Endocrine therapy for hormone treatment-naïve advanced breast cancer

A proportion of patients with hormone receptor-positive locally advanced or metastatic breast cancer will not have received prior endocrine therapy. However, there are limited clinical data specifically in these patients. We conducted a review of randomized phase II and III clinical studies of anastrozole, letrozole, exemestane, palbociclib, and fulvestrant to determine the evidence base supporting use of specific endocrine therapies in this patient population. From our findings, there is a paucity of clinical studies in patients with endocrine therapy-naïve disease; however, it appears that first-line treatment effects are consistent between patients who have and have not received prior endocrine treatment.     

The heterogeneous immune microenvironment in breast cancer is affected by hypoxia-related genes

The immune system constitutes an important first-line defence against malignant transformation. However, cancer mediated immunosuppression inactivates the mechanisms of host immune surveillance. Cancer cells shut down anti-cancer immunity through direct cell–cell interactions with leukocytes and through soluble factors, establishing an immunosuppressive environment for unimpeded cancer growth. The composition of the immunosuppressive microenvironment in breast tumours is not well documented. To address this question, selected immunosuppressive factors were analyzed in tumour specimens from 33 breast cancer patients after surgery. The mRNA expression of selected genes was quantified in fresh tumour samples. Tumour infiltrating leukocytes were characterized by flow cytometry to identify regulatory T cells, myeloid derived suppressor cells, and type 2 macrophages. Statistical analysis revealed several interesting correlations between the studied parameters and clinical features. Overall, a surprisingly high degree of heterogeneity in the composition of the immunosuppressive environment was found across all breast cancer samples which adds to the complexity of this disease. The influence of the hypoxia inducible factors (HIFs) on the immune microenvironment was also addressed. The level of HIFs correlated with hormone receptor status and the expression of several immunosuppressive molecules. Targeting HIFs might not only sensitize breast tumours for radiation and chemotherapies but also interfere with cancer immunosuppression.     

甲状腺乳头状癌雌孕激素受体的检测临床及生物学意义

对１０５例甲状腺良、恶性疾病和２４例正常的甲状腺组织采用了酶联法进行雌孕激素受体的检测。乳头状癌，腺瘤、甲状腺肿以及正常的甲状腺组织的雌、孕激素受体阳性分别为５８．３％和４８．３％；３１．２％和２８．１％；３０．８％和３０．７％；２０．８％和１６．７％。乳头状腺癌的阳性率明显要高于甲状腺良性病变。在乳头状腺癌中，小于４５岁年龄组的雌激素受体的的阳性率明显要高于其它甲状腺病变。在乳头状腺癌中，小于４５岁的年龄组的雌激素受体的阳性率明显高于大于或等于４５岁的年龄组。雌、孕激素受体的阳性率和性别、病理分期，肿块大小，以及颈部淋巴结受累情况无关。二倍体乳头腺癌的雌激素受体阳性率要比异倍体肿瘤受体阳性率要高。     

Cystic tumors of the liver: on the problems of diagnostic criteria

We report on three cases of cystic neoplasms of the liver with mucinous epithelium. Case 1 showed a low-grade cystic neoplasm with ovarian-like stroma (OS). Case 2 showed a low-grade cystic neoplasm without OS, and case 3 showed a high-grade cystic neoplasm without OS. In all three cases, bile duct communication (BDC) was absent. Currently, pancreatic mucinous cystic neoplasm (MCN) and intraductal papillary mucinous neoplasm of the pancreas (IPMN) are clearly distinguishable. However, MCN of the liver and intraductal papillary neoplasm of the bile duct (IPN-B) are not as easily distinguished. According to the latest WHO classification (2010), these conditions are classed as typical MCN of the liver, MCNs of the liver without OS, or IPN-Bs without BDC. The clinicopathological differences between MCN without OS and IPN-B without BDC are controversial. We present three cases describing these presentations and discuss the difficulties related to the diagnostic criteria used to distinguish between MCN of the liver and IPN-B.     

人消化道癌卵巢及子宫颈转移癌细胞生物学行为特征的组化研究

关于消化道癌卵巢及子宫颈转移的途径文献中很有争议。有关卵巢及宫颈转移灶建立的机制报道较少。作者对２３例人消化道癌卵巢及宫颈转移的病例进行了雌激素受体（ｅｓｔｒｏｇｅｎｒｅｃｅｐｔｏｒ，ＥＲ）和粘液组化染色，发现全部癌细胞均有不同程度粘液分泌功能分化，９４．４７％的病例中癌细胞具有较强的ＥＲ活性。本文对消化道肿瘤发生卵巢及宫颈转移的机制作了初步探讨。     

Psa immunoreactivity detected in lncap cell medium,breast tumor cytosol,and female serum

We made an effort to identify a reliable source for obtaining large quantities of both free (PSA) and PSA–ACT complex for the preparation of the calibrator for the PSA assay. Using size exclusion chromatography, we found both free PSA and PSA–ACT complex in the conditioned cell medium of the LNCaP cell line, which was derived from a human metastatic adenocarcinoma of the prostate. An assay specific for PSA–ACT reacted only with the PSA–ACT complex from cells grown in serum-free medium, and not with the complex from the cell medium grown in 10% calf serum. We also found both free PSA and PSA–ACT complex in 15% of cytosols prepared from breast tumor tissues; the cytosol PSA concentrations ranged from 0.1 to 110 ng/ml. No correlation was found between cytosol PSA and concentrations of estrogen receptor, progestin receptor, epidermal growth factor receptor, cathepsin D, or the ectodomain of c-erbB-2 protein. Based on chromatographic characterizations and the slope of their dose-response curves, it appears that both free PSA and PSA–ACT complex found in the cytosols are similar to PSA complex from the cell medium and the serum of prostate cancer patients. Ectopic PSA was also detected in pooled sera from patients with breast, ovarian, pancreatic, and colon carcinoma. The PSA concentrations in these serum pools increased with the level of their dominant tumor marker. In any event, the LNCaP cell medium appears to be a reliable source for obtaining both free and ACT-complexed PSA of human tumor origin for the preparation of PSA assay calibrators.     

Evaluation of NMU-Induced Breast Cancer Treated with Sirolimus and Sunitinib on Breast Cancer Growth

Objective: To analyze the effect of sirolimus and sunitinib in blocking the tumor growth and to evaluate the expressions of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor-2 (HER2/neu) after treated with sirolimus and sunitinib. Methods: Thirty-two female Sprague Dawley rats at age 21-days old were administered intraperitoneally with N-Methyl-N-Nitroso Urea (NMU), dosed at 70mg/kg body weight. The rats were divided into 4 groups; Group 1 (Control, n=8), Group 2 (Sirolimus, n=8), Group 3 (Sunitinib, n=8) and Group 4 (Sirolimus+Sunitinib, n=8), being treated twice when the tumor reached the size of 14.5±0.5 mm and subsequently sacrificed after 5 days. The protein expressions of ER, PgR and HER2/neu of the tumor tissues were evaluated by using immunohistochemistry analysis. Results: Treatment with sirolimus alone lowered expressions of ER and PgR of breast cancer and reduced tumor size. There was no significant difference of ER and PgR expressions between control and sunitinib treated tumor. Sunitinib treated tumors reduce in diameter after the first treatment, however the diameter increases after the second treatment. Histologically, sunitinib treated tumor did not show any aggressive invasive carcinoma of no special type (NST) histological subtypes. In addition, all NMU-induced tumors are HER2/neu-negative scoring. Conclusion: Sirolimus is neither synergistic nor additive with sunitinib for breast cancer treatment.     

Hormonal control of polyamine pools in experimental breast cancerin vivo: Correlation with estrogen and progesterone receptor levels

Summary The present experiments were designed to test whether, in the hormone responsive N-nitrosomethyl-urea (NMU)-induced rat mammary tumor, polyamine levels are under hormonal control and whether they correlate with estrogen (ER) and progesterone (PgR) receptor content. We observed that tumor regression induced by ovariectomy was associated with a decline in putrescine (Pu), spermidine (Sd) and spermine (Sm). Administration of estradiol and perphenazine (to stimulate endogenous prolactin release) to castrated rats restored tumor growth and contents of Pu and Sd to control values in a time dependent fashion while Sm levels were only modestly raised. The hormonal modulation of tumor polyamine levels was particularly obvious when the treatment effects on total pools (i.e. Pu+Sd+Sm) were analyzed. No significant correlation was observed between ER and PgR and polyamines in the tumors of intact rats as well as most of the treated groups. In contrast, a highly significant correlation was observed between ER and PgR levels. We conclude that in this experimental system cellular polyamine levels are hormonally regulated but are not correlated with the ER and PgR content of the tumor.     

乳腺癌ER、PgR及人类表皮生长因子受体2的表达与化疗疗效的关系

目的 探讨乳腺癌雌性激素受体(etrogen receptor,ER)、孕激素受体(pogesterone receptor,PgR)及人类表皮生长因子受体2(human epidermal growth factor receptor-2,HER-2)的表达与化疗疗效的关系.方法 46例女性晚期乳腺癌患者中,ER阴性(-)者(ER阴性组)14例,ER弱阳性(+)者8例、ER阳性(++)者5例、ER强阳性(+++)者5例(ER弱阳性+阳性+强阳性组),ER不详者(ER不详组)14例. PgR阴性(-)者(PgR阴性组) 9例,PgR弱阳性(+)者10例、PgR阳性(++)者9例、PgR强阳性(+++)者4例(PgR弱阳性+阳性+强阳性组),PgR不详者(PgR不详组)14例.HER-2阴性(-)者(HER-2阴性组)8例,HER-2弱阳性者(+)6例、HER-2阳性(++)者9例、HER-2强阳性(+++)者6例(HER-2弱阳性+阳性+强阳性组),HER-2不详者(HER-2不详组)17例.46例患者分别采用泰素联合吡柔比星、多西他赛联合吡柔比星和多西他赛联合顺铂化疗.观察46例患者治疗后临床疗效及不良反应等情况.结果 有43例可评价疗效者中,完全缓解(CR)4例,部分缓解(PR)21例,稳定SD(12)例,进展(PD)6例.ER弱阳性+阳性+强阳性组病例的有效率为55.6%,ER阴性组病例的有效率为41.7%;PgR 弱阳性+阳性+强阳性组病例的有效率为50.0%,PgR阴性组病例的有效率为50.0%;HER-2 弱阳性+阳性+强阳性组病例的有效率为50.0%,HER-2阴性组病例的有效率为42.9%.各弱阳性+阳性+强阳性组有效率与阴性组比较差异均无统计学意义(均P＞0.05).Ⅲ-Ⅳ度的不良反应有:白细胞下降Ⅲ度5例,Ⅳ度3例;脱发Ⅲ度 12例;恶心呕吐Ⅲ度9 例.结论 乳腺癌ER、PgR及HER-2不同表达的化疗疗效无明显差异.