Suba Zsuzsanna
National Institute of Oncology, Surgical and Molecular Tumor Pathology Centre, Address: H-1122, Ráth György str. 7-9, Budapest, Hungary.
Recent Pat Anticancer Drug Discov. 2016;11(3):254-66. doi: 10.2174/1574892811666160415160211.
Results of long-term studies justify that the rate of breast cancer recurrence and tumor-related mortality remains quite unpredictable, regardless of the use of any current therapeutic measures.
Since the application of standard therapies, such as surgery, radiation, chemotherapy and antiestrogen administration does not work as might be expected; our therapeutic practice requires thorough rethinking.
Published long-term therapeutic results on breast cancer cases were analyzed in correlation with stage at diagnosis, ER-status of tumors and patients' age. The effectiveness of current therapeutic measures was also compared by estimating the rate of tumor-free survival, breast cancer recurrence and breast cancer-specific mortality.
Diagnosis and treatment of breast cancer at an early stage cannot improve the rate of tumor-free survival. Poor differentiation of tumors, ER-negativity in particular, defines poor prognosis even after applying aggressive therapies. In patients treated with in situ breast cancer, the recurrence-rate of invasive tumor increased directly with ageing irrespective of tumor size or ER-status at diagnosis. Women who underwent lumpectomy without adjuvant radiation or chemotherapy exhibited significantly better overall and breast cancer specific survival rates than those receiving mastectomy, regardless of stage and ER-status of tumors. Antiestrogen treatment exhibited unforeseeable effectiveness even on targeted ERpositive tumors. Recent patents propose the detection of ESR1-gene amplification or restoration of ER-alpha expression for prediction of effective antiestrogen treatment, suggesting a crucial inhibitory role of estrogen-signaling against tumorgrowth.
Estradiol-induced upregulation of estrogen signaling coupled with sparing of the estrogen-rich mammary fatpad are the most effective strategies against breast cancer.
长期研究结果表明,无论采用任何当前的治疗措施,乳腺癌复发率和肿瘤相关死亡率仍然相当不可预测。
由于手术、放疗、化疗和抗雌激素给药等标准疗法的应用效果不如预期;我们的治疗实践需要彻底反思。
分析已发表的乳腺癌病例长期治疗结果,并与诊断时的分期、肿瘤的雌激素受体状态和患者年龄相关联。还通过估计无瘤生存率、乳腺癌复发率和乳腺癌特异性死亡率来比较当前治疗措施的有效性。
早期诊断和治疗乳腺癌并不能提高无瘤生存率。肿瘤分化差,尤其是雌激素受体阴性,即使采用积极治疗,预后也较差。在接受原位乳腺癌治疗的患者中,浸润性肿瘤的复发率随年龄增长而直接增加,与诊断时的肿瘤大小或雌激素受体状态无关。无论肿瘤分期和雌激素受体状态如何,接受保乳手术而未进行辅助放疗或化疗的女性的总体生存率和乳腺癌特异性生存率均显著高于接受乳房切除术的女性。抗雌激素治疗即使对靶向的雌激素受体阳性肿瘤也表现出不可预见的效果。最近的专利提出检测ESR1基因扩增或恢复雌激素受体α表达以预测有效的抗雌激素治疗,这表明雌激素信号对肿瘤生长具有关键的抑制作用。
雌二醇诱导的雌激素信号上调以及保留富含雌激素的乳腺脂肪垫是对抗乳腺癌最有效的策略。