Kriege Mieke, Seynaeve Caroline, Meijers-Heijboer Hanne, Collee J Margriet, Menke-Pluymers Marian B E, Bartels Carina C M, Tilanus-Linthorst Madeleine M A, Blom Jannet, Huijskens Elisabeth, Jager Agnes, van den Ouweland Ans, van Geel Bert, Hooning Maartje J, Brekelmans Cecile T M, Klijn Jan G M
Department of Medical Oncology, Rotterdam Family Cancer Clinic, Erasmus MC-Daniel den Hoed Cancer Center, Groene Hilledijk 301, 3075 EA Rotterdam, the Netherlands.
J Clin Oncol. 2009 Aug 10;27(23):3764-71. doi: 10.1200/JCO.2008.19.9067. Epub 2009 Jun 29.
Preclinical as well as a few small retrospective, neoadjuvant studies suggest that breast cancer (cells) without functional BRCA1 or BRCA2 protein have an increased sensitivity to some chemotherapeutic agents causing double-strand DNA breaks. In this study we assessed the sensitivity to standard first-line chemotherapy of metastatic BRCA1/2-associated breast cancer, compared with sporadic breast cancer patients.
From the Family Cancer Clinic database, we selected 93 BRCA1- and 28 BRCA2-associated breast cancer patients treated with chemotherapy for metastatic disease before January 1, 2007. Objective response (OR), progression-free survival (PFS), and overall survival (OS) after start of first-line chemotherapy were compared with those of sporadic patients, matched for year of birth, age at diagnosis of primary breast cancer, and year of detection of metastatic disease.
The chemotherapy regimens most frequently used were anthracycline-based (n = 147) and cyclophosphamide, methotrexate, and fluorouracil (CMF)/CMF like (n = 68). As compared to sporadic patients, BRCA2-associated patients had a significantly higher OR (89% v 50%; P = .001), a longer PFS (hazard ratio multivariate [HR(mult)] 0.64; P = .04) and a prolonged OS (HR(mult), 0.53; P = .005) after start of first-line chemotherapy for metastatic breast cancer. For BRCA1-associated patients, a nonsignificant trend for an increased OR (66% v 50%; P = .07), and a longer PFS (HR(mult), 0.79; P = .14) after first-line chemotherapy for metastatic breast cancer was observed, but not for OS.
BRCA2-associated breast cancer is more sensitive to standard first-line chemotherapy for metastatic breast cancer in comparison with sporadic breast cancer, especially to anthracyclines. For BRCA1-associated breast cancer no statistically significant higher sensitivity was observed.
临床前研究以及一些小型回顾性新辅助研究表明，缺乏功能性BRCA1或BRCA2蛋白的乳腺癌（细胞）对某些导致双链DNA断裂的化疗药物敏感性增加。在本研究中，我们评估了转移性BRCA1/2相关乳腺癌与散发性乳腺癌患者对标准一线化疗的敏感性。
从家庭癌症诊所数据库中，我们选取了93例BRCA1相关和28例BRCA2相关的乳腺癌患者，这些患者在2007年1月1日前接受了转移性疾病的化疗。将一线化疗开始后的客观缓解率（OR）、无进展生存期（PFS）和总生存期（OS）与散发性患者进行比较，散发性患者在出生年份、原发性乳腺癌诊断时的年龄以及转移性疾病检测年份方面进行匹配。
最常使用的化疗方案是以蒽环类为基础的方案（n = 147）以及环磷酰胺、甲氨蝶呤和氟尿嘧啶（CMF）/类CMF方案（n = 68）。与散发性患者相比，BRCA2相关患者在转移性乳腺癌一线化疗开始后，OR显著更高（89%对50%；P = 0.001），PFS更长（多变量风险比[HR(mult)] 0.64；P = 0.04），OS延长（HR(mult)，0.53；P = 0.005）。对于BRCA1相关患者，转移性乳腺癌一线化疗后OR增加（66%对50%；P = 0.07）以及PFS更长（HR(mult)，0.79；P = 0.14）有不显著的趋势，但OS无此趋势。
与散发性乳腺癌相比，BRCA2相关乳腺癌对转移性乳腺癌的标准一线化疗更敏感，尤其是对蒽环类药物。对于BRCA1相关乳腺癌，未观察到统计学上显著更高的敏感性。
