let’s talk about metastatic breast cancer: answers to your most pressing medical and

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LET’S TALK ABOUTLET’S TALK ABOUT METASTATIC BREAST CANCER: METASTATIC BREAST CANCER: Answers to Your Most Pressing Answers to Your Most Pressing

Medical Medical and and

Psychosocial Concerns Psychosocial Concerns

MissionYoung Survival Coalition (YSC) is the premier international organization dedicated to the critical issues unique to young women and breast cancer. YSC works with survivors, caregivers, and the medical, research, advocacy and legislative communities to increase the quality and quantity of life for women diagnosed with breast cancer ages 40 and under.

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Tonight’s Speakers

Generosa Grana, MDProfessor of Medicine, CMSRU

Director, Cooper Cancer Institute&

11-Year Stage IV Survivor Dikla Benzeevi

• Presentation– Sites of Disease– Prognosis

• Treatment Options– Hormonal Therapy– Chemotherapy– Biologic Therapy– Radiation

• Supportive Measures– Bisphosphonates, etc.

Metastatic Breast Cancer

• Defining goals

• Communicating with oncology team & with family

• Early use of palliative care / supportive care resources

• Use of psychosocial support services

Important Elements

Determining Factors:

• Sites of recurrence– Skin, nodes>pleura, bone >lung, liver– Brain > meninges

• Time from diagnosis to recurrence

• Type of tumor (ER, HER2/neu)

• Significant improvements with available new drugs (chemo, hormonals, biologics)

Metastatic Disease Prognosis

Current selection of therapy• Based on sites of disease – urgency• Previous therapy (prior anthracyclines, taxanes,

type of hormonal therapy)• Pre-existing toxicity (neuropathy,

cardiomyopathy, other)• Menopausal status• ER / PR status• HER2/neu status• Patient goals (weekly vs. Q 3 week, oral vs. IV,

hair loss vs. not, etc) (compliance)

• Palliation of symptoms

• Improve survival

• Tumor response

Goals of Treatment

Systemic Treatment Options

Metastatic Disease

ER &/Or PR +Non-life threatening

Disease--

Hormone Therapy

ER- / PR- Her 2 neu –

--ChemotherapySingle AgentCombination

Her 2 – neu +

Er- / Pr---

Her2 targeted + Chemo

Er &/or Pr +--

Hormone RxHormone +

Herceptin alone

Diagnosis of metastatic breast cancer

Determination of sites and extent of diseaseAssessment of HER2, HR status, disease-free interval, age, and menopausal status

No life-threatening disease,hormone responsive

Hormone unresponsive orlife-threatening disease

First-line hormonal therapy First-line chemotherapy

ResponseNo response

Second-line hormonal therapy

Second-line chemotherapy

Progression

Progression

Progression

Progression

Third-line hormonal therapy

Response

No response

No response

Third-line chemotherapy

Supportive care

Management of Metastatic Breast Cancer

• Chemotherapy vs. Hormone Therapy

• Single Agent vs. Combination Therapy

• Sequence of agents

• When to integrate hormonal agents if ER+

• Sequence in HER2/neu + disease

• Approach to triple negative disease

• Approach to BRCA1/2 + disease

Debates

What Are The Options Following Tamoxifen?

First treatment

Second treatment

Fourth treatment

Third treatment

Tamoxifen

FulvestrantNonsteroidal AI

Nonsteroidal AI Fulvestrant Steroidal AI

Steroidal AI Steroidal AINonsteroidal AI

Other options for subsequent therapy: progesterone agents, high-dose estrogen, AI + everolimus, clinical trial

Premenopausal• Antiestrogens (SERMS)

– Tamoxifen

– Toremifene

• Ovarian Suppression

• Antiestrogens + os

Postmenopausal• Antiestrogens (SERMS)

• Aromatase Inhibitors

• SERDS (Faslodex)

• Progestins

• Androgens

• Estrogen

Hormonal Therapy Options for Metastatic Disease

Recent Additions

• Chemotherapy:– Halaven (erebulin)– Others in testing

• HER2/neu based therapy:– Pertuzumab– Kadcyla– Neratinib – in testing

• Hormonal therapy:– Faslodex– Exemestane + Afinitor

• Novel compounds– Parp inhibitors– Vaccines– Others

• Genetic profile of tumor– Caris, individual institutional research

programs

• Genetic profile of host – metabolizing pathways???

• Better understanding of pathways and relationship between pathways

Future Choices

5-AzacytidineDecitabineFazarabine

Depsipeptide

OxaliplatinGemcitabine

Irofulven

Paclitaxel DocetaxelDolastatin Ixabepilone

Benzoylphenylurea

Bortezomib

CC49LMB-9

Mab CO17-1A

Survival Factors(eg, IGF1)

Hormones(eg, Bombesin)(eg, Estrogen)

TipifarnibBMS-214662

Growth Factors(eg, TGF)

ErlotinibSU6668

SexaminibGefitinib

TrastuzumabLapatinib

ECM

Cilengitide

Cells

Bryostatin-1Everolimus

Temsirolimus

BortezomibCytokines(eg, ILs, IFNs)

WNT

Flavopiridol

IL-4IL-12IFN

UCN-01 Death Factors(eg, FasL)

Oblimersen

Ad-p53

17AAG

Angiogenesis:SexaminibSU6668BevacizumabHuMV833CilengitideVitaxin 2CAIEndostatinAngiostatinThalidomideNeovastat2-Methoxy EstradiolSorafenibSunitinib VandetanibMotesanib diphosphate

Matrix Metalloproteinases:Batimastat BB-94Marimastat BB-2516BMS-275291BAY 12-9566COL3

GOOD NEWS!Breast Cancer Therapeutics: 2013

• Hormone +:– Sorafanib + Letrozole

• Triple negative– Various agents + Avastin– High GPMB expressing – CDX-011 (celldex)– Parp inhibitors

• Others:– Abraxane + Afinitor

A Few Interesting Ongoing Studies

• Bisphosphonates– Zoledronic Acid IV– Pamidronate IV

• Rank Ligand inhibitor- Denosumab sq

Importance of Bone Targeted Therapy

• Focused treatment for symptom palliation

• Quadramet IV for more general pain control

Role of Radiation

What Does It Mean In My Everyday Life?

•Common physical effects and things to watch

•Common psychosocial concerns

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Sharing Our Stories

Dikla Benzeevi

11-year Stage IV Breast Cancer Survivor and Advocate

Question and Answer Session

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