BACKGROUND & AIMS: PURPOSE:The subareolar and periareolar injection techniques result in higher detection rates and do not require tumor localization in impalpable lesions when compared with the peritumoral technique. One of the main criticisms, however, is the widely reported inability to detect internal mammary nodes. This contrasts with our clinical experience using Tc-99m antimony sulfur colloid, in which internal mammary nodes are commonly seen. METHODS:A retrospective analysis of 241 patients over 38 months was performed to investigate the ability of our periareolar injection technique to detect internal mammary lymph node drainage in breast cancer sentinel node lymphoscintigraphy. Four injections of 5 to 10 MBq (0.14-0.27 mCi) Tc-99m antimony sulfur colloid were administered on the day of surgery followed by massage and imaging. The radioisotope was suspended in 0.1 mL with a 0.5-mL air lock. Each injection was performed over 2 seconds with a 25-gauge needle at a depth of 1.1 to 1.3 cm. Patients whose records could not be retrieved or who underwent an injection technique apart from periareolar or peritumoral were removed from the analysis. RESULTS:One hundred thirty-three patients underwent the periareolar technique, 72 patients underwent the peritumoral technique, and 36 patients were excluded from the analysis. Internal mammary drainage was seen in 24 of 133 (18.0%) patients, of which 12 (9%) were seen only in the internal mammary chain. This is much higher than previous studies quoting 0.0% to 4.3% and is similar to previously reported rates using the peritumoral technique. CONCLUSIONS:Our periareolar injection technique using Tc-99m antimony sulfur colloid is able to detect internal mammary lymph nodes in at least 18.0% of patients.

背景与目标： 目的：乳晕下和乳晕周围注射技术与肿瘤周围技术相比，具有更高的检出率，并且不需要将肿瘤定位在无法触及的病变中。然而，主要的批评之一是被广泛报道的无法检测内部乳腺淋巴结。这与我们使用Tc-99m锑硫胶体的临床经验形成对比，在该实验中，通常会看到内部乳腺淋巴结。
方法：回顾性分析了241例患者，历时38个月，以探讨我们乳晕周围注射技术在乳腺癌前哨淋巴结显像术中检测内部乳腺淋巴结引流的能力。在手术当天进行四次5至10 MBq（0.14-0.27 mCi）Tc-99m锑硫胶体注射，然后进行按摩和成像。将放射性同位素悬浮在0.5 mL气闸中的0.1 mL中。每次注射都是用25号针在1.1至1.3厘米深度下进行2秒钟。无法检索记录或除了乳晕周围或肿瘤周围进行了注射技术的患者均从分析中剔除。
结果：133例患者接受了乳晕治疗，72例患者接受了肿瘤周围治疗，36例患者被排除在分析之外。 133例患者中有24例（18.0％）出现了内部乳腺引流，其中12例（9％）仅见于内部乳腺链。这比以前的研究（引用0.0％至4.3％）要高得多，并且与先前报道的使用肿瘤周围技术的比率相似。
结论：我们使用Tc-99m锑硫胶体的乳晕周围注射技术能够检测至少18.0％的患者的内部乳腺淋巴结。

BACKGROUND & AIMS: :Following surgery, the hormone dependence of breast tumors is exploited for therapy using antagonists such as tamoxifen, although occasional hormone-resistant clones do appear. Another chemotherapeutic strategy uses microtubule inhibitors such as taxanes. Unfortunately, these agents elicit toxicities such as leukocytopenia, diarrhea, alopecia, and peripheral neuropathies and are also associated with the emergence of drug resistance. We have previously described a tubulin-binding, natural compound, noscapine, that was nontoxic and triggered apoptosis in many cancer types albeit at 10 mumol/L or higher concentrations depending on the cell type. We now show that a synthetic analogue of noscapine, 9-bromonoscapine, is approximately 10-fold to 15-fold more potent than noscapine in inhibiting cell proliferation and induces apoptosis following G2-M arrest in hormone-insensitive human breast cancers (MDA-MB-231). Furthermore, a clear loss of mitochondrial membrane potential, release of cytochrome c, activation of the terminal caspase-3, and the cleavage of its substrates such as poly(ADP-ribose) polymerase, suggest an intrinsic apoptotic mechanism. Taken together, these data point to a mitochondrially mediated apoptosis of hormone-insensitive breast cancer cells. Human tumor xenografts in nude mice showed significant tumor volume reduction and a surprising increase in longevity without signs of obvious toxicity. Thus, our data provide compelling evidence that 9-bromonoscapine can be useful for the therapy of hormone-refractory breast cancer.

背景与目标： ：手术后，尽管偶尔出现激素抵抗性克隆，但利用他莫昔芬等拮抗剂开发了乳腺肿瘤的激素依赖性疗法。另一种化学治疗策略是使用微管抑制剂，例如紫杉烷类。不幸的是，这些药物引起毒性，例如白细胞减少，腹泻，脱发和周围神经病，并且还与耐药性的出现有关。先前我们已经描述了微管蛋白结合的天然化合物Noscapine，尽管在10μmol/ L或更高的浓度（取决于细胞类型）下，但在许多类型的癌症中均无毒并引发细胞凋亡。我们现在显示，Noscapine的合成类似物9-bromonoscapine在抑制细胞增殖方面比Noscapine的效力高约10倍至15倍，并在激素不敏感的人类乳腺癌（MDA-MB）中引起G2-M阻滞后诱导凋亡-231）。此外，线粒体膜电位的明显损失，细胞色素c的释放，末端caspase-3的活化以及其底物（如聚（ADP-核糖）聚合酶）的裂解表明了内在的凋亡机制。综上所述，这些数据表明了激素不敏感的乳腺癌细胞由线粒体介导的凋亡。裸鼠中的人类肿瘤异种移植物显示出明显的肿瘤体积减少和寿命的惊人增加，而没有明显的毒性迹象。因此，我们的数据提供了令人信服的证据，表明9-溴莫可可碱可用于治疗激素难治性乳腺癌。

BACKGROUND & AIMS: BACKGROUND:This study aimed at analyzing different treatments of breast cancer (BC) prevalent in the region, their effect on patients' survival, and discusses the most suitable method within available resources. METHODS:The study was set up at a tertiary care hospital in north India. We retrospectively reviewed data of 473 female BC patients who attended the departments of Surgical Oncology and Radiotherapy from January 1997 to December 1999. Patients with cTNM stage IV and inoperable stage III were included; those who defaulted or were lost to follow-up were excluded. Out of 473 patients, 372 were selected. The selected patients were divided into groups on the basis of place and type of local treatment they received: (1) local excision only, (2) standard breast conservation therapy (BCT), (3) total mastectomy (TM) + axillary lymph node dissection + radiotherapy (RT), and (4) modified radical mastectomy (MRM) + RT. Data regarding recurrence and survival were analyzed in December 2005. Minimum follow-up was 6 years. RESULTS:Overall recurrence rates were significantly higher in patients operated elsewhere (P <0.0001). Of 194 operated at our Breast Unit, 25 (14.6%) of 171 MRM patients and none of 23 BCT had recurrence. Of 178 patients operated elsewhere, 44 (100%), 6 (42.9%), 41 (41%), and 8 (40%) developed recurrence in groups 1, 2, 3, and 4 respectively. Overall survival was significantly better in patients with MRM at our unit versus TM outside (93.6% vs. 80%). CONCLUSIONS:Several types of treatment from improper local excision alone, BCT, TM, to a carefully done MRM are prevalent here. Properly done, MRM yields significant local control with survival benefit and appears to remain the gold standard in management of our BC patients.

背景与目标： 背景：本研究旨在分析该地区流行的乳腺癌（BC）的不同治疗方法，它们对患者生存的影响，并在可用资源范围内讨论最合适的方法。
方法：该研究是在印度北部的一家三级保健医院进行的。我们回顾性回顾了1997年1月至1999年12月就诊于外科肿瘤和放射治疗科的473例女性BC患者的数据。那些违约或失去随访的人被排除在外。在473名患者中，选择了372名。根据所接受的局部治疗的位置和类型将选定的患者分为几类：（1）仅局部切除，（2）标准乳房保留疗法（BCT），（3）全乳房切除术（TM）腋窝淋巴结清扫术放射疗法（RT）和（4）改良根治性乳房切除术（MRM）RT。有关复发和生存的数据于2005年12月进行了分析。最低随访时间为6年。
结果：在其他地方手术的患者的总体复发率显着更高（P <0.0001）。在我们的乳房科进行的194例手术中，171例MRM患者中有25例（占14.6％），而23例BCT均未复发。在178例在其他地方手术的患者中，分别在第1、2、3和4组中复发了44例（100％），6例（42.9％），41例（41％）和8例（40％）复发。我们单位的MRM患者的总生存期明显优于室外TM（93.6％vs. 80％）。
结论：从单独的不当局部切除，BCT，TM到精心制作的MRM的几种治疗方法在这里很普遍。正确完成后，MRM可以产生明显的局部控制并具有生存获益，并且似乎仍然是我们BC患者治疗的金标准。

BACKGROUND & AIMS: :Women of African descent have a lower incidence of breast cancer than their white counterparts; however, the overall age-adjusted breast cancer mortality rates are higher. They also present at a younger age, and have more advanced disease that exhibits poor prognostic features including significantly larger tumors of higher grade, higher rates of estrogen receptor and progesterone receptor negativity and a higher rate of p53 mutations and HRAS1 proto-oncogene expression, all of which confer a poor prognosis. While there are many possible contributory factors to the discrepancies in outcome in women of African descent, there is no satisfactory explanation as to why women of African origin tend to present at a younger age with hormone receptor-negative tumors and more adverse prognostic features.

背景与目标： ：非洲裔女性的乳腺癌发病率低于白人女性；但是，按年龄调整的总体乳腺癌死亡率更高。它们也以较年轻的年龄出现，并具有较晚期的疾病，表现出不良的预后特征，包括更高级别的明显更大的肿瘤，更高的雌激素受体和孕激素受体阴性率以及更高的p53突变和HRAS1原癌基因表达率，所有其中预后不良。尽管有许多可能的因素导致非洲人后裔的结果差异，但对于为什么非洲人后裔倾向于在年轻时出现激素受体阴性肿瘤和更不利的预后特征尚无令人满意的解释。

BACKGROUND & AIMS: The sonographic features of 22 patients with histologically benign intraductal papillomas are presented, with clinical, mammographic, galactographic, and histopathologic correlation. The most common presenting feature in this series is a palpable central breast mass in an elderly woman. Sonography was abnormal in all 22 patients. The typical sonographic features include a well-defined, smooth-walled, solid, hypoechoic nodule or a lobulated, smooth-walled, cystic lesion with solid components. Dilated ducts are a common feature, often with visible solid intraluminal echoes. These findings suggest the diagnosis of an intraductal papilloma. The differential diagnosis includes fibroadenoma and phyllodes tumor (for large solid lesions) and intracystic carcinoma (for complex cystic lesions). Mammograms are frequently normal (36% of patients). When abnormal, the mammographic features are of a smooth-walled, well-defined mass or increased retroareolar opacity. Contrary to the reported literature, calcification was seen infrequently. We conclude that ultrasonography is useful in the detection and delineation of intraductal papillomas.

背景与目标： 介绍了22例组织学上良性导管内乳头状瘤患者的超声特征，并与临床，乳房X线照片，乳腺摄影和组织病理学相关。该系列最常见的表现是一名老年妇女的中央乳腺肿块。所有22例患者的超声检查均异常。典型的超声检查特征包括界限分明的，光滑壁的实心低回声结节或具有固体成分的小叶，光滑壁的囊性病变。扩张的导管是常见特征，通常伴有可见的固体腔内回声。这些发现提示导管内乳头状瘤的诊断。鉴别诊断包括纤维腺瘤和叶状肿瘤（对于大的实体病变）和囊内癌（对于复杂的囊性病变）。乳房X线照片通常是正常的（36％的患者）。异常时，乳房X光检查的特征是壁光滑，质量明确或乳晕后不透明性增加。与报道的文献相反，很少见到钙化。我们得出的结论是，超声检查可用于导管内乳头状瘤的检测和勾画。

BACKGROUND & AIMS: BACKGROUND:Neoadjuvant chemotherapy (NAC) is increasingly used in the framework of breast-conserving therapy (BCT). Localization of the initial tumor is essential to guide surgical resection after NAC. This study describes the results obtained with I-125 seed localization in BCT including NAC. PATIENTS AND METHODS:Between January 2009 and December 2010, 85 patients treated with NAC and BCT after I-125 seed localization were included. Radiological and pathological response and resection margins were retrospectively evaluated. RESULTS:BCT was carried out in 85 patients without secondary local excisions. Nineteen patients with unifocal tumors and seven patients with multifocal tumors showed a complete pathological response (P = 0.18). Tumor-free resection margins were obtained in 78 patients (50 patients with unifocal and 28 patients with multifocal tumors, P = 0.27). Focally involved margins were found in four patients (two patients with a unifocal and two patients with a multifocal tumor, P = 0.27). A subsequent mastectomy was carried out in three patients (two patients with multifocal tumors, P = 0.29). CONCLUSIONS:BCT after NAC can be carried out successfully after initial localization with I-125 seeds in both unifocal and multifocal breast tumors with complete resection rates of >90%.

背景与目标： 背景：新辅助化疗（NAC）越来越多地用于保乳治疗（BCT）的框架中。初始肿瘤的定位对于NAC术后的手术切除至关重要。这项研究描述了I-125种子在包括NAC的BCT中的定位所获得的结果。
患者和方法：2009年1月至2010年12月，纳入I-125种子定位后接受NAC和BCT治疗的85例患者。回顾性评估放射学和病理学反应以及切除范围。
结果：85例患者均进行了BCT检查，未进行次要局部切除。 19例单灶性肿瘤患者和7例多灶性肿瘤患者表现出完全的病理反应（P = 0.18）。 78例患者获得了无肿瘤切除切缘（50例单灶患者和28例多灶肿瘤患者，P = 0.27）。在四名患者中发现了局部受累的切缘（两名单灶患者和两名多灶性肿瘤患者，P = 0.27）。随后在三名患者中进行了乳房切除术（两名患有多灶性肿瘤的患者，P = 0.29）。
结论：NAC后的BCT可以在单灶和多灶乳腺肿瘤中首次定位I-125种子后成功进行，完全切除率> 90％。

BACKGROUND & AIMS: PURPOSE:To evaluate outcomes among early-stage breast cancer patients after conservative surgery and full-dose intraoperative radiotherapy electrons (ELIOT) by applying the Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) recommendations for partial breast irradiation (APBI). MATERIALS AND METHODS:One-thousand eight-hundred and twenty-two patients were stratified into the three GEC-ESTRO categories of "good candidates", "possible candidates" and "contraindication" in order to assess outcomes. RESULTS:All the 1822 cases except 7 could be classified according to GEC-ESTRO groups: 573 patients met the criteria to be included in the "good candidates" group, 468 patients in the "possible candidates" group and 767 patients in the "contraindication" group. Median and mean follow-up length was 3.5 years (range 0-10.5 years) and 3.8 years (SD 2.2), respectively. The 5-year rate of in-breast tumor reappearances for "good candidates", "possible candidates" and "contraindication" groups were 1.9%, 7.4% and 7.7%, respectively (p 0.001). While the regional node relapse showed no difference, the rate of distant metastases was significantly different in the "contraindication" group compared to the other two categories, having a significant impact on survival. CONCLUSIONS:Among the ELIOT population, the GEC-ESTRO recommendations enabled the selection of the good candidates with a low rate of local recurrence, but failed to differentiate the "possible candidates" and the "contraindication" groups.

背景与目标： 目的：通过应用欧洲放射治疗和肿瘤学学会（GEC-ESTRO）对部分乳房照射的建议，评估保守手术和全剂量术中放疗电子（ELIOT）后早期乳腺癌患者的结局（APBI）。
材料与方法：将128例患者分为GEC-ESTRO的“好候选人”，“可能候选人”和“禁忌症”三个类别，以评估结果。
结果：除7例外，其余1822例均可以根据GEC-ESTRO组进行分类：573例符合“好候选者”组的标准，468例“可能候选”组的患者，767例“禁忌症”的患者“ 团体。中位和平均随访时间分别为3。5年（0-10。5年）和3。8年（SD 2.2）。 “好候选者”，“可能候选者”和“禁忌症”组的5年乳腺肿瘤复发率分别为1.9％，7.4％和7.7％（p 0.001）。尽管区域淋巴结复发无差异，但“禁忌”组中远处转移的发生率与其他两类相比有显着差异，对生存率有显着影响。
结论：在ELIOT人群中，GEC-ESTRO的建议使得能够选择局部复发率低的良好候选者，但未能区分“可能候选者”和“禁忌症”人群。

BACKGROUND & AIMS: BACKGROUND:Evidence-based guidelines recommend limited perioperative diagnostic imaging for new breast cancer diagnoses. For patients aged >65 years, conventional imaging use (mammography, plain radiographs, and ultrasound) has remained stable, whereas advanced imaging (computed tomography [CT], nuclear medicine scans [positron emission tomography/bone scans], and magnetic resonance imaging [MRI]) use has increased. In this study, the authors evaluated traditional and advanced imaging use among younger patients (aged ≤ 65 years) undergoing breast cancer surgery. METHODS:The MarketScan Commercial Claims and Encounters Research Database from 2005 through 2008 was analyzed to evaluate the use of conventional and advanced diagnostic imaging associated with surgery for ductal carcinoma in situ (DCIS) or stage I through III invasive breast cancer. RESULTS:The study cohort included 52,202 women (13% with DCIS and 87% with stage I-III breast cancer). The proportion of patients undergoing conventional imaging remained stable, whereas the average number of conventional imaging tests per patient increased from 4.21 tests in 2005 to 4.79 tests per patient in 2008 (P < .0001). For advanced imaging, the proportion of women who underwent imaging increased from 48.8% in 2005 to 68.8% in 2008 (P < .0001), as did the number of tests per patient (from 1.53 tests in 2005 to 1.98 tests in 2008; P < .0001). MRI examinations accounted for nearly all of the increase in advanced imaging. Patients who underwent MRI examinations received significantly more traditional imaging tests compared with to those who did not, indicating that these tests are additive and are not replacing traditional imaging. CONCLUSIONS:The current results demonstrate that the use of perioperative breast MRI has increased among women aged <65 years. Further study is indicated to determine whether the benefits of this procedure justify increased use.

背景与目标： 背景：基于证据的指南建议对新的乳腺癌进行有限的围手术期诊断成像。对于65岁以上的患者，传统的影像学检查（乳房X线照片，X线平片和超声检查）保持稳定，而高级影像学（计算机断层扫描[CT]，核医学扫描[正电子发射断层扫描/骨扫描]和磁共振成像[ MRI]）的使用有所增加。在这项研究中，作者评估了接受乳腺癌手术的年轻患者（≤65岁）的传统和高级成像使用情况。
方法：对2005年至2008年的MarketScan商业索赔和遭遇研究数据库进行了分析，以评估与导管原位癌（DCIS）或I至III期浸润性乳腺癌手术相关的常规和高级诊断成像的使用。
结果：该研究队列包括52,202名妇女（13％的DCIS患者和87％的I-III期乳腺癌患者）。接受常规影像学检查的患者比例保持稳定，而每名患者的常规影像学检查的平均次数从2005年的4.21次检查增加到2008年的4.79次检查（P <.0001）。对于高级影像学，接受影像学检查的女性比例从2005年的48.8％增加到2008年的68.8％（P <.0001），每位患者的检查次数也从2005年的1.53次增加到2008年的1.98次； P <.0001）。 MRI检查几乎占了高级影像学增长的全部。与未接受MRI检查的患者相比，接受过MRI检查的患者接受的传统成像检查要多得多，这表明这些检查是相加的，不能替代传统成像。
结论：目前的结果表明，<65岁的女性围手术期乳房MRI的使用有所增加。指示需要进一步研究以确定该程序的益处是否可以证明增加使用的合理性。

BACKGROUND & AIMS: INTRODUCTION:Fatigue after treatment for breast cancer (BC) is common, but poorly understood. We examined the fatigue levels during first year after radiotherapy (RT) according to the extent of RT (local or locoregional), hormonal therapy (HT) and chemotherapy (CT). The impact of comorbidity was also explored. Moreover, we compared fatigue levels in patients with the general population (GenPop) data. MATERIAL AND METHODS:BC patients (n = 250) referred for post-operative RT at St. Olavs Hospital, Trondheim, Norway, were enrolled. Fatigue was measured by the EORTC QLQ-C30-fatigue subscale, ranging from 0 to 100, before RT (baseline), after RT, and at three, six, and 12 months. Clinical and treatment-related factors were recorded at baseline. GenPop data was available from a previous survey (n = 652). Linear mixed models and analysis of covariance were applied. RESULTS:Compliance ranged from 87% to 98%. At baseline, mean value (SD) of fatigue in BC patients was 26.8 (23.4). The level increased during RT (mean change 8.3, 95% CI 5.5-11.1), but declined thereafter and did not differ significantly from pre-treatment levels at subsequent time points. In age-adjusted analyses, locoregional RT accounted for more overall fatigue than local RT (mean difference 6.6, 95% CI 1.2-12.0), but the association was weakened and not statistical significant when adjusting for CT and HT. Similar pattern was seen for CT and HT. The course of fatigue differed significantly by CT (p < 0.001, interaction test). At baseline, fatigue levels were higher in patients with than without CT, but at subsequent time points similar levels were evident, indicating a temporary adverse effect of CT. Comorbidity was significantly associated with increased level of fatigue, independent of other factors (mean difference 8.1, 95% CI 2.2-14.1). BC-patients were not significantly more fatigued than GenPop, except for immediately after ending RT, and then only among those without comorbidity (mean 35.9 vs. 25.8, p < 0.001). CONCLUSION:Comorbidity seems to be a more important determinant for fatigue levels than the cancer treatment.

背景与目标： 简介：乳腺癌（BC）治疗后的疲劳很普遍，但了解甚少。我们根据放疗（局部或局部），激素治疗（HT）和化学疗法（CT）的程度，检查了放疗（RT）后第一年的疲劳水平。还探讨了合并症的影响。此外，我们将一般人群（GenPop）数据的患者的疲劳水平进行了比较。
材料与方法：招募了在挪威特隆赫姆的圣奥拉夫斯医院接受手术后放疗的BC患者（n = 250）。疲劳通过EORTC QLQ-C30疲劳分量表进行测量，范围为0至100，RT前（基线），RT后以及3、6和12个月。在基线记录临床和治疗相关因素。 GenPop数据可从以前的调查中获得（n = 652）。应用线性混合模型和协方差分析。
结果：依从性从87％到98％不等。基线时，BC患者的疲劳平均值（SD）为26.8（23.4）。在放疗期间该水平升高（平均变化8.3，95％CI 5.5-11.1），但此后下降，并且在随后的时间点与治疗前水平无显着差异。在年龄校正的分析中，局部RT比局部RT引起的总体疲劳要多（平均差异6.6，95％CI 1.2-12.0），但是当校正CT和HT时，关联性减弱并且没有统计学意义。 CT和HT观察到相似的模式。 CT的疲劳过程明显不同（p <0.001，相互作用测试）。在基线时，有CT的患者的疲劳水平高于没有CT的患者，但是在随后的时间点，相似的水平也很明显，表明CT的暂时不良反应。与其他因素无关，合并症与疲劳程度增加显着相关（平均差异8.1，95％CI 2.2-14.1）。 BC患者没有比GenPop明显疲劳，除了RT结束后立即缓解，然后才出现在没有合并症的患者中（平均35.9 vs. 25.8，p <0.001）。
结论：合并症似乎是比癌症治疗更为重要的疲劳程度决定因素。

BACKGROUND & AIMS: :Upregulation of lipogenesis is a hallmark of cancer and blocking the lipogenic pathway is known to cause tumor cell death by apoptosis. However, the exact role of lipogenesis in tumor initiation is as yet poorly understood. We examined the expression profile of key lipogenic genes in clinical samples of ductal carcinoma in situ (DCIS) of breast cancer and found that these genes were significantly upregulated in DCIS. We also isolated cancer stem-like cells (CSCs) from DCIS.com cell line using cell surface markers (CS24(-)CD44(+)ESA(+)) and found that this cell population has significantly higher tumor-initiating ability to generate DCIS compared with the non-stem-like population. Furthermore, the CSCs showed significantly higher level of expression of all lipogenic genes than the counterpart population from non-tumorigenic breast cancer cell line, MCF10A. Importantly, ectopic expression of SREBP1, the master regulator of lipogenic genes, in MCF10A significantly enhanced lipogenesis in stem-like cells and promoted cell growth as well as mammosphere formation. Moreover, SREBP1 expression significantly increased the ability of cell survival of CSCs from MCF10AT, another cell line that is capable of generating DCIS, in mouse and in cell culture. These results indicate that upregulation of lipogenesis is a pre-requisite for DCIS formation by endowing the ability of cell survival. We have also shown that resveratrol was capable of blocking the lipogenic gene expression in CSCs and significantly suppressed their ability to generate DCIS in animals, which provides us with a strong rationale to use this agent for chemoprevention against DCIS.

背景与目标： ：脂肪生成的上调是癌症的标志，已知阻断脂肪生成途径会通过凋亡导致肿瘤细胞死亡。然而，尚不清楚脂肪生成在肿瘤起始中的确切作用。我们检查了乳腺导管原位癌（DCIS）临床样品中关键脂肪形成基因的表达谱，发现这些基因在DCIS中显着上调。我们还使用细胞表面标记（CS24（-）CD44（）ESA（））从DCIS.com细胞系中分离了癌干样细胞（CSCs），发现与该细胞相比，该细胞群具有更高的产生DCIS的肿瘤启动能力与非茎状种群。此外，CSCs显示所有脂肪形成基因的表达水平均高于非致瘤性乳腺癌细胞系MCF10A的对应群体。重要的是，MCF10A中脂生成基因的主要调控因子SREBP1的异位表达显着增强了干细胞样脂质的生成，并促进了细胞的生长以及乳球的形成。此外，SREBP1表达显着提高了来自MCF10AT的CSC细胞的存活能力，MCF10AT是另一种能够在小鼠和细胞培养物中产生DCIS的细胞系。这些结果表明，通过赋予细胞存活能力，脂肪生成的上调是DCIS形成的先决条件。我们还表明，白藜芦醇能够阻断CSC中脂肪基因的表达，并显着抑制其在动物体内生成DCIS的能力，这为我们提供了使用该药物化学预防DCIS的强大理由。

BACKGROUND & AIMS: :The imaging of breast cancer has undergone significant progression in recent years. A multimodality approach is often required, with ongoing developments in mammography, ultrasound, magnetic resonance and nuclear medicine all contributing to breast cancer imaging. Here we review the literature to assess how advances in well-established technologies, such as mammography, have brought added benefits both in terms of diagnostic and practical benefits, as well as allowing the application of derived technologies, such as tomosynthesis and contrast-enhanced mammography. We consider how these newer technologies may fit into clinical practice, both in terms of general population screening as well as use as problem solving tools in specific patient groups, and where the limitations for these may lie. We aim to highlight some of the promising advances in imaging that are still in earlier stages, such as magnetic resonance elastography, as well as reviewing techniques that are already becoming incorporated into clinical practice.

背景与目标： ：近年来，乳腺癌的影像学经历了重大进展。通常需要一种多模态方法，随着乳房X线照片，超声，磁共振和核医学的不断发展，所有这些都有助于乳腺癌的成像。在这里，我们回顾文献以评估诸如乳房X线照相术等成熟技术的进步如何在诊断和实际获益方面带来了额外的好处，以及如何允许诸如断层合成和对比增强的X线照相术等衍生技术的应用。我们从总体人群筛查以及在特定患者群体中用作问题解决工具的角度考虑这些更新技术如何适合临床实践，以及这些方法可能存在的局限性。我们的目标是突出显示仍处于早期阶段的一些有希望的成像进展，例如磁共振弹性成像以及已经纳入临床实践的检查技术。

BACKGROUND & AIMS: :Triple-negative breast cancer is characterized by aggressive tumours whose cells lack oestrogen and progesterone receptors and do not over-express HER2. It accounts for approximately 10-15% of breast cancer cases. We sought to generate a cellular model of chemotherapy drug resistance for this type of disease to provide the tools for the development of new therapies. Doxorubicin is a component of some chemotherapy regimes used to treat this form of cancer but resistance preventing disease eradication frequently occurs, mainly due to over-expression of drug transporters such as P-glycoprotein. CALDOX cells were generated by exposure of CAL51 to doxorubicin. Resistance to doxorubicin did not involve drug transporters, as the both parental and resistant cells accumulated doxorubicin to comparable levels. CALDOX cells had slower proliferation rate and an extended G1 cell cycle stage than the parental line, mainly due to an intrinsic activation of CDNK1 (p21), but this cell cycle block was not involved in the mechanism of resistance. CALDOX cells had reduced levels of TOP2A (topoisomerase IIα) and were cross resistant to the topoisomerase II inhibitors etoposide and mitoxantrone. CALDOX cells showed collateral sensitivity to carmustine due to the lack of O⁶-methylguanine-DNA-methyltransferase (MGMT) expression, related to the hypermethylation of its promoter. The collateral sensitivity of CALDOX cells to carmustine provides the rationale to evaluate MGMT promoter methylation status to design better therapeutic strategies for triple negative breast cancer.

背景与目标： 三阴性乳腺癌的特征是侵袭性肿瘤，其细胞缺乏雌激素和孕激素受体，并且不会过度表达HER2。它约占乳腺癌病例的10-15％。我们试图为这种类型的疾病生成化学疗法抗药性的细胞模型，以提供开发新疗法的工具。阿霉素是一些用于治疗这种形式癌症的化学疗法的组成部分，但经常会出现防止根除疾病的抗药性，这主要是由于药物转运蛋白（例如P-糖蛋白）的过度表达所致。通过将CAL51暴露于阿霉素可产生CALDOX细胞。对阿霉素的耐药性不涉及药物转运蛋白，因为亲代细胞和耐药细胞都将阿霉素蓄积到可比较的水平。 CALDOX细胞的增殖速率较亲本系慢，且G1细胞周期延长，这主要归因于CDNK1（p21）的内在激活，但该细胞周期阻滞并不参与耐药机制。 CALDOX细胞的TOP2A（拓扑异构酶IIα）水平降低，并且对拓扑异构酶II抑制剂依托泊苷和米托蒽醌具有交叉耐药性。由于缺乏与启动子的高甲基化有关的O⁶-甲基鸟嘌呤-DNA-甲基转移酶（MGMT）表达，CALDOX细胞对卡莫司汀表现出附带敏感性。 CALDOX细胞对卡莫司汀的附带敏感性为评估MGMT启动子甲基化状态提供了理论依据，从而为三阴性乳腺癌设计更好的治疗策略。

BACKGROUND & AIMS: AIM:To ascertain the negative predictive value (NPV) for atypia and malignancy of 14 G core biopsy of papillomas and to determine whether lesion type influences the likelihood of malignancy at lesion excision. MATERIALS AND METHODS:Ninety-six lesions with a 14 G core biopsy diagnosis of benign papilloma without atypia in 95 women were included. The imaging features (mass or microcalcification), biopsy mode, and number of core samples taken were documented. All patients subsequently underwent lesion excision with either extensive vacuum-assisted biopsy (VAB; 72 lesions) or surgery (24 lesions). Mammographic follow-up of at least 2 years was available for 32 lesions that were benign at VAB. RESULTS:Atypia or malignancy was found more commonly in association with microcalcification (six of 29 lesions: 21%; median number of nine 14 G cores) than a mass (five of 67 lesions: 7%; median number of three 14 G cores), although the difference does not reach statistical significance (p = 0.088). The NPV of a 14 G core biopsy diagnosis of papilloma for atypia or malignancy is 89% (85/96). Disease underestimation may be more common in microcalcification lesions despite the greater number of cores obtained. CONCLUSION:Excision (using VAB or surgically) of all papillomas diagnosed as benign on 14 G needle core biopsy is recommended. Surgery may be more appropriate than VAB for some microcalcification lesions unless they are small and can be confidently removed in their entirety using VAB.

背景与目标： 目的：确定乳头状瘤14 G核心活检的非典型性和恶性的阴性预测值（NPV），并确定病变类型是否影响切除病变的恶性可能性。
材料与方法：纳入95例经非常规检查，无异型的良性乳头瘤14G核心活检的96处病变。记录了影像学特征（质量或微钙化），活检模式和采集的核心样本数量。随后，所有患者均接受了广泛的真空辅助活检（VAB； 72个病灶）或手术（24个病灶）的病灶切除。对于VAB良性的32个病灶，可以进行至少2年的乳房X光检查。
结果：发现非典型性或恶性肿瘤与微钙化（29个病变中的六个：21％; 9个14G核的中位数）比肿块（67个病变中的7％：7％;三个14G核的中位数）更为常见，尽管差异未达到统计显着性（p = 0.088）。乳头状瘤非典型性或恶性的14 G核心活检诊断的NPV为89％（85/96）。尽管获得的核心数量较多，但疾病低估可能在微钙化病变中更为普遍。
结论：建议在14 G针芯活检中切除所有被诊断为良性的乳头状瘤（使用VAB或手术）。对于某些微钙化病变，手术可能比VAB更合适，除非它们很小并且可以使用VAB完全切除。

BACKGROUND & AIMS: :The expression of PD-L1 in breast cancer is associated with estrogen receptor negativity, chemoresistance and epithelial-to-mesenchymal transition (EMT), all of which are common features of a highly tumorigenic subpopulation of cancer cells termed cancer stem cells (CSCs). Hitherto, the expression and intrinsic role of PD-L1 in the dynamics of breast CSCs has not been investigated. To address this issue, we used transcriptomic datasets, proteomics and several in vitro and in vivo assays. Expression profiling of a large breast cancer dataset (530 patients) showed statistically significant correlation (p < 0.0001, r = 0.36) between PD-L1 expression and stemness score of breast cancer. Specific knockdown of PD-L1 using ShRNA revealed its critical role in the expression of the embryonic stem cell transcriptional factors: OCT-4A, Nanog and the stemness factor, BMI1. Conversely, these factors could be induced upon PD-L1 ectopic expression in cells that are normally PD-L1 negative. Global proteomic analysis hinted for the central role of AKT in the biology of PD-L1 expressing cells. Indeed, PD-L1 positive effect on OCT-4A and Nanog was dependent on AKT activation. Most importantly, downregulation of PD-L1 compromised the self-renewal capability of breast CSCs in vitro and in vivo as shown by tumorsphere formation assay and extreme limiting dilution assay, respectively. This study demonstrates a novel role for PD-L1 in sustaining stemness of breast cancer cells and identifies the subpopulation and its associated molecular pathways that would be targeted upon anti-PD-L1 therapy.

背景与目标： ：PD-L1在乳腺癌中的表达与雌激素受体阴性，化学抗药性和上皮间质转化（EMT）有关，所有这些都是癌细胞的高度致瘤性亚群（称为癌症干细胞（CSC））的共同特征。迄今为止，尚未研究PD-L1在乳腺CSCs动力学中的表达和内在作用。为了解决这个问题，我们使用了转录组数据集，蛋白质组学以及几种体外和体内测定方法。大型乳腺癌数据集（530例患者）的表达谱显示，PD-L1表达与乳腺癌干性评分之间具有统计学显着相关性（p <0.0001，r = 0.36）。使用ShRNA对PD-L1的特异性敲除显示出它在胚胎干细胞转录因子：OCT-4A，Nanog和干性因子BMI1的表达中的关键作用。相反，这些因素可在正常为PD-L1阴性的细胞中在PD-L1异位表达时被诱导。全球蛋白质组学分析提示AKT在PD-L1表达细胞生物学中的核心作用。实际上，PD-L1对OCT-4A和Nanog的阳性作用取决于AKT激活。最重要的是，PD-L1的下调分别损害了肿瘤球形成试验和极限稀释试验所表明的乳腺CSCs在体外和体内的自我更新能力。这项研究证明了PD-L1在维持乳腺癌细胞干性方面的新作用，并确定了针对抗PD-L1治疗的亚群及其相关的分子途径。

BACKGROUND & AIMS: :Purpose: The immune microenvironment of breast ductal carcinoma in situ (DCIS) has yet to be fully explored, and the relationship of immune cells to genetic features of DCIS is unknown.Experimental Design: We quantified tumor associated lymphocytes (TIL) and evaluated PD-L1 protein levels by immunohistochemistry in a cohort of pure DCIS (138 and 79 cases, respectively), some of which had copy number (n = 55) and mutation data (n = 20).Results: TILs were identified in the stroma surrounding DCIS (119/138, 86%) and present at a median TIL score of 5% (range, 0%-90%). Most DCIS were negative for tumor cell PD-L1 staining (89%), but 25% of cases were positive for immune cell staining. We observed that, as in invasive breast cancer, TILs and PD-L1 positivity were significantly greater in high-grade (P = 0.002/0.035), ER-negative (P = 0.02/0.02), and ERBB2-amplified tumors (P < 0.001/0.048). Comedo necrosis was significantly positively associated with TILs (P < 0.0001) but not with PD-L1. The TILs score was significantly higher in cases with TP53 mutation (P = 0.03) but not with PIK3CA or GATA3 mutation. In the cases with copy number data, both the fraction of the genome altered and the number of telomeric imbalances were significantly positively correlated with TILs (both P < 0.001). This result strongly contrasted with invasive breast cancer data, where aneuploidy was not correlated to TIL levels.Conclusions: Although a small cohort, our data suggest a preliminary model by which the progression of DCIS to invasive carcinoma may involve an altered relationship of tumor copy number with the immune microenvironment, possibly by the immunoediting of the tumor. Clin Cancer Res; 23(17); 5210-7. ©2017 AACR.

背景与目标： 目的：乳腺导管原位癌（DCIS）的免疫微环境尚未得到充分探索，并且免疫细胞与DCIS遗传特征的关系尚不清楚。实验设计：我们量化了肿瘤相关淋巴细胞（TIL）并评估了PD通过免疫组织化学检测一组纯DCIS（分别为138和79例）中的-L1蛋白水平，其中一些具有拷贝数（n = 55）和突变数据（n = 20）。 DCIS（119/138，86％），平均TIL得分为5％（范围：0％-90％）。大多数DCIS对肿瘤细胞PD-L1染色呈阴性（89％），但25％的病例对免疫细胞染色呈阳性。我们观察到，与浸润性乳腺癌一样，高级别（P = 0.002 / 0.035），ER阴性（P = 0.02 / 0.02）和ERBB2扩增的肿瘤中TIL和PD-L1阳性率显着更高（P < 0.001 / 0.048）。痤疮坏死与TILs呈显着正相关（P <0.0001），而与PD-L1无显着正相关。 TP53突变的患者的TILs评分显着更高（P = 0.03），而PIK3CA或GATA3突变的患者则没有。在具有拷贝数数据的情况下，基因组的比例改变和端粒失衡的数目均与TILs显着正相关（均P <0.001）。该结果与浸润性乳腺癌数据形成鲜明对比，后者的非整倍性与TIL水平无关。结论：尽管队列比较小，但我们的数据提示了初步模型，通过该模型DCIS向浸润性癌进展可能涉及肿瘤拷贝数关系的改变免疫微环境，可能是通过肿瘤的免疫编辑。临床癌症研究； 23（17）; 5210-7。 ©2017 AACR。