Use of trastuzumab for the treatment of early stage breast cancer

In 1985, a growth factor pathway that depends on the presence of a tyrosine kinase transmembrane receptor present on the surface of 20–25% of breast cancer cells was discovered. The receptor is called human epidermal growth factor receptor (HER)-2 and the prognosis of those patients whose tumors overexpress it is poor. In the 1980s, a monoclonal antibody against this receptor, trastuzumab, was developed and, in 1998, approved for the treatment of metastatic breast cancer. In 2005, the results of five trials evaluating trastuzumab in the adjuvant setting, involving more than 10,000 women, were presented. Despite differences in design and having a short follow-up (between 1 and 2 years), these studies show the same astonishing results that adjuvant trastuzumab therapy halves the recurrence rate and reduces mortality by 30% in those trials mature enough to show survival gains. This benefit is, on average, higher than that of adjuvant chemotherapy and similar to that seen with adjuvant hormonal therapy. The main setback of trastuzumab is its potential for cardiotoxicity, although benefits seem to outweigh risks and the ensuing congestive heart failure is generally reversible. Today, the evaluation of HER-2 expression should be mandatory in every early breast cancer patient, since without it, there is the risk that access to this highly effective drug will be denied for women belonging to this unfavorable subgroup of patients.     

Use of trastuzumab for the treatment of early stage breast cancer

In 1985, a growth factor pathway that depends on the presence of a tyrosine kinase transmembrane receptor present on the surface of 20-25% of breast cancer cells was discovered. The receptor is called human epidermal growth factor receptor (HER)-2 and the prognosis of those patients whose tumors overexpress it is poor. In the 1980s, a monoclonal antibody against this receptor, trastuzumab, was developed and, in 1998, approved for the treatment of metastatic breast cancer. In 2005, the results of five trials evaluating trastuzumab in the adjuvant setting, involving more than 10,000 women, were presented. Despite differences in design and having a short follow-up (between 1 and 2 years), these studies show the same astonishing results that adjuvant trastuzumab therapy halves the recurrence rate and reduces mortality by 30% in those trials mature enough to show survival gains. This benefit is, on average, higher than that of adjuvant chemotherapy and similar to that seen with adjuvant hormonal therapy. The main setback of trastuzumab is its potential for cardiotoxicity, although benefits seem to outweigh risks and the ensuing congestive heart failure is generally reversible. Today, the evaluation of HER-2 expression should be mandatory in every early breast cancer patient, since without it, there is the risk that access to this highly effective drug will be denied for women belonging to this unfavorable subgroup of patients.     

Mammotome在早期乳腺癌原发肿瘤诊断中的应用

为了验证Mammotome活检系统用于乳腺癌活检取材的准确性,以Mammotome活检系统对36例早期乳腺癌原发肿瘤进行活检,切取3～5条肿瘤组织进行病理诊断和ER、PR、c-erbB-2、Bcl-2和p53检测,与术后切取肿瘤组织的上述指标检测结果进行比较.结果：取材准确率为97.2%;Mammotome活检所得标本与常规手术所得标本相比,在病理类型的定性诊断、ER、PR、c-erbB-2、Bcl-2和p53检测结论各方面差异均无统计学意义,P＞0.05.初步研究结果提示,Mammotome活检系统取材准,组织量大,制作标本方便,病理诊断可靠,免疫组化检测准确,与常规手术所取标本检测结论一致,可作为微创治疗前活检取材,进行确诊的有效方法.     

Use of non-anthracycline regimens in early stage breast cancer in Australia

Various factors have recently prompted a re-evaluation of the role of non-anthracycline regimens in early stage breast cancer (ESBC). Since 1990 anthracyclines have been a key component of chemotherapy regimens. However, there is increased understanding of the long-term, irreversible toxicities associated with these therapies, including cardiac failure and secondary leukemia. The development of the taxanes in the 1990s led to new adjuvant chemotherapy regimens and trials of various combinations in an effort to further increase survival and reduce toxicity. Concerns about cardiac toxicity were reinforced with the emergence of trastuzumab for the treatment of HER2-positive breast cancer. Trastuzumab alone causes cardiac toxicity and increases the risk of cardiac toxicity when combined with anthracyclines. These data, combined with recent results demonstrating the efficacy of non-anthracycline regimens in various disease settings, have generated interest in utilizing these therapies in patients with both HER2-positive and -negative tumors. This review outlines the evidence for the use of non-anthracycline adjuvant regimens in ESBC, including cyclophosphamide, methotrexate and 5-fluoruoracil, docetaxel, carboplatin and trastuzumab and docetaxel and cyclophosphamide, which have demonstrated equivalent efficacy and reduced toxicity compared to anthracycline-based regimens in various trials. The review also examines evidence for the use of non-anthracycline regimens in patients who previously had restricted access to these therapies due to their negative lymph node status. The wider availability of these regimens increases options when deciding upon adjuvant chemotherapy for patients with ESBC, especially in patients with a high risk of cardiac toxicity.     

Cosmetic outcome of breast conservative treatment for early stage breast cancer

Purpose To evaluate the cosmetic outcome of breast conservative therapy and to examine the degree of agreement between the patients’ and oncologists’ ratings. We also analyze the influence of several factors on cosmesis. Methods and materials We retrospectively evaluated 145 patients with primary breast cancer treated by local excision and radiotherapy between January 2000 and May 2001. Cosmetic outcome was evaluated by doctors and patients and was scored as excellent, good, fair or poor. Results 73% of patients rated cosmesis as excellent or good while the percentage was 71% when rated by radiation oncologists. The degree of cosmesis concordance evaluated by oncologists and patients was low (kappa=0.3). In our study the variables which significantly influence on the cosmetic outcome were concomitant adjuvant chemotherapy (p=0.04) and radiation therapy boost, either by electron beam or brachytherapy (p=0.013). Conclusion The cosmetic outcome of breast conserving therapy was good. There was a similar rating by the patient and radiation oncologist, but the level of concordance between patients and doctors was low. Factors that significantly influence the cosmesis appear to be concomitant adjuvant chemotherapy and radiation therapy boost.     

Guidelines for systemic therapy of early stage breast cancer

Optimal treatment of early stage breast cancer remainsan active area of study. An expert multidisciplinarycommittee reviewed clinical data on systemic therapy forearly stage, stage I and II breast cancer.Guidelines for treatment were developed for Texas Oncology,P.A., the largest private practice group of oncologistsin the United States. This group of physicianstreats approximately 5000 new breast cancer patients eachyear and has a major impact on oncologycare in the state of Texas.These guidelines identify prognostic factors which help thepractitioner in choosing treatment for patients. Subsets ofpatients are identified for whom no systemic therapyis warrented. Standard chemotherapy and hormonal therapy regimensare outlined for patients with early stage diseaseat increased risk for relapse. Dose intensification forhigh risk stage II patients is reviewed. Timingof therapy and the sequencing of chemotherapy andradiation therapy is addressed. Strategies for the follow-upof patients with a history of breast cancerare outlined.     

Outcomes of bilateral mammoplasty for early stage breast cancer

Aim

Long-term oncological follow-up of oncoplastic breast surgery.

Methods

Sixthy-one (63 cancers) patients affected by breast cancer suitable for breast conservation, were treated with bilateral breast reductions. Tumours located in the inferior pole of the breast were treated by a superior pedicle technique; lesions in the upper pole or in the infero-lateral or infero-medial quadrants of the breast were removed with an inferior pedicle reduction. Small and medium size breast irrespective of tumour location required a periareolar, or comma-shaped approach.

Results

Fifty-six patients were alive at a mean follow-up of 68 months. One patient recurred locally and she is currently alive free of disease.

Conclusion

Results from this study are in accordance with those reported by other similar papers. Oncoplastic breast surgery maximizes cosmetic results and with wider excisions provides effective local control.     

放射治疗在早期乳腺癌中的应用

目前在早期乳腺癌的治疗中，保乳治疗（breast—conserving therapy）已经被广泛认为是一种安全而有效的治疗方法。过去20年中进行的大量临床试验表明：对于Ⅰ～Ⅱ期乳腺癌患者，采用保乳手术加术后放射治疗的方案已经成为标准的治疗方案；其总生存率及无病生存率均与乳腺癌根治术相等。保乳治疗的步骤主要包括：（1）原发肿瘤局部切除，切缘阴性；     

乳腺癌保乳治疗的现状和展望

本文介绍早期乳腺癌保乳治疗的现状和进展,主要从乳腺癌病理生理特点、保乳治疗与根治性手术的等效性、保乳手术的技术要求、前哨淋巴结活检、局部复发的相关风险因素和术后放疗等几个方面加以探讨。随着乳腺癌早期发现比例的逐渐提高和医患观念的更新,乳腺癌保乳治疗的应用前景将更加广阔。     

早期乳腺癌诊断的临床分析

目的：探讨早期乳腺癌的临床诊断方法。方法：对482例乳腺癌患者的诊治过程进行回顾性分析。结果：乳腺钼靶与彩超联合检查易发现早期乳癌。结论：乳腺普查可以发现无临床症状的早期乳癌患者。     

早期乳腺癌诊断的临床分析

目的:探讨早期乳腺癌的临床诊断方法.方法: 对482例乳腺癌患者的诊治过程进行回顾性分析. 结果: 乳腺钼靶与彩超联合检查易发现早期乳癌. 结论: 乳腺普查可以发现无临床症状的早期乳癌患者 .     

早期乳腺癌根治术后放射治疗靶区的确定

目的：确定早期乳腺癌根治术后放射治疗的靶区。方法：回顾分析本院行乳腺切除和腋窝淋巴结清扫的605例T1－2N0－1M0期乳腺癌患者。所有得接受乳腺癌根治术,343例接受术后放射治疗,其中,135例接受胸壁放射治疗,270例锁骨上腋顶放射治疗,98例腋窝放射治疗,340例内乳放射治疗。生存分析采用Kaplan-Meier法,局部区域复发率的差别用Logrank检验。结果：全组患者的10年胸壁复发率为5．2％,10年锁骨上淋巴结复发率为6．5％,10年腋窝淋巴结复发率为2．9％,10年内乳淋巴结复发率为0．2％。未做胸壁放射治疗时,腋窝淋巴结转移数为0,1－3和≥4个的10年胸壁复发率分别为4．9％,5．3％和11．8％,腋窝淋巴结转移数≥4个的复发率比腋窝淋巴结转移数为0和1－3个有增高的趋势（P＝0．062）,放射治疗有降低这组患者胸壁复发率的趋势（2．9％和11．8％,P＝0．089）,未做锁骨上放射治疗时,腋窝淋巴结转移数≥4个的10年锁骨上复发率明显高于腋窝淋巴结转移数为0和1－3个者（42．4％和3．1％和9．1％,P＝0．000）,放射治疗可使这组患者的锁骨上淋巴结复发率明显降低（5．3％和42．4％,P＝0．000）,腋窝淋巴结转移数≥4个的患者,做和不做腋窝放射治疗的10年腋窝淋巴结复发率分别为0％和6．5％,差别无显著性意义（P＝0．142）。全组患者只有1例出现内乳淋巴结复发,10年内乳淋巴结复发率为0．2％,结论：腋窝和内乳淋巴结复发少见,对腋窝淋巴结转移数≥4个的患者,建议行胸壁和锁骨上淋巴结照射,放射治疗有降低胸壁复发率的趋势,并能显著降低锁骨上淋巴结复发率。     

早期乳腺癌放射治疗进展

放射治疗在早期乳腺癌的综合治疗中具有重要地位。在早期浸润性乳腺癌乳房保留治疗已成熟的基础上，近年的临床研究着眼于对乳房保留治疗的标准模式的挑战，包括全乳照射后瘤床加量的意义，是否有低危复发患者可以接受单纯手术以及部分乳腺照射的可行性等。对于局部复发高危患者进行乳房切除术后胸壁和区域淋巴结的放射治疗可以降低2／3的局部和区域的复发率，但是目前仍然只有少数研究证实术后放疗提高了生存率，尤其关于中等复发危险的患者术后放疗是否有价值尚存在较多争议。本文将对上述进展和争议作一综述。     

乳腺癌保乳术后放化综合治疗疗效评价

目的:评价临床早期乳腺癌行保乳手术加术后放化疗综合治疗的疗效。方法:Ⅰ、Ⅱ期乳腺癌患者行保留乳房的肿瘤切除加腋窝淋巴结清除术患者106例(保乳组),同期行乳腺癌改良根治术患者95例(对照组),术后早期予以全身化疗、全乳腺区放疗和(或)内分泌治疗。结果:全部病例中位随访53个月,保乳组中无局部复发者,对照组局部复发1例;保乳组和对照组的3、5年生存率分别为96.34%(79/82)和95.58%(65/68),P=0.9571;90.24%(37/41)和90.47%(38/42),P=0.9870。远隔脏器转移率分别为5.7%和5.3%,P=0.9774。两组间各项指标比较差异均无统计学意义,患侧乳房外形的优良率达96.2%。结论:早期乳腺癌采用保留乳房手术加术后放化疗综合治疗,疗效与根治术相似,美容效果好,可作为首选方法之一。     

Breast imaging technology: Application of magnetic resonance imaging to early detection of breast cancer

Since its first introduction approximately 10 years ago, there has been extensive progress in the application of magnetic resonance imaging (MRI) to the detection and diagnosis of breast cancer. Contrast-enhanced MRI has been shown to have value in the diagnostic work-up of women who present with mammogram or clinical abnormalities. In addition, it has been demonstrated that MRI can detect mammogram occult multifocal cancer in patients who present with unifocal disease. Advances in risk stratification and limitations in mammography have stimulated interest in the use of MRI to screen high-risk women for cancer. Several studies of MRI high-risk screening are ongoing. Preliminary results are encouraging.     

Survival of women after breast conserving surgery for early stage breast cancer

Background. Increasing numbers of older women with breast cancer are receiving breast-conserving surgery (BCS). However, substantial numbers of them are not receiving either axillary dissection or adjuvant irradiation. Objective. To determine whether failure to perform axillary dissection or irradiation is associated with decreased survival in women with early-stage breast cancer. Method. We studied 26,290 women aged 25 in 1988-1993 from the surveillance, epidemiology, and end results (SEER) data and 5,328 women aged 65 in 1991-1993 from SEER-Medicare linked data, who had early-stage breast cancer and received BCS. Results. Twenty seven percent of women aged 25 receiving BCS did not receive axillary dissection, most of whom (74%) were age 65. Women receiving BCS with axillary dissection had lower 7-year breast cancer-specific mortality than did those without dissection (hazard ratio=0.53, 95% confidence interval: 0.44–0.63). We found an interaction between receipt of axillary dissection and radiotherapy on survival of older women after BCS. Women who received either axillary dissection or radiotherapy experienced similar survivals to those who received both axillary dissection and radiation, while women who received neither treatment experienced poorer survival (hazard ratio=1.76, 1.23–2.52), after controlling for demographics, tumor size and comorbidity. Conclusions. Women who receive neither axillary dissection nor radiation therapy after BCS experience an increased risk of death from breast cancer. The lack of improvement in the past two decades in survival of older women with breast cancer may be explained in part by the increasing use of treatments that do not address potential tumor in axillary nodes.     

Mammography, breast ultrasound, and magnetic resonance imaging for surveillance of women at high familial risk for breast cancer.

PURPOSE: To compare the effectiveness of mammography, breast ultrasound, and magnetic resonance imaging (MRI) for surveillance of women at increased familial risk for breast cancer (lifetime risk of 20% or more). PATIENTS AND METHODS: We conducted a surveillance cohort study of 529 asymptomatic women who, based on their family history and/or mutational analysis, were suspected or proven to carry a breast cancer susceptibility gene (BRCA). A total of 1,542 annual surveillance rounds were completed with a mean follow-up of 5.3 years. Diagnostic accuracies of the three imaging modalities used alone or in different combinations were compared. RESULTS: Forty-three breast cancers were identified in the total cohort (34 invasive, nine ductal carcinoma-in-situ). Overall sensitivity of diagnostic imaging was 93% (40 of 43 breast cancers); overall node-positive rate was 16%, and one interval cancer occurred (one of 43 cancers, or 2%). In the analysis by modality, sensitivity was low for mammography (33%) and ultrasound (40%) or the combination of both (49%). MRI offered a significantly higher sensitivity (91%). The sensitivity of mammography in the higher risk groups was 25%, compared with 100% for MRI. Specificity of MRI (97.2%) was equivalent to that of mammography (96.8%). CONCLUSION: Mammography alone, and also mammography combined with breast ultrasound, seems insufficient for early diagnosis of breast cancer in women who are at increased familial risk with or without documented BRCA mutation. If MRI is used for surveillance, diagnosis of intraductal and invasive familial or hereditary cancer is achieved with a significantly higher sensitivity and at a more favorable stage.     

An analysis of the cost of clinical surveillance after primary therapy for women with early stage invasive breast cancer

Summary Routine surveillance for distant metastases in women with early stage breast cancer has limited clinical utility and can result in large medical care costs. In order to estimate breast cancer surveillance costs, we used the results of a survey administered to a random sample of physician members of the American Society of Clinical Oncology. The survey measured the frequency in which radiographic and laboratory tests are ordered for postmenopausal women with stage I or II breast cancer after the completion of surgery and radiation or adjuvant chemotherapy if indicated. There were 209 completed surveys representing a response rate of 48%. The volume of tests ordered was expressed in terms of Medicare's relative value units (RVUs) and 1993 cost equivalents. The mean total RVUs over 5 years post-diagnosis was 43.8 (interquartile range 30.1–54.2) which represents a cost of $1369 using the 1993 Medicare conversion factor of $31.249. A cumulative logistic regression model categorized RVUs according to intensity of care (minimal, average, and intensive). While medical oncologists compared to surgeons and radiation oncologists, and physicians practicing in the Northeast and Midwest, compared to those practicing in the South and West, were more likely to adopt an intensive practice style, these differences were not statistically significant (p = 0.1). None of the other provider characteristics evaluated, including gender, prior experience, and practice type, had a significant effect on physician practice in a multivariate model. The data showed a wide variation among providers in surveillance practice patterns that was largely unexplained by physician demographics. These results are consistent with the physician practice style hypothesis which suggests that wide variations in treatment patterns result from uncertainty regarding effectiveness of care.