绝经后及年轻女性乳腺癌患者肿瘤分子分型及临床病理特征对比观察

目的探讨绝经后中老年女性和年轻女性乳腺癌患者的肿瘤分子分型及临床病理特点,为乳腺癌的个体化治疗和预后判断提供依据。方法 377例绝经后女性乳腺癌患者(A组)和102例年轻(≤35岁)女性乳腺癌患者(B组),采用免疫组化Envision二步法检测两组肿瘤组织的雌激素受体(ER)、孕激素受体(PR)、人表皮生长因子受体2(HER-2)、肿瘤细胞增殖相关核抗原Ki-67,并进行分子分型,分析两组病理和临床资料。结果两组患者肿瘤组织ER、PR、HER-2、Ki-67蛋白表达相比,P均<0.05。A组Luminal A型142例、Luminal B型160例、HER-2过表达型37例、三阴型38例,B组分别为26、47、12、17例;A组的Luminal A型比例高于B组(P<0.05),B组的HER-2过表达型和三阴型比例均高于A组(P均<0.05);两组乳腺癌分子亚型分布相比,P>0.05。两组患者的肿瘤病理类型、组织学分级、肿瘤大小、淋巴结转移、临床分期相比,P均<0.05。结论绝经后和年轻女性乳腺癌患者的肿瘤分子亚型相似,各有不同的临床病理特征,临床上应据此制定个体化治疗方案及进行预后风险的评估。

三阴性乳腺癌临床病理学特征分析

目的通过回顾性分析三阴性乳腺癌(TNBC)与非三阴性乳腺癌(Non-TNBC)的临床病理学特征的差异,揭示TNBC的生物学特性。方法收集浙江省肿瘤医院乳腺癌病例543例,比较TNBC与Non-TNBC在发病年龄、月经状况、家族史、身高、体质量、肿瘤大小、淋巴结状态、病理分期及病理类型等的差异。结果 TBNC发病年龄为(49±10)岁,Non-TNBC发病年龄为(47±9)岁。TNBC组与Non-TNBC组发病年龄、月经状况、家族史、BMI、病理类型差异无统计学意义(>0.05),肿瘤大小、淋巴结状态及病理分期差异有统计学意义(<0.05)。结论相对于Non-TNBC,TNBC具有肿块更大、淋巴结转移更多、分期更晚等特点,根据其临床病理学特性,规范化、个体化治疗每个TNBC病例,以降低TNBC的复发率、转移率,提高TNBC的3年无进展生存率和总生存率是临床治疗需要关注的重点。

Expression of HIF-1α in breast cancer and precancerous lesions and the relationship to clinicopathological features

Objective： The aim of this study was to observe the expressions and clinical significance of HIF-1a in breast cancer and precancerous lesions, and analyze the relationship between the expressions and clinicopathological features in breast cancer. Methods： We analyzed the HIF-1a expression in 128 cases of invasive ductal carcinomas, 146 precancerous lesions patients including 89 cases of ductal carcinoma in situ and 57 cases of atypical ductal hyperplasia. 53 cases of usual ductal hyperplasia breast tissues were selected as a control group. The specimens were evaluated for HIF-1a, estrogen receptor （ER） ＆ progesterone receptor （PR）, epidermal growth factor receptor type 2 （HER2/neu） and Ki-67. Immunoreactivity was semi-quantitatively evaluated in at least 1000 cells examined under the microscope at 40 x magnification and recorded as the percentage of positive tumor cells over the total number of cells examined in the same area. The percentage scores were subsequently categorized. The express of HIF-1a and their relationship with multiple biological parameters including ER ＆ PR, HER2/neu and Ki-67, the biomarkers levels of CA153, CA125 TSGF, and CEA in blood serum and nipple discharge, histological grade, region lymph node metastasis, distant metastasis and recurrence on files were also assessed. Results： Compared with usual ductal hyperplasia, the positive expression rate of HIF-1a in atypical ductal hyperplasia, ductal carcinoma in situ and invasive ductal carcinomas group was significantly increased （P 〈 0.01）. The positive rates of HIF-1a in invasive ductal carcinomas were 68.75%, which were significantly higher than that in ductal carcinoma in situ （43.8%）, atypical ductal hyperplasia （31.6%）, usual ductal hyperplasia （9.4%; X2 = 13.44, 22.27, 52.79, respectively, P 〈 0.01）. Statistical analysis showed that difference of abnormal expression rate of HIF-1a between ductal carcinoma in situ and usual ductal hyperplasia （X2 = 18.37, P = 0.00）, atypical ductal hyperplasia and usual ductal hyperplasia （x2 = 8.14, P = 0.00） was significant （P = 0.00）. However, no significant difference in the positive expression rate of HIF-1a was found between atypical ductal hyperplasia and ductal carcinoma in situ tissue （X2 = 2.19, P = 0.14）. There was a significantly difference in the mean HIF-1a frequency between ER ＆ PR positive invasive ductal carcinomas group and negative group, epidermal growth factor receptor type 2 （HER2/neu） positive and negative groups, Ki-67 proliferation index 〈 14% and 〉 14% groups, histological grade （I ＋ II） and grade III invasive ductal carcinomas groups, with lymph node metastasis, distant metastasis and recurrence groups （P 〈 0.05） and without groups （P 〈 0.05）. However, there was not difference in the mean HIF-1a between age （〈 50 years vs 〉 50 years）, tumor diameter （〈 2 cm vs 〉 2 cm; P 〉 0.05）. The nipple discharge and serum levels of CA153, TSGF, CA125 and CEA in invasive ductal carcinomas HIF-1a positive patients were significantly higher than those in the negative patients （P 〈 0.05）. Conclusion： In breast cancer, HIF-1a expressibn was abnormally increased. The aberration of HIF-1a may play a key role during oncogenesis （atypical ductal hyperplasia or ductal carcinoma in situ） and promote breast cellular transformation into malignancy, a finding useful for further understanding of tumorigenesis. The abnormal expression of HIF-1a may be as an early event in the development of breast tumor. The over-expression of HIF-1a might be important biological markers for invasion, metastasis and recurrence of breast cancer.

The 10-Year Local Recurrence and Partial Breast Radiotherapy for Early Breast Cancer Treated by Conservative Surgery

To study the local recurrence and the role of whole breast radiotherapy for early breast cancer treated by conservative surgery. METHODS From April 1990 to December 2000, 49 patients with early primary breast cancer were treated by conservative surgery in our hospital. The cases were comprised of Stage 0, 1; Stage Ⅰ, 31; and Stage Ⅱa, 17. Forty cases underwent quadrantectomy plus axillary lymph node dissection, and the other 9 cases had lumpectomy alone. Irradiation, which was received by 39 patients, was administered by using low tangential half fields with 6 MV X-ray to decrease the pulmonary irradiative volume. The dose to the whole breast was 45 Gy/22 ～23f/4.5W, then a 15 Gy boost dose was delivered to the tumor bed by an electron beam. The other patients underwent an irradiated regional field according to postoperative pathology. RESULTS All patients were followed-up for 10 years or more. The 10- year local recurrence rates, distant metastasis rates and survival rates were 6.1%, 4.1% and 98.0% respectively. All of the 3 patients who had a local recurrence had infiltrative carcinomas and negative lymph nodes. The 10-year local recurrence rate was higher （2.6% vs. 20.0%） with nonpostoperative whole breast radootherapy, but the statistical difference was not marked because of the low number of cases. All of the recurrent lesions localized within 3 cm of the primary lesion. CONCLUSION Original recurrence of the tumor was the main type of local recurrence. Radiotherapy after conservative surgery is very essential. After conservative surgery it is feasible that irradiation can be delivered alone to the neighboring region of the tumor bed. Partial breast radiotherapy can substitute for whole breast radiotherapy.

Expression and clinical significance of E-cadherin, β-catenin and E-cadherin-catenins complex in breast cancer and precancerous lesions

Objective： The aim of our study was to observe the expressions and clinical Significance of E-cadherin, β-catenin and E-cadherin-catenins complex in breast cancer and precancerous lesions, and analyze the relationship between the expressions and clinicopathological features in breast cancer. Methods： Immunhistochemical UltraSensitiveTM S-P method was employed to detect the expression of E-cadherin, β-catenin and E-cadherin-catenins complex in 128 cases of invasive ductal carcinomas, 89 cases of ductal carcinoma in situ and 57 cases of atypical ductal hyperplasia, 53 cases of usual ductal hyperplasia breast tissues were selected as a control group. The express of E-cadherin, β-catenin and their relationship with mult biological parameters including histological grade, region lymph node metastasis, distant metastasis and recurrence on files were also assessed. Results： （1） The staining patterns character of E-cadherin, β-catenin and E-cadherin-catenins complex： In UDH breast tissues, E-cadherin and a-catenin were expressed on cell membrane of ductal and acinic cells, showing cellular contour and border among cells. The abnormal expression of the three proteins occurred in breast invasive ductal carcinomas, ductal carcinoma in situ and atypical ductal hyperplasia tissues, showing cytoplasmic or nuclear staining, decrease and loss of cytomembrane staining. （2） The abnormal expression rates of E-cadherin, β-catenin and E-cadherin-catenins complex in invasive ductal carcinomas were 53.91%, 65.63% and 81.25%, which were significantly higher than that in ductal carcinoma in situ, atypical ductal hyperplasia, usual ductal hyperplasia tissues （P 〈 0.01）. Compared with usual ductal hyperplasia breast tissues group, the abnormal expression rates of E-cadherin, β-catenin and E-cadherin-catenins complex were significantly decreased （P 〈 0.01） in the breast cancer group. However, there was no significance of the abnormal expression rate between ductal carcinoma in situ and atypical ductal hyperplasia tissues groups （X2 = 0.76, P = 0.38; x2 = 0.14, P = 0.70; x2 = 0.81, P = 0.37; X2 = 2.19, P = 0.14） （P 〉 0.05）. （3） There was a significantly difference in the mean E-cadherin, β-catenin and E- cadherin-catenins complex frequency between estrogen receptor ＆ progesterone receptor positive IDC group and negative group, epidermal growth factor receptor type 2 （HER2/neu） positive and negative groups, Ki-67 proliferation index 〈 14% and 〉 14% groups, histological grade （I ＋ II） and grade III invasive ductal carcinomas groups, with lymph node metastasis, distant metastasis and recurrence groups （P 〈 0.05） and without groups （P 〈 0.05）. However, there was no difference in the mean E-cadherin, β-catenin and E-cadherin-catenins complex frequency between age （_〈 50 years vs 〉 50 years）, tumor diameter （〈 2 cm vs 〉 2 cm） （P 〉 0.05）. Conclusion： In breast cancer, the expressions of E-cadherin, β-catenin and E-cadherin-catenins complex are abnormally decreased and are correlated with pathology grade, differentiation disturbance and metastasis. E- cadherin and β-catenin may be as the predictors for prognosis. Combined detection may improve accuracy and sensitivity of predicting metastasis and prognosis of breast Cancer.

Clinicopathologic features and related prognosis factors analysis of the basal and non-basal phenotype of triple negative breast cancer

Objective:Triple-negative breast cancer(estrogen receptor-negative,progesterone receptor-negative and Her2-negative) can be classified into two subtypes:basal and non-basal phenotype.And the basal phenotype is associated with poor outcome.The purpose of this study was to figure out the differences of clinicopathological characters and related factors of prognosis between these two subtypes.Methods:Immunohistochemical staining was performed for the CK5/6,CK17 basal markers and EGFR on biopsy samples from 40 triple-negative patients and the clinicopathology features of these samples were investigated.Results:Seventy percent of the patients were diagnosed as the basal phenotype.Compared with the non-basal phenotype,the basal phenotype lesions were significantly larger in diameter with a high nuclear grade.In the node-negative group the basal phenotype clearly showed the same clinicopathological differences.There was statistically significant concordance among all three antibodies.Conclusion:Expression of basal markers identifies a biologically and clinically distinct subgroup of TN tumors,justifying the use of basal markers to define the basal or the non-basal phenotype.It is important to help the doctor deciding the therapeutic strategy for patient with triple-negative breast cancer.

Effect of chemotherapy before or after termination in pregnancy-associated breast cancer patients: two cases report

Pregnancy-associated breast cancer （PABC） is defined as breast cancer occurring anytime during gestation, lactation, or within 1 year after delivery. The incidence is between 1 in 3000 and 1 in 10,000 pregnancies and comprises about 0.2% to 3.8% of all breast cancers diagnosed in women under the age of 50 years. As women tend to delay childbearing into their third and fourth decades, the incidence of PABC is expected to increase. Here we reported two PABC patients with similar clinic and pathologic characters received chemotherapy before or after termination of pregnancy respectively, and found that the former got pathologic complete response. Based on the phenomena and the fact that endocrine hormones may have chemosensiUzation role in cancer chemotherapy, which is called hormonosensitizing chemotherapy （HSCT）, endocrinosensitizing chemotherapy （ESCT） or neoendocrinochemotherapy （NECT）, suggestion is proposed that chemotherapy should be taken before or immediately after termination for PABC, especially for the patients who prefer to artificial abortion, which may possibly acquire improved chemotherapeutic effect.