17742 Beach Boulevard | Suite 250 | Huntington Beach | CA 92647phone: 1.888.321.2732 | fax: 1.888.669.3292customercare@agendia.com | www.agendia.com

For more information on MammaPrint, or to locate a physicianwho offers MammaPrint, please contact us at:

decoding cancer.

U.S. Food and Drug AdministrationRockville, MD 20857-0001

U.S. Food and Drug AdministrationRockville, MD 20857-0001

ASSURANCEGene expression profiling has emerged as a powerful technology capable of assessing both the riskof recurrence and the likelihood of a patient benefiting from adjuvant chemotherapy. As a result, it isbeing used by more and more breast cancer centers in the care of their patients. As an early-stagebreast cancer patient, learning more about the diagnosis and treatment of your illness is becomingessential. That is why more patients are requesting MammaPrint.

Ask your surgeon about MammaPrint today, as the decision to run this testmust be made prior to surgery.

MammaPrint is the only FDA cleared IVDMIA gene expression test, giving you and yourdoctors the assurance that this test has been validated and is clinically proven.

"For women with early stage breast cancer,MammaPrint evaluates individual geneexpression details regarding tumor biologyto better identify who may safely omitchemotherapy. By individualizing awoman's risk for breast cancer recurrence,MammaPrint will revolutionize the way wethink about treating these women -much asbreast conservation has changed the way weapproach surgical care."

Sherin K. Shirazi, M.D.Breast SurgeonHuntington HospitalPasadena, California

Breast Cancer Center for ExcellenceDepartment of PathologyUSC Norris Cancer CenterUniversity of Southern CaliforniaLos Angeles, California

What makes the MammaPrint breast cancer recurrence testthe right choice for you and your doctor?

17742 Beach Boulevard | Suite 250 | Huntington Beach | CA 92647phone: 1.888.321.2732 | fax: 1.888.669.3292customercare@agendia.com | www.agendia.com

For more information on MammaPrint, or to locate a physicianwho offers MammaPrint, please contact us at:

decoding cancer.

U.S. Food and Drug AdministrationRockville, MD 20857-0001

U.S. Food and Drug AdministrationRockville, MD 20857-0001

CONFIDENCEMany oncologists are choosing MammaPrint to assist in their adjuvant chemotherapy decision making forearly stage breast cancer patients. They feel confident that when a patient is low-risk by MammaPrint(10% risk of distant recurrence, pre-hormonal therapy) they may be able to avoid chemotherapy; when apatient is high-risk by MammaPrint, they believe that chemotherapy will be of benefit. MammaPrint canhelp you and your oncologist determine if the addition of chemotherapy is right for you.

Ask your oncologist about MammaPrint today, as the decision to run this testmust be made prior to surgery.

MammaPrint is the only FDA cleared IVDMIA gene expression test for breast cancer recurrence and enablesyour oncologist to assess your individual risk of recurrence and therefore tailor a treatment plan for you.

"Almost all new breast cancer patientspresent with early-stage disease. With surgeryand local therapy, 70 percent of these patientswill likely be cured. However, despite earlydiagnosis and treatment, cancer will recur inabout 30% within 10 years. In many casesadjuvant chemotherapy can reduce this riskbut at identified toxicity cost. I rely onMammaPrint to help me identify those lowrisk patients who may be safely managedwithout chemotherapy."

Rowan T. Chlebowski, M.D. PhD.Harbor-UCLA Medical CenterProfessor of MedicineDavid Geffen School of MedicineUniversity of California, Los Angeles

What makes the MammaPrint breast cancer recurrence testthe right choice for you and your doctor?

B R E A S T C A N C E RT R E A T M E N T O P T I O N S

CHART YOUR COURSE

Patient Resource™ Education Handout...for Physicians and Their PatientsCANCER GUIDE

DIAGNOSIS1

Primary Treatment ChoicesLumpectomy with clear surgical margins and observation without further therapy

Secondary Treatmentno breast radiation

Treatment Based on Hormone Receptor StatusIf premenopausal: tamoxifen for 5 yearsIf post-menopausal: raloxifene or tamoxifen for 5 years

Follow-up Care Exam every 6 to 12 months Yearly mammogram Annual GYN history and exam

for women taking tamoxifen or raloxifene

Additional Comments Discuss the option of bilateral

mastectomy without lymph node removal if major risk factors present (eg, strong family history, BRCA mutation)

Primary Treatment ChoicesLumpectomy (also termed segmental or partial mastectomy) with negative surgical margins without lymph node surgery (If margins positive after lumpectomy, requires repeat lumpectomy to achieve negative margins, or total mastectomy)

Or

Total mastectomy with or without breast reconstruction without lymph node surgery (consider sentinel lymph node biopsy)

Secondary TreatmentWith lumpectomy: whole breast radiation in most cases. May be omit-ted in select cases based on size, grade, and patient circumstances (e.g. co-morbidity, advanced age)With mastectomy: no radiation

Treatment Based on Hormone Receptor StatusIn some cases to reduce risk for recurrent cancer:If ER+, consider tamoxifen for 5 years

Follow-up Care Exam every 6 to 12 months Yearly mammogram Annual GYN history and exam

for women taking tamoxifen or raloxifene

Additional Comments

Discuss tamoxifen therapy for risk reduction of cancer to the contralateral breast (the second breast without cancer)

If lumpectomy can be performed there is no survival advantage to mastectomy

Consider sentinel lymph node biopsy with mastectomy for larger tumors because this precludes subsequent SLNB if invasive cancer is identi! ed

Primary Treatment ChoicesLumpectomy & sentinel node biopsy; or if positive nodes, complete removal of underarm lymph nodes. If sentinel node positive, complete removal of underarm lymph nodes.

Secondary TreatmentNo cancer spread to lymph nodes:

Radiation to the whole breast with added boost to tumor siteCancer spread to 1-3 lymph nodes:

Radiation to the whole breast with added boost to tumor site Consider possible radiation to regional lymph node areas

Cancer spread to 4 or more lymph nodes: Radiation to whole breast with added boost to tumor site Radiation to the chest wall and supraclavicular lymph nodes, and consider radia-

tion to the internal mammary nodes

Treatment Based on HER2 and Hormone Receptor StatusAll women with invasive cancer should consider treatment with anti-estrogen hormonal drugs and/or intravenous chemotherapy. The choice of therapy depends on the risk of eventual cancer recurrence estimated from the tumor size, extent of lymph node involvement, and hormone receptor and HER2 statusHormone receptor-positive, HER2-positive:

Chemotherapy plus hormone therapy plus trastuzumab, with radiation adminis-tered after completion of chemotherapy*. Hormone therapy after radiation.

Hormone receptor-positive, HER2-negative: Hormone therapy with or without chemotherapy. If chemotherapy used, radiation

follows chemotherapy. Hormone therapy after radiation. Hormone receptor-negative, HER2-positive:

Chemotherapy plus trastuzumab, with radiation administered after chemotherapy* Hormone receptor-negative, HER2-negative:

Chemotherapy with radiation administered after. No additional therapy after radiation. *Trastuzumab administered with chemotherapy and continues through radiation for a full one year duration

Follow-up Care Physical exam every 4 to 6 months for 5 years, and then annually Mammogram every year; patients undergoing lumpectomy will have a mam-

mogram 6 months after radiation Women given tamoxifen: Annual GYN exam if uterus is present For women receiving aromatase inhibitors, monitoring of bone health with bone

mineral density measurement before and periodically after aromatase inhibitor treatment

If it is determined that treatment with aromatase inhibitors is associated with signi! cant bone loss, which is considered osteopenia/osteoporosis, then treatment with drugs called bisphosphonates may be necessary

Hormonal therapy Premenopausal women (at time of diagnosis): Tamoxifen for 5 years with or

without ovarian suppression or ablation Postmenopausal women: Aromatase inhibitors (eg, anastrozole, letrozole, exemes-

tane) for 5 years; or tamoxifen for 5 years if woman can’t take aromatase inhibitor

Additional Comments Newer gene pattern tests help doctors decide whether to give adjuvant chemo-

therapy to women with certain stage I or II breast cancers, especially in node-, ER+, and HER2- patients

Examples of such tests include Oncotype DX® and MammaPrint® These tests may help predict the risk of cancer returning after treatment

Primary Treatment ChoicesMastectomy & sentinel node biopsy; or complete removal of underarm lymph nodes. If sentinel node positive, complete removal of underarm lymph nodes; with or without immediate skin-sparing breast reconstruction.

Secondary TreatmentNo cancer spread to lymph nodes:

No radiationCancer spread to 1-3 lymph nodes:

Consider radiation to the mastectomy site (chest wall), supraclavicular nodes, and possibly internal mammary nodes

Cancer spread to 4 or more lymph nodes: Radiation to the mastectomy site (chest wall) and supraclavicular lymph nodes, and consider

radiation to the internal mammary nodes

Treatment Based on HER2 and Hormone Receptor StatusAll women with invasive cancer should consider treatment with anti-estrogen hormonal drugs and/or intravenous chemotherapy. The choice of therapy depends on the risk of eventual cancer recurrence estimated from the tumor size, extent of lymph node involvement, and hormone receptor and HER2 statusHormone receptor-positive, HER2-positive:

Chemotherapy plus hormone therapy plus trastuzumab* Hormone receptor-positive, HER2-negative:

Hormone therapy with or without chemotherapy, after radiation Hormone receptor-negative, HER2-positive:

Chemotherapy plus trastuzumab* Hormone receptor-negative, HER2-negative:

Chemotherapy only*Trastuzumab administered with chemotherapy and continues through radiation for a full one year duration

Follow-up Care Physical exam every 4 to 6 months for 5 years, and then annually Mammogram every year Women given tamoxifen: Annual GYN exam if uterus is present For women receiving aromatase inhibitors, monitoring of bone health with bone mineral

density measurement before and periodically after aromatase inhibitor treatment If it is determined that treatment with aromatase inhibitors is associated with signi! cant

bone loss, which is considered osteopenia/osteoporosis, then treatment with drugs called bisphosphonates may be necessary

Hormonal therapy Premenopausal women (at time of diagnosis): Tamoxifen for 5 years with or without ovarian

suppression or ablation Postmenopausal women: Aromatase inhibitors (eg, anastrozole, letrozole, exemestane) for 5

years; or tamoxifen for 5 years if woman can’t take aromatase inhibitor

Additional Comments Newer gene pattern tests help doctors decide whether to give adjuvant chemotherapy to

women with certain stage I or II breast cancers Examples of such tests include Oncotype DX® and MammaPrint® Breast reconstruction may be done at the same time as mastectomy (preferred), or be done

at a later date (delayed) If anticipated by stage of cancer that radiation will be needed, it may be desirable to delay

breast reconstruction

Primary Treatment Choices Chemotherapy with or without trastuzumab therapy to shrink tumor size before surgery Additional chemotherapy with di" erent drugs may also be required if the tumor does not shrink

with the drugs ! rst used in chemotherapy Postmenopausal women who are medically unable to undergo chemotherapy may be considered

for hormonal therapy before surgery

Secondary TreatmentIf signi! cant tumor shrinkage is seen:

Mastectomy or lumpectomy followed by radiation to the breast and boost to tumor site Removal of underarm lymph nodes

If tumor shrinkage is not seen or if lumpectomy is not possible: Mastectomy, with or without breast reconstructive surgery

One or more of the following options may also be necessary after surgery based on tumor characteristics ! rst observed:

Radiation to the chest wall and regional lymph nodes Hormonal therapy based on hormone receptor status One year treatment with trastuzumab, which may be given together with radiation therapy

Radiation Therapy, if indicated, is usually given after chemotherapy is completed

Treatment Based on HER2 and Hormone Receptor StatusHormone receptor-positive, HER2-positive:

Chemotherapy plus trastuzumab plus hormone therapy* Hormone receptor-positive, HER2-negative:

Hormone therapy with or without chemotherapy Hormone receptor-negative, HER2-positive:

Chemotherapy plus trastuzumab Hormone receptor-negative, HER2-negative:

Chemotherapy only* Hormone therapy administered for 5 years after completion of radiation

Premenopausal women (at time of diagnosis): Tamoxifen for 5 years with or without ovarian supression or ablation

Postmenopausal women: Aromatase inhibitors (e.g. anastrozole, letrozole, exemestane) for 5 years; or tamoxifen for 5 years if woman cannot take aromatase inhibitor

Follow-up Care Physical exam every 4 to 6 months for 5 years, and then annually Mammogram every year; patients undergoing lumpectomy will have a mammogram 6 months

after radiation Women given tamoxifen: Annual GYN exam if uterus is present For women receiving aromatase inhibitors, monitoring of bone health with bone mineral density

measurement before and periodically after aromatase inhibitor treatment If it is determined that treatment with aromatase inhibitors is associated with signi! cant bone

loss, which is considered osteopenia/osteoporosis, then treatment with drugs called bisphospho-nates may be necessary

Additional CommentsIf osteoporosis develops, give bisphosphonate therapy

Primary Treatment Choices Chemotherapy with or without trastuzumab before surgery If tumor does not shrink, then other drugs may be used alone or in combination If tumor still does not shrink, the physician will discuss speci! c recommendations

depending on what else is available

Secondary TreatmentOne of following options is possible:

Modi! ed radical mastectomy and radiation to the breast/chest wall and regional lymph nodes

Lumpectomy and radiation to the breast/chest wall and regional lymph nodes if signi! cant tumor shrinkage is seen

Radiation Therapy is usually given after chemotherapy is completed

Treatment Based on HER2 and Hormone Receptor Status Chemotherapy Chemotherapy followed by hormonal therapy, if cancer is hormone-receptor

positive Trastuzumab for 1 year if cancer is HER2-positive If hormone receptor positive, hormone therapy administered for 5 years after

completion of radiation Premenopausal women (at time of diagnosis): Tamoxifen for 5 years with or

without ovarian supression or ablation Postmenopausal women: Aromatase inhibitors (e.g. anastrozole, letrozole, ex-

emestane) for 5 years; or tamoxifen for 5 years if woman cannot take aromatase inhibitor

Radiation Therapy, if indicated, is usually given after chemotherpy is completed

Follow-up Care Physical exam every 4 to 6 months for 5 years, and then annually Mammogram every year Women given tamoxifen: Annual GYN exam if uterus is present For women receiving aromatase inhibitors, monitoring of bone health with bone

mineral density measurement before and periodically after aromatase inhibitor treatment

If it is determined that treatment with aromatase inhibitors is associated with signi! cant bone loss, which is considered osteopenia/osteoporosis, then treat-ment with drugs called bisphosphonates may be necessary

Additional CommentsIf osteoporosis develops, give bisphosphonate therapy

Primary Treatment ChoicesSystemic treatment is the best initial treatment option. The choice of the type of systemic treatment depends on several factors:

Hormone receptor and HER2 status of the cancer The presence of symptoms and pain The type and location of spread of cancer

Treatment choices include: Hormone therapy Chemotherapy Targeted therapies (e.g. HER2 targeted drugs)

Because cancer has already spread, surgery and radiation are of limited use in this setting

For HER2+ tumorsTherapy will be a combination of chemotherapy agents and trastuzumab

For hormone-receptor-positive cancerTherapy in postmenopausal women can include:

Aromatase inhibitors Antiestrogens

Therapy in premenopausal women can include: Antiestrogens Oophorectomy, followed by AI therapy used in postmenopausal

women

Hormone-receptor-negative cancerTherapy will be a combination of chemotherapy agents. The agents can include:

Anthracyclines Taxanes Cytotoxic agents Vinca alkaloids

Targeted agents (also called biologics) that may be used include: Lapatinib Trastuzumab Bevacizumab

Additional Comments If bone disease is present, zoledronic acid is given periodically to

make sure that bone metastases do not progress Because there are many treatment possibilities, if one treatment

fails, other treatment possibilities will be explored

(non-invasive) breast cancerLCIS (lobular carcinoma in situ)Stage 0

(non-invasive) breast cancerDCIS (ductal carcinoma in situ) Stage 0

Invasive breast cancer when surgery (lumpectomy) is the initial treatmentStage I (T1, N0, M0)Stage IIA (T0, N1, M0 or T1, N1, M0 or T2, N0, M0)Stage IIB (T2, N1, M0 or T3, N0, M0)

Invasive breast cancer when surgery (mastectomy) is the initial treatmentStage I (T1, N0, M0)Stage IIA (T0, N1, M0 or T1, N1, M0 or T2, N0, M0)Stage IIB (T2, N1, M0 or T3, N0, M0)

Invasive breast cancer when chemo or hormone therapy is the initial treatmentStage IIA (T0, N1, M0 or T1, N1, M0 or T2, N0, M0)Stage IIB (T2, N1, M0 or T3, N0, M0)Stage IIIA (T3, N1, M0)

Locally advanced breast cancer Stage IIIB (T4, N0, M0 or T4, N1, M0 or T4, N2, M0)Stage IIIC (Any T, N3, M0)

Stage IV – Metastatic Cancer or Recurrent CancerAny T, any N, M1

Patient Resource Cancer Guide — Breast Cancer Treatment Options

Notes: 1) The TNM staging for breast cancer is based on three criteria: size of the tumor and how far it has spread in the breast (T; a higher number

indicates increasing size; T4 indicates spread to the skin and under the chest wall), lymph nodes involved (N; the number after N indicates the number of lymph nodes near the breast that are involved) and metastatic sites (M; the number after M indicates the number of sites that the tumor has progressed to). Hence early breast cancer will always be M0.

2) HER2 indicates that the breast cancer has the HER2 gene that is expressed. This makes the cancer grow quicker; but fortunately, trastuzumab has been developed just to counteract the e" ects of HER2 and patients with HER2-positive tumors respond to the drug.

3) Hormone receptors indicate whether the breast cancer has estrogen and/or progesterone receptors (ER or PgR). The presence of these molecules makes tumors respond to hormonal agents.

4) Oncotype DX test looks for the presence or absence of 21 speci! c genes in tumor samples. Based on their presence/absence, a recurrence score (a number from 0 to 100) indicates whether a woman will be at greater risk for cancer recurrence (0-17=low risk; 18-30=intermediate risk; 31 or higher=high risk)

5) The MammaPrint test checks how many of 70 speci! c genes are present on breast cancer cells in early stage cancer. The test can be used on ER-positive or ER-negative early breast cancer. The recurrence score determines if the cancer is likely to recur to another site in the body after treatment. It tells a doctor whether additional therapy may be necessary for patients.

6) In the treatment of breast cancer oncologists have several di" erent combinations of drugs that can be used and that have been found to be e" ective in treating breast cancer. Based on pathology and other tests, the doctor will discuss the various chemotherapy options and their possible side e" ects.

7) Targeted agents or biologics are drugs that have been developed to more precisely stop a mechanism by which cancer spreads. For example, trastuzumab blocks a speci! c molecule on cancer cells called HER2, which is important for cancer cells to continue growing. Bevacizumab is a molecule that speci! cally inhibits blood vessels from growing in cancer cells.

B R E A S T C A N C E R T R E A T M E N T O P T I O N SB R E A S T C A N C E R T R E A T M E N T O P T I O N SB R E A S T C A N C E R T R E A T M E N T O P T I O N SB R E A S T C A N C E R T R E A T M E N T O P T I O N SB R E A S T C A N C E R T R E A T M E N T O P T I O N SB R E A S T C A N C E R T R E A T M E N T O P T I O N SB R E A S T C A N C E R T R E A T M E N T O P T I O N SB R E A S T C A N C E R T R E A T M E N T O P T I O N SB R E A S T C A N C E R T R E A T M E N T O P T I O N SB R E A S T C A N C E R T R E A T M E N T O P T I O N SB R E A S T C A N C E R T R E A T M E N T O P T I O N SB R E A S T C A N C E R T R E A T M E N T O P T I O N SB R E A S T C A N C E R T R E A T M E N T O P T I O N S

This information is not meant to substitute for medical advice, but is a list to help you understand treatment options you can discuss with your doctor/healthcare team. Content is adopted from NCCN Guidelines. For more information about treatment options see: www.cancer.net, www.cancer.org and www.nccn.org.