ЛЕЧЕНИЕ ТРОЙНОГО НЕГАТИВНОГО ПОДТИПА РАКА МОЛОЧНОЙ ЖЕЛЕЗЫ

А. Д. Зикиряходжаев, Мария Александровна Фролова, Елена Александровна Рассказова, Е. В. Глазкова
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Abstract

The rate of triple-negative breast cancer is 10–24  %, and in recent years it’s one of the most studied subtypes of breast cancer due to its clinical aggressiveness and a small number of molecular targets. The study objective is to evaluate effectiveness of different NAPCT regimens including their dependence on the presence of mutations in the ВRСА 1, 2, СHEK2 genes. Materials and methods . The study included 40 female patients with triple-negative breast cancer. The patients were monitored from 2012 to 2016; surgical treatment was performed at the P.A. Hertzen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Center, Ministry of Health of Russia. Median patient age was 45.9 (31–69)  years. All patients received neoadjuvant polychemotherapy (NAPCT) per different regimens. Then the patients underwent surgery of different volume (from radical mastectomies to resections), and in 25 % of cases reconstructive breast surgery was performed. In 5 patients with BRCA1, – 2 mutations, prophylactic subcutaneous mastectomy with immediate reconstruction with an implant was performed; 2 patients refused prophylactic mastectomy; in 1 patient with СНЕК2 mutation, metachronous multiple primary breast cancer was diagnosed, previously she didn»t undergo prophylactic mastectomy, and 6 years later cancer in the second breast was diagnosed. Results. The study included 11 patients under 40 (27.5 %), 4 (50 %) of them in the group with mutations in ВRCA1, -2, CHEK2. The study demonstrated high effectiveness of NAPCT regimens per the АС + Т scheme and weekly injections of doxorubicin 25 mg/m 2 , cisplatin 30 mg/m 2 , and paclitaxel 100 mg/m 2 . Grade IV treatment pathomorphosis for NAPCT per АС + Т scheme was achieved in 50.0 ± 7.9 % cases, for intensified regimen – in 62.5 ± 12.5 % cases. Median follow-up duration for this patient group was 22.1 months, and during this time disease progression was observed in 3 patients: in the 1st patient continued growth on the thoracic wall and brain metastases were diagnosed, in the 2nd patient – lung and supraclavicular lymph nodes metastases, in the 3rd patient – metastases in the cerebellum. In all of these patients, grade IV treatment pathomorphosis wasn»t achieved. Conclusions. The study demonstrated high effectiveness of NAPCT in patients with triple-negative breast cancer of different stages: objective response rate was 90.0 ± 4.7 %, grade IV treatment pathomorphosis was 50.0 ± 7.9 %. Grade IV treatment pathomorphosis for NAPCT per АС + Т scheme was achieved in 50.0 ± 7.9 % cases, for intensified regimen – in 62.5 ± 12.5 % cases. Rate of grade IV treatment pathomorphosis was higher in patients with hereditary form of the disease (62.5 ± 18.3 %) compared to the group with sporadic breast cancer (46.9 ± 8.8 %), р >0.05. In all patients, 2-year disease-free survival was 92.5 %, 2-year overall survival was 95 %.
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乳腺癌三重负亚型治疗
三阴性乳腺癌的发病率为10 - 24%,由于其临床侵袭性强,分子靶点较少,是近年来研究最多的乳腺癌亚型之一。该研究的目的是评估不同NAPCT治疗方案的有效性,包括它们对ВRСА 1,2, СHEK2基因突变存在的依赖性。材料和方法。该研究包括40名患有三阴性乳腺癌的女性患者。2012 - 2016年对患者进行监测;手术治疗在P.A. Hertzen莫斯科肿瘤研究所-俄罗斯卫生部国家医学研究放射中心分支进行。患者中位年龄为45.9岁(31-69岁)。所有患者均接受不同方案的新辅助多重化疗(NAPCT)。然后患者接受了不同体积的手术(从根治性乳房切除术到全切除术),25%的病例进行了乳房重建手术。在5例BRCA1, - 2突变患者中,进行了预防性皮下乳房切除术并立即用植入物重建;2例拒绝预防性乳房切除术;1例СНЕК2突变患者,诊断为异时性多发原发乳腺癌,此前未行预防性乳房切除术,6年后诊断为第二个乳房癌。结果。该研究包括11例40岁以下的患者(27.5%),其中4例(50%)属于ВRCA1, -2, CHEK2突变组。该研究表明,АС + Т方案和每周注射阿霉素25mg / m2、顺铂30mg / m2和紫杉醇100mg / m2的NAPCT方案具有很高的有效性。在АС + Т方案中,50.0±7.9%的患者达到了NAPCT的IV级治疗病理形态,在强化方案中,62.5±12.5%的患者达到了四级治疗病理形态。该患者组的中位随访时间为22.1个月,在此期间有3例患者出现疾病进展:1例患者胸壁持续生长并诊断为脑转移,2例患者肺和锁骨上淋巴结转移,3例患者小脑转移。在所有这些患者中,没有达到IV级病理形态治疗。结论。研究表明,NAPCT在不同分期的三阴性乳腺癌患者中具有较高的疗效:客观有效率为90.0±4.7%,IV级治疗病理形态学为50.0±7.9%。在АС + Т方案中,50.0±7.9%的患者达到了NAPCT的IV级治疗病理形态,在强化方案中,62.5±12.5%的患者达到了四级治疗病理形态。遗传型乳腺癌患者的IV级治疗性病变发生率(62.5±18.3%)高于散发型乳腺癌患者(46.9±8.8%),差异有统计学意义(p < 0.05)。所有患者2年无病生存率为92.5%,2年总生存率为95%。
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