Touboul E, Buffat L, Lefranc J P, Blondon J, Deniaud E, Mammar H, Laugier A, Schlienger M
Service de Cancérologie-Radiothérapie, Hôpital Tenon, Paris, France.
Int J Radiat Oncol Biol Phys. 1996 Mar 15;34(5):1019-28. doi: 10.1016/0360-3016(95)02207-4.
The aims of this prospective study were to evaluate the outcome and the possibility of breast conservation therapy for patients with locally advanced noninflammatory breast cancer after primary chemotherapy followed by external preoperative irradiation.
Between April 1982 and June 1990, 97 patients with locally advanced nonmetastatic and noninflammatory breast cancer were treated. The median follow-up was 93 months from the beginning of treatment. The induction treatment consisted of four courses of chemotherapy (doxorubicin, vincristine, cyclophosphamide, 5-fluorouracil) followed by preoperative irradiation (45 Gy to the breast and nodal areas). A fifth course of chemotherapy was given after irradiation therapy. Three different loco-regional approaches were proposed, depending on the tumoral response. In 37 patients (38%) with residual tumor larger than 3 cm in diameter or located behind the nipple or with bifocal tumors, mastectomy and axillary dissection were performed. Sixty other patients (62%) benefited from conservative treatment: 33 patients (34%) achieved complete remission and no surgery was done but additional radiation boost was given to the initial tumor bed; 27 patients (28%) who had a residual mass less than or equal to 3 cm in diameter were treated by wide excision and axillary dissection followed by a boost to the excision site. After completion of local therapy, all patients received a sixth course of chemotherapy. A maintenance adjuvant chemotherapy regimen without anthracycline was prescribed (12 monthly cycles).
The 5-year actuarial loco-regional relapse rate was 16% after radiotherapy alone, 16% following wide excision and radiotherapy, and 5.4% following mastectomy. The 5-year loco-regional relapse rate was significantly higher after conservative local treatment (wide excision and radiotherapy, and radiotherapy alone) than after mastectomy (p= 0.04). After conservative local treatment, the 5-year breast conserving rate of patients with loco-regional disease-free status was 84%. For all patients included in this study, the 5-year breast-conserving rate of those who were loco-regional disease-free was 52%. In multivariate analysis, the possibility of breast conservative treatment was significantly related to the initial tumor size and age (more conservative treatment for tumor size < 6cm and age < 50 years). Five- and 10-year overall survival rates and disease-free survival rates were 80, 69, 73, and 61% respectively. Five- and 10-year overall survival rates were not influenced by the local treatment (conservative vs. nonconservative local treatment, p = 0.9). On the other hand, local failure significantly decreased the 5- and 10-year overall survival rates (p , 0.0001). In multivariate analysis, three factors had a significant impact on overall survival and disease-free survival: tumor response after induction chemotherapy, initial tumor size, and clinical stage. Arm lymphedema was noted in 12.5% (8 out of 64) of the patients treated with axillary dissection and in 3% (1 out of 33) without axillary dissection. Cosmetic results were satisfactory in 79% of patients after wide excision and radiotherapy and in 71% of patients treated by radiotherapy alone.
Induction chemotherapy followed by preoperative irradiation may permit the selection of some patients with locally advanced breast cancer for conservative treatment. However, the impact of this treatment modality on long-term survival remains to be established.
本前瞻性研究的目的是评估原发性化疗后行术前体外照射的局部晚期非炎性乳腺癌患者保乳治疗的效果及可能性。
1982年4月至1990年6月,对97例局部晚期非转移性非炎性乳腺癌患者进行了治疗。从治疗开始的中位随访时间为93个月。诱导治疗包括四个疗程的化疗(阿霉素、长春新碱、环磷酰胺、5-氟尿嘧啶),随后进行术前照射(乳腺和腋窝区域45 Gy)。放疗后给予第五个疗程的化疗。根据肿瘤反应提出了三种不同的局部区域治疗方法。37例(38%)直径大于3 cm的残留肿瘤患者、乳头后方肿瘤患者或双灶性肿瘤患者行乳房切除术和腋窝淋巴结清扫术。另外60例(62%)患者接受了保乳治疗:33例(34%)达到完全缓解,未行手术,但对初始肿瘤床给予额外的放疗增敏;27例(28%)直径小于或等于3 cm的残留肿块患者行广泛切除和腋窝淋巴结清扫术,随后对切除部位进行放疗增敏。局部治疗完成后,所有患者接受第六个疗程的化疗。规定了一个不含蒽环类药物的维持辅助化疗方案(12个每月周期)。
单纯放疗后5年局部区域复发率为16%,广泛切除加放疗后为16%,乳房切除术后为5.4%。保守局部治疗(广泛切除加放疗和单纯放疗)后5年局部区域复发率显著高于乳房切除术后(p = 0.04)。保守局部治疗后,局部区域无病状态患者的5年保乳率为84%。对于本研究纳入的所有患者,局部区域无病患者的5年保乳率为52%。多因素分析显示,保乳治疗的可能性与初始肿瘤大小和年龄显著相关(肿瘤大小<6 cm且年龄<50岁时更倾向于保乳治疗)。5年和10年总生存率及无病生存率分别为80%、69%、73%和61%。5年和10年总生存率不受局部治疗(保守与非保守局部治疗,p = 0.9)的影响。另一方面,局部失败显著降低了5年和10年总生存率(p<0.0001)。多因素分析显示,三个因素对总生存和无病生存有显著影响:诱导化疗后的肿瘤反应、初始肿瘤大小和临床分期。腋窝淋巴结清扫术治疗的患者中有12.5%(64例中的8例)出现手臂淋巴水肿,未行腋窝淋巴结清扫术的患者中有3%(33例中的1例)出现。广泛切除加放疗后79%的患者和单纯放疗后71%的患者美容效果满意。
原发性化疗后行术前照射可能使部分局部晚期乳腺癌患者适合保乳治疗。然而,这种治疗方式对长期生存的影响仍有待确定。