{"entity":{"id":"letrozole","kind":"drug","name":"Letrozole (and other aromatase inhibitors)","aka":[],"tldr":"Daily pills that stop the body making oestrogen after menopause, the backbone of hormone therapy for most breast cancers.","summary":"Non-steroidal (letrozole, anastrozole) and steroidal (exemestane) aromatase inhibitors block conversion of androgens to oestrogens in fat and tumour tissue. Superior to tamoxifen for postmenopausal women in adjuvant (ATAC, BIG 1-98) and metastatic settings; the standard partner for CDK4/6 inhibitors in first-line metastatic disease. Used with ovarian suppression in premenopausal women (SOFT/TEXT). Arthralgia, bone loss, and vaginal dryness drive non-adherence.","status":"approved","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Letrozole","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Letrozole"}],"tags":[],"related":[],"cancers":["breast-hr-positive","ovarian","endometrial","granulosa-cell-tumour","low-grade-serous-ovarian-cancer"],"sections":[],"technologies":["endocrine-therapy"],"targets":["estrogen-receptor"],"drugs":[],"companies":["novartis"],"institutions":[],"pathways":["er-signaling"],"terms":["lgsoc"],"trials":["soft-text","monaleesa-2","paloma-2","monarch-3","nct06072781","nct04557449","nct04553133","nct04606446","nct07288359","nct05867251"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["In low-grade serous ovarian cancer, retrospective series and the NRG-GY019 trial support endocrine maintenance, and letrozole is now widely used after surgery or chemotherapy in LGSOC and in ER-positive endometrial cancer, often with palbociclib or abemaciclib; it is cheap and well tolerated, with bone loss and arthralgia the main issues."],"brand":"Femara; anastrozole (Arimidex); exemestane (Aromasin)","modality":"Small-molecule aromatase inhibitor","mechanism":"Competitive (letrozole, anastrozole) or irreversible (exemestane) inhibition of CYP19A1 aromatase.","approvals":[{"region":"US","year":1997,"indication":"Advanced breast cancer after tamoxifen (letrozole)"},{"region":"US","year":2005,"indication":"Adjuvant early breast cancer (letrozole)"}],"mechanismSteps":["Adrenal androgens circulate to fat, muscle, and tumour","Aromatase (CYP19A1) would convert them to oestradiol","The inhibitor occupies the enzyme's active site","Oestradiol falls by >95%","ER-dependent transcription and proliferation stop"],"dosing":{"route":"Oral","schedule":"Letrozole 2.5 mg, anastrozole 1 mg, or exemestane 25 mg once daily; 5-10 years adjuvant; until progression metastatic","modifications":"Rarely needed; switch agent for intolerable arthralgia","monitoring":"Bone density every 1-2 years; lipids","source":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020726s027lbl.pdf"},"toxicity":[{"event":"Arthralgia/myalgia","anyGradePct":35},{"event":"Hot flushes","anyGradePct":33},{"event":"Bone fracture (5-year)","anyGradePct":10},{"event":"Fatigue","anyGradePct":20}],"access":[],"regulatoryEvents":[{"date":"1997-07-25","type":"approval","region":"US","note":"Letrozole approved for advanced breast cancer"},{"date":"2004-10-29","type":"accelerated-approval","region":"US","note":"Accelerated approval on a surrogate endpoint, with a confirmatory trial required.","indication":"Extended adjuvant treatment of early breast cancer in postmenopausal women who received 5 years of adjuvant tamoxifen"},{"date":"2005-12-28","type":"accelerated-approval","region":"US","note":"Letrozole adjuvant indication","indication":"Postmenopausal women with HR positive early breast cancer"},{"date":"2010-04-30","type":"conversion","region":"US","note":"Confirmed: the accelerated approval of 2004 converted to traditional approval 5.5 years after it was granted.","indication":"Extended adjuvant treatment of early breast cancer in postmenopausal women who received 5 years of adjuvant tamoxifen"},{"date":"2010-04-30","type":"conversion","region":"US","note":"Confirmed: the accelerated approval of 2005 converted to traditional approval 4.3 years after it was granted.","indication":"Postmenopausal women with HR positive early breast cancer"}]},"route":"/drugs/letrozole/","neighbours":{"cancer":[{"id":"granulosa-cell-tumour","kind":"cancer","name":"Adult granulosa cell tumour of the ovary","route":"/cancers/granulosa-cell-tumour/"},{"id":"advanced-recurrent-endometrial-cancer","kind":"cancer","name":"Advanced or recurrent endometrial cancer","route":"/cancers/advanced-recurrent-endometrial-cancer/"},{"id":"endometrial","kind":"cancer","name":"Endometrial cancer","route":"/cancers/endometrial/"},{"id":"endometrial-nsmp","kind":"cancer","name":"Endometrial cancer with no specific molecular profile","route":"/cancers/endometrial-nsmp/"},{"id":"hr-positive-early-high-risk","kind":"cancer","name":"High-risk early HR-positive breast cancer","route":"/cancers/hr-positive-early-high-risk/"},{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"},{"id":"inflammatory-breast-cancer","kind":"cancer","name":"Inflammatory breast cancer","route":"/cancers/inflammatory-breast-cancer/"},{"id":"invasive-lobular-carcinoma","kind":"cancer","name":"Invasive lobular carcinoma of the breast","route":"/cancers/invasive-lobular-carcinoma/"},{"id":"leiomyosarcoma","kind":"cancer","name":"Leiomyosarcoma","route":"/cancers/leiomyosarcoma/"},{"id":"low-grade-serous-ovarian-cancer","kind":"cancer","name":"Low-grade serous ovarian cancer","route":"/cancers/low-grade-serous-ovarian-cancer/"},{"id":"male-breast-cancer","kind":"cancer","name":"Male breast cancer","route":"/cancers/male-breast-cancer/"},{"id":"mucinous-carcinoma-breast","kind":"cancer","name":"Mucinous carcinoma of the breast","route":"/cancers/mucinous-carcinoma-breast/"},{"id":"ovarian","kind":"cancer","name":"Ovarian cancer","route":"/cancers/ovarian/"},{"id":"platinum-resistant-ovarian-cancer","kind":"cancer","name":"Platinum-resistant ovarian cancer","route":"/cancers/platinum-resistant-ovarian-cancer/"},{"id":"tubular-carcinoma-breast","kind":"cancer","name":"Tubular carcinoma of the breast","route":"/cancers/tubular-carcinoma-breast/"},{"id":"uterine-sarcoma","kind":"cancer","name":"Uterine sarcoma","route":"/cancers/uterine-sarcoma/"}],"technology":[{"id":"acupuncture-aromatase-inhibitor-arthralgia","kind":"technology","name":"Acupuncture for aromatase-inhibitor joint pain","route":"/technologies/acupuncture-aromatase-inhibitor-arthralgia/"},{"id":"acupuncture-hot-flushes","kind":"technology","name":"Acupuncture for hot flushes on endocrine therapy","route":"/technologies/acupuncture-hot-flushes/"},{"id":"hair-antiandrogens-alopecia","kind":"technology","name":"Antiandrogens for hair: spironolactone, finasteride, dutasteride","route":"/technologies/hair-antiandrogens-alopecia/"},{"id":"cancer-treatment-bone-loss","kind":"technology","name":"Bone loss caused by cancer treatment, and what rebuilds it","route":"/technologies/cancer-treatment-bone-loss/"},{"id":"dietitian-led-weight-loss-breast","kind":"technology","name":"Dietitian-led weight-loss programmes in HR-positive breast cancer","route":"/technologies/dietitian-led-weight-loss-breast/"},{"id":"endocrine-therapy","kind":"technology","name":"Endocrine therapy (SERMs, AIs, SERDs)","route":"/technologies/endocrine-therapy/"},{"id":"fes-pet","kind":"technology","name":"FES PET (oestrogen receptor imaging)","route":"/technologies/fes-pet/"},{"id":"menopause-after-cancer-treatment","kind":"technology","name":"Menopause brought on by cancer treatment, and the options for it","route":"/technologies/menopause-after-cancer-treatment/"},{"id":"minoxidil-chemotherapy-alopecia","kind":"technology","name":"Minoxidil for persistent chemotherapy- and endocrine-therapy hair loss","route":"/technologies/minoxidil-chemotherapy-alopecia/"},{"id":"vaginal-oestrogen-after-breast-cancer","kind":"technology","name":"Vaginal oestrogen after breast cancer: what the evidence says, and where it disagrees","route":"/technologies/vaginal-oestrogen-after-breast-cancer/"}],"target":[{"id":"aromatase","kind":"target","name":"Aromatase (CYP19A1)","route":"/targets/aromatase/"},{"id":"estrogen-receptor","kind":"target","name":"Estrogen receptor (ERα)","route":"/targets/estrogen-receptor/"}],"company":[{"id":"novartis","kind":"company","name":"Novartis","route":"/companies/novartis/"}],"pathway":[{"id":"breast-cancer-signalling","kind":"pathway","name":"Breast cancer (KEGG map)","route":"/pathways/breast-cancer-signalling/"},{"id":"chemical-carcinogenesis-receptor-activation","kind":"pathway","name":"Chemical carcinogenesis - receptor activation","route":"/pathways/chemical-carcinogenesis-receptor-activation/"},{"id":"endometrial-cancer-signalling","kind":"pathway","name":"Endometrial cancer (KEGG map)","route":"/pathways/endometrial-cancer-signalling/"},{"id":"er-signaling","kind":"pathway","name":"Oestrogen receptor signalling","route":"/pathways/er-signaling/"}],"term":[{"id":"aromatase-inhibitor","kind":"term","name":"Aromatase inhibitor","route":"/terms/aromatase-inhibitor/"},{"id":"alopecia-endocrine-therapy","kind":"term","name":"Endocrine-therapy-induced alopecia","route":"/terms/alopecia-endocrine-therapy/"},{"id":"lgsoc","kind":"term","name":"Low-grade serous ovarian cancer (LGSOC)","route":"/terms/lgsoc/"}],"trial":[{"id":"nct06072781","kind":"trial","name":"A Study of Avutometinib (VS-6766) + Defactinib (VS-6063) in Recurrent Low-Grade Serous Ovarian Cancer","route":"/trials/nct06072781/"},{"id":"comet-dcis","kind":"trial","name":"COMET (Comparison of Operative versus Monitoring and Endocrine Therapy)","route":"/trials/comet-dcis/"},{"id":"nct00412022","kind":"trial","name":"HOBOE: A Phase 3 Study of Adjuvant Triptorelin and Tamoxifen, Letrozole, or Letrozole and Zoledronic Acid in Premenopausal Patients With Breast Cancer","route":"/trials/nct00412022/"},{"id":"monaleesa-2","kind":"trial","name":"MONALEESA-2","route":"/trials/monaleesa-2/"},{"id":"monarch-3","kind":"trial","name":"MONARCH 3","route":"/trials/monarch-3/"},{"id":"paloma-2","kind":"trial","name":"PALOMA-2","route":"/trials/paloma-2/"},{"id":"patina","kind":"trial","name":"PATINA","route":"/trials/patina/"},{"id":"nct04553133","kind":"trial","name":"PF-07104091 as a Single Agent and in Combination Therapy","route":"/trials/nct04553133/"},{"id":"soft-text","kind":"trial","name":"SOFT & TEXT","route":"/trials/soft-text/"},{"id":"nct05867251","kind":"trial","name":"Study of AVZO-021 in Patients With Advanced Solid Tumors","route":"/trials/nct05867251/"},{"id":"nct07288359","kind":"trial","name":"Study of GVV858 as a Single Agent or in Combination With Endocrine Therapy in Patients With HR+/HER2- Breast Cancer and Other Advanced Solid Tumors","route":"/trials/nct07288359/"},{"id":"nct04606446","kind":"trial","name":"Study of PF-07248144 in Advanced or Metastatic Solid Tumors","route":"/trials/nct04606446/"},{"id":"nct04557449","kind":"trial","name":"Study to Test the Safety and Tolerability of PF-07220060 in Participants With Advance Solid Tumors","route":"/trials/nct04557449/"}],"person":[{"id":"parulekar-wendy","kind":"person","name":"Wendy Parulekar","route":"/people/parulekar-wendy/"}],"idea":[{"id":"idea-nl-glp1-adjuvant-hr-breast","kind":"idea","name":"GLP-1 receptor agonists as adjuvant weight-loss therapy in HR-positive breast cancer","route":"/ideas/idea-nl-glp1-adjuvant-hr-breast/"},{"id":"idea-cost-pooled-procurement-essential","kind":"idea","name":"Pool purchasing of essential cancer medicines across countries","route":"/ideas/idea-cost-pooled-procurement-essential/"},{"id":"idea-cost-transparent-generic-pricing","kind":"idea","name":"Transparent cost-plus pricing for every oral oncology generic","route":"/ideas/idea-cost-transparent-generic-pricing/"}],"drug":[{"id":"aminoglutethimide","kind":"drug","name":"Aminoglutethimide","route":"/drugs/aminoglutethimide/"},{"id":"anastrozole","kind":"drug","name":"Anastrozole","route":"/drugs/anastrozole/"}],"biomarker":[{"id":"er-status","kind":"biomarker","name":"ER status (oestrogen receptor by IHC)","route":"/biomarkers/er-status/"},{"id":"pr-status","kind":"biomarker","name":"PR status (progesterone receptor by IHC)","route":"/biomarkers/pr-status/"}],"roadmap":[{"id":"hormonal-therapy-roadmap","kind":"roadmap","name":"Hormonal therapy roadmap: removing the ovaries → tamoxifen → oral degraders switched by a blood test","route":"/roadmaps/hormonal-therapy-roadmap/"}]}}