可手术乳腺癌综合治疗进展

随着研究的不断深化,乳腺癌的综合治疗趋向规范化、个体化。目前学术界在可手术乳腺癌手术前、后辅助治疗包括化学治疗、放射治疗、内分泌治疗及分子靶向治疗方面,都取得了较大共识．更多基础研究正在丰富个体化治疗的循证医学依据。     

乳腺癌内分泌治疗的进展

近年来,乳腺癌内分泌治疗在基础和临床研究方面取得了丰硕成果,现就临床研究的进展方面进行介绍。1 芳香化酶抑制剂（AI）辅助内分泌治疗AI方面的Ⅲ期临床试验主要分为4种：起始方案（upfront）、后续强化方案（extend）、转换方案（switch）和序贯方案（sequence）。起始方案试验的设计为直接比较他莫昔芬和AI单药治疗5年的疗效及安全性,如ATAC研究、BIG1—98研究和TEAM研究,纳入的患者在随机分组前未接受内分泌治疗。     

可手术乳腺癌的综合治疗

乳腺癌的综合治疗在提高乳腺癌患者的远期生存率 ,改善生活质量中的地位越来越受到重视。介绍了初治可手术乳腺癌的综合治疗策略研究的现状     

早期乳腺癌保乳治疗的临床研究

目的：探讨早期乳腺癌保乳术后综合治疗的效果。方法：对１０８例早期乳腺癌行保乳治疗,并与同期行改良根治术治疗的１２１例早期乳腺癌行对比研究。保乳治疗患者年龄３１～６１岁,中位年龄４４.５岁。保乳术后行全乳腺放疗和瘤床加量,处方剂量５０Ｇｙ／５周,瘤床追加６～９ＭｅＶ电子线１０～１５Ｇｙ／７～１０天。改良根治术患者年龄３４～６８岁,中位年龄４７.６岁。改良根治术后放疗的范围根据肿块大小和淋巴结转移情况决定,处方剂量５０Ｇｙ／５周。两组均采用ＣＡＦ或ＣＭＦ方案化疗,ＥＲ或ＰＲ阳性的患者给予内分泌治疗。结果：１０８例保乳治疗患者中３例复发,５例出现远处转移（２例为骨转移,１例为骨、肝、肺多发转移,２例为肺转移）。术后６个月美容效果评估优、良者为９１.７％,术后１年为９２.６％。１２１例改良根治术患者中３例复发,７例出现远处转移（３例为骨转移,３例为肺转移,１例为多发脏器转移）。两组的近期疗效差异均无统计学意义（Ｐ＞０.０５）。结论：早期乳腺癌采用保乳术及术后综合治疗的疗效不低于改良根治术,且美容效果更优。     

乳腺癌的内分泌治疗

乳腺癌是对内分泌治疗很敏感的为数不多的人类肿瘤之一,治疗的反应率与雌激素受体及孕激素受体状况有关.乳腺癌内分泌治疗多用于晚期病人的治疗,亦用于具有高复发危险的早期病人的辅助治疗,局部晚期患者的新辅助治疗及激素药物预防.可采用摘除内分泌器官的方法,如卵巢切除,肾上腺切除,垂体切除;然而,具有同样效果的药物治疗应用越来越多.肾上腺切除,垂体切除已被放弃,抗雌激素三苯氧胺为最常使用,且一直作为内分泌治疗的一线药物,但最近新的无雌激素样作用的抗雌激素制剂,新的选择性芳香化酶抑制剂,促性腺激素释放激素类似物正在取代三苯氧胺作为一线治疗的地位.     

可手术乳腺癌的新辅助全身治疗

新辅助全身治疗(neoadjuvant systemic treatment, NST)也称术前全身治疗。以全身治疗为原发性乳腺癌的首治方法兴起于上世纪70年代,其初衷是为了解决不可切除或切除困难的局部晚期乳腺癌(locally advanced breast cancer,LABC)和炎性乳腺     

进展期胃癌综合治疗的现状和进展

本文主要综述进展期胃癌的手术治疗、化学治疗及放射治疗的现状和进展。对于Ⅱ／Ⅲ期的胃癌主要是以D2手术根治为主，并辅以术中的热疗。对于完整的术前分期检查，使得Ⅲa／Ⅳ期的患者予以新辅助化疗后再行手术，这部分手术再切除，可提高胃癌患者的生存率，亦能改善生活质量：术后的辅助治疗，在原有的氟尿嘧啶、多柔比星（阿霉素）、顺铂治疗方案的基础上，氟尿嘧啶与奥沙利铂（乐沙定）、氟尿嘧啶、顺铂与紫杉醇组合及顺铂加CPT-11组成的方案有效率均有不同程度的提高：术后的放化疗结合也在研究探讨之中。     

早期乳腺癌术后辅助治疗现状

辅助性化疗、内分泌治疗、放射治疗已成为乳腺癌综合治疗的重要组成部分，但如何合理使用仍有争论，本文系统综述当前研究结果，为临床规范化治疗提供帮助。     

乳腺癌内分泌治疗的基本共识

内分泌治疗是乳腺癌全身治疗的主要手段之一。20世纪70年代,三苯氧胺的问世成为乳腺癌内分泌药物治疗的里程碑;90年代,第3代芳香化酶抑制剂的问世则使乳腺癌的内分泌治疗进入了一个新时代。2005年1月2日,我国北方部分从事乳腺癌临床工作的专家,根据国内外学术研究进展,结合自身临床实践经验,参考乳腺癌治疗的国际指南,就内分泌治疗在乳腺癌的复发转移、术前新辅助治疗和术后辅助治疗中的作用和地位进行了讨论,并达成基本共识,由执笔者整理成文。     

三阴性乳腺癌的认识与治疗方向

目的:总结国内外对三阴性乳腺癌分子生物学的认识,探讨其可行的治疗手段与研究进展.方法:利用 PubMed数据检索系统,以"三阴性乳腺癌、基底样乳腺癌和治疗"为关键词,检索近5年的相关文献.纳入标准:1)TNBC的来源和分子生物学特征;2)治疗包括化学治疗、放疗及靶向治疗.根据纳入标准分析54篇文献.结果:TNBC本质上起源于BLBC,即分子分型的基底样乳隙癌,恶性程度高,预后差,治疗易耐受.但对许多靶向药物显示出敏感性.结论:TNBC研究前景广阔,无论发病机制还是治疗选择都期待进一步的探讨.     

Primary medical therapy for operable breast cancer

Fifty-seven patients with large but potentially operable primary breast cancer were treated with primary medical therapy rather than initial mastectomy, using chemotherapy (15) or endocrine therapy (42) with the tumour remaining in situ. Of patients treated with chemotherapy, one (7%) achieved a complete remission, and eight (53%) a partial response (overall response rate 60%). Only one patient had progressive disease while on chemotherapy. Of patients who received endocrine therapy, one (2%) achieved a complete response, and 19 (45%) a partial response (overall response rate 47%). Two patients progressed on endocrine therapy. Only 10 patients have so far had a subsequent mastectomy (18%), and 17 (30%) have had radiotherapy and/or conservative surgery. The rest are still on medical therapy.With a median follow-up of 19 months (range 6–42 months) only two patients have had a local recurrence after being disease-free and none have developed uncontrollable local recurrence. Eight (14%) have developed distant metastases and four (7%) have died of metastatic disease.Primary medical therapy may offer an effective alternative to mastectomy for patients with operable breast carcinomas too large for conservative surgery and merits further study.     

Adjuvant endocrine therapy for operable breast cancer

A brief resume of adjuvant endocrine therapy for operable breast cancer is given. This was first suggested in the 1930's but has only become accepted in the last 10-15 years. The reason for the lack of survival benefit in the first randomised trial, which began in 1948 in Manchester, was thought to be due to the increasing use of hormone therapy for metastases. Revival of interest came with the survival gain reported in the Toronto ovarian trial and the success in post-menopausal patients of the non-toxic anti-oestrogen tamoxifen. The different dose schedules used in the various large tamoxifen trials could explain the confusingly variable results in the literature. Combined analysis of trial results indicates that CMF is the adjuvant therapy of choice for pre-menopausal patients but this therapy may in part be acting through the ovaries. The Scottish and NATO trials have an overall survival advantage from adjuvant tamoxifen, even in pre-menopausal patients, and both have shown results to be independent of oestrogen receptor (ER) status. Whether the extra 3 years given in Scotland adds an additional benefit over the more commonly used 2-year course is uncertain. A statistically invalid look at selected data in the Scottish trial suggests that, in ER positive cases, post-relapse tamoxifen may have as great an effect on total survival as adjuvant use, a finding similar to that suggested by the first ovarian ablation trial and one requiring continued review.     

Primary systemic therapy for operable breast cancer.

Eighty-eight patients presenting with operable breast cancer of 4 cm or greater in diameter (T2, T3, N0, N1, M0) have received primary systemic therapy. Response was assessed following 12 weeks of systemic therapy by linear regression analysis of changes in tumour volume. Definitive locoregional surgery (mastectomy n = 82, wide local excision n = 6) was performed on completion of systemic therapy (3-6 months). Response was observed in 24 (39%) of the 61 patients who received endocrine therapy; all 24 had tumours with an oestrogen receptor (ER) concentration of greater than or equal to 20 fmol mb-1 cytosol protein. Cytotoxic therapy was reserved for patients with tumours of ER concentration less than 20 fmol mg-1 cytosol protein (n = 27) or when endocrine therapy had failed (n = 20). Response was observed in 34 patients (72%). The overall survival rate at 3 years was 86%, with 81% remaining free from local relapse. We propose that the treatment policy outlined in this paper should now be tested against orthodox management by controlled randomised trial.     

Adjuvant therapy with high-dose medroxyprogesterone acetate for operable breast cancer

Background  Medroxyprogesterone acetate (MPA) produces a comparable or higher response rate in metastatic breast cancer compared with tamoxifen which is also commonly used for adjuvant endocrine therapy. Several studies in the West have indicated the efficacy of MPA when used as an adjuvant to surgery in certain subsets of patients. The present study was undertaken as a multicenter open study in Japan to investigate the safety and efficacy of MPA in adjuvant endocrine therapy. Method and Patients  A combination of 800 mg/day MPA and a fluorouracil compound for 6 months was given postoperatively tol 19 patients with stage II or Illa breast cancer in 32 participating hospitals between June 1987 and June 1989. Results  Among the 119 patients, 59 patients (49.6%) experienced some kind of adverse reaction. The major adverse reaction was abnormal menstruation, seen in 13 (25.0%) of the 52 premenopausal patients. Vaginal bleeding was a major adverse reaction in the 67 postmenopausal patients (8/67 or 11.9%). An increase in body weight and moon face were observed in 23 (19.3%) and 9 (7.6%) of the 1 19 patients, respectively. Administration of drugs was discontinued because of adverse reaction in 17 patients (14.3%), and dose reduction or temporary suspension was necessary in 7 patients (5.9%). Increase in body weight was the main reason for discontinuation of the treatment. No severe adverse reactions were observed. After a median follow-up of 74.5 months (range, 2.2–90.0 months), 84 of the 119 patients are alive with no evidence of disease. The 3-year and 5-year disease-free survival rates were 88.2% and 82.6% in stage II patients, and 64.7% and 52.9% in stage Illa patients, respectively. The 3-year and 5-year disease-free survival rates according to age were 87.8% and 79.3% in patients aged 50 years or more, and 78.6% and 71.4% in patients aged under 50 years. Conclusion  These results show that 800 mg/day MPA plus a fluorouracil compound can be administered with acceptable morbidity as an adjuvant treatment to selected breast cancer patients.     

Primary systemic therapy in operable breast cancer.

PURPOSE: Laboratory studies suggest that primary systemic therapy (PST) could improve control of micrometastatic disease and impact on overall survival (OS). This article examines the rationale for and preclinical and clinical data of PST in operable breast cancer and the potential role of intermediate biomarkers as predictive and/or prognostic factors for response and survival. DESIGN AND METHOD: We conducted an extensive literative review (including MEDLINE) on preclinical studies, single-arm feasibility studies, large randomized single- and multi-institutional trials, and laboratory correlate studies of PST in breast cancer. RESULTS: Small trials in locally advanced disease showed high initial rates of response and local control. Six randomized clinical trials (RCTs) of PST for palpable, operable breast cancer have been reported since 1991 (from 204 to 1,523 patients each). These data clearly show a small but significant (less than 10%) absolute increase in the use of breast-conservation treatment (BCT) with similar rates of local control. Although one study showed better disease-free survival (DFS) and another showed better OS, most studies did not show any survival advantage of primary versus adjuvant systemic therapy. Thus far, pathologic complete response seems to be the best predictor of survival, but clinical response assessment correlates poorly with pathologic response. Pilot studies demonstrated feasibility of procuring tissue at diagnosis and after treatment for assays of potential intermediate biomarkers. Initial data suggest a potential correlation between markers of proliferation and apoptosis and in vivo chemotherapy sensitivity. CONCLUSION: Thus far, RCTs of PST versus standard adjuvant therapy have not shown any clear benefit for DFS or OS in early breast cancer. Ongoing trials should determine if specific subsets of patients at risk would benefit from additional systemic therapy and the potential role of intermediate biomarkers in identifying such women. Although PST results in a small increase in the rate of BCT with similar rates of local control, current PST strategies should not replace standard adjuvant approaches. Rather, they represent an acceptable alternative to women with palpable, operable tumors and an excellent arena for clinical trials.     

Radical mastectomy for operable breast cancer

The experience with radical mastectomy in the treatment of 152 cases of operable breast cancer at the Hadassah University Hospital has been analyzed. An overall 5 year survival of 75% and a 10 year survival of 62% are reported and compared with results from other methods of treatment. Based on the excellent survival rates achieved and the low incidence of local recurrence (9.8%), the present study suggests that radical mastectomy is still the most suitable surgical procedure in the treatment of operable breast cancer.     

Neoadjuvant chemotherapy for operable breast cancer

Adjuvant systemic chemotherapy has been shown to prolong survival in all subsets of patients with breast cancer. In addition, among patients with locally advanced breast cancer, neoadjuvant orpreoperative chemotherapy has improved the ability to perform breast-conserving therapy. This observation, combined with multiple preclinical hypotheses and the results of laboratory studies, has prompted investigation of neoadjuvant chemotherapy as a treatment strategy for operable breast cancer. In this article, both the evidence supporting this treatment approach and some of the problems associated with it are reviewed. Currently, seven randomized studies comparing neoadjuvant chemotherapy followed by surgery or surgery followed, in turn, by adjuvant chemotherapy have been completed and their results analyzed. Despite exciting preclinical evidence, no trial to date has shown a survival advantage for the neoadjuvant treatment approach. Nonetheless, evidence from more recent phase III trials and the fact that neoadjuvant chemotherapy is not harmful topatients validate its use in operable breast cancer.     

可手术乳腺癌的新辅助化疗

新辅助化疗已被广泛用于局部晚期乳腺癌,早期可手术乳腺癌的新辅助化疗应用价值还在探讨之中。本文综述了新辅助化疗治疗可手术乳腺癌基础及临床方面的最新进展,认为新辅助化疗应用于早期可手术乳腺癌,可明显消退肿瘤,提高乳房保留治疗率,可获得至少与辅助化疗同样的总生存率。     

Early operable breast cancer

Opinion statement Early operable breast cancer is a potentially curable disease. However, a substantial number of patients are at risk for systemic recurrence and death. Breast conservation therapy (BCT) should be considered the preferred surgical option for most women with early operable breast cancer. Adjuvant systemic chemotherapy or hormonal therapy can substantially reduce, although not eliminate, the risk of recurrence and death. Neoadjuvant or primary systemic therapy (PST) in operable breast cancer slightly increases the number of women treated with breast conservation versus mastectomy. Although PST may identify women who are likely to have a better prognosis (those with a pathologic complete response), current PST strategies do not offer a survival advantage over standard adjuvant approaches. Early results of high-dose chemotherapy trials thus far have not shown any advantage over conventional dose therapy in high-risk patients with 10 or more positive lymph nodes. The role of adjuvant radiation therapy after mastectomy for all patients with high-risk early operable breast cancer is not fully defined.     

The role of adjuvant endocrine therapy in the management of operable breast cancer

Since June, 1982, a chemoendocrine adjuvant clinical trial has been conducted at the Aichi Cancer Center Hospital. Women with operable breast cancer were stratified on the basis of the number of positive axillary nodes. Node negative patients received tamoxifen (TAM) for 6 months (Trial I), patients with 1-7 positive nodes received either cyclophosphamide (CPA) for 4 weeks and TAM for one year (Trial II), and patients with 8 or more positive nodes received either CPA for 8 weeks and TAM for 3 years (Trial III). Numbers of evaluable cases are 449 for Trial I, 228 for Trial II and 84 for Trial III. This is an interim report, and the median follow-up time is 3 years and 5 months. This is a prospective non-randomized trial, and control groups (observation group and chemotherapy group) are historical. Results: 1. Premenopausal patients in Trial I yielded intermediate outcome between those of observation and chemotherapy groups. Thus, for this subgroup, adjuvant chemotherapy can be considered as a standard, and addition of TAM is recommended. 2. The benefit of TAM is apparent for postmenopausal patients in Trial I. 3. TAM is effective for both pre- and postmenopausal patients in Trial II. Addition of more aggressive chemotherapy should be considered. 4. Premenopausal patients in Trial III had a better disease-free survival compared with those of control groups. More effective combined chemotherapy may yield longer overall survival. 5. Postmenopausal patients in Trial III had a better disease-free and overall survival rate. Adjuvant TAM and combined chemotherapy can be considered as standard care for this subgroup.