Expression of tenascin in invasion border of early breast cancer correlates with higher risk of distant metastasis

Tenascin (Tn) is an extracellular matrix glycoprotein transiently expressed in epithelial-mesenchymal interaction areas during embryogenesis. Tn is expressed in a limited manner in adult tissues but emerges during wound healing and tumorigenesis. We have studied Tn expression by immunohistochemistry in 137 small node-negative breast cancers treated with breast-conserving surgery and post-operative radiotherapy during 1985–1996. None of the patients had undergone any adjuvant hormonal therapy or chemotherapy. Stromal Tn expression itself could not predict distant metastasis. However, Tn staining in the area of the invasion border seemed to be a strong predictor of distant metastasis, with an estimated 5-year metastasis-free survival (MFS) of 85% in Tn-positive cases compared to 98% in Tn-negative ones. The prognostic impact of Tn in the invasion border on MFS was stronger than that of tumour size and grade. This staining appears to be a useful adjunct for the estimation of breast-cancer metastasis. © 1996 Wiley-Liss, Inc.     

乳腺癌局部复发与远处转移关系的回顾性分析

目的：探讨乳腺癌局部复发和远处转移的关系及其相关因素。方法：收集我院诊治的乳腺癌根治术后经病理确诊首次局部复发且资料相对完整的97例女性患者,回顾性分析其临床特点和治疗结果。结果：97例患者中发生远处转移者75例,中位转移时间为15．2个月。单因素分析表明淋巴结转移数目、肿瘤大小和激素受体状况是影响复发后转移中位时间的相关因素。胸壁、腋窝、锁骨上区复发后转移中位时间分别为17．0、16．3和16．0个月,≥2个部位复发者发生转移中位时间为10个月,P=0．033。化疗组和未化疗组复发后发生远处转移间隔分别为16．0和11．9个月,P=0．084。内分泌治疗组和未接受内分泌治疗组复发后发生远处转移间隔分别为24．3和12．7个月,P=0．021。结论：乳腺癌局部复发是远处转移的标志。评价化疗在复发患者治疗中的作用尚需设计更严谨的随机对照临床试验。     

The link between local recurrence and distant metastases in human breast cancer

Purpose: To distinguish between two possible explanations for the increased incidence of distant metastases observed in patients with locoregional recurrences (LR). Either LR is the signature of tumor aggressiveness, and avoiding recurrences (i.e., by radiotherapy) is of little value. The alternative is that LR is a nidus for metastatic dissemination.Methods and Materials: Four thousand patients consecutively treated in the same institution from 1954 to 1975 were studied. None of them had received adjuvant chemotherapy. Tumor characteristics, local recurrence, and distant metastases had been prospectively registered. Duration of metastatic growth and probability of metastatic dissemination were estimated in the subsets of patients.Results: The proportion of metastasis-free patients was reduced by about 80% in all subsets of patients with LR. In patients without LR, the monthly rate of distant metastases incidence decreases continuously with time after initial treatment. Conversely, in patients with local recurrence, this rate increases during the first year after initial treatment and the metastases in excess appear slightly later than in patients without local recurrence. Using a mathematical model, it can be shown that, in patients with local recurrence, nearly all of the metastases in excess had been initiated after initial treatment. The data also suggest that each year a small proportion of grade 1 residual tumors progresses toward a more malignant histologic type.Conclusions: Our results are not consistent with the hypothesis that a greater tumor aggressiveness in patients with LR could explain the excess of metastases. This conclusion is supported by the analysis of the delays between metastases’ emergence, and death, which shows that tumors with or without LR have similar biological characteristics.     

Effect of HER2 status on distant recurrence in early stage breast cancer

It has long been recognized in breast cancer that the effect of hormone receptor (HR) status on recurrence rates varies over time and with the site of recurrence. However, there is relatively little in the literature on the effect of human epidermal growth factor receptor 2 (HER2) on recurrence patterns. We wanted to assess whether the effect of HER2 status on the risk of distant recurrence changed over time and/or with HR status and whether these relationships varied with site of recurrence. We retrospectively studied 11,011 women diagnosed with stage I, II, or III breast cancer after 1997 who had data on HR status and HER2 status. 20 % were HR negative and HER2 negative (so-called “triple-negatives”), 7 % were HR negative and HER2 positive, 64 % were HR positive and HER2 negative, and 10 % were HR positive and HER2 positive. The estimated overall cumulative incidence of developing distant metastases is 20 % at 4 years, 30 % at 8 years, and 36 % at 12 years. The 12-year cumulative incidence was 23 % for bone, 16 % for liver, 14 % for lung, 13 % for distant lymph node, 10 % for brain, and 8 % for pleura. After adjusting for potential confounding factors, the nature of the effect of HER2 on recurrence rates was found to differ markedly across the sites of recurrence. For brain and pleura recurrences, the effect of HER2 depended on HR status in ways that significantly changed over time. For bone recurrences, the effect of HER2 did not depend on HR status, but did change significantly over time. For liver and distant lymph node recurrences, there was a significant effect of HER2 status that did not change with time or HR status. For lung recurrences, rates did not significantly vary with HER2 status.     

Girdin protein: a new potential distant metastasis predictor of breast cancer

To investigate the expression status and the clinical implications of Girdin protein in breast cancer. The expression status of Girdin protein and clinicopathological parameters in 820 breast cancer specimens was analyzed using immunohistochemistry staining and the relationship between Girdin protein and clinicopathological parameters. The prognosis of breast cancer was subsequently determined. Girdin protein was expressed positively in 295 (35.98%) of the 820 cases examined. The expression of Girdin protein was related to histological type and CerbB2 (P = 0.001, 0.006, and 0.001, respectively). After analyzing survival rates, the cases with highly expressed Girdin protein were shown to attain a significantly more distant metastasis rate and poorer postoperative, disease-specific survival than those with none or low expressed Girdin protein (P = 0.001). In the Cox regression test, Girdin protein was detected as an independent prognostic factor (P = 0.031). Girdin protein may be a potential new distant metastasis biomarker of breast cancer.     

High RAD54B expression: an independent predictor of postoperative distant recurrence in colorectal cancer patients

We recently reported a specific mechanism that RAD54B, an important factor in homologous recombination, promotes genomic instability via the degradation of p53 protein in vitro. However, clinical significance of RAD54Bin colorectal cancer (CRC) remains unclear. Thus we analyzed RAD54B geneexpression in CRC patients. Using the training set (n = 123), the optimal cut-off value for stratification was determined, and validated in another cohort (n = 89). Kaplan–Meier plots showed that distant recurrence free survival was significantly lesser in high RAD54B expression group compared with that of low expression group in both training (P = 0.0013) and validation (P = 0.024) set. Multivariate analysis using Cox proportional-hazards model showed that high RAD54B expression was an independent predictor in both training (hazard ratio, 4.31; 95% CI, 1.53–13.1; P = 0.0060) and validation (hazard ratio, 3.63; 95% CI, 1.23–10.7; P = 0.021) set. In addition, a negative significant correlation between RAD54B and CDKN1A, a target gene of p53, was partially confirmed, suggesting that RAD54B functions via the degradation of p53 protein even in clinical samples. This study first demonstrated RAD54B expression has potential to serve as a novel prognostic biomarker, particularly for distant recurrence in CRC patients.     

早期乳腺癌保乳手术后局部复发因素的探讨

乳腺癌保乳手术最大的顾虑是肿瘤的局部复发.目前研究发现局部复发与远位转移的关系仍存在分歧,有诸多因素影响肿瘤的局部复发,其中,最重要的关键因素仍为肿瘤本身的生物学行为.现就乳腺癌保乳手术的局部复发因素进行综述,提出筛选与局部复发相关的客观指标、识别高危人群、建立乳腺癌术后局部复发的分子预测模型.     

分子分型在早期乳腺癌复发、转移中的预测价值

目的:研究0-Ⅱb期乳腺癌患者分子分型与局部复发、远处转移间的关系,为个体化治疗提供依据。方法:回顾分析2001年-2008年收治的临床分期为0-Ⅱb期乳腺癌患者369例。根据免疫组织化学、荧光原位杂交检测技术结果分为Luminal A、Luminal B、HER-2过表达和Basal-like型,比较局部复发率和远处转移率,并结合临床病理特征对其局部复发和远处转移进行分组分析。Kaplan-Meier法计算局部复发率、远处转移率并Logrank法检验和单因素预后分析。结果:Luminal A、Luminal B、HER-2过表达和Basal-like型分别占30.1%、48.5%、9.2%和12.2%。随访率95.4%,随访时间满5、10年者分别为225、85例。单因素分析显示HER-2过表达型、Basal-like型局部复发、远处转移风险均比Luminal A、Luminal B型高。5年局部复发率和远处转移率分别为23.5%、24.4%、6.3%、6.1%和26.5%、28.9%、2.7%、2.2%（P＜0.001,P＜0.001）。结论:分子分型有助于个体化区别早期乳腺癌患者间局部复发和远处转移的风险。     

乳腺癌术后局部复发因素的临床分析

目的探讨乳腺癌术后局部复发的影响因素.方法自1997年1月至2001年1月我院共收治乳腺癌患者435例.观察肿瘤自身因素和治疗因素对术后复发的影响.结果 3年复发率6.4%,总复发率7.0%.肿瘤自身因素中,患者年龄和是否绝经、病理类型和激素受体情况、原发肿瘤大小和腋窝淋巴结转移数目对术后局部复发有显著影响,而患者性别和是否有肿瘤家族史对术后局部复发无显著影响.治疗因素中,术后辅助放疗对减少局部复发有一定作用,而保乳术后局部复发率高于根治术和改良根治术.结论早期诊断、早期治疗是减少乳腺癌复发转移的有效途径,加强辅助治疗可以减少和延缓术后局部复发.     

Prognosis following local recurrence after breast conserving treatment in young women with early breast cancer

Background

Few studies have focussed on the prognosis of young women with local recurrence (LR) after breast-conserving therapy and the factors that can be used to predict their prognosis.

Methods

We studied the outcome and related prognostic factors in 124 patients with an isolated local recurrence in the breast following breast-conserving surgery and radiotherapy for early stage breast cancer diagnosed at the age of 40 years or younger.

Results

The median follow-up of the patients after diagnosis of LR was 7.0 years. At 10 years from the date of salvage treatment, the overall survival rate was 73% (95% CI, 63–83), the distant recurrence-free survival rate was 61% (95% CI, 53–73), and the local control rate (i.e. survival without subsequent LR or local progression) was 95% (95% CI, 91–99). In the multivariate analysis, the risk of distant metastases also tended to be higher for patients with LR occurring within 5 years after BCT, as compared to patients with LR more than 5 years after BCT (Hazard ratio [HR], 1.89; p = 0.09). A worse distant recurrence-free survival was also observed for patients with a LR measuring more than 2 cm in diameter, compared to those with a LR of 2 cm or smaller (HR, 2.88; p = 0.007), and for patients with a LR causing symptoms or suspicious findings at clinical breast examination, compared to those with a LR detected by breast imaging only (HR 3.70; p = 0.03).

Conclusions

These results suggest that early detection of LR after BCT in young women can improve treatment outcome.     

Surgical treatment for chest wall invasion due to the local recurrence of breast cancer

Objective

In this study, we investigated the surgical results for chest wall invasion of local recurrence of breast cancer.

Patients and methods

We reviewed eight patients who underwent a chest wall resection for local recurrence of breast cancer in our department between 1986 and 2004.

Results

All of the patients had local recurrence without any distant metastasis. All of them had skin ulcers with blood oozing. The operation procedures were Bt + Ax + Ic + Mj + Mn (Halsted mastectomy) in four patients, Bt + Ax + Ic + Mn (Patey procedure) in two patients, Bt + Ax + Ic (muscle-preserving mastectomy) in one patient, and Bt + Ax (Auchincloss procedure) in one patient. The intervals from the primary operation ranged from 14 months to 20 years. The maximum and minimum areas of the chest wall defect were 18×16 cm and 4.5×3.5 cm, respectively. Reconstruction of the chest wall was performed using a flap of the rectus abdominis muscle with polypropylene (Marlex^®) mesh in four patients, a flap of the rectus abdominis muscle combined with sandwich prosthesis of polypropylene mesh and methylmethacrylate in one patient, a flap of latissimus dorsi muscle in one patient, polypropylene mesh with pectoralis major muscle in one patient, and by direct closure in one patient. A survivial of more than 3 years was achieved in seven patients and only one patient died 1 year and 2 months after the chest wall resection.

Conclusion

In patients with the chest wall recurrence of breast cancer without distant metastasis, a surgical resection of the chest wall may be effective both for relieving pain and for control of the local hemorrhage. Seven out of the eight patients survived more than 3 years, suggesting that this surgical treatment could facilitate home health care and maintain a good quality of life for patients with breast cancer.