Tamoxifen, Raloxifene, and Exemestane in the

Chemoprevention of Breast Cancer

By: Erin Hutzell

Background: Breast CancerSecond leading cause of death due to cancer

among women in 2007 1 in 3 women diagnosed with cancer is

diagnosed with breast cancer Risk Factors

EnvironmentalGenetic

Background: Breast CancerInvasive VS. NoninvasiveEstrogen Receptor (ER) positive VS. Estrogen

Receptor negativeMechanism causing breast cancer

Background: Chemoprevention and DrugsChemoprevention

What is it?Tamoxifen

Selective Estrogen Receptor Modulator (SERM)

RaloxifeneSERM

ExemestaneAromatase Inhibitor (AI)

QuestionsHow effective is each drug in preventing

breast cancer?What are the side-effects of each drug

treatment?Which drug is the best possible

chemopreventative measure for breast cancer?

Tamoxifen

* Modified from Grese et al 1997

TamoxifenNSABP P-1 Study by Fisher et al (1998)

Subject Criteria 60 years + 35-59 years with predicted breast cancer risk History of lobular carcinoma in situ or atypical

hyperplasiaMethods

Control group Tamoxifen group

Tamoxifen

Supported By:IBIS-I Study (Cuzick et al 2002)Meta-analysis by Cuzick et al

Not Supported By:Royal Marsden (Powles et al 1998)Italian Tamoxifen Prevention Study

(Veronesi et al 1998)Top: Fisher et al. 1998Bottom: Fisher et al. 2005

* Kramer et al. 2004

Tamoxifen

NSABP P-1 (Fisher et al 1998 and 2005) Osteoporotic Fractures: REDUCED Invasive Endometrial Cancer: RISK INCREASED

Supported by IBIS-I (Cuzick et al 2002) and Royal Marsden (Powles et al 1998) Thromboembolic Events: RISK INCREASED

Supported by IBIS-I, Royal Marsden, and Italian Tamoxifen Prevention Study (Veronesi et al 1998)

Conclusion: Tamoxifen is an effective drug but has adverse side-effects

* Kramer et al. 2004

Exemestane

http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=60198

ExemestaneMammary Prevention.3 (MAP3) Trial by Goss

et al (2011)Subject Criteria

Postmenopausal Women At least one risk factor

Methods Exemestane Placebo

Exemestane

Conclusion: Exemestane is a more effective chemopreventative than Tamoxifen

Supported by: Intergroup Exemestane Study by Bliss et al (2012)

Exemestane produced better disease-free survival

Drug Regimen Risk ReductionTamoxifen (20 mg daily for

5 years)43%

Exemestane (25 mg daily for 3 years)

65%

Comparison of the risk reductions for Tamoxifen and ExemestaneTable modified from Zhang et al. 2012

* Goss et al 2011

ExemestaneDrug

RegimenEffect on

BoneCommon

Adverse EffectsSerious But

Rare Adverse Events

Indicated Population

Exemestane (25 mg daily for 3 years)

Unfavorable

Hot flashes, nausea, diarrhea, fatigue, insomnia,

joint pain, arthralgia

Not identified Not FDA approved;

postmenopausal women only

Tamoxifen (20 mg daily for 5 years)

Neutral Hot flashes, vaginal discharge, bleeding, altered menses, fluid retention, nausea, vomiting, weight loss, athralgia

Endometrial cancer, thromboembolism, stroke, heart attack, cataracts

FDA-approved for premenopausal and postmenopausal women with a 5 year risk of ≥1.66%

Comparison of the side-effects of Tamoxifen, Raloxifene, and ExemestaneTable modified from Zhang et al. 2012

ConclusionDrug Risk Reduction Side-EffectsTamoxifen Low (43%) SevereExemestane High (65%) Few/No Severe

Exemestane has the potential to be the best possible chemopreventative measure for breast cancer

Future:Research ExemestaneExplore Medication CombinationsDemographics of Patients

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Questions?