乳腺癌根治术后局部区域性复发的放射治疗和预后影响因素

背景与目的：局部和区域复发乳腺癌患者的治疗原则和预后因素仍存在一定争议。本研究旨在探讨乳腺癌术后胸壁和区域淋巴结复发患者放射治疗的疗效和影响生存率的预后因素。方法：回顾性分析复旦大学附属肿瘤医院1990—2005年收治的255例乳腺癌根治术或改良根治术后胸壁和区域淋巴结复发患者放射治疗后的生存和复发情况,并对影响生存的预后因素进行分析。结果：随访时间为9个月～15．5年,中位随访时间为45个月。首次治疗至复发的无病间期为2—260个月,中位时间为22个月．其中激素受体阳性者的中位无病间期时间为37个月。未知与阴性者为17个月。2年、5年和8年总生存率分别为86．4％、56．5％和35．0％,中位生存时间为79个月。2年、5年和8年局部控制率分别为56．1％,36．3％和27．6％。单因素检验分析发现、无病间期、复发部位、复发灶数目、激素受体状态、复发灶近期疗效是否达到完全缓解、原发灶T分期和腋窝淋巴结转移状态对生存率的影响有统计学意义（P值均〈0．05）。多因素分析结果显示,无病间期、复发部位和数目及激素受体状态是独立的影响预后的因素。根据多因素分析结果建立预后指数,将全组患者划分为预后好、中等和差3个亚组,预后好组的2年、5年、8年总生存率分别为100％、91．6％、56．4％,预后中等组和预后差组分别为88．1％、59．1％、36．8％和68．0％、8．5％、0（P〈0．001）。结论：放射治疗是乳腺癌根治术后局部和区域性复发有效的治疗手段。预后指数可以合理预测预后好、预后中等和预后差的患者。     

Isolated local-regional recurrence following mastectomy for adenocarcinoma of the breast treated with radiation therapy alone or combined with surgery and/or chemotherapy

The results of radiation therapy alone or combined with surgery and/or chemotherapy are reported for 47 patients who presented with local and/or regional recurrence without evidence of distant metastases following initial management of adenocarcinoma of the breast with radical or modified radical mastectomy (43) or simple mastectomy (4). Patients were treated between October 1964 and March 1983 at the University of Florida; all have a 2-year minimum follow-up and 42/47 (89%) have had follow-up for greater than or equal to 5 years. The overall actuarial local-regional control rates were 80% at 2 years, 68% at 5 years, and 61% at 10 years. The 5-year actuarial local-regional control rates by site and extent of disease were as follows: single chest wall nodule, 92%; multiple chest wall nodules, 49%; regional lymph nodes, 66%; and multiple sites, 64%. The 5- and 10-year actuarial determinate disease-free survival rates for all patients were 41 and 17%, respectively. The 5- and 10-year actuarial survival rates for all patients were 50 and 34%, respectively.     

Analysis of failures following local treatment of isolated local-regional recurrence of breast cancer

Obe hundred fifty-seven patients with local-regional recurrence of breast cancer but without co-existing distant metastases were reviewed. The incidence of failure to control the local-regional recurrence was essentially the same whether the recurrence was treated with radiotherapy alone (62% ), surgery alone (76% ), or with a combination of the two (60 % ). A detailed analysis of the failures occurring in the patients treated with radiotherapy, with or without surgery, showed that most of the failures were because of a) inadequate doses of irradiation, b) the use of fields that were too small, and c) the lack of elective irradiation to the chest wall and supraclavicular fossa. Of the 100 patients with uncontrolled local-regional disease, 62% developed clinical symptoms that markedly impaired the quality of life. All of these symptoms were directly caused by the uncontrolled local-regional disease. Specific recommendations for the treatment of isolated local-regional recurrence are made.     

Local-regional treatment of patients with simultaneous local-regional recurrence and distant metastases following mastectomy

High-dose, large volume local-regional irradiation has been shown to be necessary in patients with local-regional recurrence of breast cancer without coexisting distant metastases; however, no studies exist that deal with the dose and volume of local-regional irradiation required for patients with both local-regional recurrence and distant metastases. This report is an analysis of 68 patients who presented with previously untreated local-regional recurrence and coexisting distant metastases. Thirty-five of these patients were treated with local-regional irradiation and systemic therapy; the remaining 33 patients received systemic therapy only. An analysis of the dose and volume in the 35 irradiated patients showed that if the irradiation was inadequate (dose less than 4500 rad and volume not large enough to encompass the entire involved site), the incidence of uncontrolled local-regional disease for the duration of life was 79%, similar to the 64% rate of uncontrolled local-regional disease in the 33 patients not receiving local-regional irradiation. On the other hand, if the dose to the recurrence was at least 4500 rad and if the field was large enough to encompass the entire site containing the recurrence, the incidence of uncontrolled local-regional disease for the duration of life was only 27%. The present study also suggests that local-regional irradiation may be indicated in patients with asymptomatic as well as symptomatic local-regional disease. In patients with distant metastases and initially asymptomatic local-regional disease, adequate irradiation resulted in a lower incidence of ultimate local-regional symptoms when compared to similar patients who were treated with inadequate or no local-regional irradiation. This difference was not quite statistically significant because of the small number of patients in each group.     

Local recurrence following treatment for breast cancer with an endoscopic nipple-sparing mastectomy

Purpose

Endoscopic nipple-sparing mastectomy (E-NSM) has been reportedly associated with smaller scars and greater patient satisfaction; however, long-term results of this procedure have not been made. The purpose of this retrospective study was to investigate the local recurrence (LR) rate and factors associated with it after E-NSM and to examine the oncologic safety of this procedure.

Methods

We reviewed the medical records of a total of 421 breasts in 404 patients who underwent E-NSM to investigate the LR rate and the factors associated with it. The clinico-pathological features and the treatment and outcomes of the patients with LRs were also examined.

Results

Eleven breasts (2.6 %) in 11 patients presented with LR as the first site of recurrence after a median follow-up time of 61 months. Among the 11 LRs, 9 patients presented with LR only, 1 patient exhibited regional lymph node recurrence, and 1 patient exhibited distant metastasis. The median time from surgery until LR was 25 months. Eight LRs developed near the original tumor site. The risk factors for LR in a multivariate analysis were a younger age of less than 40 years (p = 0.02), Stage III tumor (p = 0.01), and an inadequate surgical margin (p = 0.001). After the treatment, 6 patients had no evidence of disease, 2 patients died from metastatic disease, 2 patients experienced repeat LR, and the remaining patient who rejected excision exhibited a persistent LR.

Conclusions

E-NSM is an oncologically safe procedure and an acceptable method in selected patients requiring a mastectomy.

     

乳腺癌改良根治术后复发的治疗进展

乳腺癌改良根治术后局部复发一般是指手术侧的胸壁及腋窝淋巴结的复发。局部复发通常是乳腺癌治疗失败的第一征象,其发病率为4．0％～32．0%,且多出现在初次治疗后的2年以内,不过初次治疗数年后才发生局部复发的情况也不少见。在1997年美国肿瘤联合会（AJCC）的分期标准中,同侧锁骨上淋巴结转移是全身性转移的范畴,但在2003年AJCC新的分期标准将其归为局部复发的范畴,现国内也广为采用。复发部位以胸壁最为常见,占所有局部复发的50．0％～94．0％,其次为锁骨上淋巴结。     

乳腺癌根治术后区域淋巴结复发放射治疗疗效分析

目的：探讨乳腺癌根治术后区域淋巴结复发患者放射治疗和其他综合治疗手段的合理联用以及影响局部控制率和生存率的预后因素。方法：回顾性分析了1994～2003年期间在我院放疗科收治的77例乳腺癌根治术后区域淋巴结复发作为术后第一次治疗失败的患者，其中45例为锁骨上淋巴结，16例腋下淋巴结，6例内乳淋巴结，10例同时有2个淋巴结区累及。中位随访时间为34．4个月。所有患者均接受放射治疗。12例在放疗前接受复发灶手术切除。照射剂量范围为50-74Gy，中位剂量为60Gy。结果：本组患者中位生存期为4．67年，二年、五年和八年生存率分别为77．8％、47．4％和31．5％。无病间期、激素受体状态为影响生存率的独立的预后因素。总计有30例(39％)发生再次局部和(或)区域性复发，其中4例发生在原复发部位，26例发生在其他部位，胸壁是发生率最高的二次复发部位，总计有18例(23％)患者发生的再次复发部位中包括胸壁。首次术后病理腋淋巴结转移数目是影响局部控制率的预后因素。结论：放射治疗是乳腺癌术后区域淋巴结复发的有效治疗手段。23％的患者治疗后发生后续的胸壁复发，建议对患侧胸壁作预防性照射。首次术后病理腋淋巴结转移数目4个及以上的患者作胸壁预防的意义更大。无病间期2年及以上，激素受体阳性的患者是相对预后较好的患者群。全身治疗在改善生存率方面的意义尚不明确。     

Predictors of local-regional recurrence after neoadjuvant chemotherapy and mastectomy without radiation.

PURPOSE: To define clinical and pathologic predictors of local-regional recurrence (LRR) for patients treated with neoadjuvant chemotherapy and mastectomy without radiation. PATIENTS AND METHODS: We analyzed the outcome of the 150 breast cancer cases treated on prospective institutional trials with neoadjuvant chemotherapy and mastectomy without postmastectomy radiation. Clinical stage at diagnosis was I in 1%, II in 43%, IIIA in 23%, IIIB in 25%, and IV in 7%. No patient had inflammatory breast cancer. RESULTS: The median follow-up period of surviving patients was 4.1 years. The 5- and 10-year actuarial rates of LRR were both 27%. Pretreatment factors that positively correlated with LRR were increasing T stage (P <.0001) and increasing combined clinical stage (P <.0001). Pathologic and treatment factors that positively correlated with LRR were size of the residual primary tumor (P =.0048), increasing number of involved lymph nodes (P <.0001), and no use of tamoxifen (P =.0013). The LRR rate for the 18 patients with a pathologic complete response of both the primary tumor and lymph nodes (pCR) was 19% (95% confidence interval, 6% to 48%). In a forward stepwise Cox logistic regression analysis, clinical stage IIIB or greater (hazard ratio of 4.5, P <.001), pathologic involvement of four or more lymph nodes (hazard ratio of 2.7, P =.008), and no use of tamoxifen (hazard ratio of 3.9, P =.027) independently predicted for LRR. CONCLUSION: Advanced disease at presentation and positive lymph nodes after chemotherapy predict for clinically significant rates of LRR. Achievement of pCR does not preclude the need for postmastectomy radiation if warranted by the pretreatment stage of the disease.     

影响乳腺癌根治术后局部区域性复发后放疗的局部控制因素

目的分析影响乳腺癌根治术或改良根治术后胸壁和／或区域淋巴结复发者局部控制的因素，探讨放疗及与综合治疗配合在降低再次复发的意义。方法回顾分析255例乳腺癌根治术或改良根治术后以胸壁和／或区域淋巴结复发为首次治疗失败者，其中单纯胸壁复发109例，区域淋巴结复发114例，同时累及胸壁和区域淋巴结32例，共计累及复发部位304处。所有患者接受放疗，55例首先接受手术切除或活检，227例照射范围仅覆盖复发灶累及部位，28例对未复发部位进行预防性照射。照射42-74Gy，中位值60ey。190例接受了针对复发的全身治疗，其中171例化疗，69例内分泌治疗，41例先后接受化疗和内分泌治疗。结果随访9月至15．5年，中位值45个月。2、5、8年局部控制率分别为56．1％、36．3％、27．6％，中位局部控制时间为28个月。79处原发部位再次复发和83处其他部位后续复发，其中胸壁是再次复发频率最高部位。多因素分析证实复发灶未累及胸壁，病灶为单个或两个以上独立结节以及照射野覆盖完整的复发区域是影响原复发部位局部控制的独立预后因素，复发灶累及胸壁和内分泌治疗的运用是影响其他部位后续复发的独立预后因素。胸壁复发者采用全胸壁和局部小野照射的5年局部控制率分别为55．6％和33．6％（P=0．023）。结论放疗是乳腺癌根治术后局部和区域性复发有效的局部治疗手段，胸壁复发者需采用全胸壁照射以降低再次复发率。鉴于区域淋巴结复发者高比例的胸壁后续复发率，建议对该组患者进行胸壁预防性照射。内分泌治疗体现了降低其他部位后续复发的意义，但需更多临床前瞻性研究予以证实。     

乳腺癌不同临床亚型术后局部复发特征的对比分析

目的 研究乳腺癌不同临床亚型术后局部复发的不同特征,从而针对不同临床亚型制定不同治疗方案。方法 回顾性分析天津肿瘤医院2002年7月—2005年2月期间收治的477例乳腺癌术后复发患者,通过免疫组化方法分为luminal A型,luminal B型,HER-2(+)型,基底样型,分析各亚型之间局部复发的不同特征。结果 477例复发病例中,1年内复发率26.2%(125/477),2年内复发率61.2%(292/477),2年以上复发率38.8%(185/477)。按照临床分型luminal A型63例,luminal B型67例,HER-2(+)型110例,基底样型237例,各亚型在2年内和2年以上复发率之间的差异有统计学意义(P＜0.01)。局部复发后转移例数共310例,占65.0%(310/477),复发后转移率luminal A型28.6%(18/63),luminal B型40.3%(27/67),HER-2(+)型60.9%(67/110),基底样型83.5%(198/237),各亚型复发后转移率之间的差异有统计学意义(P＜0.01)。各亚型单纯骨转移组的差异有统计学意义(P＜0.01),而单纯肺转移、单纯肝转移和多部位转移发生率的差异无统计学意义(P＞0.05)。各亚型复发后疾病进展时间的差异有统计学意义(P＜0.05)。复发后5年总生存率48.4%(231/477),各亚型生存率luminal A型68.3%(43/63),luminal B型62.7%(42/67),HER-2(+)型49.1%(54/110),基底样型38.8%(92/237),各亚型生存率之间的差异有统计学意义(P＜0.01)。结论 乳腺癌术后2年内是复发的高峰期。基底样型乳腺癌最易复发,复发后转移率最高,疾病进展时间最短,且生存率最低,HER-2(+)型次之,luminal B型复发率较低,复发后转移较少,疾病进展较慢且生存率较高,luminal A型复发率最低,复发后转移最少,疾病进展最慢且生存率最高。luminal B型更容易发生骨转移。     

A 23-year delayed locoregional recurrence of breast carcinoma following mastectomy

A 77-year-old woman who underwent a right modified radical mastectomy 23 years ago with no further adjuvant treatment presented with a right chest wall mass (3 x 4 x 2 cm) at the scar. She had no symptoms nor metastasis. The laboratory data were normal including tumor marker. The mass was diagnosed as compatible with a local recurrence tumor from the previous breast cancer on the ultrasonography and chest CT. After obtaining her informed consent for the therapy, we performed 60 Gy/30 fr radiotherapy on the recurrent tumor on her right chest wall with concurrent oral chemo-endocrine therapy. The first regimens were tamoxifen 20 mg/day and 5'-DFUR 600 mg/day, followed by toremifene 80 mg/day and 5'-DFUR 600 mg/day, and then the tumor disappeared. But three years later, we found tumor regrowth. We changed the regimen, giving 5'-DFUR 1,200 mg/day and cyclophosphamide 100 mg/day for 2 weeks followed by a 1-week drug-free period, then added 10 Gy/5 fr radiotherapy and hyperthermia twice a week. Final regimens were anastrozole 1 mg/day and capecitabine 900 mg/day. The recurrent tumor decreased and the disease stabilized. After these therapies, she had very good quality of life. We recommend radiation and/or hyperthermia with concurrent oral chemo-endocrine therapy as useful for the delayed recurrence of elderly breast cancer after a modified radical mastectomy.     

Molecular and genetic markers in the local-regional management of breast cancer

The clinical application of molecular markers in the diagnosis, staging, and management of breast cancer continues to expand. Although the use of molecular markers in local-regional disease does not approach the level of their application in the systemic management of breast cancer, a growing body of rature supports the potential for molecular and genetic factors in clinical decision making regarding the local-regional management of breast cancer. As with conventional clinical and histopathologic factors, data regarding molecular and genetic factors as they relate to local-regional relapse may be conflicting and are subject to the usual limitations of predominantly retrospective studies. There are, however, some consistent data suggesting associations between local-regional control of disease and several molecular markers, including hormone receptor status, HER2/neu, p53, proliferative markers, and others. Interpretation of these data and how to use this information in clinical practice remains challenging. The available rature regarding the use of genetic and molecular markers in the local-regional management of breast cancer is summarized in this review.     

乳腺癌乳房切除术后局部区域复发的研究现况

 乳腺癌在乳房切除术后出现局部区域复发（LRR）,虽是疾病进展的一个信号,但LRR不同于远处转移。其中部分患者经积极治疗后仍预后较好,尤其是孤立的LRR患者;复发间隔、复发位点和复发灶数目等对LRR患者预后有较大影响;对适合的LRR患者,手术切除和内分泌治疗的价值已被证实,化疗的价值仍有待进一步研究。     

Significance of local recurrence after mastectomy for breast cancer.

In a retrospective study 678 patients who underwent (modified) radical mastectomy between 1970 and 1986 were analysed. By comparing the groups of patients who experienced local recurrence, regional recurrence or distant metastasis during follow-up with patients who remained free of disease, we have tried to gain some insight into the significance of local recurrence. By looking at the prognostic factors and the disease-free period there is hardly any difference between the patients with either a local, regional or distant recurrence. Actuarial survival of patients with local recurrence is slightly better than the survival of patients with distant metastasis (P = 0.009). From our results and from the literature we conclude that an isolated local recurrence after mastectomy for breast cancer is, in most cases, a first manifestation of metastatic disease. Probably only a minority of the local recurrences is caused by tumour cells left behind in the operation field.     

乳腺癌术后胸壁复发的放射治疗

目的探讨放射治疗在乳腺癌根治术或改良根治术后胸壁复发患者中的合理应用及影响生存率的预后因素。方法接受放射治疗的乳腺癌术后胸壁复发患者共86例。中位随访时间为77.4个月。51例复发灶为单结节,19例为多结节,16例为弥散。67例为单纯胸壁复发,19例同时合并区域淋巴结复发。30例在放射治疗前接受手术切除。27例照射野为全胸壁,59例为局部小野。中位照射剂量为58Gy。结果①近期疗效65例(76%)病灶达到临床完全消退(CR)。单因素分析显示复发灶数目、直径和有无手术切除与临床CR率有关。②胸壁再次复发47例(55%)出现胸壁再次复发。采用小野照射发生野外复发的几率明显高于全胸壁照射(58%∶15%)。③生存率中位生存时间为6.3年,2、5和8年生存率分别为88%、62%和34%。62%的患者在随访期内出现远地转移。多因素分析发现无病间期长短和有无区域淋巴结累及是影响生存率的独立因素。结论照射野必须包括完整的胸壁以避免小野照射带来的高比例胸壁再次复发率。直径3cm以上或弥散的病灶需要综合治疗的配合以提高局部控制率。生存率预后良好的因素包括无病间期>2年,无区域淋巴结累及和复发灶表现为单结节。