Editing Breast cancer (section)

== '''Endocrine therapy''' ==

* '''Rationale'''
** 60% of breast cancers express ER or PR or both
** Interruption of either production of oestrogen or of the ability of oestrogen to interact with the ER causes improved DFS and OS
** Reduces risk of death by about one third
** Risk of mortality from PE or uterine cancer is only 0.2% per 10 years
* '''SERMs (Selective ER Modulators)'''
** Tamoxifen
*** Competitively inhibits the binding of oestradiol to oestrogen receptors in the breast, but has agonist activity in endometrial tissue
*** Reduces the risk of breast cancer recurrence (by 41%) and death (by 30%) in premenopausal and postmenopausal women with ER+ tumours
*** Oral drug taken daily, typically 20mg, typically for 5 years (although some studies are showing good results from longer courses e.g. 10 years)
*** Tamoxifen can cause endometrial hyperplasia, fibroids, polyps, endometrial tumours, vaginal discharge, menstrual irregularities, sexual dysfunction.
*** Other side effects - hot flushes, VTE
** Raloxifene
*** Anti-oestrogenic in breast and endometrium
* '''Aromatase inhibitors (AIs)'''
** Only indicated for '''postmenopausal''' patients with ER+ tumours
*** Superior to SERMs due to improved effectiveness and lower toxicity
** Blocks the action of adrenal aromatase, and therefore prevents the conversion of adrenally-synthesised androgens to oestrogens, the final step in conversion to the active hormone. Does not interfere with production of corticosteroids or mineralocorticoids. 
** Does not block aromatase action outside the adrenal gland - ovarian synthesis of oestrogens continues unabated, and therefore, if the patient is pre-menopausal, aromatase inhibitors will be ineffective
** Will likely give them osteoporosis 
** Exemestane, anastrazole, letrozole
* Treatment approach:
** '''Postmenopausal''' (age > 60, or amenorrhoeic for 12 months without endocrine blockers) patients with ER/PR positive disease
*** Aromatase inhibitor is preferred, but if not tolerated, can use tamoxifen
**** Anastrazole/exemestane/letrozole
*** Treat for 5 years usually, but can be given for another 5 years if the cancer is high-risk (larger tumours or node-positive disease) and/or the therapy is well-tolerated, which has been shown to improve survival further
*** Start 4-6 weeks after surgery if no CTX
*** Start concurrently with RTX
*** Start after CTX if receiving CTX
** '''Premenopausal''' patients with ER/PR positive disease
*** Aromatase inhibitors will be ineffective due to ongoing ovarian function. If used, ovarian ablation must occur first.
*** Ovarian suppression (e.g. with goserelin)  leads to significant side effects in 30% - hot flushes, MSK pain, HTN
*** High-risk patients (younger <35, or those in whom CTX is indicated) should have ovarian suppression therapy and either aromatase inhibitors or tamoxifen
*** Otherwise use tamoxifen for 5 years
*** If the patient remains premenopausal after five years, offer an additional 5 years of endocrine therapy, which has been shown to reduce recurrence further
[[File:AdjvntendcrntxHRpsbrca.gif|none|frame|Algorithm for choice of ET - from UTD]]