評估乳癌病人使用輔助性化學治療之時間點與存活率之關係

Evaluating the Association between Time to Adjuvant Chemotherapy and Survival Rates in Breast Cancer Patients

余信毅(Sin-Yi Yu)

指導教授 ： 楊奕馨

高雄醫學大學/藥學院/臨床藥學研究所/碩士(2013年)

https://doi.org/10.6832/KMU.2013.00140

摘要

前言：
早期乳癌病人中使用輔助性化學治療(adjuvant chemotherapy, ACT)已被證實可增進病人之存活率，但從手術結束到開始ACT的適當時間點則目前仍有爭議。因此本研究之目的為：一、探討會影響延遲ACT超過一個月之因素；二、探討使用ACT之時間點與存活率之關係

方法：
本研究為回溯性世代研究，使用台灣全民健康保險研究資料庫中之癌症病人特殊需求檔作分析。納入之族群為2003-2010年之間18到100歲之新診斷女性乳癌病人，並追蹤至2011年。化療時間點(time to chemotherapy, TTC)的定義為最後一次手術到第一個化療處方藥物的天數，並分成 ≦30天、31-60天、61-180天三組。針對影響延遲ACT超過一個月之影響因素，使用對數回歸(logistic regression)進行分析，三個TTC組別之整體存活(overall survival, OS)率及無進行病況存活 (progression-free survival, PFS)率，使用Kaplan-Meier estimates分析，並利用COX迴歸分析(COX proportional hazards regression)調整其他干擾變項後，得到TTC超過60天對於病人整體死亡(all-cause mortality)及癌症惡化(cancer progression)之風險比(hazard ratios, HRs)。

結果：
共有29,307位使用ACT之乳癌病人納入至本研究。平均(±標準差) TTC為29.6(±16.9)天，其中有18,566 (63.4%) 位病人在手術後的30天內開始ACT。顯著影響延遲ACT超過一個月以上之因素包括：年紀較大、有其他共病症、接受全乳房切除術及接受賀爾蒙治療。Kaplan-Meier estimates的結果顯示TTC在30天之內的病人有較好的存活率(7年OS：86.3%, 84.5%及83.0%, P=0.0067；7年PFS：72.1%, 70.9%及68.7%, P=0.0866；分別為TTC≦30天、31-60天、61-180天)。TTC超過60天相較於TTC在30天內會顯著增加死亡率23% (HR=1.23, 95% CI=1.03-1.47, P=0.0205)，在癌症惡化方面會增加11%的風險，但沒有顯著差異 (HR=1.11, 95% CI=0.99-1.26, P=0.0749)。

結論：
本研究結果顯示，TTC超過60天相較於TTC在30天內會增加死亡的風險，由於先前的相關文獻對於開始化療的適當時間點仍然具有爭議，本研究提供了亞洲人的資料以及到目前為止納入病人數最多的結果。

關鍵字

乳癌 ； 輔助性化學治療 ； 存活率 ； 化療時間點 ； 以人口為基礎之研究

並列摘要

INTRODUCTION:
Adjuvant chemotherapy (ACT) can improve survival in early stage breast cancer patients. However, the optimal time interval between definitive surgery and ACT is still controversial. The aim of the study was to: 1) investigate the factors associated with delaying ACT, and 2) investigate the survival rates in different timing of surgery to ACT.

METHODS:
We conducted a population-based retrospective cohort study using the Taiwan Health Insurance Research Database (NHIRD), specific subject datasets for breast cancer patients. We included newly-diagnosed female breast cancer patients aged from 18 to 100 during 2003‐2010 with follow-up until December 31, 2011. Time to chemotherapy (TTC) was defined as the time interval in days between the last surgical procedure and the first ACT prescription date. Factors associated with TTC greater than one month were evaluated by logistic regressions. Overall survival (OS) and progression-free survival (PFS) rates were computed for three TTC groups (≦30 days, 31-60 days and 61-180 days). The COX proportional hazard regression models were used to estimate the hazard ratios (HRs) of delaying TTC on survival after adjusting for other confounding covariates.

RESULTS:
There were 29,307 breast cancer patients with ACT included in our final study cohort. Overall, the mean (±SD) TTC was 29.6(±16.9) days. There were 18,566 (63.4%) patients starting ACT within 30 days after surgery. Initiation of ACT greater than one month was significantly associated with older age, having comorbid conditions, receiving mastectomy and hormonal therapy. Kaplan-Meier estimates showed TTC ≦30 days had a better survival (7-year OS: 86.3%, 84.5% and 83.0%, P=0.0067; 7-year PFS: 72.1%, 70.9% and 68.7%, P=0.0866, for TTC ≦30, 31-60 and 61-180 days). TTC more than 60 days was significantly associated with increasing 23% of all-cause mortality (HR=1.23, 95% CI=1.03-1.47, P=0.0205) compared to TTC ≦30 days, and increased 11% of cancer progression rate (HR=1.11, 95% CI=0.99-1.26, P=0.0749)

CONCLUSIONS:
Our results indicate that TTC more than 60 days was associated with 23% in increasing all-cause mortality. Given the controversial results of previous study, we provide the information from Asian population and results from the largest sample size so far.

並列關鍵字

Breast cancer ； Adjuvant chemotherapy ； Survival ； Time to chemotherapy ； Population-based study

參考文獻

1. Cancer statistics: worldwide. World Cancer Research Fund (WCRF) International (Accessed June, 2013, at http://www.wcrf.org/cancer_statistics/world_cancer_statistics.php)

2. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011;61:69-90.

3. Cancer Registry Annual Report 2010. In: Bureau of Health Promotion, Department of Health, Executive Yuan, Taiwan (R.O.C); 2013.

4. Leong SP, Shen ZZ, Liu TJ, Agarwal G, Tajima T, Paik NS, Sandelin K, Derossis A, Cody H, Foulkes WD. Is breast cancer the same disease in Asian and Western countries? World J Surg 2010;34:2308-24.

5. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005;365:1687-717.