Does local recurrence affect the rate of distant metastases and survival in patients with early-stage breast carcinoma treated with breast-conserving therapy?

BACKGROUND: The purpose of the current analysis was to evaluate the impact of local recurrence (LR) on the development of distant metastases (DM), overall survival (OS), and cause specific survival (CSS) in patients with early-stage breast carcinoma who underwent conservative surgery (CS) and received postoperative radiotherapy (RT). METHODS: Between 1980 and 1995, 1169 patients underwent CS and received RT. All patients were followed for > 1 year and had < or = 4 lymph nodes involved with disease. The median duration of follow-up was 7.7 years. A Cox proportional hazards model was performed to evaluate the effect of LR on the development of DM and CSS. A matched-pair analysis that controlled for multiple prognostic factors also was performed comparing the outcomes of patients with and without LR. RESULTS: The LR rate was 11% at 12 years. For the entire population, LR led to poorer OS and CSS rates at 12 years compared with local control (LC) (71% vs. 81% [P = 0.001] and 69% vs. 88% [P < 0.001], respectively). In a Cox multiple regression model, LR was a significant predictor of disease specific mortality. The hazard ratio (HR) associated with LR was 2.69 for mortality and 2.67 for DM (P < 0.001 and P < 0.001, respectively). The median time from surgery to the development of DM was 3.8 years for patients without LR compared with 4.7 years for patients with LR. Patients who developed LR also had two peaks in the rate of DM (at 2.5 years and at 6.5 years) compared to only one peak (at 1.5 years) for patients who did not develop LR. The impact of LR on DM still was evident in patients with small tumors (< or = 2.0 cm; P < 0.001), negative lymph nodes (P = 0.004), or both (P < 0.001). Recurrent disease that developed outside of the surgical bed region had no negative effect on survival. In the matched-pair analysis (controlling for age, tumor size, grade, number of positive lymph nodes, and estrogen receptor status), LR remained the most significant predictor of mortality (HR: mortality, 5.86; DM, 6.43). CONCLUSIONS: The current results suggest that LR may be responsible for an increase in DM and disease specific mortality in patients who undergo CS and receive RT. This suggestion is reinforced by the distinct difference seen in the time distribution of DM after LR developed and by the fact that recurrent disease that originated outside of the surgical bed did not affect OS. These data reinforce the necessity to insure optimal LC in patients who are treated with breast-conserving therapy.     

Prognostic significance of soluble urokinase plasminogen activator receptor in serum and cytosol of tumor tissue from patients with primary breast cancer.

PURPOSE: The aim of the study was to evaluate the prognostic value of soluble urokinase plasminogen activator receptor (suPAR) in preoperatively obtained sera samples (s-suPAR) from breast cancer patients. EXPERIMENTAL DESIGN: suPAR levels were determined by the use of a kinetic ELISA in sera from 274 breast cancer patients and in tumor cytosols (c-suPAR) from 188 of these patients. In addition, s-suPAR levels were analyzed in 174 female blood donors. RESULTS: The mean s-suPAR level was 3.8 ng/ml (range, 1.6-9.2 ng/ml) in the patients and 3 ng/ml (range, 1.3-6.4 ng/ml) in the donors. The mean c-suPAR level was 0.55 ng/mg protein (range, 0.07-2.83 ng/mg protein). A weak but significant linear association was found between s-suPAR and age in the donors; thus, all of the s-suPAR levels were adjusted for this age dependency (aa-s-suPAR). The aa-s-suPAR levels were significantly increased in the patients as compared with the donors (P < 0.0001). No difference was found in aa-s-suPAR levels between the lymph node-positive and -negative patients (P = 0.27), and no correlation was seen between aa-s-suPAR and c-suPAR (sigma = 0.08; P = 0.71). During the follow-up period (5.9 years) 77 patients experienced a relapse and 69 died. aa-s-suPAR as a continuous variable was significantly associated with relapse-free survival [hazard ratio (HR), 1.4; 95% confidence interval (CI), 1.1-1.8; P = 0.003] and overall survival (HR, 1.6; 95% CI, 1.2-2.0; P < 0.0001). In multivariate Cox analysis including the classical prognostic parameters in breast cancer, continuous aa-s-suPAR was significantly associated with both relapse-free survival (HR, 1.4; 95% CI, 1.1-1.7; P = 0.001) and overall survival (HR, 1.4; 95% CI, 1.1-1.8; P = 0.002). In these analyses positive lymph nodes, tumor size >2 cm, and negative estrogen receptor content were also significantly associated with patient outcome. CONCLUSION: This study shows that high preoperative aa-s-suPAR levels are significantly associated with poor outcome for breast cancer patients independent of lymph node status, tumor size, and estrogen receptor status.     

Prognosis after local recurrence after conservative surgery and radiation for early-stage breast cancer

PURPOSE: To determine the long-term prognosis of patients who develop a local recurrence (LR) after conservative surgery (CS) and radiation therapy (RT) for early-stage invasive breast cancer. METHODS AND MATERIALS: Between 1970 and 1987, 2102 patients with clinical Stage I-II breast cancer were treated with CS+RT. LR was defined as any recurrence within the ipsilateral breast with or without simultaneous regional nodal or distant metastasis. Patients were at risk for a LR until the first of distant metastases, second nonbreast malignancy, or death (DF/S/D). The final study population comprised 341 patients with LR. The median time to LR was 72 months. The median follow-up time after LR was 85 months. A proportional hazards model of time from LR to DF/S/D was done to investigate the influence of factors at initial diagnosis and at LR on subsequent outcome. RESULTS: The actuarial freedom from DF/S/D 5 years after LR was 65% and the survival was 81%. Variables significantly associated with time to DF/S/D were: LR histology (invasive vs. ductal carcinoma in situ, hazard ratio [HR] = 4.1, p < 0.0001); local therapy for LR (none vs. mastectomy or unknown, HR = 3.2, p < 0.0001; and CS +/- RT vs. mastectomy or unknown, HR = 2.0, p = 0.02); time to LR (< or =2 years vs. >5 years, HR = 2.6, p < 0.0001; and 2-5 years vs. >5 years, HR = 1.8, p = 0.006); and age at initial diagnosis (> or =60 vs. <60, HR = 1.6, p = 0.01). CONCLUSIONS: Many patients with LR after CS+RT have prolonged distant disease-free survival, particularly those able to be treated with mastectomy. Patients with a noninvasive LR, longer interval to LR, or age <60 had a longer time to distant failure, second malignancy, or death than other patients.     

Treatment results and prognostic factors of early breast cancer treated with a breast conserving operation and radiotherapy

BACKGROUND: The purpose of this study was to analyze the prognostic factors affecting local control and survival rates for patients with early breast cancer who received breast conserving treatment (BCT) and to find out the optimal treatment according to their risk factors. METHODS: From October 1994 to December 2001, 605 patients with 611 stage I and II breast cancers received BCT, and the results were analyzed retrospectively. BCT consists of breast conserving surgery and whole breast irradiation. All the patients underwent lumpectomy or quadrantectomy. Axillary lymph node dissection or sentinel lymph node biopsy was performed in 608 cases (99.5%). The radiation dose to the whole breast was 50.4 Gy over 5 weeks with a 1.8 Gy daily fraction and with boost doses of 9-14.4 Gy administered to the tumor bed. Adjuvant chemotherapy was performed in most of the patients with axillary lymph node metastasis or tumors larger than 1 cm. The median follow-up period was 47 months. RESULTS: Local relapse, regional relapse and distant metastasis occurred in 15 (2.5%), 16 (2.6%) and 43 patients (7.1%), respectively. The 5-year overall survival, local-relapse-free survival, distant-metastasis-free survival and disease-free survival rates were 95.3%, 97.2%, 91.3% and 88.5%, respectively. On multivariate analysis, age (P = 0.02), number of involved axillary lymph nodes (P = 0.01) and nuclear grade (P = 0.01) affected the local-relapse-free survival. The factors associated with disease-free survival were the T stage (P = 0.05), number of involved axillary lymph nodes (P = 0.01) and nuclear grade (P = 0.001). Overall survival was associated with the T stage (P = 0.02), number of involved axillary lymph nodes (P = 0.01) and c-erb B2 overexpression (P = 0.05). Patients with more than two factors among (i) age 1 cm, (ii) positive lymph node metastasis and (iii) high nuclear grade showed an inferior 5-year disease-free survival rate compared with others (P = 0.0005). CONCLUSIONS: The most important prognostic factor affecting local control, disease-free survival and overall survival was axillary lymph node metastasis. The nuclear grade influenced local control and disease relapse. Patients with multiple unfavorable risk factors such as positive axillary lymph nodes, high nuclear grade, young age and large tumor showed poorer local control and disease-free survival than patients without any risk factors, and so more aggressive treatment is required for these patients.     

Improving local control with breast-conserving therapy: a 27-year single-institution experience

BACKGROUND: The risk of ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy (BCT) is associated with treatment and tumor-related variables, such as surgical margin status and the use of systemic therapy, and these variables have changed over time. Correspondingly, the authors of the current study hypothesized that the contemporary multidisciplinary management of breast carcinoma would lead to an improvement in IBTR rates after BCT. METHODS: Between 1970 and 1996, 1355 patients with pathologic Stage I-II invasive breast carcinoma underwent BCT (breast-conserving surgery and adjuvant radiation therapy) at The University of Texas M. D. Anderson Cancer Center. Contemporary methods of analyzing surgical margins were in routine use by 1994. To analyze the effect of this variable and others, patient and tumor characteristics and IBTR rates in patients treated during 1994-1996 were compared with those in patients treated from 1970 to 1993. RESULTS: Characteristics were similar in patients treated during 1994-1996 (n = 381) and those treated before 1994 (n = 974) except for patients aged >50 years (63.3% vs. 51.7%, P < 0.001), and patients who had a family history of breast carcinoma (37.9% vs. 30.8%, P = 0.017). Patients treated after 1994 were less likely to have positive or unknown margins (2.9 % vs. 24.1 %, P = 0.0001), more likely to receive chemotherapy (40.5% vs. 26%, P < 0.001), and more likely to receive hormonal therapy (33.3% vs. 19.4%, P < 0.001), but less likely to receive radiation boosts to the primary tumor bed (59.8% vs. 89%, P < 0.001). The 5-year cumulative IBTR rate was significantly lower among patients treated in 1994-1996 than among patients treated before 1994 (1.3% vs. 5.7%, P = 0.001) largely because of the drop in IBTR rates among patients aged < or = 50 years (1.4 % vs. 9.1 %, P = 0.0001). On multivariate analysis, age > 50 (hazards ratio [HR] = 0.401; P = 0.0001), presence of negative surgical margins (HR = 0.574; P = 0.017), and use of adjuvant hormonal therapy (HR = 0.402; P = 0.05) were independent predictors of improved 5-year IBTR-free survival. On subgroup analysis, use of chemotherapy was associated with increased IBTR-free survival among women aged < or = 50 years (HR = 0.383; P = 0.001). Although 5-year cumulative IBTR rates were lower among women aged > 50 years than among younger women before 1994 (2.6 % vs. 9.1%, P < 0.0001), no such difference was found in the group treated in 1994-1996 (1.2 % for age > 50 yrs vs. 1.4 % for < or = 50 yrs, P = 0.999). CONCLUSIONS: The IBTR rate after BCT appears to be declining, especially among patients < 50 years of age. However, long-term follow-up is necessary to confirm this finding. This finding may reflect changes in surgical approaches and pathologic evaluation as well as an increased use of systemic therapy. The current low incidence of IBTR with multidisciplinary management of breast carcinoma may result in more patients choosing BCT over mastectomy.     

Luminal 型乳腺癌 P53表达与临床病理特征及预后的关系

目的：探讨 Luminal 型乳腺癌 P53表达与临床病理特征及预后的关系。方法选取2009年1月至2012年12月在上海交通大学附属第一人民医院手术治疗的283例 Luminal 型乳腺癌患者作为研究对象,采用免疫组织化学法测定 P53表达。生存分析采用 Kaplan-Meier 曲线评估和 Log-rank 检验比较,并用 Cox 比例风险回归模型进行单因素和多因素分析。结果 Luminal 型乳腺癌患者 P53表达与肿瘤最大径（χ2＝6．285,P ＝0．043）、淋巴结转移（χ2＝15．881,P ＝0．000）、组织分级（χ2＝8．132,P ＝0．043）、Ki-67（χ2＝6．476,P ＝0．039）有关;而与年龄（χ2＝0．955,P ＝0．328）、月经状态（χ2＝3．808,P ＝0．051）、病理类型（χ2＝0．847,P ＝0．655）、雌激素受体（χ2＝1．867,P ＝0．172）、孕激素受体（χ2＝0．937, P ＝0．333）及人表皮生长因子受体-2（χ2＝0．110,P ＝0．741）无关。在283例患者中,P53阴性组和阳性组5年无复发生存率分别为90．7％、66．7％（χ2＝12．609,P ＝0．000）,5年总生存率分别为93．4％、84．4％（χ2＝4．153,P ＝0．042）,差异均有统计学意义。Cox 多因素分析发现,淋巴结转移（HR ＝2．484,95％CI 为1．393～4．431,χ2＝9．497,P ＝0．002）和 P53阳性（HR ＝3．627,95％CI 为1．061～12．401;χ2＝4．220,P ＝0．040）是 Luminal 型乳腺癌患者无复发生存的独立危险因素;淋巴结转移（HR ＝3．451,95％CI为1．891～6．297;χ2＝16．290,P ＝0．000）和高组织学分级（HR ＝2．806,95％CI 为1．091～7．219;χ2＝4．582,P ＝0．032）是总生存时间的独立危险因素。结论 Luminal 型乳腺癌患者 P53过表达与淋巴结转移、组织分级等预后因素相关,且 P53过表达患者预后更差。     

Low number of examined lymph nodes in node-negative breast cancer patients is an adverse prognostic factor.

BACKGROUND: The aim of the study was to determine whether the number of lymph nodes removed at axillary dissection is associated with recurrence and survival in node-negative breast cancer (NNBC) patients. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 1606 women with pathologically node-negative T1-T3 invasive breast cancer. Median follow-up was 61 months (range 2-251). Potential prognostic factors assessed included: number of axillary lymph nodes examined, age, menopausal status, tumor size, histological type, tumor grade, estrogen receptor(ER), progesterone receptor (PR) and HER2. RESULTS: At 5 years, relapse-free survival (RFS) rate was 85% and breast cancer-specific survival (BCSS) rate was 94%. In univariate analysis, factors significantly associated with lower RFS and BCSS were: fewer than six lymph nodes examined (RFS, P = 0.01; BCSS, P = 0.007), tumor size >2 cm, grade III, negative ER or PR. Statistically significant factors for lower RFS and BCSS in multivariate analysis were: fewer than six lymph nodes examined [RFS, hazard ratio (HR) 1.36, P = 0.029; BCSS, HR 1.87, P = 0.005], tumor size >2 cm, tumor grade III and negative PR. CONCLUSIONS: Examination of fewer than six lymph nodes is an adverse prognostic factor in NNBC because it could lead to understaging. Six or more nodes need to be examined at axillary dissection to be confident of a node-negative status. This may be useful, in conjunction with other prognostic factors, in the assessment of NNBC patients for adjuvant systemic therapy.     

T1-2N1M0期乳腺癌新辅助化疗后疗效分析及放疗选择的探讨

目的 评价T_1-2N₁M₀期乳腺癌新辅助化疗后辅助放疗对LC率的影响及地位。方法收集2005—2010年间收治的新辅助化疗患者资料,筛选出T_1-2N₁M₀人群,并对其辅助放疗的临床结果进行分析。共入组T_1-2N₁M₀患者144例,中位年龄45岁(23~72岁)。结果 术后30例(21%)获得乳腺原发灶和腋窝淋巴结pCR者均接受了辅助放疗,45例仅腋窝淋巴结阳性转阴性者中10例未接受辅助放疗,69例腋窝淋巴结转移仍为阳性者中6例未接受放疗,其余患者均接受了辅助放疗。全组中位随访时间88个月,46例复发转移(32%),其中pCR者5年LR率为3.0%。5年LR率新辅助化疗后腋窝淋巴结阳性转阴性者放疗组为7%、未放疗组为16%(P=0.181),腋窝淋巴结仍为阳性者放疗组为15.9%、未放疗组为33%(P=0.267)。全组pCR者DFS时间较非pCR者延长(P=0.017)。结论 新辅助化疗后获pCR者DFS期优于未获pCR者,获pCR患接受辅助放疗的LR率较低,腋窝淋巴结阳性转阴性者未能从术后辅助放疗中获益,而腋窝淋巴结转移仍为阳性者的LR率高,辅助放疗有获益趋势。     

The prognostic value and relationships of patient characteristics, estrogen and progestin receptors, and site of relapse in primary breast cancer

Estrogen and progestin receptor levels (ER and PgR) in tumors from 506 patients with primary breast cancer diagnosed in 1979, 1980, and 1981 were measured by a Scatchard plot analysis. At a median follow-up time of 3.5 years the prognostic value of the receptor levels was evaluated and compared with other tumor and patient characteristics. No relation was found between receptor levels and tumor, lymph node, metastasis (TNM) classification or location of the primary tumor. A significant positive rank correlation was observed between ER and PgR levels (rs = 0.57) and between ER level and age of the patients (rs = 0.39, P less than 0.001). The observed association between ER level and menopause status could not be maintained after correction for age. Independent prognostic factors for overall survival were tumor size (P = 0.002), the number of positive lymph nodes (P less than 0.001), age at primary surgery (P less than 0.001), the PgR level of the tumor (P less than 0.001), but not ER level. Independent prognostic factors for relapse were tumor size (P = 0.003), number of positive lymph nodes (P less than 0.001), age (P = 0.006), menopause status (P = 0.02), PgR level (P = 0.007), but not ER level. Finally, for death rate after relapse the following prognosticators were identified: size of the primary tumor (P = 0.03), number of positive lymph nodes (P = 0.03), age (P = 0.003), site of relapse (P less than 0.001), ER level (P = 0.02), and PgR level (P = 0.04). Patients with tumors containing low positive PgR levels (10 to 20 fmol/mg protein) had a slightly better prognosis than patients with PgR-negative tumors. It is concluded that the PgR level of the primary tumor is a better prognosticator than the ER level. The ER offered no additional ability for discriminating between low- and high-risk patients once PgR was included in the model. In contrast, PgR was capable of improving on the discriminating ability of ER. In addition, patients with tumors containing both PgR and ER showed the best prognosis. Therefore, it is recommended that ER and PgR should be assayed in all breast cancer biopsies.     

Biomarkers and outcome after tamoxifen treatment in node-positive breast cancers from elderly women

The predictive role of tumour proliferative rate and expression of p53, bcl-2 and bax proteins, alone and in association with tumour size, nodal involvement and oestrogen receptors (ER), was analysed on 145 elderly patients (> or =70 years of age) with histologically assessed node-positive breast cancers treated with radical or conservative surgery plus radiotherapy followed by adjuvant tamoxifen for at least 1 year. The 7-year probability of relapse was significantly higher for patients with tumours rapidly proliferating (hazard ratio (HR) = 2.0, P = 0.01), overexpressing p53 (HR = 4.4, P = 0.0001), weakly or not exhibiting bcl-2 (HR = 1.9, P = 0.02), without ERs (HR = 3.4, P = 0.0001) or with > or = 4 positive lymph nodes (HR = 2.3, P = 0.003) than for patients with tumours expressing the opposite patho-biological profile. Conversely, tumour size and bax expression failed to influence relapse-free survival. Adjustment for the duration of tamoxifen treatment did not change these findings. Oestrogen receptors, cell proliferation, p53 accumulation and bcl-2 expression were also predictive for overall survival. Within ER-positive tumours, cell proliferation, p53 accumulation, bcl-2 expression and lymph node involvement provided significant and independent information for relapse and, in association, identified subgroups of patients with relapse probabilities of 20% (low-risk group, exhibiting only one unfavourable factor) to 90% (high-risk group, exhibiting three unfavourable factors). Such data could represent the initial framework for a biologically tailored therapy even for elderly patients and highlight the importance of a patho-biological characterization of their breast cancers.     

CONUT评分在乳腺癌患者术后复发转移中的预测价值

目的 探讨控制营养状态(CONUT)评分在乳腺癌患者术后复发转移中的预测价值.方法 回顾性收集于2013年4月至2019年8月南通大学附属如皋医院接受手术治疗的168例乳腺癌患者的临床病理特征与生存随访数据,根据患者术前外周血淋巴细胞计数、血清白蛋白及总胆固醇水平,计算CONUT评分.以3分为CONUT评分的临界值,将...     

Incidence and prognostic significance of complete axillary downstaging after primary chemotherapy in breast cancer patients with T1 to T3 tumors and cytologically proven axillary metastatic lymph nodes.

PURPOSE: To determine the incidence and prognostic significance of eradication of cytologically proven axillary lymph node metastases in breast cancer patients treated with primary chemotherapy. PATIENTS AND METHODS: Between January 1985 and December 1994, 152 breast cancer patients with invasive T1 to T3 tumors and axillary metastases cytologically proven by fine-needle sampling underwent primary chemotherapy followed by lumpectomy or mastectomy, level I and II axillary lymph node dissection, and irradiation. We studied pathologic complete responses (pCRs) of axillary nodes and breast tumors, as well as predictors of distant metastases. RESULTS: Thirty-five patients (23%) had axillary pCRs, and 20 patients (13.2%) had pCRs of primary breast tumors. Scarff-Bloom-Richardson grade 3 tumors (P =.04) and a clinical response to chemotherapy > or = 50% (P =.003) were associated with negative axillary status at dissection. An initial tumor size < or = 3 cm (63 patients) was associated with pCR of the primary tumor (P =.02) but not with complete histologic clearance of axillary lymph nodes. The median length of follow-up was 75 months. In the univariate analysis, age greater than 40 years (P =.003), absence of residual nodal disease (P =.01), and pCR of the tumor (P =.05) were associated with better distant disease-free survival. Five-year distant disease-free survival rates were 73.5% +/- 14.9% among patients with no involved nodes at the time of surgery and 48.7% +/- 9.2% among patients with residual nodal disease. In the multivariate Cox regression analysis, parameters associated with poor distant disease-free survival were age < or = 40 years (P =.002), persistence of nodal involvement (P =.03), and S-phase fraction greater than 4% (P =.02). CONCLUSION: Our results suggest that axillary status is a better prognostic factor than response of the primary tumor to primary chemotherapy.     

全身免疫炎症指数（SII）与胃癌患者临床病理因素及预后的相关性

目的:探讨术前全身免疫炎症指数（SII）与胃癌患者临床病理因素及预后的相关性。方法:回顾性分析2010年1月至2013年12月哈尔滨医科大学附属肿瘤医院胃肠外科行根治性手术治疗的823例患者的临床病理资料,根据术前化验结果计算出SII值(SII=血小板×中性粒细胞/淋巴细胞),采用ROC曲线截取最佳临界值。将SII分为高低两组,分析SII与患者临床病理因素之间的关系,Kaplan-Meier法绘制生存曲线,Log-rank法进行单因素分析,COX回归风险模型进行多因素分析。结果:最佳SII截取值为427.3,SII≤427.3组有459例,SII>427.3组有364例。SII与患者的年龄、肿瘤浸润深度、淋巴结转移数目、肿瘤TNM分期、白蛋白、前白蛋白、白球比、癌胚抗原（CEA）水平均有关（均P<0.05）。截止到2018年3月存活514例,死亡309例,SII≤427.3组患者总体生存期（OS）明显优于SII>427.3组患者,差异具有统计学意义（P=0.000）。单因素分析结果显示,年龄、肿瘤位置、组织分化程度、肿瘤浸润深度、淋巴结转移数目、肿瘤TNM分期、白蛋白、前白蛋白、白球比、CEA、糖类抗原199（CA-199）及SII与行根治性手术胃癌患者的预后相关（P均<0.05）。多因素分析结果显示,年龄（HR=1.487,95%CI=1.162~1.902,P=0.020）、肿瘤位置（HR=0.696,95%CI=0.597~0.811,P=0.000）、肿瘤浸润深度（HR=2.241,95%CI=1.184~4.244,P=0.013）、淋巴结转移数目（HR=1.337,95%CI=1.121~1.595,P=0.001）、肿瘤TNM分期（HR=1.289,95%CI=1.067~1.558,P=0.008）、前白蛋白（HR=0.720,95%CI=0.560~0.926,P=0.010）、CA-199（HR=1.513,95%CI=1.204~1.901,P=0.000）、SII（HR=1.577,95%CI=1.253~1.984,P=0.000）是影响根治性胃癌手术患者预后的独立危险因素。结论:对于行根治性手术的胃癌患者SII是一种可靠的预测预后的指标,术前高的SII值预示着差的预后。     

Hypomethylation of LINE-1 in primary tumor has poor prognosis in young breast cancer patients: a retrospective cohort study

Long interspersed element 1 (LINE-1), a non-coding genomic repeat sequence, methylation status can influence tumor progression. In this study, the clinical significance of LINE-1 methylation status was assessed in primary breast cancer in young versus old breast cancer patients. LINE-1 methylation index (MI) was assessed by absolute quantitative assessment of methylated alleles (AQAMA) PCR assay. Initially, LINE-1 MI was assessed in a preliminary study of 235 tissues representing different stages of ductal breast cancer development. Next, an independent cohort of 379 primary ductal breast cancer patients (median follow-up 18.9 years) was studied. LINE-1 hypomethylation was shown to occur in DCIS and invasive breast cancer. In primary breast cancer it was associated with pathological tumor stage (p = 0.026), lymph node metastasis (p = 0.022), and higher age at diagnosis (>55, p < 0.001). In multivariate analysis, LINE-1 hypomethylation was associated with decreased OS (HR 2.19, 95 % CI 1.17-4.09, log-rank p = 0.014), DFS (HR 2.05, 95 % CI 1.14-3.67, log-rank p = 0.016) and increased DR (HR 2.83, 95 % CI 1.53-5.21, log-rank p = 0.001) in younger (≤55 years), but not older patients (>55 years). LINE-1 analysis of primary breast cancer demonstrated cancer-related age-dependent hypomethylation. In patients ≤55 years, LINE-1 hypomethylation portends a high-risk of DR.     

DNA-PKcs表达与乳腺癌临床病理特征关系的研究

目的:研究DNA依赖蛋白激酶催化亚单位(DNA-PKcs)表达与浸润性乳腺癌临床病理特征的关系。方法:应用组织芯片技术和免疫组织化学方法检测101例浸润性乳腺癌中DNA-PKcs以及ER、PR、c-erbB-2的表达情况,采用χ2检验及Spearman秩和相关检验分析结果。结果:DNA-PKcs表达与浸润性乳腺癌的肿瘤大小、淋巴结转移数量、TNM分期均呈负相关(分别为r=-0.319,P=0.001;r=-0.378,P=0.000;rs=-0.428,P=0.000);与ER表达呈正相关(rs=0.279,P=0.005);与患者年龄、肿瘤组织学分级、及PR、c-erbB-2表达的关系无统计学意义(P>0.05)。结论:DNA-PKcs低表达与浸润性乳腺癌的进展及淋巴结转移关系密切,有可能成为预测乳腺癌预后重要的生物学指标。     

Local recurrence in breast carcinoma patients with T(1-2) and 1-3 positive nodes: indications for radiotherapy.

AIMS: To investigate the relationship between local recurrence (LR) and distant recurrence (DR) and to determine a subgroup of patients who could benefit from radiotherapy among breast carcinoma patients with T(1-2) and N(1a). METHODS: Univariate and multivariate Cox regression analyses were carried out in the retrospective data of 326 eligible patients. RESULTS: Fourteen (4.3%) patients had LR and 46 (14.1%) patients suffered DR, in their follow-up periods. The multivariate time-dependent Cox model for DR showed that ratio of positive nodes (PN) (p=0.004; hazard ratio (HR), 1.05; 95% confidence interval (CI), 1.02-1.09) and LR (p=0.05; HR, dependent on time) were strongly associated with DR. In the multivariate Cox analysis for LR, age (35 years; p<0.0001; HR, 6.8; CI, 2.3-19.9), lymphatic vascular invasion (LVI) (yes vs no; p=0.03; HR, 3.3; CI, 1.2-9.8), and a ratio of PN (>15% vs 相似文献   

Expression of stromal cell-derived factor-1α is an independent risk factor for lymph node metastasis in early gastric cancer

Lymph node metastasis is considered to be a significant prognostic factor for early gastric cancer (EGC). However, no real consensus exists on which patient and/or tumor characteristics are associated with lymph node metastasis. We investigated whether stromal cell-derived factor (SDF)-1α expression correlates with lymph node metastasis in patients with EGC by immunohistochemically examining the expression of SDF-1α in 138 archival tissue specimens of EGC. Of these specimens, 59 (42.8%) and 79 (57.2%) were grouped into SDF-1α-positive and SDF-1α-negative groups, respectively. No significant differences existed with respect to age, gender, tumor location, proportion of tumors >20 mm in size, macroscopic type, depth of invasion or histology between the SDF-1α-positive and -negative groups. However, the SDF-1α-positive group was significantly correlated with lymphovascular invasion and lymph node metastasis. Results of the univariate analyses indicated that lymphovascular invasion, undifferentiated histology and SDF-1α positivity were statistically significant risk factors affecting lymph node metastasis in patients with EGC. Multivariate analyses showed that lymphovascular invasion [hazard ratio (HR), 8.595; 95% confidence interval (CI), 1.694-43.595; P=0.009], undifferentiated histology (HR, 2.965; 95% CI, 1.037-8.471; P=0.043) and SDF-1α positivity (HR, 2.108; 95% CI, 1.316-10.135; P=0.013) were independent risk factors predicting lymph node metastasis in EGC. In conclusion, these results suggest that SDF-1α expression in tumor cells is a predictive marker of lymph node metastasis in EGC.     

Partial breast irradiation as second conservative treatment for local breast cancer recurrence

PURPOSE: Mastectomy is the treatment of reference for local relapse after breast cancer (BC). The aim of this study was to document the feasibility and the results of associating lumpectomy with partial breast irradiation by interstitial brachytherapy (IB) as local treatment for an isolated ipsilateral BC local recurrence (LR). METHODS AND MATERIALS: Between 1975 and 1996 at Marseille and Nice Cancer Institutes, 4026 patients received lumpectomy and radiotherapy (RT) (50-80 Gy) for a localized breast cancer of which 473 presented a LR. Among these patients, 69 (14.6%) received a second lumpectomy followed by IB, which delivered 30 Gy (Nice, n = 24) or 45-50 Gy (Marseille, n = 45) with 3 to 8 (192)Ir wires in 1 or 2 planes on the 85% isodose. RESULTS: Median age at LR was 58.2 years, median follow-up since primary BC was 10 years, and median follow-up after the second conservative treatment was 50.2 months (range, 2-139 months). Immediate tolerance was good in all cases. Grade 2 to 3 long-term complications (LTC) according to IB dose were 0%, 28%, and 32%, respectively, for 30 Gy, 45 to 46 Gy, and 50 Gy (p = 0.01). Grade 2 to 3 LTC according to total dose were 4% and 30%, respectively, for total doses (initial RT plus IB) < or = 100 Gy or >100 Gy (p = 0.008). Logistic regression showed that the only factor associated with Grade 2 to 3 complications was higher IB doses (p = 0.01). We noted 11 second LRs (LR2), 10 distant metastases (DM), and 5 specific deaths. LR2 occurred either in the tumor bed (50.8%) or close to the tumor bed (34.3%) or in another quadrant (14.9%). Kaplan-Meier 5-year freedom from (FF) LR2 (FFLR2), FFDM, and DFS were 77.4%, 86.7%, and 68.9%, respectively. Overall 5-year survival (OS) was 91.8%. Univariate analysis showed the following factors associated with a higher FFLR2: (1) number of wires used for IB (3-4 vs. 5-8 wires, p = 0.006), (2) IB doses (30-45 Gy vs. 46-60 Gy, p = 0.05), (3) number of planes (1 vs. 2, p = 0.05), (4) interval between primary breast cancer and LR (< 36 months vs. > or =36 months, p = 0.06). Multivariate analysis showed two factors associated with better local control: (1) number of wires (5-8 wires, p = 0.013) and (2) interval between primary breast cancer and LR > or =36 months (p = 0.039). The multivariate analysis showed two factors associated with better FFDM: (1) absence of initial axilla involvement (p = 0.019) and (2) relapse in a different location (p = 0.04). These two factors were also associated with a higher OS. CONCLUSION: Our experience showed that second conservative treatments for local relapse were feasible and gave results comparable to standard mastectomy. We recommend delivering IB doses of at least 46 Gy in 2 planes when initial radiotherapy delivered 50 Gy. The study gives enough information to encourage a Phase III trial that compares radical mastectomy to conservative procedures for localized breast cancer recurrences.     

Expression of chemokine receptors predicts the site of metastatic relapse in patients with axillary node positive primary breast cancer.

BACKGROUND: Recent studies have suggested that chemokine receptors are involved in development of organ-specific pattern of metastases. In the present study, we evaluated the association between the chemokine receptors expressed in primary tumor cells and the site of metastatic relapse in patients with breast cancer. METHODS: Primary tumors were obtained from 142 patients with axillary node-positive breast cancer and stained for CX3CR1, CXCR4, CCR6, and CCR7 expression. All statistical analyses were adjusted for systemic post-operative treatment. RESULTS: After a median follow-up of 13 years, none of the chemokine receptors was associated with overall survival or disease free survival. However, expression of chemokine receptors was found to be associated with increased risk of relapse in certain organs. By estimating the Mantel-Haenszel odds ratios (OR), CXCR4 was associated with increased risk of metastasis to the liver (OR = 3.71, P = 0.005), CX3CR1 was associated with metastasis to the brain (OR = 13.18, P = 0.01). Patients with CCR6 positivity were more likely to develop a first metastasis in the pleura (OR = 2.82, P = 0.06). In addition, CCR7 expression was associated with the occurrence of skin metastases (11% versus 0%, P = 0.017). INTERPRETATION: Expression of chemokine receptors in the primary tumor predicts the site of metastatic relapse in patients with axillary node positive breast cancer. This study, in concordance with the data obtained in animal models, suggests that the chemokine receptors family could be the biological support of the 'seed and soil' theory.