Julie R. Gralow, M.D.Julie R. Gralow, M.D.Director, Breast Medical Oncology, Seattle Cancer Care AllianceDirector, Breast Medical Oncology, Seattle Cancer Care Alliance

Professor, Medical Oncology, University of Washington School of Professor, Medical Oncology, University of Washington School of MedicineMedicine

Member, Clinical Division, Fred Hutchinson Cancer Research CenterMember, Clinical Division, Fred Hutchinson Cancer Research Center

Treatment Overview: The Treatment Overview: The Multidisciplinary TeamMultidisciplinary Team

Breast Cancer Treatment: Breast Cancer Treatment: A Multidisciplinary Team ApproachA Multidisciplinary Team Approach

•RadiologyRadiology

•PathologyPathology

•SurgerySurgery

•Radiation Radiation OncologyOncology

•Medical Medical OncologyOncology

Fighting the Crab – Kiev, UkraineFighting the Crab – Kiev, Ukraine

Personalized Cancer MedicinePersonalized Cancer Medicine

New Strategies in Treating Breast Cancer:New Strategies in Treating Breast Cancer: Better TargetingBetter Targeting

Individualized ApproachesIndividualized Approaches

Cancer Treatment: Defining the Cancer Treatment: Defining the CancerCancer

• The first step in designing the treatment The first step in designing the treatment plan is carefully defining the cancerplan is carefully defining the cancer–Clinical examinationClinical examination–Radiology testsRadiology tests–Pathology testsPathology tests–Blood testsBlood tests

Diagnosing the Cancer: Ultrasound-Diagnosing the Cancer: Ultrasound-Guided Breast BiopsyGuided Breast Biopsy

Defining the Cancer: PathologyDefining the Cancer: Pathology

• Treatment recommendations are aided with Treatment recommendations are aided with the help of pathologic factorsthe help of pathologic factors–Prognostic factorsPrognostic factors: aid in estimating : aid in estimating

likelihood of cancer recurrence and deathlikelihood of cancer recurrence and death–Predictive factorsPredictive factors: predict likelihood of : predict likelihood of

response to a given therapyresponse to a given therapy

The First Step in Making a Treatment Plan The First Step in Making a Treatment Plan for Breast Cancer:for Breast Cancer: Defining the CancerDefining the Cancer

• StageStage– Tumor sizeTumor size– Lymph node statusLymph node status–Metastatic sitesMetastatic sites

• GradeGrade• Surgical marginsSurgical margins• Tumor expression of genes and Tumor expression of genes and

proteinsproteins– Estrogen receptor (ER)Estrogen receptor (ER)– Progesterone receptor (PR)Progesterone receptor (PR)– HER-2HER-2

Estrogen ReceptorEstrogen Receptor

Invasive Breast CancerInvasive Breast Cancer

HER-2HER-2

Defining the Cancer: RadiologyDefining the Cancer: Radiology

• Radiologic imaging can help determine the Radiologic imaging can help determine the location and spread of the cancerlocation and spread of the cancer– Local extentLocal extent–Regional lymph nodesRegional lymph nodes–Distant spread (metastases)Distant spread (metastases)

Mammogram: Area of abnormality extends over 60 Mammogram: Area of abnormality extends over 60 mmmm

Evaluating Extent of Local Disease: Evaluating Extent of Local Disease: Breast CancerBreast Cancer

Bone Scan Bone Scan

Staging for Distant Disease: Breast Staging for Distant Disease: Breast CancerCancer

Multiple Multiple bone bone

metastasesmetastases

Patient APatient A

The most common sites of distant disease in breast The most common sites of distant disease in breast cancer are the bones, liver and lungscancer are the bones, liver and lungs

Breast Cancer SurgeryBreast Cancer SurgerySometimes “less” Sometimes “less” surgery is bettersurgery is better

•Mastectomy vs. Mastectomy vs. lumpectomylumpectomy

•Lymph node Lymph node dissection vs. sentinel dissection vs. sentinel lymph node biopsylymph node biopsy

Lumpectomy: Wire Localization of Non-Lumpectomy: Wire Localization of Non-Palpable, Imaging-Detected Breast CancersPalpable, Imaging-Detected Breast Cancers

Lumpectomy Margin Evaluation: Inking Lumpectomy Margin Evaluation: Inking the Tumor Specimen in the Operating the Tumor Specimen in the Operating

Room Room

Sentinel Lymph Node BiopsySentinel Lymph Node Biopsy

1. Inject around area 1. Inject around area of tumor with blue of tumor with blue dye, radioactivity, or dye, radioactivity, or bothboth

2. Track the 2. Track the lymphatic drainage lymphatic drainage of the tumorof the tumor

sentinel node biopsy sentinel node biopsy requires substantial requires substantial

technology, technology, resources, and resources, and

trainingtraining

Breast Cancer Radiation Breast Cancer Radiation TherapyTherapy

• The future: is “less” radiation The future: is “less” radiation sometimes better?sometimes better?

–Whole breast versus Whole breast versus partial breast radiation partial breast radiation (brachytherapy)(brachytherapy)

– Hypofractionation (shorter Hypofractionation (shorter course)course)

– 3D conformal radiation 3D conformal radiation planningplanning

Indications for Radiation Indications for Radiation Therapy After MastectomyTherapy After Mastectomy

• Tumor size > 5 cmTumor size > 5 cm• Inflammatory features or skin Inflammatory features or skin

involvementinvolvement• Multiple positive lymph nodesMultiple positive lymph nodes• Extracapsular lymph node extensionExtracapsular lymph node extension• Positive surgical marginsPositive surgical margins

Systemic Therapy for Breast CancerSystemic Therapy for Breast Cancer

Endocrine TherapyEndocrine TherapyChemotherapyChemotherapy

Biologically-targeted TherapyBiologically-targeted Therapy

New Strategies: Individualizing treatment New Strategies: Individualizing treatment to the cancer and the patientto the cancer and the patient

Identifying New Targets in the Identifying New Targets in the Treatment of Breast CancerTreatment of Breast Cancer

Death Death ReceptorsReceptors

Tubulin-Tubulin-interacting interacting

AgentsAgents

HDAC HDAC InhibitorsInhibitors

Metastasis Metastasis InhibitorsInhibitors

Anti-Anti-AngiogenesisAngiogenesis

HER-2 HER-2 InhibitorsInhibitors IGF-R IGF-R

InhibitorsInhibitors MUC-1 MUC-1 AntibodiesAntibodies

Proteosome Proteosome InhibitorsInhibitors

mTOR mTOR InhibitorsInhibitors Farnesyl Farnesyl

Transferase Transferase InhibitorsInhibitors

Mdm2 Mdm2 InhibitorsInhibitors

Pro-apoptotic Pro-apoptotic DrugsDrugs

KinesinsKinesins

Aurora Kinase Aurora Kinase InhibitorsInhibitors

MEK MEK InhibitorsInhibitorsHIF HIF

InhibitorsInhibitors

Raf Raf InhibitorsInhibitors

EGFR EGFR InhibitorsInhibitors

HSP90 HSP90 InhibitorsInhibitors

Src Src InhibitorsInhibitors

Cell Cycle Cell Cycle InhibitorsInhibitors

Optimizing Health and Wellness After Optimizing Health and Wellness After Treatment of Breast Cancer: Treatment of Breast Cancer:

SurvivorshipSurvivorship

• Many breast cancer Many breast cancer patients can look patients can look forward to a long life forward to a long life after treatmentafter treatment

• Breast cancer patients Breast cancer patients and their health care and their health care team need to pay team need to pay attention to all aspects attention to all aspects of health and well-beingof health and well-being

Team Survivor NorthwestTeam Survivor Northwest