건강보험심사평가원 자료를 활용한 안트라사이클린 표준 화학 요법이 50대 유방암 생존자의 후기 심부전 발생에 미치는 영향 분석

학위논문 (박사) -- 서울대학교 대학원 : 의과대학 의학과, 2021. 2. 노동영.Introduction Although chemotherapy-induced congestive heart failure (CHF) is a critical adverse event in cancer survivors, there is no consensus regarding long-term monitoring of CHF among international guidelines. The incidence and risk factors of late CHF in real-world practice have not yet been thoroughly scrutinized. This study aimed to investigate the age groups vulnerable to chemotherapy-induced late CHF, assess the risk of late CHF following (neo)adjuvant chemotherapy regimens, and define the long-term effects of standard low-dose anthracycline on late CHF in high-risk age groups among breast cancer survivors. Methods This nationwide retrospective cohort study analyzed the national insurance claims data for nearly 98% of Korean citizens. A total of 56,338 newly diagnosed female breast cancer survivors without a previous or recent history of CHF or other cancers were included (between Jan 2010 and Dec 2015). The main outcome was late CHF after 2 years following breast cancer diagnosis. Results The total number of person-years was 199,648 (mean follow-up, 66.8 months) and 713 survivors developed late CHF. The incidence rate of late CHF was 3.57 per 1,000 person-years. In multivariate analysis according to the subject’s age at diagnosis, anthracycline-based [hazard ratio (HR) 1.765, 95% confidence interval (CI) 1.206-2.583] and taxane plus anthracycline-based regimens (HR 1.816, 95% CI 1.192-2.768) significantly increased the risk of late CHF only in the 50-59 age group. In this population, after adjustment for age, insurance, past medical history, and other adjuvant treatments, cyclophosphamide plus anthracycline (HR 1.672, 95% CI 1.095-2.555), fluorouracil plus anthracycline plus cyclophosphamide (HR 2.006, 95% CI 1.260-3.196) and anthracycline plus cyclophosphamide plus taxane (HR 1.922, 95% CI 1.260-2.932) regimens were significant risk factors for late CHF. Among the 50-59 age group, standard low-dose anthracycline significantly increased the risk of late CHF (HR 1.627, CI 1.080-2.451) in the Cox proportional hazard regression models. In competing risk model, standard low-dose anthracycline was a significant risk factor for late CHF [subdistribution hazard ratio (SHR) 1.553, 95% CI 1.029–2.340]. Conclusions This nationwide cohort study showed that standard low-dose anthracycline is a risk factor for late-onset CHF in breast cancer survivors who were in their 50s at breast cancer diagnosis. Tailored screening strategies should be considered for breast cancer survivors at different levels of risk for developing late CHF.서론: 항암치료로 인하여 발생하는 심부전은 암생존자에 있어 중요한 부작용 중에 하나이다. 이러한 심부전은 암생존자의 생존율 및 삶의 질에 중대한 영향을 미칠 수 있다. 그러나 현재까지 국제 가이드라인에서는 이들 심부전에 대한 장기적 추적 관찰의 필요성에 대하여 논란이 있다. 방법: 본 후향적 코호트 연구는 2008년부터 2018년까지 건강보험심사평가원 자료를 활용하여 유방암 생존자에 있어 후기 심부전 발생의 빈도를 조사하였고, 후기 심부전과 관련된 인자들을 확인하였다. 한편, 표준 요법으로 사용되는 저용량 안트라사이클린이 후기 심부전에 미치는 영향을 분석하였다. 2010년 1월부터 2015년 12월까지 심부전의 과거력이 없는 총 56,338명의 새롭게 유방암으로 진단받은 환자를 추출하였다. 후기 심부전은 유방암 진단 후 2년 이후에 발생한 심부전으로 정의하였다. 결과: 중간 추적 기간 66.8개월 동안(총 199,648인년) 713명의 유방암 생존자에서 후기 심부전이 발생하였다. 후기 심부전의 발생률은 1,000인년당 3.57명이었다. 나이대 별 콕스 비례 위험 모형에서 다변량 분석에서 안트라사이클린 [hazard ratio (HR) 1.765, 95% confidence interval (CI) 1.206-2.583] 및 안트라사이틀린-탁산 병합요법 (HR 1.816, 95% CI 1.192-2.768) 은 유방암 진단 당시 50대 여성에서 통계적으로 의미있게 후기 심부전의 발생을 증가시켰다. 50대 여성에서는 나이, 보험, 과거력 및 다른 치료를 보정하였을 때에도 동일하게 안트라사이클린이 포함된 항암제가 후기 심부전의 발생을 의미있게 증가시켰다. 50대 유방암으로 진단받은 여성의 경우 표준 저용량 안트라사이클린이 후기 심부전을 의미있게 증가시켰다 (HR 1.627, CI 1.080-2.451). 결론: 본 국가 단위 코호트 연구에서 표준 저용량 안트라사이클린은 50대에 유방암으로 진단받았던 유방암 생존자에 있어 후기 심부전을 증가시켰다. 환자별로 후기 심부전의 발생 위험을 고려하여 맟춤형 심부전 관리가 고려되어야 한다.Abstract i Contents iv List of Tables and Figures v Introduction 1 Methods 5 Results 11 Discussion 32 Conclusion 36 Reference 37 Abstract (Korean) 44Docto

휴대전화 문자메시지를 이용한 알림 서비스가 유방암 환자의 유방자가검진 행태에 미치는 효과

학위논문 (석사)-- 서울대학교 대학원 : 의학과 의과학 전공, 2013. 2. 김성원.서론: 본 연구는 휴대전화 문자메시지를 이용한 알림 서비스가 유방암환자의 유방자가검진 시행에 미치는 영향을 평가하고자 하였다. 방법: 분당서울대학교병원에서 유방암으로 수술을 받고 휴대전화 단문 메시지 서비스를 사용할 수 있는 20-65세의 여성 환자를 대상으로 무작위배정 대조군 연구를 시행하였다. 참가자는 블록 무작위배정으로 문자메시지군과 대조군으로 나뉘었고 문자메시지군은 매월 1일에 유방자가검진을 알리는 문자메시지와 매월 15일에 유방암에 관한 정보를 제공하는 문자메시지를 받았다. 본 연구에서는 문자메시지군이 대조군보다 유방자가검진 시행률이 높을 것으로 가정하였고, 일차 목표는 유방자가검진 시행률 (6개월간 유방자가검진을 5회 이상 시행한 비율) 과 이차 목표는 6개월간의 유방자가검진 횟수였다. 결과: 2010년 8월부터 2011년 12월까지 216명의 환자를 문자메시지군 (n = 110)과 대조군 (n =106)에 배정하였고, 202명이 최종 분석에 포함되었다. 문자메시지군에서 유방자가검진 시행률 (자가검진 미시행에 대한 상대위험도 0.49, 95% 신뢰구간 0.36 - 0.67P < 0.001)과 6개월간의 유방자가검진횟수 (평균차 1.66, 95% 신뢰구간 1.03 - 2.29P < 0.001)가 통계적으로 유의하게 높았다. 이분형 로지스틱 회귀분석에서 문자메시지가 유방자가검진 시행률을 유의하게 높이는 유일한 요인이었다. (교차비 [OR] 4.08, 95% 신뢰구간 2.24 - 7.43P < 0.001) 결론: 휴대전화 문자메시지를 이용한 알림 서비스는 유방암 환자의 유방자가검진 시행을 높이는 효과적인 수단이다. 임상연구등록: 임상연구정보서비스, KCT0000018Introduction: To assess the effectiveness of short message service (SMS) as a reminder for breast self-examination (BSE) in patients who underwent breast cancer surgery. Methods: This study was a single-blind, parallel group, randomized controlled trial of the effect of SMS on adherence to BSE. Participants who underwent surgery for breast cancer were recruited from the Breast Care Center at Seoul National University Bundang Hospital. Patients were eligible if they were women between the ages of 20 and 65 years and had their own cellular phone with text-message features. Participants were randomized by block randomization to the intervention (SMS) group or the control group. Subjects in the SMS group received one text message on the first day of every month that reminded them to complete a monthly BSE and one text message on the fifteenth day of that contained information about breast cancer. During the follow-up visit, researchers who were blind to participants allocations conducted post-intervention assessments. Primary and secondary outcomes were self-reported BSE adherence and the frequency of BSE over 6 months. Results: Between August 2010 and December 2011, 216 patients were randomly assigned to the SMS group (n = 110) or the control group (n = 106). A total of 202 patients were included in the final analysis. Self-reported BSE adherence (relative risk [RR] for non-adherence 0.49, 95% CI 0.36 to 0.67P < 0.001) and the frequency of BSE over the past six months (mean difference 1.66, 95% CI 1.03 to 2.29P < 0.001) were significantly higher in the intervention group than in the control group. Multivariate analysis showed that the SMS intervention was the only significant factor for self-reported BSE adherence (n = 199, odd ratio [OR] 4.08, 95% CI 2.24 to 7.43P < 0.001). There were no reports of harmful effects of the intervention from participants. Conclusions: The short-term results of our study suggest that SMS reminders are an effective and low-cost method to enhance adherence to BSE by using existing information technology infrastructure. Trial Registration: Clinical Research Information Service KCT0000018Abstract ⅰ Contents ⅲ List of Tables & Figures List of Tables ⅳ List of Figures ⅴ Introduction… 1 Materials and Methods 6 Results 12 Discussion 22 Conclusions 28 Competing interests 29 References 30 Abstract – Korean 37 Acknowledgement 39Maste

Optimal shape design in 2-D of a load-carrying hook by boundary element method

학위논문(석사) - 한국과학기술원 : 기계공학과, 1990.8, [ iv, 41 p. ]한국과학기술원 : 기계공학과

Long?term survival outcomes of repeat lumpectomy for ipsilateral breast tumor recurrence: a propensity score?matched analysis

Purpose This study aimed to compare long-term survival outcomes of repeat lumpectomy with total mastectomy after ipsilateral breast tumor recurrence (IBTR) using propensity score matching (PSM). Methods We retrospectively analyzed patients with IBTR who had undergone initial breast-conserving surgery for breast cancer at our institution between January 1990 and December 2013. The Kaplan?Meier method and Cox proportional hazards model were used to compare survival rates between the two groups. PSM was performed using the following covariates: age at initial operation, initial T stage, N stage, hormone receptor status, human epidermal growth factor receptor 2 status, chemotherapy, radiotherapy, and IBTR tumor size. Results We enrolled 335 IBTR patients with a median follow-up of 126.6 months. No significant differences were observed in the 5-year overall survival (OS), breast cancer-specific survival (BCSS), OS after IBTR, and BCSS after IBTR and 10-year survival probability between the two groups in a multivariate analysis. After PSM, patients who had undergone repeat lumpectomy and total mastectomy (n = 90 in both groups) were included. No significant differences were observed in the 10-year OS (hazard ratio [HR] 1.08, 95% confidence interval [CI] 0.49?2.39), BCSS (HR 0.83, 95% CI 0.35?1.95), OS after IBTR (HR 0.83, 95% CI 0.38?1.83), and BCSS after IBTR (HR 0.64, 95% CI 0.28?1.47) between the two groups. Conclusions No significant differences were observed in survival outcomes between patients with IBTR who underwent repeat lumpectomy or total mastectomy. Our results can be helpful in selecting the appropriate surgical method for IBTR

Risk of Endometrial Cancer and Frequencies of Invasive Endometrial Procedures in Young Breast Cancer Survivors Treated With Tamoxifen: A Nationwide Study

Background Although the guidelines recommend gynecological assessment and close monitoring for symptoms of endometrial cancer in postmenopausal breast cancer survivors taking tamoxifen (TAM), the risk of endometrial cancer in young breast cancer survivors has not yet been fully assessed. This study aimed to investigate the risk of developing endometrial cancer and the frequencies of gynecological examinations in young breast cancer survivors taking TAM in South Korea. Methods A nationwide retrospective cohort study was conducted using the Health Insurance Review and Assessment Service claims data. Kaplan-Meier analyses and log-rank tests were used to assess the probability of endometrial cancer, benign endometrial conditions, and the probability of invasive endometrial procedure. To analyze the risk of endometrial cancer and benign endometrial conditions, we used a multivariable Cox proportional hazards regression model. Results Between 2010 and 2015, 60,545 newly diagnosed female breast cancer survivors were included. The total person-years were 256,099 and 140 (0.23%) patients developed endometrial cancer during the study period. In breast cancer survivors aged &gt;= 60 years [hazard ratio (HR), 5.037; 95% confidence interval (CI), 2.185-11.613], 50-59 years (HR, 4.343; 95% CI, 2.122-8.891), and 40-49 years (HR, 2.121; 95% CI, 1.068-4.213), TAM was associated with an increased risk of endometrial cancer. In subjects aged below 40 years, TAM did not significantly increase the risk of endometrial cancer. However, among the TAM subgroups, breast cancer survivors aged below 40 years [1.61 per 1,000 person-years (PY); HR, 12.460; 95% CI, 2.698-57.522] and aged 40-49 years (2.22 per 1,000 PY; HR, 9.667; 95% CI, 4.966-18.819) with TAM-related endometrial diseases showed significantly increased risks of endometrial cancer. Among the TAM subgroup with benign endometrial conditions, the ratios of the frequency of invasive diagnostic procedures to the incidence of endometrial cancer were higher in subjects under 40 than subjects aged 60 or more. Conclusion Young breast cancer survivors with TAM-related benign endometrial diseases are at a higher risk of developing endometrial cancer. Gynecological surveillance should be tailored to the risk of endometrial cancer in young breast cancer survivors to improve the early detection of endometrial cancer and avoid unnecessary invasive procedures

Tumor-Infiltrating Lymphocytes in Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Receiving Neoadjuvant Docetaxel, Carboplatin, Trastuzumab, and Pertuzumab

Purpose: The tumor-infiltrating lymphocytes (TILs) expression in breast cancer is a positive prognostic marker for certain breast cancer subtypes. We evaluated the efficacy of dual antihuman epidermal growth factor receptor 2 (HER2) blockade in HER2-positive breast cancer and hypothesized that high TILs tumors are associated with better outcomes. Methods: A total of 176 patients who were treated with neoadjuvant docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP) between December 2015 and December 2018 were reviewed. They were grouped based on a cut-off value of the stromal TILs grade (&lt;= 20% TILs, &gt; 20% TILs). Results: In total, 107 patients (60.8%) achieved pathological complete response (pCR). Hormone receptor (HR)-negativity (p = 0.001) and a high TILs grade (p = 0.022) were independent predictors of pCR. Among the HR-negative patients, high TILs tumors were significantly associated with pCR (p = 0.035). Conclusion: HR status and the TILs grade are significantly correlated with pCR in dual anti-HER2 neoadjuvant therapy. The evaluation of the TILs at baseline may be beneficial for predicting pCR in HER2-positive breast cancer

Prognostic value of p53 expression in hormone receptor-positive and human epidermal growth factor receptor 2-negative breast cancer patients receiving neoadjuvant chemotherapy

Purpose The aim of this study was to determine whether the outcome to neoadjuvant chemotherapy (NAC) can be predicted by analyzing p53 expression in hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients. Methods We retrospectively reviewed 594 patients diagnosed with stage I-III HR-positive, HER2-negative breast cancer, and treated with NAC at the Asan Medical Center between 2008 and 2014. Expression of p53 was assessed, and overall survival (OS) and breast cancer-specific survival (BCSS) were investigated and compared between groups. Results At a median follow-up period of 69.8 months, OS and BCSS were higher in the p53-negative (p53(-)) group than in the p53-positive (p53(+)) group. Five-year OS was 95.4% in the p53(-) and 92.1% in the p53(+) group (p = 0.005). BCSS was 96.2% in the p53(-) group and 93% in the p53(+) group (p = 0.008). Conclusion High expression of immunohistochemically detected p53 was strongly and significantly associated with decreased OS and BCSS than low p53 expression, suggesting that p53 may be a powerful prognostic factor in HR-positive, HER2-negative breast cancer patients receiving NAC