oncology Flashcards
overview of tamoxifen
Tamoxifen is a selective oestrogen receptor modulator (SERM) drug used in the treatment of women with oestrogen receptor positive breast cancers as an adjuvant to chemotherapy post-surgical excision. It is commonly prescribed to both pre- and post-menopausal women in the setting of breast cancer, although the aromatase inhibitor class of compounds is preferred in post-menopausal women unless these cause unpalatable side effects.
In breast tissue, the drug acts as an antagonist at the oestrogen receptor although it acts as an agonist at other tissues in the body such as the endometrium. Since oestrogen receptor positive breast cancers require the action of oestrogen on the neoplastic cells to grow, blockade at the level of the receptor by tamoxifen reduces the risk of neoplastic transformation or tumour growth. However, in the endometrium, tamoxifen is an agonist at oestrogen receptors and this has the potential to promote carcinomatous growth. For this reason, use of tamoxifen is generally restricted to a maximum of five years to reduce the likelihood of endometrial cancer.
Another site where tamoxifen acts as an agonist is at bone. The effect of activation of oestrogen receptors on bone is to inhibit osteoclast activity and so it acts as a bone density protector and reduces the incidence of osteoporosis.
Tamoxifen, similar to most sex hormone modulators, carries a risk of venous thromboembolism and patients commenced on these drugs are taught the signs of deep vein thrombosis and pulmonary embolism and must be vigilant while on therapy. This is especially important in periods of immobility such as around times of surgery and thrombosis prophylaxis should be used. Very rarely, tamoxifen can precipitate blood dyscrasias including neutropenia, thrombocytopenia and occasionally disseminated intravascular coagulation, although these are very infrequent.
An effect of oestrogen receptor blockade in the breast tissue is to cause degeneration of ductal tissue and thus reduces lactation. In pre-menopausal, breastfeeding women tamoxifen is best avoided as it can impair the mother’s ability to lactate. Signs of galactorrhoea or leakage from the nipple in breast cancer patients taking tamoxifen should be investigated quickly as it may be a sign that there is neoplastic change within the ductal tissues of the breast.
Tamoxifen rarely causes vaginal dryness although there may be intense itching in the vulval area on taking this drug. Patients may actually notice an increase in vaginal discharge or bleeding while on tamoxifen due to the agonist effect on the endometrium although persistent bleeding should be investigated early to rule out endometrial malignancy.
