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.     

乳腺干细胞和乳腺癌

乳腺干细胞是一种未分化的细胞，具有永远增殖和自我更新能力。乳腺癌中的癌症干细胞可能起源于正常干细胞，以细胞表面标志CD44^＋/CD24^-/low识别。癌症干细胞可能为肿瘤转移和复发的原因。识别乳腺癌干细胞和普通癌症细胞之间的差异，可以发展更有效的诊断和治疗方法。     

乳腺癌保留乳房治疗10a疗效分析

目的:研究评价保乳治疗的效果,分析1985年—1995年111例在该院行保乳治疗患者的远期疗效。方法:111例临床Ⅰ期、Ⅱ期患者行保乳手术,术后行全乳放疗,局部缩野照射。用SAS软件分析患者年龄,肿瘤大小,组织学类型,切缘,淋巴结转移,术后放疗与复发的关系,分析切除组织量与复发率和美容效果的关系。结果:中位随访10 a,10 a复发率10 % ,转移率27 %,生存率81 %。年龄、组织学类型、淋巴结转移与复发无显著性关系(P >0.05)。肿瘤大小,切缘情况与复发有关(P <0.01)。术后未行放疗的复发率高,达75 %。60Co放疗复发率高于加速器(11 % vs 5 %)。单纯局部复发与转移无明显相关性(P >0.05)。行象限切除复发率不低于肿瘤扩大切除(P >0.05),但明显影响美容效果。结论:保乳治疗适合不同年龄、不同组织学类型的早期乳腺癌,在保证切缘阴性的前提下,扩大切除范围不提高疗效反而会影响美容效果。放疗技术的提高有助于减少复发。     

Management of Rare Breast Tumors and Male Breast Cancer

Purpose of Review

There is very little clinical trial data available to guide the management of uncommon breast cancers. This review draws on classic and recent retrospective data to synthesize a clearer understanding of the biology and behavior of these rare tumors.

Recent Findings

Avoid disfiguring surgery in the pursuit of very wide margins for benign phyllodes tumors unless there are adverse histological features. Encapsulated papillary carcinoma is very good prognosis breast cancer; do not over treat. Metaplastic carcinoma is a basal type breast cancer that may be more responsive to “BRCA1-like” treatments. Complete excision of the capsule is curative for most implant-associated anaplastic large cell lymphomas. Aromatase inhibitors are still controversial for male breast cancer; tamoxifen is standard.

Summary

Available data are useful for guiding the treatment of rare breast cancers, but it must be recognized that there is still a great deal to be learned about each of these entities.

     

Breast Ductal Lavage for Assessment of Breast Cancer Biomarkers

Lavage of the ductal systems of the breast provides fluid (DLF) containing hormones and products of hormone actions that may represent more accurately the composition of the breast than samples collected from blood or urine. The present study was undertaken to assess the presence of potential cancer biomarkers, their variation among individuals at high risk for breast cancer, and differences associated with menopause and tamoxifen treatment. Seventy seven tamoxifen-eligible subjects with a 5-year breast cancer risk estimate (Gail > 1.6%)(N = 53) or recently diagnosed breast cancer (N = 24) were offered tamoxifen therapy; those not accepting tamoxifen were under observation only. After six months, all subjects underwent ductal lavage (DL) in an unaffected breast. Estradiol (E2), estrone sulfate, androstenedione, dehydroepiandrosterone (DHEA), DHEA sulfate, progesterone, cathepsin D and epidermal growth factor (EGF) were measured in DLF by immunoassays. Data were expressed as the mass of analyte per mg of protein in DLF and normalized by natural log transformation. With the exception of DHEA, none of the analytes measured were significantly lower in postmenopausal women than in premenopausal women. The mean log(e) concentration difference in estradiol was 10.9%. Tamoxifen treatment for 6 months did not result in a significantly greater concentration of E2 or in any of the other analytes in DLF of pre- or postmenopausal women. The between-duct variance of the concentration of free steroids within the same breast averaged 51% less than that between subjects, and was similar to that of non-diffusible proteins. The maintenance of estradiol concentrations in the breast after menopause demonstrates the importance of local biosynthesis. The fact that DLF E2 does not reflect the high serum concentrations of E2 during tamoxifen treatment indicates that breast concentrations of estradiol may be under feedback control. Unlike studies of low risk populations, progesterone concentrations were not significantly less in postmenopausal than in premenopausal women. The similarity in variance of free steroids and protein analytes between ducts of a breast indicates little transfer of steroids between lobules.     

乳腺癌保乳治疗的临床研究体会

回顾乳腺癌保乳治疗的演变，结合206例实践及学习体会，从病例选择，手术要点，放疗及其它辅助治疗，前哨淋巴结活检，保乳美容评估等方面，探讨保乳综合治疗模式。     

血管生成在乳腺非典型增生及癌变过程中的作用

为探讨乳腺非典型增生至癌变过程中血管生成的作用及其规律以及血管生成与非典型增生程度及癌变的关系，本研究应用免疫组化法，以ＦⅧ为标志物对８６例良、恶性乳腺病变组织中的血管内皮细胞进行组化染色。分别以微机图像分析系统和人工计数对微血管内皮细胞面积（ＭＥＡ）和微血管密度（ＭＶＤ）进行定量分析。结果发现，中重度非典型增生及癌变组织中的血管生成量ＭＥＡ和ＭＶＤ均明显高于正常乳腺、单纯上皮增生和轻度非典型增生（Ｐ＜０．０５）。结论：乳腺非典型增生过程中已有血管生成并随非典型增生程度的增加而增多；乳腺增生组织中的血管生成可反映乳腺癌前病变的恶性倾向     

A Review of Breast Density Implications and Breast Cancer Screening

Breast density is an independent risk factor for breast cancer and significantly decreases the sensitivity of mammography. Assessing a woman’s risk of developing breast cancer is becoming increasingly important for establishing individual screening recommendations and preventive strategies. This article reviews the factors influencing mammographic density (MD), the available methods of MD assessment, and its effect on breast cancer. Finally, we discuss the supplemental screening methods for women with dense breast tissue.     

Diagnostic Performance of Breast MRI in the Evaluation of Contralateral Breast in Patients with Diagnosed Breast Cancer

Aims: The purpose of our study was to evaluate the diagnostic performance of breast magnetic resonance imaging (MRI) in the evaluation of contralateral breast  in patients with diagnosed breast cancer. A secondary objective was to determine accuracy of breast MRI in diagnosing multi-focal and multicentric lesions in the ipsilateral breast. Materials and Methods: Using a non-probability convenience sampling technique, patients with histopathologically diagnosed breast cancer with MRI of breast performed to exclude additional lesions were included. MRI findings were correlated with histopathology. In addition, follow-up imaging with mammography and ultrasound was also assessed for establishing stability of negative findings and for the detected of benign lesions. Results: Out of 157 MRI breast conducted during the period of 2008 to 2013, 49 were performed for patients with diagnosed breast cancer. The sample comprised of all females with mean age 50.7±11.0 years. The patient follow-up imaging was available for a period of 2-5 years. The sensitivity, specificity, and positive and negative predictive values of MRI in the detection of multifocal/multicenteric lesions was 85.7%, 88.8%, 60% and 96.6% respectively and for the detection of lesions in the contralateral breast were 100%, 97%, 83.3% and 100% respectively. Conclusions: Our study highlights the diagnostic performance and the added value of MRI in the detection of multifocal /multicenteric and contralateral malignant lesions. In patients with diagnosed breast cancer having dense breast parenchyma and with infiltrating lobular carcinoma as the index lesion MRI is particularly useful with excellent negative predictive value in the exclusion of additional malignant foci in the ipsilateral and contralateral breasts.     

Breast cancer

In Japan, the incidence rate of breast cancer is increasing every year so as to become the most common cancer among Japanese women. One of every 16 women is anticipated to eventually suffer from breast cancer. However, unlike the incidence rate, the mortality rate of breast cancer is low, and the 5-year survival rate is about 80%. Mammography screening has been shown to be effective, but the screening rate is still low(20-30%), compared to screening rates for other organs. To increase the screening rate, the Japanese government has introduced free breast cancer screening. To make the system for breast cancer screening more efficient, we should determine the risk factors for Japanese women, and conduct such screening at public expense.     

Breast cancer

As most of the clinical evidence that has a significant impact on the care of breast cancer is based on studies conducted in Western countries, it is important to understand the differences in the natural history of the disease as well as in the patterns of care before applying that evidence to daily practice in Japan. For example, the EORTC 22881 study demonstrated significant improvement of local control after breast conserving therapy with the additional use of 16 Gy of boost irradiation to the tumor bed after 50 Gy of whole breast irradiation for margin negative patients. However, the extent of the surgery in this study was smaller than that common in Japan, and the criteria for a negative margin was less strict than that in Japan. Therefore, it may be over-treatment to give boost irradiation routinely to margin negative patients in Japan. On the other hand, as it is a universal observation that patients under the age of 40 have greater risk of local recurrence, the result of EORTC 22881 study that the benefit of boost irradiation was greatest in patients younger than age of 40 encourages us to confirm this finding in our own clinical settings. It is desirable to develop clinical evidence of high quality in Japan that are directly applicable to Japanese patients.     

Breast cancer

Several interesting aspects of breast cancer were covered at this year's American Society of Clinical Oncology meeting. Sentinel lymph node (SN) mapping is now in widespread use, in concert with the general trend toward trying to decrease the morbidity of breast cancer surgery. With every advance, however, comes new challenges, and there was a timely presentation from Giuliano's group addressing the controversial issue of how to interpret the presence of cells in the SN seen only with keratin stains but not by routine hematoxylin and eosin stains. Two abstracts addressed the issue of whether for certain women with invasive breast cancer radiation therapy could be omitted after lumpectomy. Another interesting topic related to hormonal issues in the adjuvant treatment of premenopausal women. An analysis from the ZIPP-TRIAL reported on bone marrow density studies in young women given two years of ovarian suppression in the adjuvant setting: it seems that the loss of bone density may be reversible and, more interestingly, may be prevented with concurrent tamoxifen. Two other presentations looked at the prognostic significance of drug-induced amenorrhea in young women treated with adjuvant chemotherapy and at the efficacy of ovarian suppression during chemotherapy in preserving fertility. In an unpublicized presentation, Mary-Claire King presented very interesting results from the National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial suggesting that tamoxifen may be an effective chemopreventive drug for women with BRCA2, but not BRCA1, mutations. Two important presentations re-analyzed the outcome of the pivotal trials using Herceptin to treat metastatic breast cancer and nicely show that FISH analysis of HER-2 overexpression is a more accurate indicator of response to Herceptin than immunohistochemical staining. Finally, there were two interesting presentations related to tamoxifen resistance which may be relevant clinically, pertaining to subsequent raloxifene use and the interaction of the estrogen receptor and EGF receptor pathways, respectively.     

乳腺癌相关成纤维细胞对乳腺癌细胞的作用

目的研究乳腺癌相关成纤维细胞（CAFs）对乳腺癌细胞株增殖和乳腺癌干细胞比例的影响。方法分离和鉴定人乳腺癌相关成纤维细胞和非肿瘤成纤维细胞（NAFs）,用无血清培养液培养CAFs和NAFs,收集上清液,分别与乳腺癌细胞株MCF-7和MDA-MB-468共培养48h,通过细胞计数以及流式细胞术,检测其对乳腺癌细胞增殖和细胞周期的影响;并利用流式细胞术,检测乳腺癌干细胞（CD44+CD24-）的细胞比例。结果NAFs和CAFs中表达α-平滑肌肌动蛋白（α-SMA）的细胞比例分别为（6.00±0.57）% 、（53.33±2.33）%(P<0.001);培养NAFs和CAFs的上清液对乳腺癌细胞株的增殖和细胞周期没有明显的影响,上清液处理48h后,MCF-7细胞对照组、NAFs组和CAFs组的G2/M期细胞比例分别为（5.32±0.02）%、（5.63±0.03）%、（6.03±0.03）%(P>0.05);CAFs和NAFs均能诱导乳腺癌干细胞的产生,CAFs组和NAFs组的MCF-7干细胞比例分别为对照组的3.51和1.41倍(P<0.05);MDA-MB-468干细胞比例分别为对照组的4.76和1.35倍(P<0.05)。结论乳腺CAFs高表达α-SMA,培养CAFs的上清液在体外对乳腺癌细胞的增殖没有明显影响,但能诱导乳腺癌干细胞的产生,提示其可能在肿瘤复发和转移中起重要作用。     

243例早期乳腺癌保乳治疗的效果分析

目的：分析总结早期乳腺癌保留乳房综合治疗的效果，观察5年无瘤生存率、总生存率和美容效果。方法：选择符合保留乳房标准的早期乳腺癌患者243例，实施保留乳房的局部广泛肿瘤切除手术及腋窝Ⅰ、Ⅱ水平淋巴结清扫或腋窝前哨淋巴结活检，对术中病理报告标本切缘阳性者实施再切除检验，保证切缘阴性后乳腺切除残腔放置银夹标记切除范围和深度。根据术后病理报告确定个体化的综合治疗。根据临床分期需要化疗患者常规行术后辅助全身化疗6个周期；常规放射治疗于术后或化疗2～3个周期后开始，患侧乳房放射剂量50Gy，瘤床部位根据肿瘤大小、所在部位和肿瘤标本切缘状况电子线补充照射10～20Gy。腋窝淋巴结有转移者预防性照射患侧锁骨上淋巴区域50Gy。放疗结束后继续化疗，化疗结束后开始三苯氧胺内分泌治疗5年。定期随访患者局部和全身情况。生命表法计算5年无瘤生存率和总生存率；按Harris标准评估美容效果；按RTOG标准评估急性和晚期放射性损伤。结果：243例早期乳腺癌符合保留乳房治疗标准，实施了保乳治疗并且能够接受定期随访，随访中位时间56个月（12～84个月）。7例患者出现局部区域复发；2例患者非肿瘤猝死。5年无瘤生存率93%，5年总生存率98%。美容效果及患者满意度均超过94%。所有患者均未出现严重的急性和晚期放射性损伤。结论：符合保乳治疗标准的早期乳腺癌施行保留乳房的综合治疗是可行的，绝大多数患者可以获得满意的美容效果，提高了早期乳腺癌患者的生存质量。