Protein Biomarkers for Breast Cancer Risk Are Specifically Correlated with Local Steroid Hormones in Nipple Aspirate Fluid

The local endocrine environment of the breast may have stronger relations to breast cancer risk than systemic hormones. Nipple aspiration fluid (NAF) provides a window into this milieu. We hypothesized that the correlations between proteins and steroid hormones in NAF are stronger, and specific relationships may reveal links to breast cancer risk. NAF and blood samples were obtained simultaneously from 54 healthy women and from the contralateral unaffected breast of 60 breast cancer patients. The abundance of five proteins, superoxide dismutase (SOD1), C-reactive protein (CRP), chitinase-3-like protein 1 (YKL40), cathepsin D (CatD), and basic fibroblast growth factor (bFGF) in NAF was measured using ELISA. The NAF and serum concentrations of estradiol, estrone, progesterone, androstenedione, testosterone, and dehydroepiandrostrerone (DHEA) were measured using ELISA or RIA. The correlations between proteins and hormones revealed that NAF proteins correlated with each other: SOD1 with CRP (R?=?0.276, P?=?0.033) and CatD (R?=?0.340, P?=?0.0036), and bFGF with CRP (R?=?0.343, P?=?0.0021). NAF proteins displayed significant correlations with NAF steroids, but not with serum steroids: SOD1 with DHEA (R?=?0.333, P?=?0.019), YKL40 with testosterone (R?=?0.389, P?=?0.0012), and bFGF negatively correlated with testosterone (R?=??0.339, P?=?0.015). The regulation of YKL40 and bFGF by testosterone was confirmed in breast cancer cell lines. In summary, NAF proteins were more strongly related to local hormone levels than to systematic hormone levels. Some proteins were specifically correlated with different NAF steroids, suggesting that these steroids may contribute to breast cancer risk through different mechanisms.     

Presence of Epithelial Cells in Nipple Aspirate Fluid is Associated with Subsequent Breast Cancer: a 25-Year Prospective Study

Fluid and epithelial cells obtained from the breasts of non-pregnant, non-lactating women by nipple aspiration, can be used for early diagnosis of breast neoplasms. However, since nipple aspirate fluid (NAF) with cells is obtainable from less than half of women sampled, the question arises: Is this method capable of targeting the women most likely to develop breast cancer? We approached this question with a 25-year prospective study to determine if subjects yielding NAF with or without epithelial cells were more likely to develop breast cancer during the follow-up period than subjects from whom no NAF or epithelial cells were obtained. Logistic regression analysis was used to determine relative risk (RR) with 95% confidence intervals (CI). The follow-up cohort of 972 was representative of the eligible cohort of 1605 for factors related to breast cancer risk and nipple aspiration outcome, and representative of the general population for breast cancer risk. After a mean follow-up period of 25 years, women with epithelial cells in NAF were significantly more likely to develop breast cancer (RR=1.92; CI=1.22-3.01; p相似文献   

Postmenopausal Hormone Therapy is Associated with in Situ Breast Cancer Risk

Background: The relationship between postmenopausal hormone therapy (HT) and invasive breast cancerhas been extensively investigated, but that with breast carcinoma in situ (BCIS) has received relatively littleattention. The aim of our present study was to review and summarize the evidence provided by longitudinalstudies on the association between postmenopausal HT use and BCIS risk. Methods: A comprehensive literaturesearch for articles published up to May 2012 was performed. Prior to performing a meta-analysis, the studies wereevaluated for publication bias and heterogeneity. Relative risk (RR) or odds ratio (OR) values were calculatedusing 14 reports (8 case–control studies and 6 cohort studies), published between 1986 and 2012. Results: Therewas evidence of an association between ever postmenopausal estrogen use and BCIS based on a random-effectsmodel (RR = 1.25, 95% confidence interval (CI) = 1.01, 1.55). However, we found no strong evidence of anassociation between ever postmenopausal estrogen combined with progesterone use and BCIS using a randomeffectsmodel (RR = 1.55, 95% CI = 0.95, 2.51). Furthermore, our analysis showed a strong association between“> 5 years duration” of estrogen or estrogen combined with progesterone use and BCIS. Furthermore, currentuse of any HT is associated with increased risk of BCIS in cohort studies. Additional well-designed large studiesare now required to validate this association in different populations.     

Comparison of Random Periareolar Fine Needle Aspirate versus Ductal Lavage for Risk Assessment and Prevention of Breast Cancer

Random periareolar fine needle aspiration (RPFNA) and ductal lavage (DL) are research techniques developed to (1) assess short-term breast cancer risk in asymptomatic women who are at increased risk for breast cancer and (2) track cytological response to risk reduction strategies. RPFNA and DL provide minimally invasive methods to repeatedly sample epithelial cells and research tools to investigate the biological origins of breast cancer in high-risk women. This review gives an overview of the strengths and limitations of both RPFNA and DL for risk assessment and breast cancer prevention in asymptomatic high-risk women.     

血浆性激素水平和绝经前女性患乳腺癌危险性的关系

目的评价血浆类固醇性激素水平与绝经前女性患乳腺癌危险性的关系。方法采用放射免疫法测定75例绝经前女性乳腺癌病例和78例匹配对照的血浆雌二醇(E₂)、孕酮(P)及睾酮(T)水平,并应用条件Logistic回归分析绝经前女性血浆E2、P、T水平与患乳腺癌危险性的关系。结果(1)病例组血浆E2和T水平均显著高于对照组;病例组血浆P水平低于对照组,但差异无统计学意义。（2）以下四分位数（P₂₅）为非暴露参考,血浆P上四分位数（P₇₅）水平调整OR（95%CI）为0.43（0.20~0.85）,趋势P=0.023;血浆T上四分位数（P₇₅）水平调整OR为3.63（1.82~7.45）,趋势P=0.015;血浆E₂上四分位数（P₇₅）水平调整OR为2.48（1.27~5.14）,但差异无统计学意义,趋势P=0.270。结论血浆T水平与绝经前女性患乳腺癌的危险性呈正相关,血浆P水平与绝经前女性患乳腺癌的危险性呈负相关。     

Failure of High Risk Women to Produce Nipple Aspirate Fluid Does Not Exclude Detection of Cytologic Atypia in Random Periareolar Fine Needle Aspiration Specimens

INTRODUCTION: Evidence of hyperplasia with atypia found both on random periareolar fine needle aspiration (RPFNA) and in nipple aspirate fluid (NAF) fluid are associated with an increased risk for breast cancer. AIM: In this study, we report the correlation of NAF production with cytological assessment of ductal cells obtained by RPFNA. METHODS: 113 women at high risk for development of breast cancer attending the Breast Cancer Prevention Clinic at the University of Kansas Medical Center underwent a single NAF collection attempt and RPFNA. RESULTS: NAF was successfully collected in 51% of women. There was no significant difference in age, 5-year Gail risk assessment, menopausal status, hormone use, family history of breast cancer, history of prior atypical hyperplasia/LCIS or history of contralateral DCIS/invasive breast cancer between women who produced NAF and those that did not. The only significant difference between the two groups was in history of prior lactation (p = 0.018). Twenty-seven of the 113 subjects were found to have hyperplasia with atypia by RPFNA was 31% in women who produced NAF versus 16% in those who did not (p = 0.07). CONCLUSION: Although prevalence of RPFNA atypia was numerically higher in NAF producers than non-producers the difference did not reach statistical significance. Failure to produce NAF does not exclude the presence of hyperplasia with atypia by random periareolar fine needle aspiration.     

女性原发乳腺癌浸润乳头的临床病理前瞻性研究

对131例女性乳腺癌进行前瞻性研究。首次采用乳头横断多层面取材病检方法检出乳头浸润者28例，总阳性率21．4％。其中Ⅰ期乳腺癌乳头阳性率13．6％，Ⅱ期16．7％，Ⅲ期38．7％。观察研究肿瘤期别、肿瘤位置、乳头临床表现等特征与乳头受累的密切关系。肿瘤期别与乳头受累成正比（P＜0．05）。肿瘤位置距乳头越近，乳头受累机率越大（P＜0．01），肿瘤伴于中央区或距乳头5cm以内者，乳头受累已难幸免。不宜行保守性手术。乳头临床表现一旦异常，镜下多已有浸润（P＜0．05）。     

Galactogram Grading System for Identifying Breast Cancer With Nipple Discharge

BackgroundGalactography is a primary recommendation in the management of nipple discharge (ND), which may be caused by benign or malignant lesions. We aimed to establish a galactogram grading system (GGS) and investigate its role in identifying breast cancer with ND.Patients and MethodsA total of 350 patients were included in our study. All patients received preoperative mammographic galactography successfully and underwent surgery at Qilu Hospital of Shandong University between January 2011 and August 2015. We first performed a retrospective study in a consecutive series of 250 patients with ND to establish a GGS. Then the subsequent consecutive series of 100 patients was analyzed to validate the grading system.ResultsOur data showed that the GGS can well assess the risk of a galactogram's being malignant. Galactograms classified into grade I have a lower risk of being malignant, while those classified into grade III have a higher risk of being malignant. Thus, our GGS was useful for distinguishing malignant from benign lesions.ConclusionWe established a scoring system for breast disease with ND. This GGS may be a novel approach for identifying breast cancer with ND.     

Thyroid Hormone in the Clinic and Breast Cancer

There is preclinical and recent epidemiological evidence that thyroid hormone supports breast cancer. These observations raise the issue of whether management of breast cancer in certain settings should include consideration of reducing the possible contribution of thyroid hormone to the advancement of the disease. In a preliminary experience, elimination of the clinical action of endogenous L-thyroxine (T₄) in patients with advanced solid tumors, including breast cancer, has favorably affected the course of the cancer, particularly when coupled with administration of exogenous 3,5,3′-triiodo-L-thyronine (T₃) (euthyroid hypothyroxinemia). We discuss in the current brief review the possible clinical settings in which to consider whether endogenous thyroid hormone—or exogenous thyroid hormone in the patient with hypothyroidism and coincident breast cancer—is significantly contributing to breast cancer outcome.     

Familial Breast Cancer Risk

The most well recognized breast cancer susceptibility genes are BRCA1 and BRCA2. Studies in individuals carrying mutations in these genes have led to clinical care guidelines for screening and prevention. Beyond BRCA1 and BRCA2, mutations in TP53, PTEN, STK11, and CDH1 also significantly increase the risk of breast cancer. Early identification of women at increased risk of breast cancer due to specific genetic susceptibility may lead to enhanced screening and prevention strategies and potentially improved overall survival for this group of patients as has been seen with carriers of BRCA1 and BRCA2 mutations. In addition to high penetrance genes, increasing numbers of genes that confer a moderate risk of breast cancer have been identified such as CHEK2, PALB2, and ATM; however, the clinical application of these genes is much more challenging. This review will discuss both high and moderate penetrance breast cancer susceptibility genes.     

Weight Gain after Hormone Receptor-Positive Breast Cancer

Obesity following breast cancer diagnosis is associated with poor overall survival. Understanding weight trajectories will help inform breast cancer survivors at greater risk of weight gain, and those who would benefit from earlier anti-obesity interventions. We performed a retrospective chart review of women from the Breast Cancer Program Longitudinal Repository (BCPLR) at Johns Hopkins diagnosed with hormone receptor-positive Stage I-III breast cancer from 2010 to 2020. We investigated obesity (measured by body mass index [BMI]) over time, patient and tumor characteristics, as well as treatment and recurrence. We observed a significant ≥5% increase in BMI from diagnosis to most recent follow-up (p = 0.009), particularly among those who were overweight at diagnosis (p = 0.003). Additionally, among those up to 5 years since diagnosis, there was a significant association between experiencing a ≥0.1 kg/m² increase per year since diagnosis and baseline BMI status (p = 0.009). A ≥0.6 kg/m² decrease in BMI was observed for participants with obesity at diagnosis (p = 0.006). Our study highlights (i) the significant burden of obesity in women with a history of breast cancer and (ii) higher risks for increases in BMI and shifts in class of obesity among women who are overweight at diagnosis.     

Steroid Hormone Receptor Positive Breast Cancer Patient-Derived Xenografts

The vast majority of breast cancers are positive for estrogen receptor (ER) and depend on estrogens for growth. These tumors are treated with a variety of ER-targeted endocrine therapies, although eventual resistance remains a major clinical problem. Other steroid hormone receptors such as progesterone receptor (PR) and androgen receptor (AR) are emerging as additional prospective targets in breast cancer. The fundamental mechanism of action of these steroid receptors in gene regulation has been defined mainly by several breast cancer cell lines that were established in the late 1970s. More recently, breast cancer patient-derived xenografts (PDX) have been developed by multiple groups at institutions in several countries. These new models capture the large degree of heterogeneity between patients and within tumors and promise to advance our understanding of steroid hormone receptor positive breast cancer and endocrine resistance. Unfortunately, steroid hormone receptor positive breast cancers are much more difficult than their receptor negative counterparts to establish into sustainable PDX. Herein we discuss the derivation of steroid hormone receptor positive breast cancer PDX, several pitfalls in their genesis, and their utility in preclinical and translational steroid hormone receptor research.     

Estimating Contralateral Breast Cancer Risk

Purpose of review

Accurate estimates of contralateral breast cancer (CBC) risk are necessary around the time a first breast cancer is diagnosed to aid surgical decision-making. This review will discuss the known risk factors for contralateral breast cancer (CBC) and present methods for calculating CBC risk that can be utilized when breast surgeons counsel patients.

Recent findings

In addition to the well-known factors that impact contralateral breast cancer risk, such as BRCA1/BRCA2 mutation carrier status and history of chest wall radiation, other factors that affect CBC risk are being better defined. Recent studies that take into account important covariates in contralateral breast cancer risk, such as BRCA1 and BRCA2 mutation carrier status, family history, and systemic treatment, are further improving estimates of contralateral risk. Recent studies show family history, especially of breast cancer in a young relative or of bilateral breast cancer, hormone receptor status, lobular histology, and breast density are important in accurately estimating contralateral breast cancer risk. The Manchester formula, a pen and paper calculation for contralateral breast cancer risk estimation, and CBCRisk, a recently developed online CBC risk calculator, are two tools now available to clinicians.

Summary

Despite a decreasing incidence of contralateral breast cancer over the last few decades, there has been a steady increase in the number of women undergoing contralateral prophylactic mastectomy (CPM). The reasons for this are multifactorial, but fear of a contralateral breast cancer and a tendency to overestimate the risk of a contralateral breast cancer are two factors. Therefore, a critical element in decision-making for women considering CPM is having an accurate estimate of contralateral breast cancer risk. Models for estimating contralateral breast cancer risk are not widely used, but are available.

     

乳腺癌高危因素

0 引言 乳腺癌已经成为严重威胁女性健康的恶性肿瘤,在西方发达国家发病率较发展中国家高.但随着经济水平不断提高,发展中国家乳腺癌发病率逐年上升,越来越接近欧美等国家.文献报道[1],北京城区1982-2001年间,女性乳腺癌发病率呈逐年上升趋势,平均每年递增4.6%;35～64岁截缩发病率高达95.3/10万.     

Interactions between Body Mass Index and Hormone Therapy and Postmenopausal Breast Cancer Risk (United States)

Objective To assess interactions between use of estrogen plus progestin hormone therapy (EPHT) and body mass index (BMI) in relation to risks of different types of breast cancer, based on histology and hormone receptor status. Methods We conducted a population-based case-control study that compared 975 postmenopausal breast cancer cases to 1,007 controls. Interactions between menopausal hormone therapy (HT) and BMI in relation to risk of different breast cancer types were evaluated using logistic regression. Results Obese (BMI ≥30.0 kg/m²) never users of HT had 1.7–fold to 2.3–fold elevated risks of ductal and ER+/PR+ tumors, respectively, compared to thinner women. BMI was not related to breast cancer risk among current HT users. Current EPHT users for ≥5 years had 2.1 to 9.6-fold elevated risks of lobular and ER+/PR+ tumors compared to never users of HT regardless of BMI. Current EPHT users for ≥5 years with a BMI ≤24.9 kg/m² also had a 2.6-fold elevated risk of ductal carcinoma. However, none of the interactions between BMI and HT use evaluated reached statistical significance. Conclusions While interactions between HT and BMI are well established, they appear to only be present among certain breast cancer types. Since obesity is related to breast cancer risk only among never users of HT, as HT use declines the relative impact of obesity on breast cancer incidence may grow.     

乳腺癌内分泌治疗的地位

在乳腺癌治疗中内分泌治疗是主要方法之一。随着新药的问世，乳腺癌内分泌治疗取得了重要进展，但就整体而言，内分泌治疗的好处主要见于ER和（或）PR阳性肿瘤病人。本文总结了内分泌治疗在乳腺癌治疗中的地位及近几年的新进展。     

The Impact of Breast Density on Breast Cancer Risk and Breast Screening

Whether measured by qualitative assessment of the parenchyma pattern or quantitatively by percent mammographic density, breast density is consistently a strong and independent risk factor for breast cancer (BC). Density is also a relatively common risk factor, and therefore an important contributor to BC risk at a population level. Including density (with other risk factors) in risk prediction models improves predictive accuracy; however, better standardization and/or automation of density measures will make the integration of breast density into risk assessment, and its application in tailored screening and primary prevention, more feasible. High breast density reduces screening sensitivity and is associated with risk of interval BC in screening; it is also associated with cancers that have poorer prognostic features. Non-randomized studies of adjunct ultrasound screening in women with mammography-negative dense breasts have provided evidence on incremental detection of BC with adjunct ultrasound and high false-positives but have not examined impact on clinical end-points, mortality, or balance of potential benefits versus harms.     

Techniques and Outcomes of Nipple Sparing Mastectomy in the Surgical Management of Breast Cancer

Tailored therapy for breast cancer with conservation of uninvolved tissue is becoming increasingly important, especially as the benefits of breast reconstruction are recognized. Preservation of the nipple areolar complex during mastectomy is emerging as a viable option in selected patients. Technical considerations for prevention of adverse outcomes such as nipple necrosis are reviewed, along with implications for reconstructive method and outcomes. Finally, the oncologic efficacy of nipple-sparing mastectomy is discussed in the context of occult nipple disease and local recurrence. Standardization of technique, optimization of aesthetic outcome, and examination of long-term prognosis represent future areas of development.     

乳腺X线实质分型及其发生乳腺癌的危险性

乳腺二级预防已被公认为是降低乳腺癌死亡率的有效途径。乳腺X线摄影是进行乳腺癌普查的主要手段,该方法不但有助于发现无临床体征的早期乳腺癌,而且可以藉其对乳腺实质的不同分型,判断其发生乳腺癌的不同潜在危险性,从而有助于明确须重点予以监视的普查对象,以提高普查效益。