Abreu M H, Gomes M, Menezes F, Afonso N, Abreu P H, Medeiros R, Pereira D, Lopes C
Department of Medical Oncology, Portuguese Institute of Oncology of Porto, António Bernardino de Almeida Street, 4200-072 Porto, Portugal.
Molecular Oncology Group, Portuguese Institute of Oncology of Porto, António Bernardino de Almeida Street, 4200-072 Porto, Portugal.
Breast. 2015 Aug;24(4):481-6. doi: 10.1016/j.breast.2015.04.010. Epub 2015 May 8.
Tamoxifen remains the standard hormonotherapy for Male breast cancer patients (MBC). Previous studies, in women, tried to evaluate the impact of CYP2D6 polymorphisms in tamoxifen efficacy with conflicting results. Herein we analyze the relation between CYP2D6*4 polymorphism and survival in MBC patients.
Fifty-three patients, proposed to tamoxifen in adjuvant setting, were enrolled. Clinical information was collected from records and histological revision with additional immunochemistry analysis was done to better characterize the tumors. Comprehensive CYP2D6*4 genotyping from blood or tumor tissue was performed and translated into two predicted metabolic activity groups.
Patients included in the two CYP2D6*4 groups did not differ concerning to age, histological characteristics, and primary treatments performed. Median age at diagnosis was 63 years-old and patients were submitted at least to mastectomy and adjuvant hormonotherapy. Recurrence was observed in 7 patients (13.2%) and 13 patients (25.5%) died with a 5-year disease-free survival of 86.2%. The poorer metabolizer group had a high risk for recurrence (p = 0.034) and this outcome effect remains in different subgroups: in tumors larger than 2 cm (p < 0.001), nodal status, N0 vs N+ (p = 0.04) and in advanced stage, stage III (p < 0.001). Poorer metabolizer patients had also a worse overall survival when tumors were larger than 2 cm (p = 0.03).
In our series, there was an association between CYP2D6*4 polymorphism and a probability of recurrence, with a consistent effect in risk groups defined by classic prognostic factors. Multicentric studies with larger samples are needed to validate these results.
他莫昔芬仍是男性乳腺癌患者（MBC）的标准激素疗法。先前针对女性的研究试图评估CYP2D6基因多态性对他莫昔芬疗效的影响，但结果相互矛盾。在此，我们分析了CYP2D6*4基因多态性与MBC患者生存率之间的关系。
纳入53例接受辅助性他莫昔芬治疗的患者。从病历中收集临床信息，并进行组织学复查及额外的免疫化学分析，以更好地对肿瘤进行特征描述。对血液或肿瘤组织进行全面的CYP2D6*4基因分型，并将其转化为两个预测的代谢活性组。
两个CYP2D6*4组的患者在年龄、组织学特征和所接受的主要治疗方面无差异。诊断时的中位年龄为63岁，患者至少接受了乳房切除术和辅助性激素疗法。7例患者（13.2%）出现复发，13例患者（25.5%）死亡，5年无病生存率为86.2%。代谢较差组复发风险较高（p = 0.034），且这一结果在不同亚组中均存在：肿瘤大于2 cm（p < 0.001）、淋巴结状态，N0与N+（p = 0.04）以及晚期，Ⅲ期（p < 0.001）。当肿瘤大于2 cm时，代谢较差的患者总生存率也较差（p = 0.03）。
在我们的研究系列中，CYP2D6*4基因多态性与复发概率之间存在关联，在由经典预后因素定义的风险组中具有一致的影响。需要进行更大样本量的多中心研究来验证这些结果。
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