program in the Netherlands. Instrumental Neutron Activation Analysis was used to measure the selenium content of toenail clippings. The 69 cases of breast cancer found during follow-up after screening represent recent tumours since all women had a negative screening mammogram 3–5 years previously.No decreased selenium levels, as measured in nail clippings from the big toes, could be detected in cases-to-be, either when compared to 4 age matched controls per case or when compared with a random control group drawn from the entire cohort. On the contrary, a tendency for slightly higher selenium levels among future cancer cases was observed.As to the sensitivity of detecting differences in selenium by nail clippings, lower selenium could be detected in nails of current smokers. The smoking-related decrease in nail selenium level was of the same order as the differences between breast cancer cases and controls, but was independent of the breast cancer risk.Results are similar to a comparable study on premenopausal breast cancer and argue against a preventive role for selenium on breast cancer risk.