探討前導性化學治療對乳癌預後之影響及影響前導性化療效果之預後因子

Long-term Outcomes and Predictors for response of Breast Cancer following Neoadjuvant Chemotherapy

王董華(Dong-Hua Wang)

指導教授 ： 陳芬如

義守大學/醫學院/醫務管理學系/碩士(2019年)

摘要

背景及目的：
105年台灣癌症登記年報統計，女性乳癌為國人十大癌症發生率之首，女性乳癌為十大癌症死因中的第四位，也是女性十大癌症死因之第四位。前導性化學治療是目前用來治療局部進展階段（II~III期）乳癌患者常用的治療方式，可讓腫瘤縮小，增加乳房保留手術的機會，以提升病人生活品質。過去的研究顯示，若在進行前導性化學治療後能達到病理完全緩解，可提升其整體存活率及無病存活率，本研究希望探討前導性化學治療對於乳癌預後之影響及找出影響前導性化療效果之預後因子，期望可以找出真正需要接受前導性治療之個案。
方法：
本研究採用回溯性資料分析，研究對象為某準醫學中心癌症登記資料庫收錄之2010-2016年新診斷之乳癌個案，經排除未於院內接受首次療程、男性、組織型態不適用AJCC 7th分期、之前有其他癌症發生、臨床分期非第二及第三期、未接受手術及治療資料不完整之個案後利用傾向分數配對，控制腫瘤大小、ER、PR、HER-2、臨床T、臨床區域淋巴結轉移及分化程度等因素，分為接受前導性化學治療及無前導性化學治療兩組，分析其整體存活率、無病存活率。利用卡方檢定分析病理完全緩解之影響因素，並以Kaplan-Meier進行存活率分析。
結果：
經篩選後，符合條件之個案共458例，接受前導性化療者68例（14.85%），170例接受乳房保留術（37.12%），68例接受前導性化療之個案中有7例達到病理完全緩解（10.29%），配對後接受前導性化療即位皆是前導性化療各62例，共計134例納入分析，研究結果顯示有無前導性化學治療之整體存活率及無病存活率皆無統計上顯著差異，分析期別有無前導性化學治療之整體存活率及無病存活率結果顯示期別有無前導性化療於整體存活率(p=0.007)及無病存活率(p=0.002)皆有統計上顯著差異，研究結果顯示整體存活率在第二期無前導性化療較有前導性化療高，第三期則是有前導性化療較無前導性化療高。是否達到病理完全緩解於整體存活率（p=0.995）及無病存活率（p=0.459）皆無統計上顯著差異。分析結果顯示最後一次化療與手術間隔天數於整體存活率（p=0.280）及無病存活率（p=0.280）皆無顯著差異。最後一次化療與手術間隔天數≦4週者，五年整體存活率為90.0%，最後一次化療與手術間隔天數＞4週者五年整體存活率為70.7%。最後一次化療與手術間隔天數≦4週者，五年無病存活率為80.8%，最後一次化療與手術間隔天數＞4週者，五年無病存活率為58.1%。
結論：
依據研究結果發現整體存活率在第二期無前導性化療較有前導性化療高，建議第二期之個案若為荷爾蒙受體陽性或分化程度較低者可考慮直接進行手術，第三期則是有前導性化療較無前導性化療高，建議第三期之個案可先進行前導性化學治療。雖然研究結果顯示無顯著差異，但可看出於4週內進行手術者於整體存活率及無病存活率皆明顯高於大於4週才進行手術者，故建議於前導性化療後4週內進行手術。

關鍵字

乳癌 ； 前導性化療 ； 傾向分數配對 ； 病理完全緩解

並列摘要

Objective：According to the 2018 Taiwan Cancer Registry Report, female breast cancer was the commonest cancer and the fourth leading cause of death for women with malignancies. Nowadays neoadjuvant chemotherapy is widely used to treat locally advanced breast cancer (Stage II~III). It can reduce the tumor size to facilitate breast conservative surgery for patients with large breast tumor. Pathological complete remission（pCR）after neoadjuvant chemotherapy is an important prognostic factor regarding overall survival and disease free survival. The purpose of this study is to figure out the predictive factors of pCR and find out the candidate of neoadjuvant chemotherapy.
Methods：The data is from the Cancer Registry database of a tertiary center in southern Taiwan medical center between 2010 and 2016. The enrollment criteria include stage II or stage III breast cancer, female patient, and complete treatment. The latter includes surgery and chemotherapy planned. Male patients and those with missing data are excluded. Those with histological subtypes not feasible for AJCC 7th stage are not included in this study, either. The propensity score matching method is used for comparing the effect of neoadjuvant chemotherapy. With logistic regression analysis, tumor size、ER、PR、HER-2、clinical T、clinical lymph metastasis and grade are selected as the covariate for balancing the baseline characteristics of the two groups. To compare overall survival and disease-free survival, Kaplan-Meier method and log-rank are used. The difference of pCR rate was tested by Chi-square test.
Result：Total 458 patients met the study entrance criteria. Among them, sixty eight（14.85%）patients received neoadjuvant chemotherapy and surgery and seven patients achieved pCR. After propensity score matching, both neoadjuvant chemotherapy and upfront surgery arm have 62 patients. Between the two arms, no significant difference in the overall survival and disease-free survival. Regarding the potential impact or interaction between stage and neoadjuvant chemotherapy, statistically significant differences in overall survival (p = 0.007) and disease-free survival (p = 0.002) is noted after stratification with stage and neoadjuvant chemotherapy. For stage II breast cancer patients, those receiving upfront surgery have better overall survival than those with neoadjuvant chemotherapy. However, patients would have better overall survival with neoadjuvant chemotherapy if they are diagnosed with stage III disease.
There was no statistically significant difference in the overall survival (p=0.995) and disease-free survival (p=0.459) between pCR and non-pCR patients.
Regarding the interval between neoadjuvant chemotherapy and surgery, the five year overall survival and disease-free survival for those with the interval not longer than 4 weeks were 90.0% and 80.8%, respectively. The 5-year overall survival and disease-free survival were 70.7% and 58.1% for patients with the interval longer than 4 weeks. The difference between OS and DFS were not statistically significant (both p =0.280).
Conclusion：Our study showed the overall survival is higher for stage II patients without neoadjuvant chemotherapy than those with neoadjuvant chemotherapy. It is suggested that stage II breast cancer patients with either hormonal receptor positive or low grade tumor may be beneficial of upfront surgery. However, the administration of neoadjuvant chemotherapy makes stage III patients overall survival better. Thus, the patients with stage III disease should consider neoadjuvant chemotherapy first. Although not reaching statistical significance, there is a trend that the interval between neoadjuvant chemotherapy and surgery more than 4 weeks is associated with worse survival. Therefore, the surgery should be done within 4 weeks after neoadjuvant chemotherapy is recommended.

並列關鍵字

Breast cancer ； Neoadjuvant Chemotherapy ； Propensity score matching ； Pathological complete remission

參考文獻

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英文文獻