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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