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醫學六 梁華昌 黃哲緯 王劭中 DISCUSSION Outline Uterine cancer following breast cancer Risk: Breast cancer→ second primary cancer Risk: Tamoxifen → endometrial cancer Monitor: Tamoxifen → endometrial lesions Role of image: Diagnosis of endometrial abnormalities: Trans-vaginal ultrasound VS Hysteroscopy Adenosarcoma Adenosarcoma with sarcomatous overgrowth Increased Risk for Second Primary Malignancies in Women with Breast Cancer Diagnosed at Young Age: A Population-Based Study in Taiwan Lee KD et al. Cancer Epidemiol Biomarkers Prev 2008;17(10) Population-based (n=53,783) Standardized incidence ratio Nine second primary cancers had significant higher risk Bone, corpus uteri, ovary nonmelanoma skin, thyroid Esophagus, leukemia/lymphoma, kidney ,lung Tamoxifen-Treatment for Breast Cancer and Risk of Endometrial cancer: a case control study Control: 1067 breast cancer patients with no subsequent endometrial cancer Case: 813 breast cancer patients who had subsequent endometrial cancer Swerdlow AJ, et al. JNCI J Natl Cancer Inst. 2005;97(5): 375-384 Tamoxifen use (yes vs no): cancer risk, OR = 2.4 Duration of treatment positively associated with endometrial cancer OR = 1.3 (< 2y ) increased to 7.2 (10-17y) Swerdlow AJ, et al. J Natl Cancer Inst. 2005 ;97(5):375-84. Increasing daily dosage did not increase the risk of endometrial cancer Swerdlow AJ , et al. J Natl Cancer Inst. 2005;97(5):375-84. Histology Type Endometrial adenocarcinoma and mucinous carcinoma OR = 2.1, p < 0.001 Clear cell and papillary serous carcinoma OR = 3.1, p = 0.119 Mullerian and mesodermal mixed tumor and sarcoma OR = 13.5, p<0.001 Swerdlow AJ, et al. J Natl Cancer Inst. 2005 ;97(5):375-84. Treatment No association with chemotherapy and non-tamoxifen hormonal therapy Decreased risk with radiotherapy (RT) to breast area OR = 0.7, p = 0.002 Increased risk with RT to pelvic area OR = 11.7, p = 0.012 Swerdlow AJ, et al. J Natl Cancer Inst. 2005 ;97(5):375-84. Diagnostic Approaches to Endometrial Lesions in Patients taking Tamoxifen Goodman A et al. Ann Intern Med. 1999: 131 Role of Ultrasound and Hysteroscopy in Early Detection of Endometrial Abnormalities Transvaginal Ultrasound (TV-US) Review of 35 studies, 5892 women, for detecting endometrial abnormalities Sensitivity 92~96%; specificity 61~80% Smith-Bindman R, et al. JAMA. 1998;280(17):1510-7. 53 breast cancer women treated with tamoxifen Sensitivity 92%; specificity 80% Timmerman D, et al. Am J Obstet Gynecol. 1998;179(1):62-70. 247 tamoxifen-treated women and 98 controls High false-positive rate 46% Gerber B, et al. J Clin Oncol. 2000;18(20):3464-70. Love CD, et al . J Clin Oncol. 1999;17(7):2050-4. Hysteroscopy Quantitative systematic review of 65 studies, including 26,346 women Highly accurate in diagnosing endometrial cancer Sensitivity 86.4%; Specificity 99.2% Clark TJ, et al. JAMA. 2002;288(13):1610-21. Retrospective study of patients with endometrial cancer underwent hysteroscopy (69) or not (112) Sensitivity 93.10%; specificity 99.96% Marchetti M, et al. Eur J Gynaecol Oncol. 2002;23(2):151-3. Ultrasound vs Hysteroscopy 5 systemic review studies Transvaginal ultrasound excluding endometrial cancer in women with abnormal vaginal bleeding Hysteroscopy Effectively detecting endometrial cancer, but less effective at excluding serious at excluding serious disease Clark TJ, et al. Curr Opin Obstet Gynecol. 2004;16(4):305-11. TV-US was cost-effective in initial evaluating abnormal bleeding Clark TJ, et al. BJOG. 2006;113(5):502-10. Adenosarcoma Prevalence Uterine sarcomas account for approximately 1% of female genital tract malignancies and 3-7% of uterine cancers Major FJ, et al. Cancer. 1993;71:1702–9. Adenosarcomas account for 5.5% of uterine sarcomas Abeler VM, et al. Histopathology. 2009;54:355–364. Mullerian Adenosarcoma With Sarcomatous Overgrowth (MASO) First introduced by Clement and Scully in 1989 More than 25% of the adenosarcoma is composed of pure sarcoma Clement PB, et al. Am J Surg Pathol. 1989;13:28–38. Uterine MASO: an aggressive variant of adenosarcoma overall survival was similar with that of malignant mixed müllerian tumors Krivac T, et al. Gynecol Oncol. 2001; 83: 89–94. Recurrence Occurs in 38% of cases (n=41) Median time to recurrence is 12 months Verschraegen CF, et al. Oncol Rep. 1998;5(4):939-44. Recurrences are mostly composed of solely sarcoma which is always higher grade than the original tumor Clement PB, et al. Cancer. 1974;34(4):1138-49. Predictors of Recurrence Clinical: Extrauterine spread and myometrial invasion were associated with higher rates of recurrence Clement PB, et al. Cancer. 1974;34(4):1138-49 Kaku T, et al. Int J Gynecol Pathol. 1992;11(2):75-88 Pathological: 44% in sarcomatous overgrowth compared to 14% in adenosarcomas without sarcomatous overgrowth Kaku T, et al. Int J Gynecol Pathol. 1992;11(2):75-88 Treatment Hysterectomy with bilateral salpingo-oophorectomy Amant F, et al. Lancet Oncol. 2009 ;10(12):1188-98 Adjuvant radiotherapy appears to have a role in better pelvic control and decrease in local recurrence of the tumor. Chemotherapy: doxorubicin, ifosfamide, and cisplatin. Acharya S, et al. Lancet Oncol. 2005;6(12):961-71 Mullerian Adenosarcoma with Sarcomatous Overgrowth REVIEW OF CASE REPORTS Search in Pubmed Key word: uterine adenosarcoma Total 14 papers, including 54 patients were reported adenosarcoma with sarcomatous overgrowth Clinical data were only found in 14 patients Krivak TC et al. Gynecol Oncol. 2001;83(1):89-94. Stage Age Treatment Recurrence Outcome I 75 TAHBSO, PPLND, pelvic XRT 4050 None Alive 18 months I 68 Declined None Alive 19 months I 57 THBSO, PPLND, pelvic XRT Pelvis PFI 22 months, died 39 months II 41 TAHBSO, PPLND Pelvis PFI 7 months, died 11 months II 76 TAHBSO Declined adjuvant therapy Pelvis PFI 16 months, died 28 months II 40 TAHBSO, PPLND Adjuvant therapy: Whole-Pelvis radiation therapy 5040 cGy Lung, liver Died 1 month III 66 TAHBSO Adjuvant therapy: doxorubicin Abdomen, pelvis Died 1 month IV 33 TAHBSO Adjuvant therapy: cisplatin, doxorubicin Lung Died 8 months IV 51 TAHBSO Adjuvant therapy: doxorubicin Abdomen, lung Died 1 month IV 33 TAHBSO Adjuvant therapy: cisplatin, ifosfamide Lung PFI 8 months, died 13 months IV 63 TAHBSO Abdomen, pelvis, Adjuvant therapy: cisplatin, ifosfamide lung Died 2 months Gallardo A. Am J Surg Pathol. 2009;33(2):278-88. Stage Age Treatment Recurrence Outcome III 58 TAHBSO, Pelvic irradiation None Died 2 months Farhat MH et al. J Med Case Reports. 2007;1:103. Stage Age Treatment Recurrence Outcome II 37 TAHBSO, omentectomy Abdomen Died 1 month Nagai Y et al. Int J Gynecol Cancer. 2002;12(5):501-5. Stage Age Treatment Recurrence Outcome II 80 TAHBSO None Died 1 months Age Range from 33 to 80 years (mean: 55.6 years) Treatment All treated with (TAH+BSO), with or without radiotherapy and chemotherapy Stage 4/14 (29%) patients was diagnosed as stage IV dx at diagnosis Recurrence 10 out of 14 (71.4%) Site: pelvis, abdomen, lung Survival 7/14 (50%) patients died within 2 months after diagnosis Within these 7 expired patients, only 2 patients didn’t receive adjuvant therapy