Research Unit in Medical Senology, Department of Medicine, European Institute of Oncology, Università degli Studi di Milano, Milan, Italy.
J Clin Oncol. 2010 Jun 20;28(18):2966-73. doi: 10.1200/JCO.2009.25.9549. Epub 2010 May 10.
Retrospective studies suggest that primary breast cancers lacking estrogen receptor (ER) and progesterone receptor (PR) and not overexpressing human epidermal growth factor receptor 2 (HER2; triple-negative tumors) are particularly sensitive to DNA-damaging chemotherapy with alkylating agents.
Patients enrolled in International Breast Cancer Study Group Trials VIII and IX with node-negative, operable breast cancer and centrally assessed ER, PR, and HER2 were included (n = 2,257). The trials compared three or six courses of adjuvant classical cyclophosphamide, methotrexate, and fluorouracil (CMF) with or without endocrine therapy versus endocrine therapy alone. We explored patterns of recurrence by treatment according to three immunohistochemically defined tumor subtypes: triple negative, HER2 positive and endocrine receptor absent, and endocrine receptor present.
Patients with triple-negative tumors (303 patients; 13%) were significantly more likely to have tumors > 2 cm and grade 3 compared with those in the HER2-positive, endocrine receptor-absent, and endocrine receptor-present subtypes. No clear chemotherapy benefit was observed in endocrine receptor-present disease (hazard ratio [HR], 0.90; 95% CI, 0.74 to 1.11). A statistically significantly greater benefit for chemotherapy versus no chemotherapy was observed in triple-negative breast cancer (HR, 0.46; 95% CI, 0.29 to 0.73; interaction P = .009 v endocrine receptor-present disease). The magnitude of the chemotherapy effect was lower in HER2-positive endocrine receptor-absent disease (HR, 0.58; 95% CI, 0.29 to 1.17; interaction P = .24 v endocrine receptor-present disease).
The magnitude of benefit of CMF chemotherapy is largest in patients with triple-negative, node-negative breast cancer.
回顾性研究表明，缺乏雌激素受体（ER）和孕激素受体（PR）且不高表达人表皮生长因子受体 2（HER2；三阴性肿瘤）的原发性乳腺癌对含烷化剂的 DNA 损伤化疗特别敏感。
纳入了国际乳腺癌研究组试验 VIII 和 IX 中无淋巴结转移、可手术的乳腺癌患者，这些患者的 ER、PR 和 HER2 经中心评估，且接受了三或六疗程辅助经典环磷酰胺、甲氨蝶呤和氟尿嘧啶（CMF）联合或不联合内分泌治疗与单纯内分泌治疗（n=2257）。我们根据三种免疫组织化学定义的肿瘤亚型（三阴性、HER2 阳性和内分泌受体缺失、内分泌受体阳性）的治疗方式探讨了复发模式。
与 HER2 阳性、内分泌受体缺失和内分泌受体阳性的肿瘤亚型相比，三阴性肿瘤（303 例；13%）患者的肿瘤直径>2cm 和 3 级的比例显著更高。在内分泌受体阳性疾病中，并未观察到明确的化疗获益（风险比[HR]，0.90；95%CI，0.74 至 1.11）。与无化疗相比，三阴性乳腺癌患者化疗获益具有统计学意义（HR，0.46；95%CI，0.29 至 0.73；交互 P=0.009 与内分泌受体阳性疾病）。在 HER2 阳性、内分泌受体缺失疾病中，化疗效果的幅度较低（HR，0.58；95%CI，0.29 至 1.17；交互 P=0.24 与内分泌受体阳性疾病）。
CMF 化疗的获益幅度在三阴性、淋巴结阴性乳腺癌患者中最大。
