SHARE and WEILL CORNELL BREAST CENTER

Metastatic breast cancer:Update 2012

Anne Moore, MD Linda Vahdat, MD

Christine

Metastatic breast cancer

• Spread of breast cancer outside of the breast and axillary lymph nodes– About 20-30 % of women treated for stage 1, 2 or

3 breast cancer will later develop metastatic cancer

– Breast cancer can start as metastatic cancer

Metastatic breast cancer

• Now considered “a chronic disease”• Have a strategic plan

The woman with metastatic disease

• Tools:– Surgery– Radiation therapy– Zometa for bone strengthening

The woman with metastatic disease

• Tools:– Chemotherapy– Hormonal therapy for ER/PR positive – Her-2 directed therapy for HER 2 positive – Anti-angiogenesis approach – Clinical trials

• New drugs, new approaches• Vaccines

• What about diet, supplements, vitamins, immune boosters?

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Luis, DFCI. ASCO education session 2012

Does the ER/PR/HER 2 change between the primary cancer and the metastasis?

• Estrogen receptor- 126 patients– Was positive and now negative-14%– Was negative and now positive-8%

• HER 2- 121 patients– Was positive and now negative-17%– Was negative and now positive- 0%

Luis, ASCO education session, 2012

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How do we stop cancer cells from dividing?

DNA

How do we stop cancer cells from dividing?

Chemotherapy directly attacks the DNA: Cells cant divide.

BUT DNA can repair itself so we need to outsmart cell division in other ways

DNA

Estrogen

Estrogen receptor

TARGETED TREATMENT: INACTIVATE THE ESTROGEN RECEPTOR

TARGETED TREATMENT: INACTIVATE THE ESTROGEN RECEPTOR

Take away estrogen

Use a “fake” estrogen: Tamoxifen

Destroy the estrogen receptor: Faslodex

BUT the cells can bypass the estrogen receptor blockade and start to divide again so we need to outsmart estrogen dependent cell division in other ways

Estrogen activates the estrogen receptor and cells proliferate through activation of the mTOR pathway

mTOR blockade blocks estrogen receptor activation

Block mTOR

EVEROLIMUS IS AN MTOR INHIBITOR

BOLERO 2: ASCO UPDATE

RESULTS

• CLINICAL BENEFIT RATE-Those women who had a complete response, a partial response or stable disease for more than 6 months– 26.4% for exemestane– 51.3% for exemestane and everolimus

Characteristics of these women with metastatic ER+ breast cancer

• Average age: 61• Disease free interval before first recurrence: 5

year• All had received anastrazole or letrozole- 84% had

shown a response. • 53% had received >3 treatments for metastatic

disease including chemotherapy• The women were in good shape

Women receiving both pills, Exemestane (Aromasin) and Everolimus (Afinitor)

had more side effects

• mouth sores • Infections • Rash • Pneumonitis • high blood sugar

Will we use everolimus with hormone therapy?

Pt. recurs on or after adjuvant letrozole:TamoxifenFulvestrantThen: ?exemestane alone or with

everolimus as an alternative to chemotherapy

This trial is exciting because it opens a new pathway for drug development in breast cancer

HER-2 POSITIVE METASTATIC BREAST CANCER

Lapatinib (Tykerb) (a pill) targets the Her2 receptor

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PERTUZUMAB HAS JUST BEEN APPROVED FOR HER 2 + METASTATIC BREAST CANCER

Pertuzumab

• Approved for first line metastatic breast cancer treatment with herceptin and docetaxel (taxotere)

• Very weak by itself but boosts herceptin effect even for women who have had herceptin already

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Herceptin linked to a strong chemotherapy drug

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The Future is Promising for Metastatic Breast Cancer