{"id":252,"date":"2019-10-09T20:41:08","date_gmt":"2019-10-09T15:11:08","guid":{"rendered":"https:\/\/medicineplexus.com\/?p=252"},"modified":"2019-10-09T20:41:08","modified_gmt":"2019-10-09T15:11:08","slug":"adjuvant-endocrine-therapy-for-non-metastatic-hr-breast-cancer","status":"publish","type":"post","link":"https:\/\/medicineplexus.com\/adjuvant-endocrine-therapy-for-non-metastatic-hr-breast-cancer\/","title":{"rendered":"Adjuvant endocrine therapy for non-metastatic, HR+ breast cancer"},"content":{"rendered":"\n<p><strong>Adjuvant endocrine therapy for non-metastatic, hormone\nreceptor-positive breast cancer<\/strong><\/p>\n\n\n\n<ul><li>leading cause of death from\ncancer in women worldwide. <\/li><li>Hormone receptor-positive (ie, <strong>estrogen [ER] and\/or progesterone [PR]\nreceptor-positive<\/strong>) breast cancers comprise the most common types of breast\ncancer, accounting for <strong>75 percent of all\ncases.<\/strong><\/li><\/ul>\n\n\n\n<p><strong>OVERVIEW OF TREATMENT\nOPTIONS<\/strong><\/p>\n\n\n\n<ul><li>selective estrogen receptor\nmodulator (SERM), tamoxifen<\/li><li>Aromatase inhibitors, which\nblock the peripheral conversion of androgens to estrogens.<\/li><li>Ovarian suppression or\nablation, which inhibits endogenous estrogen production from the ovaries, which\ncan be done on a temporary basis (ovarian suppression) or permanently through\noophorectomy or radiation therapy to the ovaries (ovarian ablation). <\/li><\/ul>\n\n\n\n<p><strong>TREATMENT APPROACH<\/strong><\/p>\n\n\n\n<ul><li>For women with estrogen\nreceptor- or progesterone receptor-positive breast cancer, \u00e0 <strong>adjuvant endocrine therapy. <\/strong><\/li><li>the approach is supported by\nthe <strong>consistent improvements in rates of\nrecurrence, second breast cancers, and survival<\/strong> that have been observed in\nclinical trials enrolling patients with hormone receptor-positive tumors <strong>of any size.<\/strong><\/li><li><strong>approach<\/strong> to treatment decisions for\nwomen with nonmetastatic, hormone receptor-positive breast cancer \u00e0 &nbsp;<strong>according to menopausal status.<\/strong><\/li><\/ul>\n\n\n\n<ul><li><strong>Definition of menopause<\/strong> \u2014<\/li><li>For <strong>women with breast cancer<\/strong> who were premenopausal at diagnosis,\nparticularly those treated <strong>with adjuvant\nchemotherapy, amenorrhea is not a reliable indicator<\/strong> of menstrual status. <\/li><li>following definitions of\nmenopause <\/li><li>women <strong>60 years and older postmenopausal<\/strong>.<\/li><li>women less than 60 years\npostmenopausal if one of the following conditions are met:<\/li><li>previously underwent a <strong>bilateral oophorectomy.<\/strong><\/li><li><strong>have not had any menstrual periods for 12 months<\/strong> or more in the absence of tamoxifen, chemotherapy, or ovarian\nsuppression, and the serum estradiol is in the postmenopausal range.<\/li><li><strong>are amenorrheic on tamoxifen<\/strong>, and\nfollicle-stimulating hormone (FSH) and serum estradiol are in the\npostmenopausal range.<\/li><li>For women who were\npremenopausal prior to chemotherapy but experience therapy-induced amenorrhea,\noophorectomy or serial measurement of FSH and estradiol are needed to ensure\npostmenopausal status if considering initiation of an aromatase inhibitor (AI).\n<\/li><\/ul>\n\n\n\n<ul><li><strong>Premenopausal women<\/strong> \u2014 <\/li><\/ul>\n\n\n\n<ul><li>For women with <strong>high-risk breast cancer<\/strong>\u00e0 ovarian suppression plus exemestane rather than tamoxifen <\/li><\/ul>\n\n\n\n<ul><li>For women with <strong>low-risk breast cancer<\/strong>\u00e0 tamoxifen as single-agent therapy, given better tolerability than\novarian suppression plus either an aromatase inhibitor (AI) or tamoxifen.<\/li><\/ul>\n\n\n\n<ul><li><strong>ovarian suppression plus exemestane rather than tamoxifen as\nsingle-agent therapy. <\/strong><\/li><li>the recommendation is based on\nthe results of the Suppression of Ovarian Function Trial (SOFT) and the Tamoxifen\nand Exemestane Trial (TEXT)<\/li><li>An <strong>AI is not appropriate as single-agent therapy for women with intact\novarian function<\/strong>. <\/li><\/ul>\n\n\n\n<p><strong>Postmenopausal women<\/strong> \u2014 <\/p>\n\n\n\n<ul><li><strong>AI rather than tamoxifen. <\/strong><\/li><li>While AIs are associated with\nimproved outcomes compared with tamoxifen, both agents reduce recurrences and\nnew primary breast cancers, and some women may tolerate the risks and\ntoxicities of tamoxifen better than AI. <\/li><li>For women who wish to\ndiscontinue an AI, it would be reasonable to switch to tamoxifen. The duration\nof endocrine therapy is discussed below.<\/li><\/ul>\n\n\n\n<p><strong>OVARIAN SUPPRESSION OR\nABLATION<\/strong><\/p>\n\n\n\n<ul><li>For <strong>premenopausal women<\/strong>, ovarian function can be <strong>permanently suppressed by surgery (oophorectomy) or pelvic radiation\n(ovarian ablation<\/strong>). <\/li><\/ul>\n\n\n\n<ul><li><strong>Temporary amenorrhea<\/strong> is also possible\nwith the administration of pharmacologic interventions to induce ovarian\nsuppression (OS), such as the <strong>gonadotropin-releasing\nhormone agonists (GnRHa<\/strong>). <\/li><\/ul>\n\n\n\n<ul><li><strong>Ovarian suppression plus tamoxifen or aromatase inhibitors<\/strong><\/li><li>The use of OS with either\ntamoxifen or aromatase inhibition (AI) provides some benefit over tamoxifen\nalone, but also is associated with increased toxicity <\/li><li>recommendation is based on the\nresults of the Suppression of Ovarian Function Trial (SOFT) and the Tamoxifen\nand Exemestane Trial (TEXT)<\/li><li>Across both trials, <strong>toxicities were greater among those\nreceiving OS, with osteoporosis and musculoskeletal side effects being most\ncommon<\/strong> among patients receiving exemestane in combination with OS. <\/li><li>Taken together, the data\nsuggest a possible modest DFS benefit with the addition of OS to either\ntamoxifen or AI over tamoxifen alone for patients with hormone\nreceptor-positive breast cancer, but may not justify the added toxicities for\nmost average-risk patients.<\/li><\/ul>\n\n\n\n<ul><li><strong>OTHER FORMS OF ENDOCRINE THERAPY<\/strong><\/li><\/ul>\n\n\n\n<p><strong>Tamoxifen <\/strong>\u2014 <\/p>\n\n\n\n<ul><li>selective estrogen receptor\nmodulator (SERM) <\/li><li>inhibits the growth of breast\ncancer cells by competitive antagonism of the estrogen receptor (ER). <\/li><li>adjuvant treatment of\npremenopausal women and for postmenopausal women who are not candidates for an\naromatase inhibitor (AI) <\/li><li>Dosing &#8212; 20 mg pill taken on a\ndaily basis.<\/li><li>Side effects \u2014 significantly\nincreased risk of thromboembolic disease (ie, deep vein thrombosis and\npulmonary emboli) <\/li><li>increased the risk of uterine\ncancer, fatty liver disease, hot flashes, vaginal discharge, sexual\ndysfunction, menstrual irregularities, and increased risk of diabetes <\/li><\/ul>\n\n\n\n<ul><li>Resistance \u2014 A number of\nfactors may contribute to tamoxifen resistance in breast cancer, including <\/li><li>Variable expression of ER-alpha\nand beta isoforms<\/li><li>Interference with the binding\nof coactivators and corepressors<\/li><li>Alternative splicing of ER mRNA\nvariants<\/li><li>Modulators of ER expression\n(eg, epidermal growth factor and its receptors such as EGFR1 and EGFR2, also\ncalled human epidermal growth factor receptor 2 [HER2])<\/li><li>Inherited drug metabolizing\nCYP2D6 genotypes<\/li><\/ul>\n\n\n\n<p><strong>Aromatase inhibitors<\/strong> <\/p>\n\n\n\n<ul><li>AIs suppress plasma estrogen\nlevels by inhibiting or inactivating aromatase, the enzyme responsible for the\nperipheral conversion of androgens to estrogens<\/li><li>improve outcomes for\npostmenopausal women with hormone receptor-positive breast cancer compared with\ntamoxifen. <\/li><li>inactive in women with intact\novarian function, including those who experienced therapy-induced amenorrhea.\n(See &#8216;Definition of menopause&#8217; above and &#8216;Reactivation of ovarian function&#8217;\nbelow.<\/li><li>Dosing \u2014 Drugs in this class,\nwith usual dosing, include:<\/li><li>Anastrozole (1 mg daily)<\/li><li>Letrozole (2.5 mg daily)<\/li><li>Exemestane (25 mg daily)<\/li><\/ul>\n\n\n\n<p><strong>Versus tamoxifen<\/strong><\/p>\n\n\n\n<ul><li>Reduced breast cancer\nrecurrence<\/li><li>Lower 10-year breast cancer\nmortality <\/li><\/ul>\n\n\n\n<ul><li><strong>Comparison between AIs \u2014<\/strong> Evidence\nsuggests <strong>similar clinical outcomes<\/strong>\nand tolerability between the aromatase inhibitors (AIs). As such, <strong>anastrozole, exemestane, and letrozole are\nall appropriate options<\/strong> for those warranting adjuvant treatment with an AI.\n<\/li><\/ul>\n\n\n\n<ul><li><strong>Side effects \u2014<\/strong>The AIs are associated\nwith <strong>musculoskeletal side effects\nincluding carpal tunnel syndrome as well as AI-associated musculoskeletal\nsyndrome (AIMSS), characterized by joint pain and stiffness <\/strong><\/li><li>Sexual dysfunction \u2013 Because\nAIs block peripheral estrogen production, women are at an increased risk for\nvaginal symptoms and sexual dysfunction. <\/li><li>Hot flashes <\/li><li><strong>Compared with tamoxifen, the AIs are also associated with a higher\nrisk of osteoporosis, fractures, cardiovascular disease, diabetes, and\nhypercholesterolemia<\/strong> <\/li><li><strong>By contrast, they are associated with a lower risk of venous\nthrombosis and endometrial cancer and a lower risk of fatty liver disease <\/strong><\/li><\/ul>\n\n\n\n<ul><li><strong>Timing of endocrine therapy \u2014<\/strong><\/li><li>For patients <strong>receiving adjuvant chemotherapy, the\ninitiation of endocrine therapy is commonly begun after chemotherapy has\ncompleted<\/strong> (ie, sequentially) rather than during chemotherapy (ie,\nconcurrently).<\/li><\/ul>\n\n\n\n<ul><li>For women receiving adjuvant <strong>radiation therapy (RT) for breast cancer,\ninitiate endocrine therapy concurrently with RT<\/strong>. Multiple studies show that\nthe timing of endocrine therapy in relation to RT does not impact survival <\/li><\/ul>\n\n\n\n<ul><li><strong>PATIENTS WITH HER2-POSITIVE TUMORS<\/strong><\/li><\/ul>\n\n\n\n<ul><li>Most patients with estrogen\nreceptor (ER)-positive, human epidermal growth factor receptor 2\n(HER2)-positive early breast cancer are treated with adjuvant <strong>chemotherapy plus trastuzumab<\/strong> followed\nby <strong>maintenance trastuzumab to complete\none year of treatment<\/strong><\/li><\/ul>\n","protected":false},"excerpt":{"rendered":"<p>Adjuvant endocrine therapy for non-metastatic, hormone receptor-positive breast cancer leading cause of death from cancer in women worldwide. Hormone receptor-positive (ie, estrogen [ER] and\/or progesterone [PR] receptor-positive) breast cancers comprise the most common types of breast cancer, accounting for 75 percent of all cases. OVERVIEW OF TREATMENT OPTIONS selective estrogen receptor modulator (SERM), tamoxifen Aromatase[&#8230;]\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_seopress_robots_primary_cat":"","_seopress_titles_title":"","_seopress_titles_desc":"","_seopress_robots_index":"","footnotes":""},"categories":[3],"tags":[],"_links":{"self":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/252"}],"collection":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/comments?post=252"}],"version-history":[{"count":0,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/252\/revisions"}],"wp:attachment":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/media?parent=252"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/categories?post=252"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/tags?post=252"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}