乳癌的輔助性化療

Trends of Breast Cancer Adjuvant Chemotherapy in Last Decade

莊岳泉(Yoke-Chun Chung) ； 趙祖怡(Tsu-Yi Chao)

《中華民國癌症醫學會雜誌》 24卷2期 (2008/04) Pp. 112-120

https://doi.org/10.6588/JCOS.2008.24.2.6

摘要

早期乳癌接受輔助性化療的觀念源自於1960至1970年代初期。自1970至1985年間，許多相關的臨床試驗紛紛進行以決定化療的最佳處方，劑量多寡，使用的時間頻率，以及anthracycline之角色。然而，大多數試驗均因病人人數不足而無法達到統計學上有意義的結論。目前EBCTCG的研究證實早期乳癌使用輔助性化療以及賀爾蒙治療（tamoxifen及卵巢切除術）是有助益的，實證強度屬於第一級(level I)。合理的使用輔助性化療及賀爾蒙治療（同時或前後接續使用），可以降低復發率及死亡率達50%以上，且其效果可以維持長達15~20年。2005-6年EBCTCG對未曾接受全身性治療的患者進行評估，發現長期預後和淋巴結轉移較有關係，和動情激素受體(ER)的狀態較無關。根據EBCTCG2007年最新的數據顯示，含有anthracycline處方的化療比CMF處方可以更降低11%的復發率，這樣的好處不管淋巴結有無轉移，ER是否存在，組織分化程度如何，或年齡是否不同均一致存在。
在經過三十多年的研究後，我們知道CMF處方具有延長無病存活期和整體存活期的效益。此外，含有anthracycline化療處方之療效優於CMF處方，前者的效益可以持續到十五年以上，並且降低年輕乳癌族群26%的死亡率，不過，目前大家也同意並非所有含anthracycline處方的化療都優於傳統之CMF，此外anthracycline也會帶來晚期的毒性，例如心臟衰竭，急性血癌，以及因提早進入更年期而導致的併發症如骨質疏鬆症等。除了作為治療的考量外，ER和Her-2的狀態也用來作為風險的評估。針對Her-2陽性的病患，trastuzumab的加入是必須的。此外近幾年來紫杉醇類藥物已被使用於高風險，甚至某些中度風險患者的輔助性化療，這其中也涵蓋了劑量頻繁型的治療方式。雖然輔助性化療可提高存活率及降低復發率，但也會帶來相當程度的副作用，故仍有改善空間。針對個別病患，應有量身而定的治療方式。另外，預後因子的考量包含腋下淋巴結轉移的數目，Her-2的表現，腫瘤的大小，以及賀爾蒙的反應等等。在治療前和患者的溝通尤其重要。為了讓患者可以清楚瞭解及抉擇治療方式並樂於遵從醫囑，在說明治療計畫時可以運用類似這類型網站輔助解釋。除了考慮傳統的條件以外，隨著基因紀元的來到，越來越多基因表現將可以作為臨床病患預後的評估與治療抉擇的考量。

關鍵字

乳癌 ； 輔助性化療 ； anthracyclines ； 紫杉醇

並列摘要

The concept and hypothesis of adjuvant chemotherapy in the treatment of early breast cancer (EBC) was formulated in late 1960s to early 1970s. From 1970 to 1985, many trials were done to determine the optimal regimens, advantageous doses, the interval of adjuvant chemotherapy given, and the role of anthracycline. Nevertheless, most of the data lacked statistical power owing to insufficient patients enrolled. Current evidences of EBCTCG show that adjuvant chemo- and hormono-therapy (including tamoxifen or ovarian ablation) are beneficial to EBC patients (Evidence Level 1). The optimal use of these modalities may decrease the risk of recurrence and death for more than 50% and with a long-lasting benefit as 15 to 20 years. Studies of EBCTCG at 2005-6 found that the long term prognosis is more related to the metastatic status of lymph nodes than ER status in those patients who have not received any systemic treatment. Besides, the evidence of 2007 showed that adjuvant chemotherapy with anthracy-cline-based regimen provides additional 11% reduction in recurrence than CMF regimen (ratio of annual events=0.89, 2p=0.002). Similar degree of benefit exists in all patients regardless of the nodal status, ER, differentiation, and ages.
After thirty years of follow up, CMF was proved to prolong the disease-free survival and overall survival of those patients with EBC. Additionally, the anthracycline-containing regimen is superior to CMF, and its effect can last even longer than 15 years with a 26% reduction of breast cancer death in young patients. However, it is known that not every anthracycline-containing regimen is superior to the standard CMF regimen. Besides, the long term toxicities of anthracyclines such as heart failure, acute leukemia and early menopause deserve further attentions. Nowadays, the status of ER and Her-2 were taken into consideration not only for treatment choice but on risk determination. The addition of trastuzumab is warranted for those tumors with Her-2 overexpression. Moreover, taxanes are incorporated into the adjuvant treatment for those patients with high risk and some patients with intermediate risk, including the dose-dense protocol. Although taxanes may improve the survival and reduce the recurrence rate, yet it may also bring more side effects. Therefore the optimal way of using taxanes in the adjuvant setting can be further improved. The protocol of adjuvant chemotherapy in EBC should be individualized. To determine the risk of recurrence should consider the number of the metastatic axillary lymph nodes, presence of Her-2, tumor size, and the ER/PR status. A detailed explanation of treatment choices to patient and families is essential before the execution of chemotherapy. The website Adjuvant! could be considered as a supplement for treatment explanation. Through the online illustration, the patients may improve their awareness and compliance to the treatment course. In this genomic era, more and more gene expression pattern will be considered for prognosis determination and treatment references.

並列關鍵字

breast cancer ； adjuvant chemotherapy ； anthracyclines ； taxanes