Is there an association between long-term tamoxifen treatment and the development of carcinosarcoma (malignant mixed Müllerian tumor) of the uterus?

Evans, M; Langlois, Neil E. I.; Kitchener, H.; Miller, I.D.

doi:10.1046/j.1525-1438.1995.05040310.x

Cited by 44 publications

(19 citation statements)

References 3 publications

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“…Despite surgical cytoreduction and subsequent chemotherapy being considered the best primary treatment for uterine CS, the overall five-year survival rate is 30 ± 9% for all stages and recurrence is very common (50–80%) [5,6,38]. The characteristics of uterine CS are very different from other types of gynecological cancer, such as ovarian [79,80,81,82,83,84,85], endometrial [86,87], cervical [88,89] and vulvar [90,91] cancers.…”

Section: Discussionmentioning

confidence: 99%

“…In general, uterine sarcoma represents 3–5% of all corpus uteri malignancies, occurring in 1–4 per 1000 women in the USA [4]. CS shares similar risk factors with endometrial carcinomas; both of them are associated with obesity, nulliparity, and the use of exogenous estrogen and tamoxifen [5,6,7]. Conversely, progestin-containing contraceptives are protective against both types of neoplasms.…”

Section: Introductionmentioning

confidence: 99%

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Target Therapies for Uterine Carcinosarcomas: Current Evidence and Future Perspectives

Vitale

Laganà

Capriglione

et al. 2017

IJMS

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Carcinosarcomas (CS) in gynecology are very infrequent and represent only 2–5% of uterine cancers. Despite surgical cytoreduction and subsequent chemotherapy being the primary treatment for uterine CS, the overall five-year survival rate is 30 ± 9% and recurrence is extremely common (50–80%). Due to the poor prognosis of CS, new strategies have been developed in the last few decades, targeting known dysfunctional molecular pathways for immunotherapy. In this paper, we aimed to gather the available evidence on the latest therapies for the treatment of CS. We performed a systematic review using the terms “uterine carcinosarcoma”, “uterine Malignant Mixed Müllerian Tumors”, “target therapies”, “angiogenesis therapy”, “cancer stem cell therapy”, “prognostic biomarker”, and “novel antibody-drug”. Based on our results, the differential expression and accessibility of epithelial cell adhesion molecule-1 on metastatic/chemotherapy-resistant CS cells in comparison to normal tissues and Human Epidermal Growth Factor Receptor 2 (HER2) open up new possibilities in the field of target therapy. Nevertheless, future investigations are needed to clarify the impact of these new therapies on survival rate and medium-/long-term outcomes.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Target Therapies for Uterine Carcinosarcomas: Current Evidence and Future Perspectives

Vitale

Laganà

Capriglione

et al. 2017

IJMS

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show abstract

“…This is, however, controversial, with some studies suggesting that type-2 cancers, such as serous carcinoma, are proportionally more common in association with tamoxifen. 39 40 Indeed, it has been suggested that carcinosarcomas (in reality, metaplastic carcinomas often associated with an epithelial component of type-2 carcinoma 41 42 ) are particularly likely to be associated with tamoxifen, [43][44][45] and adenosarcomas have also been reported. 46 Other studies, however, have found most tamoxifen-associated endometrial neoplasms to be low-grade endometrioid adenocarcinomas.…”

Section: Effects Of Tamoxifen On the Endometriummentioning

confidence: 99%

My approach to the interpretation of endometrial biopsies and curettings

McCluggage¹

2006

J Clin Pathol

121

132

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A major proportion of the workload in many histopathology laboratories is accounted for by endometrial biopsies, either curettage specimens or outpatient biopsy specimens. The increasing use of pipelle and other methods of biopsy not necessitating general anaesthesia has resulted in greater numbers of specimens with scant tissue, resulting in problems in assessing adequacy and in interpreting artefactual changes, some of which appear more common with outpatient biopsies. In this review, the criteria for adequacy and common artefacts in endometrial biopsies, as well as the interpretation of endometrial biopsies in general, are discussed, concentrating on areas that cause problems for pathologists. An adequate clinical history, including knowledge of the age, menstrual history and menopausal status, and information on the use of exogenous hormones and tamoxifen, is necessary for the pathologist to critically evaluate endometrial biopsies. Topics such as endometritis, endometrial polyps, changes that are induced by hormones and tamoxifen within the endometrium, endometrial metaplasias and hyperplasias, atypical polypoid adenomyoma, adenofibroma, adenosarcoma, histological types of endometrial carcinoma and grading of endometrial carcinomas are discussed with regard to endometrial biopsy specimens rather than hysterectomy specimens. The value of ancillary techniques, especially immunohistochemistry, is discussed where appropriate.

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“…In recent years, there have been occasional reports of uterine carcinosarcoma arising in patients taking tamoxifen for breast cancer (2–7) . The aim of this report is to describe the clinical and pathological findings in 19 patients (two of these have been previously reported (5) ) who developed uterine carcinosarcoma while taking tamoxifen.…”

mentioning

confidence: 99%

Uterine carcinosarcomas in patients receiving tamoxifen. A report of 19 cases

McCluggage¹,

Abdulkader²,

Price³

et al. 2000

Int J Gynecol Cancer

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Uterine carcinosarcomas are highly aggressive neoplasms with a tendency to early extrauterine spread, high stage at diagnosis, and a poor prognosis. Tamoxifen is widely used as adjuvant therapy in the treatment of breast cancer and is known to cause endometrial proliferative lesions, including adenocarcinoma. In recent years, there have been occasional reports of uterine carcinosarcoma in patients taking tamoxifen. The aim of this study is to describe the clinicopathologic profile in 19 women taking tamoxifen who subsequently developed uterine carcinosarcoma. Nineteen patients were identified from cases of uterine carcinosarcoma diagnosed at three institutions. The case notes were examined and the pathology reviewed. The age at diagnosis of carcinosarcoma ranged from 47 to 91 years (mean 71 years). All patients were postmenopausal and received 20 mg tamoxifen daily; the duration of treatment ranged from 1 to 15 years (mean 7.1 years). The cumulative dose of tamoxifen ranged from 7.3 to 109.5 g. Ten tumors were stage I, one stage II, seven stage III, and one stage IV. Ten of the carcinosarcomas were homologous, and nine contained heterologous elements in the form of rhabdomyoblasts (six cases) or malignant cartilage (three cases). The overall prognosis was extremely poor. Fifteen patients died within 35 months of the diagnosis of carcinosarcoma (mean 12 months). Two patients are alive with very short follow-up periods, and two were lost to follow-up. The reported data support an association between tamoxifen therapy and the development of uterine carcinosarcoma. The risk is likely to be highest in those patients who have been taking tamoxifen for a prolonged period. A majority of tumors in the present study were stage I, and this suggests that uterine carcinosarcomas in patients taking tamoxifen may be diagnosed at an earlier stage than those arising de novo. However, the prognosis was still poor even with low-stage disease. Properly controlled epidemiological studies are necessary to confirm an association between tamoxifen and uterine carcinosarcoma.

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Is there an association between long-term tamoxifen treatment and the development of carcinosarcoma (malignant mixed Müllerian tumor) of the uterus?

Cited by 44 publications

References 3 publications

Target Therapies for Uterine Carcinosarcomas: Current Evidence and Future Perspectives

Target Therapies for Uterine Carcinosarcomas: Current Evidence and Future Perspectives

My approach to the interpretation of endometrial biopsies and curettings

Uterine carcinosarcomas in patients receiving tamoxifen. A report of 19 cases

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