Risk and prognosis of endometrial cancer after tamoxifen for breast cancer

Bergman, Liesbeth; Beelen, Maureen L R; Gallee, M.P.W.; Hollema, Harry; Benraadt, J.; Leeuwen, Flora E. van

doi:10.1016/s0140-6736(00)02677-5

Cited by 472 publications

(181 citation statements)

References 29 publications

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“…This risk is proportional both to the dose of the drug and the duration of therapy, with those women treated for 5 or more years experiencing a fourfold risk 36,37 (Class 4). Some evidence exists that, for women in whom endometrial carcinoma develops following prolonged tamoxifen use, both the grade and stage of the tumor may be higher, thereby potentially compromising survival 38 (Class 4). Formerly there was controversy regarding the most appropriate approach to monitoring the endometrium in women using tamoxifen, with some investigators suggesting that routine endometrial sampling be performed on an annual basis.…”

Section: Endometrial Cancer and Tamoxifenmentioning

confidence: 99%

Investigation of Women with Postmenopausal Uterine Bleeding: Clinical Practice Recommendations

Munro

2014

TPJ

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Section: Endometrial Cancer and Tamoxifenmentioning

confidence: 99%

Investigation of Women with Postmenopausal Uterine Bleeding: Clinical Practice Recommendations

Munro

2014

TPJ

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“…Use of tamoxifen as adjuvant treatment for breast cancer for more than 5 years is known to increase the risk of endometrial cancer [8], but in our patient, it is about 12 months.…”

Section: Discussionmentioning

confidence: 76%

Multiple Metachronous Malignancies, One Patient with Three Primary Malignancies

Jayaraman¹,

Sadasivam²,

Rao³

2011

Indian J Surg

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Development of a primary cancer after treatment of the first with radiotherapy or chemotherapy is well documented, but it is common with hematological malignancies. Variety of reasons are suggested by various researchers, but a conclusive evidence is not yet available. Excepting a few correlations like the tamoxifen therapy and endometrial cancer, angiosarcoma of the breast following radiotherapy, occurrence of other metachronous malignancies seem to be dependent on genetic and environmental factors. A patient with three primary malignancies is presented here. Keywords Multiple malignancies . Metachronous . Gene disorders Case ReportA 54 year old female presented with a painless swelling in the anterior part of the neck for over 3 years' duration. On examination, the swelling was globular measuring about 3 cm in diameter in the region of right lobe of thyroid and was moving with deglutition. There was no retrosternal extension and cervical lymphadenopathy. A clinical diagnosis of thyroid adenoma was made. Right hemithyroidectomy was done, and the histopathology was minimally invasive follicular carcinoma of thyroid. She was suggested completion thyroidectomy which she refused. By the end of 1 year, she developed swelling of the left lobe, which on CT showed calcified deposits, and the FNAC showed scanty colloid material with follicular cells with no evidence of malignancy. She was lost to follow up since then.Five years after right hemithyroidectomy, she developed a malignant lump in the left breast, for which she underwent simple mastectomy with axillary clearance. Six courses of adjuvant chemotherapy (Cyclophosphamide, Epirubicin and 5 flurouracil) was given, and was advised to take Tamoxifen for 5 years.A year after mastectomy, during regular follow up, the abdominal ultrasound showed thickened endometrium of about 13 mm. On curettage, it was well differentiated adenocarcinoma, for which she refused any treatment. At this point, Tamoxifen was stopped and Letrozole was started.About 18 months after mastectomy, she developed hard nodules on the mastectomy scar, which were histologically proved to be infiltrating duct carcinoma. On further investigations, her CTs showed multiple hypodense lesions of varying size with variegated post contrast enhancement in the arterial phase in the liver, metastatic deposits in the lungs and pleural effusion (Fig. 1), though she remained asymptomatic. Only treatment she accepted was the local radiotherapy for the recurrent nodules, for which 56 Gy of radiation was given to the chest wall. In the meantime, she developed abdominal distension due to ascites, which showed malignant cells. She later succumbed to further complications. DiscussionMultiple metachronous primary cancers are known to occur in an individual, but it is often seen with hematological malignancies of childhood. The reasons are many; BRCA gene mutation, viral cause like HPV

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“…42 Tamoxifen, a therapeutic agent used for breast carcinoma, is a potent synthetic estrogen known to increase the risk of developing endometrial carcinoma. 43 PCOS with unopposed estrogen action on the endometrium is associated with endometrial carcinoma. 44 Obesity with unopposed estrogen action is also a well-known risk factor for endometrial carcinomas.…”

Section: Discussionmentioning

confidence: 99%

Neonatal estrogenic exposure suppresses PTEN-related endometrial carcinogenesis in recombinant mice

Begum

Tashiro

Katabuchi

et al. 2006

Laboratory Investigation

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Human endometrial carcinomas, as well as complex atypical hyperplasias (CAH), are estrogen related and frequently have mutations in the PTEN gene. However, the mutual contribution of estrogen and PTEN mutations to endometrial carcinogenesis in vivo is unknown. To address this issue, we investigated whether neonatal estrogenic treatments augment the incidence of CAH and carcinomas in murine PTEN (mPTEN) heterozygous ( þ /À) mutant mice, an animal model for endometrial carcinoma. Low doses of diethylstilbestrol (1 ng/g/day), genistein (50 lg/g/day) in phytoestrogens, estriol (E 3 ) (4 lg/g/day), and vehicle (ethanol and corn oil) were administered subcutaneously daily to neonatal pups from the 1st to 5th day after birth. At 52 weeks of age, the morphological changes in the endometrium, and uterine expression of Hoxa 10 and Hoxa 11, were evaluated. These Hoxa genes are abdominal B-type homeobox genes, which normally regulate differentiation of the Mü llerian duct. The incidence of CAH and adenocarcinomas of the endometrium was significantly decreased by the neonatal estrogenic treatments in the mPTEN þ /À mice. Coincidentally, all treatments significantly decreased the stromal cell density, and CAH and adenocarcinomas rarely developed in the epithelium adjacent to the affected endometrial stroma. Moreover, the uterine expression of Hoxa 10 in mice with neonatal genistein and E 3 treatments, and that of Hoxa 11 in mice with all treatments, was significantly lower when compared with vehicle alone. Taken together, neonatal estrogenic exposure induced stromal atrophy and/or hyalinization accompanied by repressed expression of Hoxa 10 and Hoxa 11, and exerted an inhibitory effect on PTEN-related tumorigenesis. These findings provide new insight into the interaction between endometrial epithelium and stroma in endometrial carcinogenesis in vivo.

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Risk and prognosis of endometrial cancer after tamoxifen for breast cancer

Cited by 472 publications

References 29 publications

Investigation of Women with Postmenopausal Uterine Bleeding: Clinical Practice Recommendations

Investigation of Women with Postmenopausal Uterine Bleeding: Clinical Practice Recommendations

Multiple Metachronous Malignancies, One Patient with Three Primary Malignancies

Neonatal estrogenic exposure suppresses PTEN-related endometrial carcinogenesis in recombinant mice

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