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標題: | 乳癌病人使用tamoxifen發生子宮相關病變及婦科監測之研究 Tamoxifen-related Uterine Events and Gynecologic Surveillance in Breast Cancer Patients |
作者: | Wan-Jyun Peng 彭琬珺 |
指導教授: | 陳燕惠(Yen-Hui Chen) |
共同指導教授: | 魏凌鴻(Lin-Hung Wei) |
關鍵字: | tamoxifen,子宮體癌,乳癌,危險因子, tamoxifen,uterine cancer,breast cancer,risk factor, |
出版年 : | 2019 |
學位: | 碩士 |
摘要: | 研究背景:Tamoxifen 為 ER/PR(+) 乳癌病人的抗荷爾蒙用藥。有研究顯示使用 tamoxifen 從 5 年延長至 10 年,可以更有效地降低乳癌的復發率及死亡率。治療指引因此建議將 tamoxifen 的服藥期延長至 10 年,但罹患子宮體癌的機率也相對提高。雖曾有研究以台灣健保資料庫分析,發現年齡及 tamoxifen 之服藥期與罹患子宮體癌風險有關,但仍需更多研究探討延長 tamoxifen 之服藥期(超過5年)是否有較高機率罹患子宮體癌。另外有些研究以子宮內膜厚度作為子宮體癌的替代終點,仍存有爭議,因此需更多研究評估使用 tamoxifen 乳癌病人,所接受之例行性婦科監測。
研究目的: 1.分析國內病人使用tamoxifen後,子宮體癌的發生率,並分析相關風險因子,如:年齡、延長tamoxifen服藥期等。 2.分析國內病人使用tamoxifen後,子宮體癌的相關診療資料,如:組織類型等。 3.分析國內病人使用tamoxifen後,接受子宮內膜搔刮術的發生率及其病理結果。 研究方法:以臺大醫院的相關資料,進行回溯性世代研究。在臺大醫院癌症登記檔中,確診為原發性乳癌的女性病人,經納入以及排除標準篩選後,共 9,668 人納入,依照所接受之乳癌輔助性荷爾蒙治療,分為只使用過 tamoxifen(以 Tamoxifen-only 簡稱,共 2612 人,27.0%),皆曾使用過 tamoxifen 和 aromatase inhibitor(以 Both 簡稱,共 1754 人,18.1%),只使用過 aromatase inhibitor(以 AI-only 簡稱,共 1536 人,15.9%),未使用過乳癌輔助性荷爾蒙治療(以 Non-user 簡稱,共 3766 人,39.0%),並分析子宮體癌的發生率及相關風險因子。 研究結果:在 9,668 位乳癌病人之中,後續被診斷為子宮體癌共有40人,其中 Tamoxifen-only 組的發生率最高(19/2612=0.7%),相較於 AI-only 組(4/1536=0.3%)或 Non-user 組(11/3766=0.3%)。就子宮體癌組織類型而言,Tamoxifen-only組最多為癌瘤(carcinoma)(84.2%),包含子宮內膜腺癌(endometrioid adenocarcinoma)(78.9%),亮細胞腺癌(clear cell adenocarcinoma)(5.3%);另一類則為肉瘤(sarcoma)(15.8%)包含惡性肉瘤(carcinosarcoma)(10.5%)和基質惡性肉瘤(endometrial stromal sarcoma)(5.3%),其中並沒有一般子宮體癌之肉瘤族群(sarcoma)較常發生的平滑肌肉瘤(leiomyosarcoma)。由 KM 存活曲線顯示,Tamoxifen-only 組相較於其他三組,有顯著較低的無子宮體癌存活率(p=0.038)。 由單變項比例風險迴歸分析結果得知,在整體族群中,BMI≥25 kg/m2 、乳小葉原位癌(LCIS)和乳管原位癌(DCIS),皆顯著增加子宮體癌發生風險。由多變項比例風險迴歸分析結果得知,Tamoxifen-only組,相較於Non-user組,有較高的子宮體癌發生風險,且達統計顯著。另外,乳癌診斷年齡50 歲以上及BMI≥25 kg/m2 皆顯著增加子宮體癌發生風險。另將 tamoxifen 開始使用至追蹤結束之間隔時間,以每年做次族群之多變項比例風險迴歸分析,並同時放入年齡≥50歲與 BMI≥25 kg/m2作校正。迴歸分析的結果顯示tamoxifen 在開始使用後4年之內,每一年分層之Tamoxifen only組,相較於Non-user 組皆有顯著增加子宮體癌的風險。 於乳癌診斷後接受子宮內膜搔刮術共 507 次,其中最多為 Tamoxifen-only 組(354/507=69.8%),相較於 Both 組(16.4%),Non-user 組(11.0%),以及AI-only 組(2.8%)。病理結果顯示為子宮體癌或內膜增生,最多為 Tamoxifen-only 組(21/354=5.9%),大部分在接受子宮搔刮術前,沒有異常子宮出血(237/354=66.9%),但仍有一定比例之病理結果顯示為子宮體癌或內膜增生(9/354=2.6%)。 結論:由多變項比例風險迴歸分析結果得知,Tamoxifen-only 組、乳癌診斷年齡 50 歲以上以及 BMI≥25 kg/m2皆顯著增加子宮體癌發生風險。就子宮體癌組織類型而言,Tamoxifen-only 組雖最多為癌瘤(carcinoma),但另一類肉瘤(sarcoma)較一般子宮體癌族群發生比例高(15.8% 相較於 2~5%)。此外,於乳癌診斷後,接受子宮內膜搔刮術者,Tamoxifen-only 組大部分在接受子宮搔刮術前,沒有異常子宮出血,但仍有一定比例的病理結果顯示為子宮體癌或內膜增生。因此病人在開始使用 tamoxifen,尤其具上述風險因子時,應每年定期接受婦科檢查。 Background: Tamoxifen is an anti-hormonal drug which is commonly used for hormone receptor-positive breast cancer patients. Two randomized controlled trials showed that the extended use of tamoxifen for 10 years, compared to 5 years, significantly reduced the recurrence and mortality of breast cancer. However, the risk of endometrial cancer increased. Few publications examine whether the extended use of tamoxifen (>5 years) have a higher risk of tamoxifen-related uterine events. Since the increase in endometrium thickness is still controversial as a surrogate measure of uterine cancer, studies are needed to evaluate feasible routine gynecologic surveillance in breast cancer patients with tamoxifen regimen. Study objectives: 1.To analyze the rates of uterine cancer in patients treated with tamoxifen and to identify the risk factors of tamoxifen-related uterine cancer such as age, extended use of tamoxifen, etc. 2.To evaluate tamoxifen-related uterine cancer characteristics, such as histology, etc. 3.To evaluate the event count and pathological diagnosis in patients proceeding dilatation and curettage (D and C) after tamoxifen use. Methods: This is a retrospective cohort study enrolling female patients diagnosed with breast cancer from the National Taiwan University Hospital cancer register. A total of 9,668 patients who fulfilled inclusion and exclusion criteria were grouped by the treatment with tamoxifen-only (N=2612, 27%), both tamoxifen and aromatase inhibitor (N=1754, 18.1%), aromatase inhibitor-only (N=1536, 18.1%), and non-user (N=3766, 39%) for analyses of incidence rates and risk factors of uterine cancer. Results: In the 9668 breast cancer patients, 40 patients were subsequently diagnosed with uterine cancer. The tamoxifen-only group had higher incidence rate (19/2612, 0.7%) than AI-only or non-user group (4/1536, 0.3% or 11/3766, 0.3%). Uterine cancer in tamoxifen-only group was mostly carcinoma (84.2%), including endometrioid adenocarcinoma (78.9%) and clear cell adenocarcinoma (5.3%), subtyped by histologic classification. Sarcoma was found 15.8%, including carcinosarcoma (10.5%) and endometrial stromal sarcoma (5.3%). None was leiomyosarcoma which had been mostly found in all cause uterine sarcoma. The Kaplan-Meier survival curve showed that tamoxifen-only group had the lowest uterine cancer-free probability among the four groups (p=0.038). BMI≥25 kg/m2, lobular carcinoma in situ (LCIS), ductal carcinoma in situ (DCIS) breast cancer were significant risk factors of uterine cancer in the total population using a univariate cox regression model. Furthermore, the multivariate cox regression model indicated significantly higher risk of uterine cancer in the tamoxifen-only group than the non-user group. Age above 50 years and BMI≥25 kg/m2 also increased the risk of uterine cancer significantly. When patients were stratified with time from tamoxifen treatment to the end of follow-up in one-year intervals, the multivariate cox regression model, adjusted by age above 50 years and BMI above 25 kg/m2, indicated that the uterine cancer risk was higher in the tamoxifen-only group than the non-user group within 4 years of tamoxifen use. The dilatation and curettage (D and C) events were counted 507 in all patients after breast cancer diagnosis. The tamoxifen-only group contributed to the total event mostly (354/507, 69.8%), compared to the both group (16.4%), non-user group (11.0%) and AI-only group (2.8%). The tamoxifen-only group had the highest event count of either uterine cancer or endometrial hyperplasia (21/354, 5.9%) among the four groups. Two third of the tamoxifen-only patients had no abnormal uterine bleeding before D and C (237/354, 66.9%) with positive rate of uterine cancer or endometrial hyperplasia as much as 2.6% (9/354). Conclusion: The tamoxifen-only group vs non-user group, age above 50 years and BMI≥25 kg/m2 increased the risk for uterine cancer significantly. Most uterine cancer in tamoxifen-only group was histologically classified as carcinoma while the sarcoma rate was higher than all cause uterine cancer population (15.8% vs 2-3%). Positive rate of uterine cancer or endometrial hyperplasia was as much as 2.6% in the tamoxifen-only patients without abnormal uterine bleeding before D and C. It indicates that routine gynecological check is an important follow-up in breast cancer patients with tamoxifen treatment. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78768 |
DOI: | 10.6342/NTU201901486 |
全文授權: | 有償授權 |
電子全文公開日期: | 2024-08-28 |
顯示於系所單位: | 臨床藥學研究所 |
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