Yu Ke-da, Di Gen-hong, Wu Jiong, Lu Jin-song, Shen Kun-wei, Liu Guang-yu, Shen Zhen-zhou, Shao Zhio-ming
Department of Breast Surgery, Cancer Hospital/Cancer Institute, Fudan University, 200032 Shanghai, China.
J Cancer Res Clin Oncol. 2008 Dec;134(12):1347-54. doi: 10.1007/s00432-008-0414-2. Epub 2008 May 17.
Most breast cancer patients with estrogen receptor-negative/progesterone receptor-positive (ER-/PgR+) tumors are premenopausal cases, with few alternatives of adjuvant endocrine therapy but tamoxifen (TAM). The efficacy of adjuvant TAM on ER-/PgR+ patients is still controversial. In this study, we evaluated the efficacy of adjuvant TAM on patients with ER-/PgR+ tumors.
Among all 1,836 consecutive patients with operable primary breast cancer, 798 cases were with ER+/PgR+ tumors and 205 with ER-/PgR+ tumors. By sub-grouping the patients according to ER/PR phenotypes and whether the patients had been treated with adjuvant TAM therapy or not, we investigated the differences of survivals between groups.
Patients with ER-/PgR+ tumors were younger than those with ER+/PgR+ tumors (P = 0.021), and were mainly premenopausal (P = 0.013). ER-/PgR+ patients were related to more involved lymph nodes and later stage. In the absence of TAM treatment, ER+/PgR+ group had a similar survival to ER-/PgR+ group in terms of 5-year disease-free survival (DFS), as well as overall survival (OS). After TAM treatment, both groups had increased survival rates comparing with the baseline of non-TAM-treated groups. Moreover, significant survival differences were then observed between TAM-treated ER+/PgR+ group and TAM-treated ER-/PgR+ group either in DFS (P = 0.016) or OS (P = 0.007). Of the TAM-treated patients, by sub-dividing the chemotherapy-treated population into CMF (cyclophosphamide, methotrexate and 5-fluorouracil) group and CA(E)F (cyclophosphamide, doxorubicin/epirubicin and 5-fluorouracil) group, we found that ER-/PgR+ group got more benefits from CMF regimen than from CA(E)F. Subpopulation treatment effect pattern plot (STEPP) analysis showed that the ER-/PgR+ group had an obvious worse survival than ER+/PgR+ group in younger patients (<55 years). Axillary lymph nodes involvement was the only independent prognostic factor for ER-/PgR+ group.
Our results indicate that patients with ER-/PgR+ tumors are mainly premenopausal and young. Although patients with ER-/PgR+ tumors are generally considered as candidates for endocrine therapy clinically, the ER-/PgR+ group gains less benefits from adjuvant TAM treatment than ER+/PgR+ group.
大多数雌激素受体阴性/孕激素受体阳性(ER-/PgR+)肿瘤的乳腺癌患者为绝经前患者,辅助内分泌治疗除他莫昔芬(TAM)外几乎没有其他选择。辅助TAM对ER-/PgR+患者的疗效仍存在争议。在本研究中,我们评估了辅助TAM对ER-/PgR+肿瘤患者的疗效。
在1836例连续的可手术原发性乳腺癌患者中,798例为ER+/PgR+肿瘤患者,205例为ER-/PgR+肿瘤患者。通过根据ER/PR表型以及患者是否接受辅助TAM治疗对患者进行亚组划分,我们研究了各组之间生存率的差异。
ER-/PgR+肿瘤患者比ER+/PgR+肿瘤患者更年轻(P = 0.021),且主要为绝经前患者(P = 0.013)。ER-/PgR+患者的腋窝淋巴结受累更多且分期更晚。在未接受TAM治疗的情况下,就5年无病生存率(DFS)和总生存率(OS)而言,ER+/PgR+组与ER-/PgR+组的生存率相似。接受TAM治疗后,与未接受TAM治疗组的基线相比,两组的生存率均有所提高。此外,在TAM治疗的ER+/PgR+组与TAM治疗的ER-/PgR+组之间,无论是DFS(P = 0.016)还是OS(P = 0.007),均观察到显著的生存差异。在接受TAM治疗的患者中,将接受化疗的人群分为CMF(环磷酰胺、甲氨蝶呤和5-氟尿嘧啶)组和CA(E)F(环磷酰胺、阿霉素/表柔比星和5-氟尿嘧啶)组,我们发现ER-/PgR+组从CMF方案中获得的益处比从CA(E)F方案中更多。亚组治疗效果模式图(STEPP)分析显示,在年轻患者(<55岁)中,ER-/PgR+组的生存率明显低于ER+/PgR+组。腋窝淋巴结受累是ER-/PgR+组唯一的独立预后因素。
我们的结果表明,ER-/PgR+肿瘤患者主要为绝经前且年轻。尽管临床上ER-/PgR+肿瘤患者通常被视为内分泌治疗的候选者,但ER-/PgR+组从辅助TAM治疗中获得的益处比ER+/PgR+组少。