Wanebo H J, Rosen P P, Thaler T, Urban J A, Oettgen H F
Ann Surg. 1976 Sep;184(3):258-67. doi: 10.1097/00000658-197609000-00003.
The concept of whether immune function was related to risk of recurrence was examined in patients with operable breast cancer in whom careful clinical and pathologic staging had been performed. Patients were classified according to the risk of recurrence. The "low risk" group included patients with minimal breast cancer, noninfiltrating cancer, or infiltrating cancer less than 1 cm with negative nodes. The "high ridk" group included patients with lesions greater than 1 cm or who had greater than or equal to 4 nodal metastases or who had macrometastases at Level II or III (apex). In the "intermediate risk" group were patients with infiltrating cancer less than 1 cm or with less than 4 nodal metastases at I only. Immune reactivity was assessed by skin tests, by measurement of absolute lymphocyte count, T and B cells, lymphocyte stimulation by mitogens and a battery of common antigens, serum immunoglobulins and complement levels. There were 134 patients with operable breast cancer and 63 patients with benign breast lesions. The breast cancer patients showed minimal or no impairment of DNCB skin test. Only patients with nodal metastases showed a slight but not significant impairment of DNCB responses (80% were DNCB positive compared to 90% in the controls.) The lymphocyte responses to mitogens were normal in the breast cancer patients, but there was a significant depression of lymphocyte responses to certain recall antigens such as Candida albicans and E coli. The absolute lymphocyte count and the T cell counts were normal, but B cells bearing complement receptors were decreased and B cells bearing sufface immunoglobulins were increased in the breast cancer patients. Analysis of immune function according to the pathologic stage of disease "risk of recurrence" categories showed no correlation with skin tests or lymphocyte levels. A striking and paradoxical finding was the demonstration that patients with "low risk" cancer overall had markedly lower responses to the battery of stimulating mitogens and antigens than found in patients with "high risk" or "intermediate risk" disease. Only the lymphocyte responses to PHA showed a significant linear correlation with increasing pathologic stage or "risk of recurrence." Current evidence from this study suggests that PHA response is markedly influenced by the primary tumor burdenand thus indirectly reflects the risk of recurrence.
在已进行仔细临床和病理分期的可手术乳腺癌患者中，研究了免疫功能与复发风险是否相关的概念。患者根据复发风险进行分类。“低风险”组包括微小乳腺癌、非浸润性癌或浸润性癌小于1厘米且淋巴结阴性的患者。“高风险”组包括病变大于1厘米、有4个或更多淋巴结转移或在II级或III级（尖部）有大转移灶的患者。“中度风险”组包括浸润性癌小于1厘米或仅在I级有少于4个淋巴结转移的患者。通过皮肤试验、测量绝对淋巴细胞计数、T细胞和B细胞、有丝分裂原和一系列常见抗原刺激淋巴细胞、血清免疫球蛋白和补体水平来评估免疫反应性。有134例可手术乳腺癌患者和63例良性乳腺病变患者。乳腺癌患者的二硝基氯苯（DNCB）皮肤试验显示轻微或无损害。只有有淋巴结转移的患者DNCB反应有轻微但不显著的损害（80%为DNCB阳性，而对照组为90%）。乳腺癌患者对有丝分裂原的淋巴细胞反应正常，但对某些回忆抗原如白色念珠菌和大肠杆菌的淋巴细胞反应有显著降低。绝对淋巴细胞计数和T细胞计数正常，但乳腺癌患者中带有补体受体的B细胞减少，带有表面免疫球蛋白的B细胞增加。根据疾病的病理分期“复发风险”类别分析免疫功能，与皮肤试验或淋巴细胞水平无相关性。一个显著且矛盾的发现是，总体而言，“低风险”癌症患者对一系列刺激有丝分裂原和抗原的反应明显低于“高风险”或“中度风险”疾病患者。只有对PHA的淋巴细胞反应与病理分期增加或“复发风险”呈显著线性相关。本研究的现有证据表明，PHA反应受原发肿瘤负荷的显著影响，因此间接反映复发风险。
