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[局部晚期非炎性乳腺癌的联合化疗及术前放疗治疗:120例患者的最新结果]

[Locally advanced non inflammatory breast cancer treated by combined chemotherapy and preoperative irradiation: updated results in a series of 120 patients].

作者信息

Lerouge D, Touboul E, Lefranc J P, Genestie C, Moureau-Zabotto L, Blondon J

机构信息

Service d'oncologie-radiothérapie, hôpital Tenon AP-HP, 4, rue de la Chine, 75020 Paris, France.

出版信息

Cancer Radiother. 2004 Jun;8(3):155-67. doi: 10.1016/j.canrad.2004.01.001.

DOI:10.1016/j.canrad.2004.01.001
PMID:15217583
Abstract

PURPOSE

To evaluate our updated data concerning survival and locoregional control in a study of locally advanced non inflammatory breast cancer after primary chemotherapy followed by external preoperative irradiation.

PATIENTS AND METHODS

Between 1982 and 1998, 120 patients (75 stage IIIA, 41 stage IIIB, and 4 stage IIIC according to AJCC staging system 2002) were consecutively treated by four courses of induction chemotherapy with anthracycline-containing combinations followed by preoperative irradiation (45 Gy to the breast and nodal areas) and a fifth course of chemotherapy. Three different locoregional approaches were proposed, depending on tumour characteristics and tumour response. After completion of local therapy, all patients received a sixth course of chemotherapy and a maintenance adjuvant chemotherapy regimen without anthracycline. The median follow-up from the beginning of treatment was 140 months.

RESULTS

Mastectomy and axillary dissection were performed in 49 patients (with residual tumour larger than 3 cm in diameter or located behind the nipple or with bifocal tumour), and conservative treatment in 71 patients (39 achieved clinical complete response or partial response >90% and received additional radiation boost to initial tumour bed; 32 had residual mass <or=3 cm in diameter and were treated by wide excision and axillary dissection followed by a boost to the excision site). Ten-year actuarial local failure rate was 13% after irradiation alone, 23% after wide excision and irradiation, and 4% after mastectomy (p =0.1). After multivariate analysis, possibility of breast-conserving therapy was related to initial tumour size (<6 vs. >or=6 cm in diameter, p =0.002). Ten-year overall metastatic disease-free survival rate was 61%. After multivariate analysis, metastatic disease-free survival rates were significantly influenced by clinical stage (stage IIIA-B vs. IIIC, p =0.0003), N-stage (N0 vs. N1-2a, and 3c, p =0.017), initial tumour size (<6 vs. >or=6 cm in diameter, p =0.008), and tumour response after induction chemotherapy and preoperative irradiation (clinically complete response + partial response vs. non-response, p =0.0015). In the non conservative breast treatment group, of the 32 patients with no change in clinical tumour size after induction chemotherapy, the 10-year metastatic disease-free survival rate was 59% with only one local relapse. Arm lymphedema was noted in 17% (14 of 81) following axillary dissection and in 2.5% (1 of 39) without axillary dissection. Cosmetic results were satisfactory in 70% of patients treated by irradiation alone and in 51.5% of patients after wide excision and irradiation.

CONCLUSION

Despite the poor prognosis of patients with locally advanced non inflammatory breast cancer resistant to primary anthracycline-based regimen, aggressive locoregional management using preoperative irradiation and mastectomy with axillary dissection offers a possibility of long term survival with low local failure rate for patients without extensive nodal disease. On the other hand, the rate of local failure seems to be high in patients with clinical partial tumour response following induction chemotherapy and breast-conserving treatment combining preoperative irradiation and large wide excision.

摘要

目的

在一项针对局部晚期非炎性乳腺癌患者进行初始化疗后行术前体外照射的研究中,评估我们关于生存及局部区域控制的最新数据。

患者与方法

1982年至1998年间,120例患者(根据2002年美国癌症联合委员会分期系统,75例为IIIA期,41例为IIIB期,4例为IIIC期)先后接受了四个疗程含蒽环类药物联合方案的诱导化疗,随后进行术前照射(乳腺及区域淋巴结45 Gy)及第五个疗程的化疗。根据肿瘤特征及肿瘤反应,提出了三种不同的局部区域治疗方法。局部治疗完成后,所有患者接受第六个疗程的化疗及不含蒽环类药物的维持辅助化疗方案。从治疗开始的中位随访时间为140个月。

结果

49例患者(残留肿瘤直径大于3 cm或位于乳头后方或为双灶性肿瘤)接受了乳房切除术及腋窝淋巴结清扫术,71例患者接受了保乳治疗(39例达到临床完全缓解或部分缓解>90%,并对初始肿瘤床进行了额外的放疗增敏;32例残留肿块直径≤3 cm,接受了广泛切除及腋窝淋巴结清扫术,随后对切除部位进行了放疗增敏)。单纯放疗后的10年精算局部失败率为13%,广泛切除加放疗后为23%,乳房切除术后为4%(p = 0.1)。多因素分析后,保乳治疗的可能性与初始肿瘤大小有关(直径<6 cm与≥6 cm,p = 0.002)。10年无远处转移疾病生存率为61%。多因素分析后,无远处转移疾病生存率受临床分期(IIIA - B期与IIIC期,p = 0.0003)、N分期(N0与N1 - 2a及3c,p = 0.017)、初始肿瘤大小(直径<6 cm与≥6 cm,p = 0.008)以及诱导化疗和术前照射后的肿瘤反应(临床完全缓解 + 部分缓解与无反应,p = 0.0015)显著影响。在非保乳治疗组中,32例诱导化疗后临床肿瘤大小无变化的患者,10年无远处转移疾病生存率为59%,仅1例局部复发。腋窝淋巴结清扫术后17%(81例中的14例)出现上肢淋巴水肿,未行腋窝淋巴结清扫术的患者中2.5%(39例中的1例)出现上肢淋巴水肿。单纯放疗治疗的患者中70%美容效果满意,广泛切除加放疗后的患者中51.5%美容效果满意。

结论

尽管对基于蒽环类药物的初始方案耐药的局部晚期非炎性乳腺癌患者预后较差,但对于无广泛区域淋巴结疾病的患者,采用术前照射及乳房切除加腋窝淋巴结清扫的积极局部区域治疗方法可提供低局部失败率的长期生存可能性。另一方面,诱导化疗后临床部分肿瘤反应且采用术前照射联合广泛切除的保乳治疗患者局部失败率似乎较高。

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