Tamoxifen syndrome

Women with anovulatory infertility should be offered full endocrinological evaluation, considering potential diagnoses such as hypothalamic-pituitary disease, polycystic ovary syndrome and primary gonadal disease. Hyperprolactinaemia must be sought as a potential cause, and its treatment is outlined below. The main treatments available include the anti-oestrogens clomiphene and tamoxifen, and gonadotrophin therapy. 

Several other aromatase inhibitors are undergoing clinical trials in patients with breast cancer. Fadrozole is an oral nonsteroidal (triazole) inhibitor of aromatase activity. These compounds appear to be as effective as tamoxifen. In addition to their use in breast cancer, aromatase inhibitors have been successfully employed as adjuncts to androgen antagonists in the treatment of precocious puberty and as primary treatment in the excessive aromatase syndrome. 

Carpal tunnel syndrome has been reported in six patients taking aromatase inhibitors (29). Most subsequently experienced relief after withdrawal and/or switching to tamoxifen. In clinical trials of anastrozole and exemestane, carpal tunnel syndrome occurred in about 3% (30,31,32). 

Some helpful evidence comes from related fields. It should be borne in mind, for example, that the question of an increased risk of endometrial hyperplasia and endometrial cancer also arises in patients with estrogen-producing tumors of the ovaries, obesity, and polycystic ovarian syndrome (101) and in patients with breast cancer who are using tamoxifen (102). 

An unusual case of rapidly fatal renal failure reported in 1993 could reflect an interaction between tamoxifen and one or more cytostatic agents, with mitomycin C a prime suspect in a series of breast cancer patients some 10% of those treated both with tamoxifen and a cytostatic agent developed abnormal renal function, progressing towards various stages of hemolytic-uremic syndrome (118). 

Montes A, Powles TJ, O Brien ME, Ashley SE, Luckit J, Treleaven J. A toxic interaction between mitomycin C and tamoxifen causing the haemolytic uraemic syndrome. Eur J Cancer 1993 29A(13) 1854-7. 

Tamoxifen decreases the rate of proliferation of breast cancer cells in vitro by inhibiting the estrogen-dependent production of specific proteins and growth factors that exert autocrine effects on cell division. Antiandrogenic compounds antagonize the effects of testosterone and are of value in the treatment of hirsutism and other masculinizing syndromes. 

MITOMYCIN HORMONES AND HORMONE ANTAGONISTS -TAMOXIFEN t incidence of anaemia and thrombocytopenia and risk of haemolytic-uraemic syndrome Mitomycin causes subdinical endothelial damage in addition to the thrombotic effect on platelets caused by tamoxifen, which leads to haemolytic-uraemic syndrome Monitor renal function at least twice weekly during concurrent therapy and watch clinically for bleeding episodes, e.g. nose bleeds, bleeding from the gums, skin bruising... 

Hemolytic anemia, thrombocytopenia and renal dysfunction, leading to potentially fatal hemolytic uremic syndrome, can occur in patients given tamoxifen with or shortly after mitomycin C. Mitomycin C is contraindicated in patients with preexisting myelosupress-ion and anemia. 

Haemolytic anaemia, thrombocytopenia and renal impairment, leading to potentially fatal haemolytic uraemic syndrome, has occurred in a few patients given tamoxifen with, or shortly after, mitomycin. 

The authors of the first study suggested that this haemolytic uraemic syndrome was due to a combination of subclinical endothelial damage induced by mitomycin C, and a thrombotic effect on platelets caused by tamoxifen. They advise the avoidance of tamoxifen with or shortly after mitomycin C unless concurrent use ean be earefully monitored. Erythropoietin may be useful in managing the syndrome. This syndrome has also occurred rarely with mitomycin alone, or when combined with fluorouracil, see Mitomycin + Fluorouracil , above. 

EUis PA, Luckitt J, Treleaven J, SmithlE. Haemotytic uraemic syndrome in a patient with lui cancer further evidence for ataxic interaction between mitomycin-C and tamoxifen. Clin Oncol (R CollRadiol) (1996) 8,402-3. 

O Brien MER, Casey S, Treleaven J, Powles TJ. Use of eiythnpoietin in the management of die haemol34 ic uraemic syndrome induced by mitomycin C/tamoxifen. EurJ Cancer (1994)... 

Mieog JS, Morden JP, BHss JM, Coombes RC, van de Velde CJ, lES Steering Committee. Carpal turmel syndrome and musculoskeletal symptoms in postmenopausal women with early breast cancer treated with exemestane or tamoxifen after 2-3 years of tamoxifen a retrospective analysis of the Intergroup Exemestane Study. Lancet Oncol 2012 13(4) 420-32. 

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