Breast Cancer Treatment : Aromatase Inhibitors vs. Tamoxifen Elizabeth Geddes March 9, 2006 Advisor - Dr. Hadley

Breast Cancer Brief Breast cancer is the MOST common cancer in womenBreast cancer is the MOST common cancer in women 2 nd leading cause of cancer deaths in women2 nd leading cause of cancer deaths in women Over 212,000 women will be diagnosed with breast cancer and over 40,000 will die in 2006Over 212,000 women will be diagnosed with breast cancer and over 40,000 will die in 2006

Types of Cancer Ductal vs. LobularDuctal vs. Lobular Lobular – can be in lobes or lobulesLobular – can be in lobes or lobules In Situ vs. InvasiveIn Situ vs. Invasive Ductal Invasive is most commonDuctal Invasive is most common Hormone receptor positive or negativeHormone receptor positive or negative Estrogen receptor / Progesterone receptorEstrogen receptor / Progesterone receptor Hormone receptor positive cancers are dependent on estrogen/progesterone for growthHormone receptor positive cancers are dependent on estrogen/progesterone for growth

Treatment Options ChemotherapyChemotherapy RadiationRadiation MastectomyMastectomy LumpectomyLumpectomy Alternative MedicineAlternative Medicine HORMONE THERAPYHORMONE THERAPY

Hormone Therapy Hormone therapy is effective in hormone receptor positive tumorsHormone therapy is effective in hormone receptor positive tumors 75% of all breast cancers are receptor positive75% of all breast cancers are receptor positive Treatment is non-invasive, fairly non- toxicTreatment is non-invasive, fairly non- toxic Used to inhibit progression or recurrence of diseaseUsed to inhibit progression or recurrence of disease

Tamoxifen Selective estrogen receptor modulatorSelective estrogen receptor modulator Estrogen agonist and antagonistEstrogen agonist and antagonist Reversibly blocks estrogen binding to receptor in tumor cellsReversibly blocks estrogen binding to receptor in tumor cells Agonist effects include decreased blood lipid changes, and increased bone densityAgonist effects include decreased blood lipid changes, and increased bone density

Adverse Effects Thromboembolic eventsThromboembolic events Endometrial cancerEndometrial cancer Hepatic carcinomasHepatic carcinomas Menstrual dysregularitiesMenstrual dysregularities Vaginal dryness and bleedingVaginal dryness and bleeding Hot flushesHot flushes

Tamoxifen Resistance Tamoxifen has only been proven effective for a maximum of 5 yearsTamoxifen has only been proven effective for a maximum of 5 years The risks are greater than the benefits past this time frameThe risks are greater than the benefits past this time frame Resistance of the tumors is attributed to this decrease in efficacyResistance of the tumors is attributed to this decrease in efficacy Resistance is thought to be due to the tumor becoming estrogen independentResistance is thought to be due to the tumor becoming estrogen independent

Aromatase Inhibitors Block aromatase, inhibiting estrogen synthesisBlock aromatase, inhibiting estrogen synthesis SteroidalSteroidal ExemestaneExemestane Irreversibly inhibitIrreversibly inhibit Non-SteroidalNon-Steroidal Anastrozole and LetrozoleAnastrozole and Letrozole Reversibly inhibitReversibly inhibit

Aromatase Inhibitors Only useful in postmenopausal womenOnly useful in postmenopausal women Production of estrogen in premenopausal women overrides aromatase inhibitorsProduction of estrogen in premenopausal women overrides aromatase inhibitors

Adverse Effects OsteoporosisOsteoporosis Thromboembolic EventsThromboembolic Events Cardiac EventsCardiac Events Vaginal drynessVaginal dryness

Clinical Trials Aromatase Inhibitors vs. Tamoxifen ATAC trialATAC trial 68 months follow-up there was improved disease free survival with Anastrozole over Tamoxifen68 months follow-up there was improved disease free survival with Anastrozole over Tamoxifen Big 1-98Big months follow-up there was improved disease free survival with Letrozole over Tamoxifen25.8 months follow-up there was improved disease free survival with Letrozole over Tamoxifen

Sequential Treatments It has been proven that there is an increased disease free survival after 5 years of therapy in patients who switched to aromatase inhibitors after 2-3 years of Tamoxifen compared to those who remained on TamoxifenIt has been proven that there is an increased disease free survival after 5 years of therapy in patients who switched to aromatase inhibitors after 2-3 years of Tamoxifen compared to those who remained on Tamoxifen ABSCG/ARNO - AnastrozoleABSCG/ARNO - Anastrozole ITA - AnastrozoleITA - Anastrozole IES – ExemestaneIES – Exemestane

Long term treatments Early results of the MA.17 clinical trial show promise for aromatase inhibitor effectiveness after 5 years of treatmentEarly results of the MA.17 clinical trial show promise for aromatase inhibitor effectiveness after 5 years of treatment Increased disease free survival in patients continuing treatments compared to those on no treatmentIncreased disease free survival in patients continuing treatments compared to those on no treatment Letrozole has shown positive effect in overall survivalLetrozole has shown positive effect in overall survival

Current Debates Aromatase inhibitors as initial treatment versus post-Tamoxifen treatmentAromatase inhibitors as initial treatment versus post-Tamoxifen treatment How many years of Tamoxifen before beginning aromatase inhibitors?How many years of Tamoxifen before beginning aromatase inhibitors? Effective length of treatment with aromatase inhibitorsEffective length of treatment with aromatase inhibitors Efficacy between different aromatase inhibitorsEfficacy between different aromatase inhibitors

Tolerability In ATAC trial fewer patients withdrew and there were less reported side effects in the aromatase inhibitor populationIn ATAC trial fewer patients withdrew and there were less reported side effects in the aromatase inhibitor population

Why should a primary care PA care? Some of our patients will be diagnosed with breast cancerSome of our patients will be diagnosed with breast cancer Patients will follow-up with PCP after seeing oncologistPatients will follow-up with PCP after seeing oncologist We need to be aware of these drugsWe need to be aware of these drugs When to use themWhen to use them Which is the best option for our patientWhich is the best option for our patient Adverse EffectsAdverse Effects Be knowledgeable for patient educationBe knowledgeable for patient education

Conclusion Tamoxifen was gold standardTamoxifen was gold standard Aromatase inhibitors are proving to be more effectiveAromatase inhibitors are proving to be more effective Increased disease free survivalIncreased disease free survival Longer treatment optionsLonger treatment options Better tolerabilityBetter tolerability Several questions remain unansweredSeveral questions remain unanswered Hormonal therapies are effective in halting the progression and recurrence of breast cancerHormonal therapies are effective in halting the progression and recurrence of breast cancer

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