乳腺导管原位癌的间质微浸润危险因素分析

目的：分析乳腺导管原位癌（ductal carcinoma in situ,DCIS）间质微浸润的危险因素,探讨导管原位癌伴微浸润（ductal carcinoma in situ with microinvasion,DCIS-MI）患者的腋窝淋巴结术式。方法：回顾性分析2013年2 月至2016年2 月南京大学医学院附属金陵医院经手术后病理证实为DCIS、DCIS-MI 共45例患者临床资料,依据是否伴微浸润分为DCIS与DCIS-MI 组,对患者年龄、就诊时是否绝经、肿瘤大小等因素行统计学分析。结果：就诊时未绝经（P = 0.006）、肿物直径≥ 3.15cm（P = 0.006）、有恶性肿瘤家族史（P = 0.002）的患者更易发生肿瘤间质微浸润。结论：具有可触及腋窝肿物、未绝经、乳腺巨大肿物、有恶性肿瘤家族史危险因素,同时术前行穿刺或术中冰冻提示DCIS、DCIS伴可疑微浸润的患者存在微浸润可能性大,应予前哨淋巴结活检。触及腋窝肿物为首要症状患者,腋窝淋巴结清扫术应作为首选方式。     

Abortion history and breast cancer risk: results from the Shanghai Breast Cancer Study

Studies of the association between induced abortion and breast cancer risk have been inconsistent, perhaps due to underreporting of abortions. Induced abortion is a well-accepted family planning procedure in China, and women who have several induced abortions do not feel stigmatized. The authors used data from a population-based case-control study of breast cancer among women age 25-64 conducted between 1996 and 1998 in urban Shanghai to assess whether a history of and the number of induced abortions were related to breast cancer risk. In-person interviews were completed with 1,459 incident breast cancer cases ascertained through a population-based cancer registry, and 1,556 controls randomly selected from the general population in Shanghai (with respective response rates of 91% and 90%). After adjusting for confounding, there was no relation between ever having had an induced abortion and breast cancer (odds ratio [OR] = 0.9, 95% confidence interval [CI] 0.7-1.2). Women who had 3 or more induced abortions were not at increased risk of premenopausal breast cancer (OR = 0.9, 95% CI 0.6-1.4) or postmenopausal breast cancer (OR = 1.3, 95% CI 0.8-2.3). These results suggest that a history of several induced abortions has little influence on breast cancer risk in Chinese women.     

Invasive breast cancer following ductal and lobular carcinoma in situ of the breast

We considered the risk of subsequent invasive breast cancer in a population-based series of 579 carcinomas in situ (CIS) of the breast (482 ductal, 88 lobular) registered between 1977 and 2002 in the Swiss Canton of Vaud. A total of 55 cases of invasive breast cancer were observed vs. 12.3 expected, corresponding to a standardized incidence ratio (SIR) of 4.5 (95% confidence interval [CI], 3.4-5.8). The SIR was 4.6 after ductal and 4.2 after lobular CIS, was similar with passing time since CIS diagnosis, but was higher (SIR = 5.5) for women aged <55 years. At 20 years following CIS, the cumulative risk of invasive breast cancer was 26%, similar for lobular and for ductal CIS. The incidence of invasive breast cancer following CIS showed no consistent pattern of trends with age, all rates in subsequent age groups ranging between 10 and 18 in 1,000. This is compatible with the occurrence of a single mutational event in a population of susceptible women.     

A comparison of reproductive risk factors for CIS lesions and invasive breast cancer

A differential effect of reproductive factors on the incidence of carcinoma in situ of the breast (CIS) and invasive cancer may indicate that hormonal factors related to reproductive history not only influence the initial steps towards breast cancer but also preinvasive malignant lesions. A comparison of reproductive factors was performed using a population-based cohort of 1.5 million Danish women born between 1935 and 1978. Between 1983 and 1998, 15,590 cases of invasive breast cancer and 871 cases of CIS were identified using a database with extensive clinical information. Number of births and age at first birth were similarly associated with the risk of being diagnosed with ductal carcinoma in situ (DCIS) compared to invasive breast cancer [RR(DCIS)(per birth)/RR(invasive)(per birth) = 1.03(0.93-1.14), RR(DCIS)(per 5yr) /RR(invasive)(per 5yr) = 1.06(0.96-1.17)]. Also, the short-term risk the first 10 years after birth was similar for DCIS and invasive cancer [RR(DCIS) /RR(invasive) = 0.90 (0.74-1.09)]. Additional analyses were performed according to characteristics of the DCIS lesion (size, malignancy grade, noncomedo or comedo type). In conclusion, our observations do not support the theory that reproductive history is associated with progression from noninvasive to invasive breast cancer.     

从原位癌到微小浸润：乳腺肿瘤的临床病理分析及对外科治疗的影响

背景对乳腺原位癌（CIS）是否应进行前哨淋巴结活检（SLNB）目前仍处于争议中。临床诊疗中常遇到：一些在术前穿刺或术中活检被诊断为原位癌且未进行SLNB的患者,术后却经病理确诊为乳腺微小浸润性癌（MIBC）。此时,是否二次手术进行腋窝淋巴结状态评估对外科医师来说是一个困难的选择。一方面,MIBC淋巴结转移风险尚不明确;另一方面,再次手术时SLNB的准确性及可操作性往往受到质疑,多数情况下腋窝淋巴结清扫成为唯一的选择。目的识别原位癌伴发微小浸润的危险因素;比较CIS和MIBC腋窝淋巴结的转移风险;探索选择合适的病例直接进行术中前哨淋巴结活检以避免二次手术的合理性。方法对接受手术且经病理确诊的乳腺原位癌（493例）及微小浸润癌（199例）患者的临床病历资料进行回顾性的统计分析;采用Pearson卡方检验和Fisher确切概率法进行组间比对;通过单因素分析和多因素Logistic回归识别原位癌伴发微小浸润的危险因素。结果原位癌组中出现4例小叶原位癌（LCIS）,其余均为导管原位癌（DCIS）,而MIBC所伴发的原位癌均以DCIS为主。单因素分析显示,X线片BI-RADS≥4级的钙化,肿瘤﹥2.5 cm,高级别DCIS,ER（－）,PR （－）,HER-2（+++）是原位癌伴微小浸润的危险因素（P均﹤0.05）;Ki-67≥20%也可能与发生微小浸润有关（P=0.057）。使用Logistic回归将重要协变量（年龄）与上述危险因素一起进行多因素分析显示,年龄﹥50岁（P=0.034）,肿瘤﹥2.5 cm（P=0.033）,高级别DCIS（P=0.011）等是原位癌伴微小浸润的独立危险因素。此外,相对于2.0%的原位癌淋巴结转移概率,MIBC的淋巴结转移概率为5.5%,二者比较差异具有统计学意义（P=0.029）。结论 MIBC淋巴结转移风险为5.5%,多伴发于患者年龄超过50岁的较大范围的高级别DCIS中。目前来说,对合并这些高风险因素的原位癌患者直接进行SLNB是一种合理和稳妥的诊治手段,可以有效避免二次手术的发生并为下一步治疗提供依据。     

Circulating levels of biomarkers and risk of ductal carcinoma in situ of the breast in the UK Biobank study

Observational studies have shown associations between circulating levels of various biomarkers (eg, total cholesterol [TC], low-density lipoprotein cholesterol [LDL], insulin-like growth factor-1 [IGF-1], C-reactive protein [CRP] and glycated hemoglobin-1c [HbA1c]) and the risk of invasive breast cancer (IBC). Ductal carcinoma in situ of the breast (DCIS) is a nonobligate precursor of IBC and shares several risk factors with it. However, the relationship between these biomarkers and DCIS risk remains unexplored. We studied the association between circulating levels of TC, LDL-C, high-density lipoprotein cholesterol (HDL-C), Lipoprotein (a) (Lp-(a)), IGF-1, CRP and HbA1c, with the risk of DCIS in 156801women aged 40 to 69 years and breast cancer-free at enrolment when blood samples and information on demographic and health-related factors were collected. Incident cases of DCIS were ascertained during the follow-up via linkage to the UK cancer registries Multivariable-adjusted Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of interest. In all, 969 DCIS incident cases were diagnosed during 11.4 years of follow-up. Total cholesterol was inversely associated with the risk of DCIS (HR_{quintile(Q)5vsQ1} = 0.47, 95% CI: 0.27-0.82, P_trend = .008). Conversely, LDL-C was positively associated with DCIS risk (HR_Q3vsQ1 = 1.43, 95% CI: 1.01-2.04, HR_Q4vsQ1 = 1.60, 95% CI: 1.04-2.47, HR_Q5vsQ1 = 2.29, 95% CI: 1.36-3.88, P_trend = .004). In postmenopausal women, CRP had a weak positive association with DCIS risk, while HbA1c showed a nonlinear association with the risk. These results, in conjunction with those from previous studies on IBC, provide support for the association of several biomarkers with the risk of an early stage of breast cancer.     

Menstrual and reproductive factors and endometrial cancer risk: Results from a population-based case-control study in urban Shanghai

The purpose of our study was to evaluate the association of menstrual and reproductive factors with the risk of endometrial cancer. In a population-based case-control study conducted in urban Shanghai, in-person interviews were completed for 833 women aged 30-69 years and an equal number of controls frequency-matched to cases by age. All cases were newly diagnosed with endometrial cancer between January 1, 1997 and December 31, 2001. The unconditional logistic regression model was employed to derive the adjusted odds ratios (ORs) of endometrial cancer and 95% confidence intervals (CIs) in relation to menstrual and reproductive factors. Earlier menarche age, particularly among premenopausal women, and later menopausal age were associated with an elevated risk of endometrial cancer. A clear dose-response relation between endometrial cancer risk and years of menstruation was observed (p for trend < 0.01). Compared to women ever having a pregnancy and women ever having had a live birth, respectively, nulligravity and nulliparity were both associated with a more than one-fold elevated risk of endometrial cancer. Both completed (OR = 3.02, 95% CI 1.10-8.32 for women never having a complete pregnancy) and incomplete pregnancy (OR = 0.69, 95%CI 0.55-0.87) conferred a protective effect against endometrial cancer, and the protective effect appeared to increase with total number of pregnancies (p for trend = 0.01). The effect of pregnancy on endometrial cancer remained unchanged with increasing time since the last pregnancy. Stillbirth and age at first pregnancy was unrelated to endometrial cancer risk. Our study suggests that prolonged menstruation was related to an increased risk of endometrial cancer while pregnancy, including induced abortion, reduced the risk of endometrial cancer.     

Telomerase activity in ductal carcinoma in situ of the breast

Telomerase plays an important role in maintaining the stability of the chromosomes. Activity of telomerase has been detected in proliferating and immortalized cell lines and in a number of malignant tumors including invasive breast cancer. The aim of the study was to examine telomerase activity in ductal carcinoma in situ (DCIS), which is considered to be a precursor lesion of infiltrating breast carcinoma, using a PCR-based telomerase activity protocol (TRAP). We examined 35 samples obtained from histologically confirmed breast biopsies, including 13 normal breast tissues, 11 infiltrating ductal carcinoma (IDC), nine DCIS, and two DCIS with microinvasion. Telomerase activity was demonstrated in 8/9 samples of DCIS, both samples of DCIS with microinvasion, and all but one sample of IDC. Normal breast tissue had no demonstrable telomerase activity. Our results indicate that telomerase is activated frequently in early breast carcinogenesis, although its utilization as a biomarker in DCIS is questionable.     

Recent trends of in situ carcinoma of the breast and mammographic screening in the Florence area, Italy

Objectives: The study analyzes the relationship between the incidence trends of breast carcinoma in situ (CIS) and the spread of mammography screening in the Italian area of Florence (about 608,000 female residents).Setting: In this area, since the seventies, a mammographic screening by personal invitation was performed by the Center for Cancer Prevention (CSPO) in some rural municipalities. After 1990, the municipality of Florence and other municipalities were involved in the screening.Methods: The study included all cases of female breast carcinomas in situ reported to the population-based Tuscany Cancer Registry between 1985 and 1995. On the basis of information from the CSPO files, the cases were categorized into: screen-detected, self-referrals, and other (CSPO cases diagnosed in symptomatic women or at periodic check up after breast cancer plus hospital cases).Results: Overall, 332 women with breast carcinoma in situ (CIS) were registered between 1985 and 1995. The CIS incidence rate increased from 2.39/100,000 women in 1985–87 to 6.22/100,000 in 1994–95. The largest increase was observed for the ductal carcinoma in situ (2.9 times) and in women aged 50–69 years (3.8 times). In this age group, cases diagnosed at the screening by personal invitation accounted for 69% of the rise in CIS incidence. The proportion of mastectomy lowered from 41% before 1990 to 25% after 1990.Conclusion: In the Florence area the CIS incidence trend, showing a marked increase beginning in 1991, was mainly explained by the spread of the mammographic screening by personal invitation. The period during which mammographic screening became widespread coincided with a change in the treatment policy of breast cancer, with a high proportion of breast conserving surgery also for CIS. Therefore, the rise in CIS incidence rates correlated with the widespread use of mammographic screening did not substantially increase the number of women treated by mastectomy.     

乳腺导管原位癌伴微小浸润的临床分析

目的 随着乳腺X射线摄影技术的进步及普及,使得乳腺导管原位癌伴微小浸润(ductal carcinoma in situ with microinvasion,DCIS-MI)在乳腺癌中比例增高,但所占比例＜1.0％.由于DCIS-MI术前确诊困难,病理和预后不同,同时缺乏大规模的循证医学证据指导治疗方案的选择,并存在着诸多争议,现已成为临床医师及病理医师普遍关注的热点.本研究总结和分析DCIS-MI的临床病理特征,加深对DCIS-MI的认识并探讨其合理的治疗方式.方法 回顾性分析2004-01-01-2014-12-31新疆医科大学附属肿瘤医院收治的318例患者的临床病理资料,其中乳腺导管原位癌(ductal carcinoma in situ,DCIS)患者239例,DCIS-MI患者79例.结果 DCIS与DCIS-MI在核分级(x2=29.699,P＜0.001)、粉刺型(x2=26.242,P＜0.001)、ER(x2=11.807,P=0.001)、PR(x2=7.623,P=0.006)、Ki-67阳性表这率(x2 =5.185,P=0.023)、分子分型(x2=16.570,P＜0.001)和手术方式(x2 =29.713,P＜0.001)方面均不同,差异均有统计学意义.在年龄(x2 =4.563,P=0.102)、民族(x2=2.102,P=0.147)、月经情况(x2=0.455,P=0.500)、肿块位置(x2 =0.267,P=0.605)、临床表现[包括乳房肿决(x2=1.393,P=0.238)、乳头改变(x2=1.345,P=0.246)、无症状(x2 =3.077,P=0.079)]、钙化(x2=0.010,P=0.920)、肿块的大小(x2=3.370,P=0.066)和HER-2阳性表达率(x2=0.317,P=0.574)方面差异均无统计学意义.中位随访时间为66个月,共有4例患者复发,其中DCIS组有2例胸壁复发,复发率为0.8％ (2/239);DCIS-MI组有2例胸壁复发,复发率为2.5％(2/79).DCIS组和DCIS-MI组复发率(x2=1.373,P=0.241)和总生存率(x2=1.397,P=0.237)相比,差异无统计学意义.DCIS与DCIS-MI的复发与手术方式、核分级、微浸润和腋窝淋巴结清除差异均无统计学意义,P＞0.05.结论 DCIS-MI预后较好,是一种少见的乳腺癌亚型.DCIS-MI与DCIS的腋窝淋巴结转移率和预后无差别,提示对DCIS-MI的处理应该按照DCIS的治疗方式进行处理.     

乳腺导管原位癌和乳腺导管原位癌伴微浸润的分子分型差异性研究

背景与目的：乳腺导管原位癌伴微浸润（ductal carcinoma in situ with microinvasion,DCISMI）是乳腺导管原位癌（ductal carcinoma in situ,DCIS）发展到浸润性乳腺癌（invasive breast cancer,IDC）的中间阶段,该研究旨在分析乳腺DCIS和DCIS-MI这两类早期乳腺癌不同临床病理学特征和各个分子分型间的差异。方法：本回顾性研究纳入了317例DCIS患者,其中227例（71.6%）为纯DCIS患者,90例（28.4%）为DCIS-MI患者。所有患者根据其DCIS成分而非微浸润成分的免疫组织化学检查结果分成腔面A型［雌激素受体（estrogen receptor,ER）和（或）孕激素受体（progesterone receptor,PR）阳性,人类表皮生长因子受体2（human epidermal growth factor receptor 2,HER-2）阴性］、腔面B型［ER和（或）PR阳性,HER-2阳性］、HER-2过表达型（ER和PR阴性,HER-2阳性）和基底样型（ER和PR阴性,HER-2阴性）。结果：DCIS-MI患者的肿瘤大小倾向更大（P=0.059）,病理核分级显著更高（P=0.002）。和DCIS患者相比,乳腺DCIS-MI患者中腔面A型比例较低而基底样型比例较高（P=0.001）。结论：乳腺DCIS和DCIS-MI间分子分型分布不同,临床病理特征迥异,提示DCIS-MI是DCIS发展的新阶段,有了“质”的改变,本结论有待后续更大样本量的研究进行验证。     

Concurrent lobular neoplasia increases the risk of ipsilateral breast cancer recurrence in patients with ductal carcinoma in situ treated with breast‐conserving therapy

BACKGROUND:

Multiple clinicopathologic factors have been analyzed for their association with an increased risk of ipsilateral breast tumor recurrence (IBTR) after women receive breast‐conserving treatment (BCT) for ductal carcinoma in situ (DCIS). The reported incidence of proliferative lesions, such as atypical ductal hyperplasia (ADH), columnar cell changes (CCC), and lobular neoplasia associated with breast cancer, has been as high as 23%; however, the relevance of these lesions on the natural history of DCIS and the risk of IBTR remains unknown.

METHODS:

Two hundred ninety‐four patients with DCIS who received BCT between 1991 and 1995 were identified from the authors' institutional database. Slides were reviewed by a dedicated breast pathologist with particular attention to the presence of lobular neoplasia, ADH, and CCC. The actuarial 5‐, 10‐, and 15‐year IBTR rates were calculated using the Kaplan‐Meier method and were compared using the log‐rank test.

RESULTS:

Concurrent lobular neoplasia was present in 41 of 294 patients (14%), ADH was present in 37 of 294 patients (13%), and CCC was present in 71 of 294 patients (24%). The median follow‐up was 11 years. IBTR occurred in 40 of 227 patients without lobular neoplasia (18%) versus 15 of 41 patients with lobular neoplasia (37%; P=.005; hazard ratio [HR], 2.49). The 5‐, 10‐, and 15‐year cumulative incidence rates of IBTR were twice as high in women who had DCIS and lobular neoplasia compared with women who had DCIS alone (P=.002). Concomitant ADH (HR, 1.53) and CCC (HR, 1.24) were not associated significantly with IBTR (P=.20 and P=.44, respectively).

CONCLUSIONS:

Concurrent lobular neoplasia is associated with a significantly higher risk of IBTR in women with DCIS who received BCT. Women with coexisting DCIS and lobular neoplasia who receive BCT should consider using additional risk‐reducing strategies. Cancer 2009. © 2009 American Cancer Society.     

Postmenopausal levels of sex hormones and risk of breast carcinoma in situ: results of a prospective study

We report on a prospective study to assess the association of postmenopausal serum levels of sex hormones with subsequent risk of breast carcinoma in situ. We conducted a case-control study nested within the cohort of the New York University Women's Health Study, a large prospective study documenting a positive association of circulating levels of estrogens and androgens with invasive breast cancer. The study included 69 cases of incident in situ carcinoma and 134 individually matched controls. No statistically significant trend of increasing risk with increasing level of any of the hormones was observed. Odds ratios (95% CIs) for the highest tertile relative to the lowest were 1.10 (0.51-2.39) for estradiol, 0.95 (0.41-2.19) for estrone, 1.63 (0.69-3.88) for testosterone, 0.99 (0.44-2.24) for androstenedione, 0.99 (0.45-2.20) for dehydroepiandrosterone sulfate and 0.81 (0.38-1.74) for sex hormone-binding globulin. Adjusting for potential confounders did not materially affect the results, nor did limiting the analysis to the 59 cases of ductal carcinoma in situ, the lesion thought to be the direct precursor of most invasive breast cancers. Our results are at variance with the positive associations observed in this same cohort with risk of invasive breast cancer. Possible explanations for our results include lack of power, an effect of sex hormones limited to the progression from in situ to invasive tumors, overrepresentation of indolent tumors or an effect of sex hormones on the induction of only a subset of in situ tumors, those that would develop into invasive tumors.     

Ductal carcinoma in situ (DCIS) of the breast: perspectives on biology and controversies in current management

The incidence of ductal carcinoma in situ (DCIS) has increased because of increasing use of sensitive imaging modalities. MRI is commonly used for the detection of breast cancer but has not yet been validated in randomized trials. There have not been randomized trials addressing optimal margins of excision or axillary sampling. Whole breast radiation after lumpectomy decreases the risk of recurrence but may be omitted in selected patients. Adjuvant Tamoxifen reduces the risk of recurrence but has no impact on overall survival rates.     

超声及钼靶X线对乳腺导管内癌与乳腺浸润性导管癌的诊断价值

目的:探讨乳腺导管内癌（ductal caicinoma in situ,DCIS）与乳腺浸润性导管癌（invasive ductal carcinoma,IDC）的超声及钼靶X线影像特征差异。方法:回顾性分析160例患者（包括62例DCIS患者及98例IDC患者）的超声及钼靶X线资料。结果:161个乳腺病灶中,有62个DCIS病灶（DCIS组）及99个IDC病灶（IDC组）。超声对IDC组病灶的检出率明显高于DCIS组,两组间的检出率有统计学意义（P＜0.05）;两组间病灶超声表现中形状、边界、边缘特征及血流信号差异有统计学意义（P＜0.05）。钼靶X线在两组病灶检出率差异有统计学意义（P＜0.05）;两组间病灶钼靶X线表现形状及边缘特征的例数差异有统计学意义（P＜0.05）。对于DCIS组,超声及钼靶X线病灶的检出率差异有统计学意义（P＜0.05）;在病灶边缘及乳腺腺体内钙化检出率这些方面,两种方法有统计学意义（P＜0.05）。结论:乳腺钼靶X线对DCIS腺体内钙化灶诊断率较高,乳腺超声对DCIS病灶检出、病灶边缘特征显示具有诊断优势。     

Impact of race and ethnicity on features and outcome of ductal carcinoma in situ of the breast

BACKGROUND:

The impact of race and ethnicity on the biologic features and outcome variables of women who are diagnosed with preinvasive breast cancer—ductal carcinoma in situ (DCIS)—has not been addressed widely in the published literature.

METHODS:

Patient demographic, clinical, and pathologic features and outcome variables were analyzed with respect to the patient's initial self‐reported race/ethnicity among women who received treatment for a diagnosis of pure DCIS from 1996 to 2009.

RESULTS:

Of 1902 patients, 1411 were white (74.2%), 214 were African American (11.3%), 175 were Hispanic (9.1%), and 102 were Asian/Pacific Islander (5.4%). The majority of patients were between ages 41 and 70 years (83%). Patients of Hispanic and Asian/Pacific Islander descent were significantly younger than white and African American patients (P < .001). DCIS size and grade, the presence of necrosis, and the frequency of breast‐conserving surgery did not differ significantly between groups. African American patients aged >70 years and Hispanic patients aged <50 years were significantly more likely to have estrogen receptor‐positive DCIS than patients of other races in the same age categories (P < .001). Adjuvant radiotherapy and tamoxifen were received significantly less often by white women (P < .001). At a median follow‐up of 4.8 years (range, 1‐14 years), recurrence rates and the development of contralateral breast cancer did not differ significantly among racial/ethnic groups when stratified by treatments received.

CONCLUSIONS:

There was variation in age at presentation, biologic features, and treatment of DCIS among the different ethnic groups. Additional studies with larger numbers of ethnic minority patients are needed to confirm whether the consistent application of evidence‐based treatment practices presents an opportunity for reducing disparities in patients with DCIS. Cancer 2013. © 2012 American Cancer Society.     

Associations of reproductive time events and intervals with breast cancer risk: A report from the Shanghai Breast Cancer Study

While there is clear evidence for an association between later age at first live birth and increased breast cancer risk, associations with the timing of other reproductive events are less clear. As breast tissues undergo major structural and cellular changes during pregnancy, we examined associations between reproductive time events and intervals with breast cancer risk among parous women from the population‐based Shanghai Breast Cancer Study (SBCS). Unconditional logistic regression was used to evaluate associations with breast cancer risk for 3,269 cases and 3,341 controls. In addition to later age at first live birth, later ages at first pregnancy and last pregnancy were significantly associated with increased breast cancer risk (p‐trend = 0.002, 0.015, 0.008, respectively); longer intervals from menarche to first or last live birth were also associated with increased risk (p‐trend < 0.001, =0.018, respectively). Analyses stratified by menopausal status and estrogen receptor (ER)/progesterone receptor (PR) status revealed that associations for later age at first pregnancy or live birth and longer intervals from menarche to first or last live birth occurred among premenopausal women and ER+/PR+ breast cancers, whereas the association for later age at last pregnancy occurred among postmenopausal women and women with ER+/PR? or ER?/PR+ breast cancers. Because of the high correlation with other reproductive variables, models did not include adjustment for age at first live birth; when included, the significance of all associations was attenuated. These findings suggest that while reproductive time events and intervals play an important role in breast cancer etiology, contributions may differ by menopausal status and hormone receptor status of breast cancers.     

Circulating estrogens and progesterone during primiparous pregnancies and risk of maternal breast cancer

Pregnancy reduces maternal risk of breast cancer in the long term, but the biological determinants of the protection are unknown. Animal experiments suggest that estrogens and progesterone could be involved, but direct human evidence is scant. A case-control study (536 cases and 1,049 controls) was nested within the Finnish Maternity Cohort. Eligible were primiparous women who delivered at term a singleton offspring before age 40. For each case, two individually matched controls by age (± 6 months) and date of sampling (± 3 months) were selected. Estradiol, estrone and progesterone in first-trimester serum were measured by high-performance liquid chromatography tandem mass spectrometry and sex-hormone binding globulin (SHBG) by immunoassay. Odds ratios (OR) and 95% confidence intervals (CI) were estimated through conditional logistic regression. In the whole study population there was no association of breast cancer with any of the studied hormones. In analyses stratified by age at diagnosis, however, estradiol concentrations were positively associated with risk of breast cancer before age 40 (upper quartile OR, 1.81; CI, 1.08-3.06), but inversely associated with risk in women who were diagnosed ≥ age 40 (upper quartile OR, 0.64; CI, 0.40-1.04), p(interaction) 0.004. Risk estimates for estrone mirrored those for estradiol but were less pronounced. Progesterone was not associated with risk of subsequent breast cancer. Our results provide initial evidence that concentrations of estrogens during the early parts of a primiparous pregnancy are associated with maternal risk of breast cancer and suggest that the effect may differ for tumors diagnosed before and after age 40.     

Oral contraceptive use and risk of breast carcinoma in situ (United States)

Objective Our study assesses the impact of oral contraceptive use on breast carcinoma in-situ (BCIS) risk. Methods We conducted a population based case–control study of incident BCIS among black and white women ages 35–64 years residing in Los Angeles County. Case patients (n = 567) were newly diagnosed with BCIS and control participants (n = 614) were identified by random digit dialing between 1 March 1995 and 31 May 1998. All subjects were required to have had a mammogram in the 2 years before case diagnosis or control recruitment. Data were collected during in-person interviews. Multivariable logistic regression analyses provide estimates of odds ratios (ORs) and 95% confidence intervals (95% CIs). Results Oral contraceptive use was not associated with risk of BCIS (OR = 1.04, 95% CI (0.76–1.42)). Risk did not increase with longer periods of use. No associations with BCIS risk were observed for oral contraceptive use before first term pregnancy, age at first oral contraceptive use, or for time since last use. Risk was not modified by estrogen dose, age, race, or parity. Conclusions Our results are consistent with recent results on invasive breast cancer reported for the Women’s Contraceptive and Reproductive Experiences Study and show no association between oral contraceptive use and risk of BCIS.