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Contrary to our initial concern, DFS tdoay for young postmenopausal patients who did not receive chemotherapy and patients with chemotherapy-induced menopause parallel the letrozole benefit seen in the Rbeast population as a whole. These data support the use of letrozole even in such patients. Aromatase inhibitor, Menopause, Hormonal therapy, Letrozole, Tamoxifen, Chemotherapy-induced amenorrhea Introduction Aromatase inhibitors AI are recommended for the adjuvant treatment of postmenopausal endocrine-responsive early breast cancer [ 1 ] and are now widely used in this setting globally.
Letrozole, a third generation AI, exerts its clinical effect by reversibly inhibiting the aromatase enzyme thereby profoundly reducing estrogen levels in postmenopausal women. This enzyme in the cytochrome P super family and the product of the CYP19 gene occurs in a number of tissues including subcutaneous fat, liver, muscle, brain, normal breast tissue, and mammary adenocarcinoma [ 2 ]. The aromatase enzyme is responsible for blocking the final step in the conversion of the adrenal androgen substrate androstenedione to estrogen in the peripheral tissues, the predominant source of estrogen in postmenopausal women.
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However, in women whose ovaries are active, the temporary reduction in estradiol production Girl code cast members dating by aromatase inhibition will increase gonadotrophin release and in turn stimulate follicular Looking for big breast today in herning and further estrogen production, thus rendering letrozole and other AIs ineffective in this setting. Case reports suggest that this stimulatory effect on gonadotrophin production may induce ovarian activity and estrogen production in women with chemotherapy-induced amenorrhea or in those close to the menopausal transition [ 45 ].
AIs have also been used therapeutically in premenopausal women to stimulate gonadotrophin production and ovulation for treatment of infertility [ 67 ]. The results of the BIG clinical trial indicate that among postmenopausal women with endocrine-responsive early breast cancer adjuvant letrozole is superior to tamoxifen both in terms of disease-free survival DFS and overall survival [ 8 — 11 ]. Patients eligible for BIG met criteria for post-menopausal status, but were heterogeneous in that some of the patients had become postmenopausal as a result of chemotherapy and others had experienced a natural menopause at various periods prior to study entry.
We hypothesized that patients with chemotherapy-induced menopause and those with recent natural menopause without chemotherapy might derive reduced benefit from letrozole due to their potential for ovarian estrogen production. The current analysis therefore explores whether patients with chemotherapy-induced menopause and those with potential residual ovarian function, defined as aged less than or equal to 55 years with natural menopause who did not receive chemotherapy, derived lesser benefit from letrozole as compared to tamoxifen than was seen in the trial as a whole. From March to May8, postmenopausal women with hormone receptor-positive early breast cancer were randomized to one of the four following treatment arms: Patients were enrolled in the two-arm randomization option of letrozole or tamoxifen from March to March and the four-arm option from April to May The current analysis focuses on the 4, patients who were randomized to the two monotherapy arms two- and four-arm randomization options at 76 months median follow-up [ 1011 ].
The trial protocol did not dictate whether or not to give chemotherapy adjuvant or neoadjuvant. In most cases chemotherapy was completed prior to study entry. Visit the Wiki for more information regarding guides, stores, and tailoring help. Where do questions go? For all requests and questions, please post in the weekly sticky at the top of the subreddit.
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