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Exemestane

Class: Antiestrogens
- Aromatase Inhibitors
VA Class: AN900
Molecular Formula: C20H24O2
CAS Number: 107868-30-4
Brands: Aromasin

Medically reviewed by Drugs.com. Last updated on Jan 11, 2021.

Introduction

Antineoplastic agent; irreversible, selective steroidal aromatase inhibitor (type I), structurally related to the natural substrate androstenedione.1 2 3 4 5 6

Uses for Exemestane

Early-stage Breast Cancer in Postmenopausal Women

Sequential adjuvant therapy in postmenopausal women with early-stage estrogen receptor-positive breast cancer who have received 2–3 years of adjuvant tamoxifen and are switched to exemestane to complete a total of 5 consecutive years of adjuvant hormonal therapy.1 8 9 11

May be considered a reasonable choice (accepted, with possible conditions) for initial adjuvant therapy in postmenopausal women with early-stage hormone receptor-positive breast cancer.10001 10002 10008

May be considered a reasonable choice (accepted, with possible conditions) for extended adjuvant therapy in postmenopausal women with early-stage hormone receptor-positive breast cancer who have received 5 years of adjuvant tamoxifen therapy.10005 10009

Aromatase inhibitors are a treatment of choice for adjuvant hormonal therapy to lower risk of breast cancer recurrence in postmenopausal women with early-stage hormone receptor-positive breast cancer.10 17 An aromatase inhibitor-containing regimen is modestly more effective than tamoxifen alone.10 17

ASCO states that most postmenopausal women with early-stage hormone receptor-positive breast cancer should consider receiving an aromatase inhibitor during the course of adjuvant therapy, either as primary (initial) therapy or following 2–3 years of tamoxifen (sequential therapy), for a total of 5 years of adjuvant endocrine therapy.10 Data also support switching to an aromatase inhibitor following 5 years of adjuvant tamoxifen (extended adjuvant therapy).10

Consider adverse effects, patient preference, and preexisting conditions when selecting an adjuvant regimen in postmenopausal women.10 10008 10009 Adverse cardiovascular (e.g., hypertension, cardiac ischemia) and musculoskeletal effects (e.g., arthralgia/arthritis, osteoporosis, fracture, carpal tunnel syndrome) reported more frequently in patients receiving adjuvant exemestane, whereas venous thromboembolism and adverse gynecologic effects (e.g., vaginal bleeding, endometrial hyperplasia, uterine dilatation and curettage, uterine polyp/fibroid) reported more frequently in those receiving tamoxifen.1 9 11

Early-stage Breast Cancer in Premenopausal Women

Use of endocrine therapy (i.e., anastrozole, exemestane, letrozole, tamoxifen) in combination with ovarian suppression as adjuvant therapy in premenopausal women with early-stage hormone receptor-positive breast cancer may be considered a reasonable choice (accepted).10010 10011 10012 10013 10023 10026 10028

Advanced Breast Cancer in Postmenopausal Women

Treatment of advanced breast cancer in postmenopausal women whose disease has progressed following tamoxifen therapy.1 16

Exemestane Dosage and Administration

Administration

Oral Administration

Administer orally after a meal.1

Dosage

Adults

If used with a potent CYP3A4 inducer, dosage adjustment recommended.1 (See Interactions.)

Early-stage Breast Cancer in Postmenopausal Women
Sequential Adjuvant Treatment
Oral

25 mg once daily.1 Initiate following completion of 2–3 years of adjuvant tamoxifen therapy to complete a total of 5 consecutive years of adjuvant hormonal therapy.1

Initial Adjuvant Treatment†
Oral

25 mg once daily for 5 years has been used.10001 10002

Extended Adjuvant Treatment†
Oral

25 mg once daily for 5 years following 5 years of adjuvant tamoxifen therapy has been recommended.10 10005

Early-stage Breast Cancer in Premenopausal Women†
Adjuvant Treatment
Oral

25 mg once daily for 5 years has been used in combination with ovarian suppression.10010 10011 10012

In clinical studies, ovarian suppression achieved with goserelin 3.6 mg implanted sub-Q every 4 weeks, leuprolide acetate 3.75 mg by IM injection every 4 weeks, triptorelin 3.75 mg by IM injection every 4 weeks, or surgical or radiation ablation.10010 10011 10012 10013 10023 10026

Advanced Breast Cancer in Postmenopausal Women
Second-line Treatment
Oral

25 mg once daily; continued in clinical trial until tumor progression or unacceptable toxicity occurred.1 16

Prescribing Limits

Adults

Dosages >25 mg daily not shown to provide substantially greater suppression of plasma estrogens but may increase adverse effects.1 2 3

Special Populations

Hepatic Impairment

Dosage adjustment does not appear to be necessary.1 (See Special Populations under Pharmacokinetics.)

Renal Impairment

Dosage adjustment does not appear to be necessary.1 (See Special Populations under Pharmacokinetics.)

Cautions for Exemestane

Contraindications

  • Known hypersensitivity to exemestane or any ingredient in the formulation.1

Warnings/Precautions

Effects on Bone

Postmenopausal women receiving an aromatase inhibitor as adjuvant therapy are at high risk for osteoporosis.12 13

Greater reductions in bone mineral density (BMD) at lumbar spine and hip observed over 2 years in patients receiving exemestane (3.1 and 4.2%, respectively) versus tamoxifen (0.2 and 0.3%, respectively).1 Another study showed greater reductions in lumbar spine and hip BMD over 2 years in patients receiving exemestane (3.5 and 4.6%, respectively) versus placebo (2.4 and 2.6%, respectively).1

Incidence of fractures higher in patients switched to exemestane after receiving 2–3 years of adjuvant tamoxifen than in those continuing tamoxifen to complete 5 years of adjuvant therapy.1 11

Evaluate all postmenopausal women initiating adjuvant aromatase inhibitor therapy for risk of osteoporotic fractures;70 71 73 74 determine BMD and assess other risk factors for fracture (e.g., age, low body mass index, family history of hip fracture, prior fragility fracture, history of cigarette smoking, excess alcohol consumption, current or prior corticosteroid use).70 71 73 74 Closely monitor patients for changes in risk status during therapy, and assess BMD at regular intervals (e.g., every 1–2 years in those with osteopenia or osteoporosis).1 70 71 73 74 Consider other potential causes of osteoporosis (e.g., vitamin D deficiency, hyperthyroidism, hyperparathyroidism, hypercalciuria).70 71 73 74 Manufacturer recommends routine measurement of 25-hydroxyvitamin D concentration before initiating exemestane; supplement vitamin D in women with vitamin D deficiency.1

Initiate appropriate therapy to prevent further bone loss as clinically indicated.1 71 Base decision to initiate antiresorptive therapy (e.g., bisphosphonate, denosumab) on overall risk of fracture and rate of bone loss.70 71 72 73 74

All women receiving adjuvant therapy with an aromatase inhibitor should be advised to adopt lifestyle changes (e.g., weight-bearing exercise, abstinence from smoking, moderation in alcohol consumption) and dietary supplementation with calcium and vitamin D to reduce the risk of osteoporosis.12 13 14 15 70 71 72 73 74

Estrogenic Agents

Do not administer estrogenic agents concomitantly with exemestane.1 (See Specific Drugs under Interactions.)

Hematologic Effects

Grade 3 or 4 lymphocytopenia reported in 20% of exemestane-treated patients with advanced breast cancer.1 Most patients (89%) had preexisting lower-grade lymphocytopenia; 40% recovered or improved during exemestane therapy.1 No substantial increase in viral infections and no opportunistic infections observed in clinical studies.1

In early-stage breast cancer, hematologic abnormalities reported less frequently with exemestane than with tamoxifen treatment; grade 3 or 4 abnormalities reported rarely.1

Hepatic Effects

In advanced breast cancer, serum AST, ALT, alkaline phosphatase, and γ-glutamyltransferase (γ-glutamyltranspeptidase, GGT, GGTP) concentrations >5 times the ULN (i.e., grade 3 or worse) reported rarely in patients receiving exemestane; generally attributable to bone or liver metastasis.1 In patients without evidence of liver metastasis, grade 3–4 GGT elevations reported at similar rates in exemestane- or megestrol-treated patients.1

In early-stage breast cancer, elevated bilirubin and alkaline phosphatase concentrations reported more frequently with exemestane than with tamoxifen or placebo treatment.1 Grade 3–4 bilirubin elevations reported rarely.1

Renal Effects

Elevated Scr reported.1

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; embryotoxic, fetotoxic, and abortifacient in animals.1 Test for pregnancy status within 7 days prior to initiation of the drug.1 Advise females of reproductive potential to use effective contraceptive methods during therapy and for 1 month after discontinuance of the drug.1 If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard and potential risk for pregnancy loss.1 (See Premenopausal Women under Cautions.)

Impairment of Fertility

May impair female and male fertility.1

Specific Populations

Pregnancy

May cause fetal harm.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Distributed into milk in rats; not known whether distributed into human milk.1 Effects on nursing infant and milk production also unknown.1 Discontinue nursing during therapy and for ≥1 month after drug discontinuance.1

Pediatric Use

Not indicated; safety and efficacy not established.1

Geriatric Use

No special precautions.1

Premenopausal Women

Manufacturer states exemestane is not indicated for treatment of breast cancer in premenopausal women.1 Possible incomplete estrogen suppression and reflex increases in gonadotropin levels (ovarian hyperstimulation syndrome).6

However, used in combination with ovarian suppression as adjuvant therapy in premenopausal women with early-stage hormone receptor-positive breast cancer.10010 10011 10013 10023 10026 (See Early-stage Breast Cancer in Premenopausal Women under Uses.)

Hepatic Impairment

Systemic exposure increased in patients with moderate or severe hepatic impairment; however, dosage adjustment does not appear to be necessary.1

Renal Impairment

Systemic exposure increased in patients with moderate or severe renal impairment; however, dosage adjustment does not appear to be necessary.1

Common Adverse Effects

Early-stage breast cancer: Hot flushes (flashes), fatigue, arthralgia, headache, insomnia, increased sweating.1

Advanced-stage breast cancer: Fatigue, nausea, hot flushes.1

Interactions for Exemestane

Metabolized by CYP3A4.1 Does not inhibit CYP1A2, 2C9, 2D6, 2E1, or 3A4.1

Drugs Affecting Hepatic Microsomal Enzymes

CYP3A4 inhibitors: Clinically important pharmacokinetic interactions are unlikely.1

CYP3A4 inducers: Possible decreased exposure to exemestane.1 If a potent CYP3A4 inducer is used concomitantly, increase exemestane dosage to 50 mg once daily.1

Specific Drugs

Drug

Interaction

Comments

Anticonvulsants (carbamazepine, phenobarbital, phenytoin)

Possible decreased exposure to exemestane1

Increase exemestane dosage to 50 mg once daily after a meal1

Estrogenic agents

May diminish pharmacologic action of exemestane1

Do not use concomitantly1

Ketoconazole

No substantial effect on pharmacokinetics of exemestane1

Rifampin

Decreased AUC and peak plasma concentrations of exemestane 1

Increase exemestane dosage to 50 mg once daily after a meal1

St. John's wort (Hypericum perforatum)

Possible decreased exposure to exemestane1

Increase exemestane dosage to 50 mg once daily after a meal1

Exemestane Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed following oral administration; peak concentrations in women with breast cancer or healthy women attained within about 1.2 or 2.9 hours, respectively.1 Approximately 42% of an oral dose is absorbed from the GI tract.1

Following repeated doses, mean AUC in women with breast cancer is approximately twice that in healthy women.1

Food

High-fat meal increases AUC and peak plasma exemestane concentrations by 59 and 39%, respectively.1

Special Populations

Age (43–68 years) and sex do not affect pharmacokinetics.1

Distribution

Extent

Extensively distributed into tissues.1

Crosses placenta.1

Distributed into milk in animals; not studied in pregnant or nursing women.1

Plasma Protein Binding

90% (mainly α1-acid glycoprotein and albumin).1

Elimination

Metabolism

Extensively metabolized via CYP3A4 and aldoketoreductases; metabolites are inactive or inhibit aromatase with decreased potency compared with parent drug.1 One metabolite, 17-hydroexemestane, may have androgenic activity.1

Elimination Route

Excreted similarly (42%) in both urine and feces; <1% excreted as unchanged drug in urine.1

Half-life

Approximately 24 hours.1

Special Populations

In patients with moderate or severe hepatic (Child-Pugh class B or C) or renal (Clcr <35 mL/minute per 1.73 m2) impairment, AUC is approximately 3 times higher than in healthy individuals.1

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C).1

Actions

  • Acts as a false substrate and is converted by aromatase to reactive alkylating intermediates that bind covalently to the substrate binding site of the enzyme; this irreversible binding to the active site of aromatase results in its inactivation (i.e., “suicide” inhibition).1 2 4 5 6

  • Selectively inhibits conversion of androgens to estrogens;1 2 4 5 6 resulting reduction in serum and tumor concentrations of estrogen inhibits tumor growth and delays disease progression.1 6

  • Selectively inhibits synthesis of estrogens; does not affect synthesis of adrenal corticosteroid, aldosterone, or thyroid hormone.1 2 3 6

  • Dose-dependent decrease in sex hormone binding globulin (SHBG) observed with dosages ≥ 2.5 mg daily.1 2

  • Slight, dose-independent increases in serum LH and FSH concentrations observed even at low dosages as result of negative feedback on the pituitary gland.1 2 3

  • At dosages ≤25 mg daily, no clinically important effect on circulating concentrations of androstenedione, dehydroepiandrostenedione sulfate, or 17-hydroxyprogesterone and only small decreases in circulating concentrations of testosterone observed.1 3

  • At dosages ≥200 mg daily, testosterone and androstenedione concentrations are increased.1 3 17-Hydroexemestane, a metabolite, exhibits substantial intrinsic androgenic activity, which may become clinically important at high (e.g., 200 mg daily) dosages.1 2 3

Advice to Patients

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal supplements, as well as any concomitant illnesses.1 Importance of not taking estrogenic agents concomitantly.1

  • Risk of osteoporosis.1 12 Life-style changes (e.g., weight-bearing exercise, abstinence from smoking, moderation of alcohol consumption) and dietary supplementation with calcium and vitamin D advised.12 13 14 15 Importance of BMD monitoring.1 12 13 15 71 73

  • Risk of fetal harm and pregnancy loss.1 Necessity of advising females of reproductive potential to use effective contraception during exemestane therapy and for 1 month after the last dose.1 Importance of women informing clinicians immediately if they are pregnant or become pregnant during therapy.1 If pregnancy occurs, advise pregnant women of potential risk to the fetus.1 Advise patients that exemestane is FDA-labeled for use only in postmenopausal women.1

  • Importance of advising women to avoid breast-feeding while receiving exemestane and for 1 month following discontinuance of therapy.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Exemestane

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

25 mg*

Aromasin

Pfizer

Exemestane Tablets

AHFS DI Essentials™. © Copyright 2021, Selected Revisions January 11, 2021. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Pharmacia and Upjohn Company division of Pfizer. Aromasin (exemestane) tablets prescribing information. New York, NY; 2018 May.

2. Johannessen DC, Engan T, Di Salle E et al. Endocrine and clinical effects of exemestane (PNU 155971), a novel steroidal aromatase inhibitor, in postmenopausal breast cancer patients: a phase I study. Clin Cancer Res. 1997; 3:1101-8. http://www.ncbi.nlm.nih.gov/pubmed/9815789?dopt=AbstractPlus

3. Evans TRJ, Di Salle E, Ornati G et al. Phase I and endocrine study of exemestane (FCE 24304), a new aromatase inhibitor, in postmenopausal women. Cancer Res. 1992; 52:5933-9. http://www.ncbi.nlm.nih.gov/pubmed/1394219?dopt=AbstractPlus

4. Geisler J, King N, Anker G et al. In vivo inhibition of aromatization by exemestane, a novel irreversible aromatase inhibitor, in postmenopausal breast cancer patients. Clin Cancer Res. 1998; 4:2089-93. http://www.ncbi.nlm.nih.gov/pubmed/9748124?dopt=AbstractPlus

5. Reddy P. A review of the newer aromatase inhibitors in the management of metastatic breast cancer. J Clin Pharm Ther. 1998; 23:81-90. http://www.ncbi.nlm.nih.gov/pubmed/9786093?dopt=AbstractPlus

6. Goss PE, Gwyn KMEH. Current perspectives on aromatase inhibitors in breast cancer. J Clin Oncol. 1994; 12:2460-70. http://www.ncbi.nlm.nih.gov/pubmed/7964964?dopt=AbstractPlus

7. Anker GB, Refsum H, Ueland PM et al. Influence of aromatase inhibitors on plasma total homocysteine in postmenopausal breast cancer patients. Clin Chem. 1999; 45:252-6. http://www.ncbi.nlm.nih.gov/pubmed/9931048?dopt=AbstractPlus

8. Coombes RC, Hall E, Gibson LJ et al. A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med. 2004; 350:1081-92. http://www.ncbi.nlm.nih.gov/pubmed/15014181?dopt=AbstractPlus

9. Coombes RC, Kilburn LS, Snowdon CF et al. Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet. 2007; 369:559-70. http://www.ncbi.nlm.nih.gov/pubmed/17307102?dopt=AbstractPlus

10. Burstein HJ, Prestrud AA, Seidenfeld J et al. American Society of Clinical Oncology clinical practice guideline: update on adjuvant endocrine therapy for women with hormone receptor-positive breast cancer. J Clin Oncol. 2010; 28:3784-96. http://www.ncbi.nlm.nih.gov/pubmed/20625130?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=5569672&blobtype=pdf

11. Bliss JM, Kilburn LS, Coleman RE et al. Disease-related outcomes with long-term follow-up: an updated analysis of the intergroup exemestane study. J Clin Oncol. 2012; 30:709-17. http://www.ncbi.nlm.nih.gov/pubmed/22042946?dopt=AbstractPlus

12. Gaillard S, Stearns V. Aromatase inhibitor-associated bone and musculoskeletal effects: new evidence defining etiology and strategies for management. Breast Cancer Res. 2011; 13:205. http://www.ncbi.nlm.nih.gov/pubmed/21457526?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=3219175&blobtype=pdf

13. Hilner BE, Ingle JN, Chelbowski RT et al. American Society of Clinical Oncology 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer. J Clin Oncol. 2003; 21:4042-57. http://www.ncbi.nlm.nih.gov/pubmed/12963702?dopt=AbstractPlus

14. Goss PE, Ingle JN, Martino S et al. A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer. N Engl J Med. 2003; 349: 1793-802. http://www.ncbi.nlm.nih.gov/pubmed/14551341?dopt=AbstractPlus

15. Reviewers’ comments (personal observations) on letrozole.

16. Kaufmann M, Bajetta E, Dirix LY et al. Exemestane is superior to megestrol acetate after tamoxifen failure in postmenopausal women with advanced breast cancer: results of a phase III randomized double-blind trial. The Exemestane Study Group. J Clin Oncol. 2000; 18:1399-411. http://www.ncbi.nlm.nih.gov/pubmed/10735887?dopt=AbstractPlus

17. Breast cancer. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2011 Nov 21.

70. Hadji P, Aapro MS, Body JJ et al. Management of aromatase inhibitor-associated bone loss in postmenopausal women with breast cancer: practical guidance for prevention and treatment. Ann Oncol. 2011; 22:2546-55. http://www.ncbi.nlm.nih.gov/pubmed/21415233?dopt=AbstractPlus

71. Reid DM, Doughty J, Eastell R et al. Guidance for the management of breast cancer treatment-induced bone loss: a consensus position statement from a UK Expert Group. Cancer Treat Rev. 2008; 34 Suppl 1:S3-18. http://www.ncbi.nlm.nih.gov/pubmed/18515009?dopt=AbstractPlus

72. Aapro M, Abrahamsson PA, Body JJ et al. Guidance on the use of bisphosphonates in solid tumours: recommendations of an international expert panel. Ann Oncol. 2008; 19:420-32. http://www.ncbi.nlm.nih.gov/pubmed/17906299?dopt=AbstractPlus

73. Body JJ, Bergmann P, Boonen S et al. Management of cancer treatment-induced bone loss in early breast and prostate cancer -- a consensus paper of the Belgian Bone Club. Osteoporos Int. 2007; 18:1439-50. http://www.ncbi.nlm.nih.gov/pubmed/17690930?dopt=AbstractPlus

74. Hadji P, Aapro MS, Body JJ et al. Management of Aromatase Inhibitor-Associated Bone Loss (AIBL) in postmenopausal women with hormone sensitive breast cancer: Joint position statement of the IOF, CABS, ECTS, IEG, ESCEO IMS, and SIOG. J Bone Oncol. 2017; 7:1-12. http://www.ncbi.nlm.nih.gov/pubmed/28413771?dopt=AbstractPlus

10001. van de Velde CJ, Rea D, Seynaeve C et al. Adjuvant tamoxifen and exemestane in early breast cancer (TEAM): a randomised phase 3 trial. Lancet. 2011; 377:321-31. http://www.ncbi.nlm.nih.gov/pubmed/21247627?dopt=AbstractPlus

10002. Goss PE, Ingle JN, Pritchard KI et al. Exemestane versus anastrozole in postmenopausal women with early breast cancer: NCIC CTG MA.27--a randomized controlled phase III trial. J Clin Oncol. 2013; 31:1398-404. http://www.ncbi.nlm.nih.gov/pubmed/23358971?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=3612593&blobtype=pdf

10003. Suppression of ovarian function and either tamoxifen or exemestane with or without chemotherapy in treating premenopausal women with resected breast cancer (PERCHE). From ClinicalTrials.gov Registry. Accessed 2013 Dec 12.

10004. Winer EP, Hudis C, Burstein HJ et al. American Society of Clinical Oncology technology assessment on the use of aromatase inhibitors as adjuvant therapy for women with hormone receptor-positive breast cancer: status report 2002. J Clin Oncol. 2002; 20:3317-27. http://www.ncbi.nlm.nih.gov/pubmed/12149306?dopt=AbstractPlus

10005. Mamounas EP, Jeong JH, Wickerham DL et al. Benefit from exemestane as extended adjuvant therapy after 5 years of adjuvant tamoxifen: intention-to-treat analysis of the National Surgical Adjuvant Breast And Bowel Project B-33 trial. J Clin Oncol. 2008; 26:1965-71. http://www.ncbi.nlm.nih.gov/pubmed/18332472?dopt=AbstractPlus

10006. Letrozole in Treating Women With Primary Breast Cancer Who Have Received 5 Years of Aromatase Inhibitor Therapy. Clinical Trials (PDQ) (database). Bethesda, MD: National Cancer Institute; 2014 Jan 13.

10007. Winer EP, Hudis C, Burstein HJ et al. American Society of Clinical Oncology technology assessment on the use of aromatase inhibitors as adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer: status report 2004. J Clin Oncol. 2005; 23:619-29. http://www.ncbi.nlm.nih.gov/pubmed/15545664?dopt=AbstractPlus

10008. AHFS Final Determination: Exemestane for initial adjuvant treatment of early-stage breast cancer. Published 2014 June.

10009. AHFS Final Determination: Exemestane for extended adjuvant treatment of early-stage breast cancer. Published 2014 June.

10010. Francis PA, Regan MM, Fleming GF et al. Adjuvant ovarian suppression in premenopausal breast cancer. N Engl J Med. 2015; 372:436-46. http://www.ncbi.nlm.nih.gov/pubmed/25495490?dopt=AbstractPlus

10011. Pagani O, Regan MM, Walley BA et al. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N Engl J Med. 2014; 371:107-18. http://www.ncbi.nlm.nih.gov/pubmed/24881463?dopt=AbstractPlus

10012. Francis PA, Pagani O, Fleming GF et al. Tailoring Adjuvant Endocrine Therapy for Premenopausal Breast Cancer. N Engl J Med. 2018; 379:122-137. http://www.ncbi.nlm.nih.gov/pubmed/29863451?dopt=AbstractPlus

10013. Tevaarwerk AJ, Wang M, Zhao F et al. Phase III comparison of tamoxifen versus tamoxifen plus ovarian function suppression in premenopausal women with node-negative, hormone receptor-positive breast cancer (E-3193, INT-0142): a trial of the Eastern Cooperative Oncology Group. J Clin Oncol. 2014; 32:3948-58. http://www.ncbi.nlm.nih.gov/pubmed/25349302?dopt=AbstractPlus

10016. Pan K, Bosserman LD, Chlebowski RT. Ovarian Suppression in Adjuvant Endocrine Therapy for Premenopausal Breast Cancer. J Clin Oncol. 2019; 37:858-861. http://www.ncbi.nlm.nih.gov/pubmed/30742565?dopt=AbstractPlus

10017. Burstein HJ, Lacchetti C, Anderson H et al. Adjuvant Endocrine Therapy for Women With Hormone Receptor-Positive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update on Ovarian Suppression. J Clin Oncol. 2016; 34:1689-701. http://www.ncbi.nlm.nih.gov/pubmed/26884586?dopt=AbstractPlus

10018. Burstein HJ, Lacchetti C, Anderson H et al. Adjuvant Endocrine Therapy for Women With Hormone Receptor-Positive Breast Cancer: ASCO Clinical Practice Guideline Focused Update. J Clin Oncol. 2019; 37:423-438. http://www.ncbi.nlm.nih.gov/pubmed/30452337?dopt=AbstractPlus

10020. Dowsett M, Lønning PE, Davidson NE. Incomplete Estrogen Suppression With Gonadotropin-Releasing Hormone Agonists May Reduce Clinical Efficacy in Premenopausal Women With Early Breast Cancer. J Clin Oncol. 2016; 34:1580-3. http://www.ncbi.nlm.nih.gov/pubmed/26729430?dopt=AbstractPlus

10023. Gnant M, Mlineritsch B, Stoeger H et al. Adjuvant endocrine therapy plus zoledronic acid in premenopausal women with early-stage breast cancer: 62-month follow-up from the ABCSG-12 randomised trial. Lancet Oncol. 2011; 12:631-41. http://www.ncbi.nlm.nih.gov/pubmed/21641868?dopt=AbstractPlus

10024. Gnant M, Mlineritsch B, Stoeger H et al. Zoledronic acid combined with adjuvant endocrine therapy of tamoxifen versus anastrozol plus ovarian function suppression in premenopausal early breast cancer: final analysis of the Austrian Breast and Colorectal Cancer Study Group Trial 12. Ann Oncol. 2015; 26:313-20. http://www.ncbi.nlm.nih.gov/pubmed/25403582?dopt=AbstractPlus

10025. Bellet M, Gray KP, Francis PA et al. Twelve-Month Estrogen Levels in Premenopausal Women With Hormone Receptor-Positive Breast Cancer Receiving Adjuvant Triptorelin Plus Exemestane or Tamoxifen in the Suppression of Ovarian Function Trial (SOFT): The SOFT-EST Substudy. J Clin Oncol. 2016; 34:1584-93. http://www.ncbi.nlm.nih.gov/pubmed/26729437?dopt=AbstractPlus

10026. Perrone F, De Laurentiis M, De Placido S et al. Adjuvant zoledronic acid and letrozole plus ovarian function suppression in premenopausal breast cancer: HOBOE phase 3 randomised trial. Eur J Cancer. 2019; 118:178-186. http://www.ncbi.nlm.nih.gov/pubmed/31164265?dopt=AbstractPlus

10027. Chlebowski RT, Pan K, Col NF. Ovarian suppression in combination endocrine adjuvant therapy in premenopausal women with early breast cancer. Breast Cancer Res Treat. 2017; 161:185-190. http://www.ncbi.nlm.nih.gov/pubmed/27785653?dopt=AbstractPlus

10028. AHFS final determination of medical acceptance: Off-label use of endocrine therapy in combination with ovarian suppression for the adjuvant treatment of early-stage hormone receptor-positive breast cancer in premenopausal women. Published January 4, 2021.

Frequently asked questions