Aromatase Aromatase inhibitors act by inhibitors act by lowering estrogen lowering estrogen in the circulation in the circulation and in tumor cells and in tumor cells in post-in post-menopausal menopausal womenwomen

Aromatase Inhibitors in Breast Cancer

Clinical Trials with Aromatase Clinical Trials with Aromatase InhibitorsInhibitors

Adverse Effects Adverse Effects Associated with Associated with Anastrozole and Anastrozole and

Tamoxifen in TrialsTamoxifen in Trials

Leuprolide (LupronLeuprolide (Lupron®®))

GnRH analogGnRH analog continuous GnRH analog turns off the continuous GnRH analog turns off the

production of gonadotropins (LH,FSH) and production of gonadotropins (LH,FSH) and decreases testosterone synthesis by 90-95%decreases testosterone synthesis by 90-95%

slow release implantable devices (Durosslow release implantable devices (Duros®®) lasts ) lasts 12 mos.12 mos.

used to treat advanced prostate cancerused to treat advanced prostate cancer cancer can escape and become androgen cancer can escape and become androgen

independent after 18-36 mos.independent after 18-36 mos.

Concerns related to the Concerns related to the success of chemotherapy success of chemotherapy in curing primary cancerin curing primary cancer

Quality of life: fertilityQuality of life: fertility

Increased risk: secondary cancerIncreased risk: secondary cancer

Late Complications of Cancer Late Complications of Cancer ChemotherapyChemotherapy

NormalNormal after Chemoafter Chemo

Testis HistologyTestis Histology

Risk of Secondary Cancer after Risk of Secondary Cancer after ChemotherapyChemotherapy

Combination Therapy Examples: Combination Therapy Examples: Hodgkin’s DiseaseHodgkin’s Disease

• MOPPMOPP– mechlorethamine, vincristine, procarbazine, mechlorethamine, vincristine, procarbazine,

prednisoneprednisone

• ABVDABVD– doxorubicin, bleomycin, vinblastine, doxorubicin, bleomycin, vinblastine,

dacarbazinedacarbazine

• Stanford VStanford V * Mechlorethamine by vein once every 4 weeks* Mechlorethamine by vein once every 4 weeks * Doxorubicin (Adriamycin) by vein every odd * Doxorubicin (Adriamycin) by vein every odd

weekweek * Vinblastine (Velban) by vein every odd week* Vinblastine (Velban) by vein every odd week * Vincristine (Oncovin) by vein every even week* Vincristine (Oncovin) by vein every even week * Bleomycin (Blenoxane) by vein every even week* Bleomycin (Blenoxane) by vein every even week * Etoposide by vein 2 days in a row weeks 3, 7, 11* Etoposide by vein 2 days in a row weeks 3, 7, 11 * Prednisone by mouth every other day* Prednisone by mouth every other day

high risk of high risk of secondary cancers, secondary cancers, infertilityinfertility

lower risk: lower risk: contraindicated if contraindicated if heart or lung heart or lung diseasedisease

complex but may be complex but may be better than ABVDbetter than ABVD

DNA Microarray Analysis and Cancer Diagnosis: how does it work?

78 non-lymph node positive78 non-lymph node positivesporadic Breast CA tumors sporadic Breast CA tumors were chosenwere chosen

70 genes that were best discriminators

black=disease free at 5 yrblack=disease free at 5 yr

white = metastases

Tumors

Future of Gene Array Analysis in Future of Gene Array Analysis in ChemotherapyChemotherapy

1. establish a prognosis directly from gene 1. establish a prognosis directly from gene expressionexpressiondata on primary tumor sample--determine data on primary tumor sample--determine whether adjuvant therapy is warranted?whether adjuvant therapy is warranted?

2. expression analysis may predict which tumors 2. expression analysis may predict which tumors will respond to which drugswill respond to which drugs