1. Biology and Treatment of Breast Cancer
Julie R. Gralow, M.D.
Director, Breast Medical Oncology
Jill Bennett Endowed Professor of Breast Cancer
Professor, Global Health
University of Washington School of Medicine
Fred Hutchinson Cancer Research Center
Seattle Cancer Care Alliance

2. Breast Cancer Biology: Not all Breast Cancers are the Same!!
Estrogen Receptor (ER) + 75% of Breast Cancer
HER-2 +
20-25% of Breast Cancer
Tumor ER and HER2 status are CRITICAL in selecting therapy in both early stage and metastatic breast cancer!

3. Breast Cancer Biology: Triple Negative Breast Cancer (TNBC)
Breast cancer that does not express:
Estrogen Receptor (ER)
Progesterone Receptor (PR)
HER-2
15 to 20 percent of breast cancers
Virtually always high grade
Common in BRCA1 mutation carriers (over 80%)
Overrepresented in premenopausal and African women
Poor prognosis
Sensitive to chemotherapy

4. Determining ER and HER-2 Status Tissue Processing: Each Step Matters!
Cold ischemia time: time from tissue removal to placement in fixative
Fixation parameters: type of fixative and duration

5. Breast Cancer Treatment: A Multidisciplinary Team Approach
Radiology
Pathology
Surgery
Radiation Oncology
Medical Oncology
Fighting the Crab – Kiev, Ukraine

6. Breast Cancer Systemic Therapies
Drug treatments that can attack cancer cells throughout the body
Endocrine (hormonal) therapy
Chemotherapy
Targeted therapy

7. Estrogen Receptor as a Target for Therapy
Aromatase inhibitors, ovarian suppression
SERMS (tamoxifen), SERDS
Cell Growth and Division
Estrogen
Estrogen Receptor
Endocrine therapy is effective only in ER-positive breast cancer

8. WHO Model List of Essential Medicines 19th Edition (April 2015)
Antineoplastic drugs relevant to breast cancer
Endocrine therapy:
Tamoxifen
Anastrozole (Arimidex) – aromatase inhibitor, postmenopausal only
Leuprolide (Lupron) – ovarian suppression, premenopausal only

9. WHO Model List of Essential Medicines 19th Edition (April 2015)
Antineoplastic drugs relevant to breast cancer
Chemotherapy:
Doxorubicin (Adriamycin)
Cyclophosphamide (Cytoxan)
Paclitaxel (Taxol)
Docetaxel (Taxotere)
Fluorouracil (5-FU)
Methotrexate
Carboplatin
Gemcitabine (Gemzar)
Capecitabine (Xeloda)
Vinorelbine (Navelbine)

10. HER-2 as a Target for Therapy
Pertuzumab
Anti-HER-2 Antibody
HER-2
Trastuzumab
Anti-HER-2 Antibody
cancer cell
nucleus
Lapatinib
Dual HER-1/HER-2 Tyrosine Kinase Inhibitor
T-DM1
Ado-trastuzumab emtansine
Antibody-Drug Conjugate
cell division

11. WHO Model List of Essential Medicines 19th Edition (April 2015)
Antineoplastic drugs relevant to breast cancer
Targeted Therapy
Trastuzumab (Herceptin)

12. Targeting the Cancer Environment In Addition to Targeting the Cancer Cell, We Can Also Target the Cancer Environment
Cancer cell
Fibroblast
Immune cell
Blood vessels
Osteoclast (bone cells)

13. Targeting the Cancer Environment: Bone Inhibition
cancer cells
osteoclasts
osteoblasts, macrophages
Drugs that block bone destruction:
Bisphosphonates (zoledronic acid, pamidronate)
RANK ligand inhibitor (denosumab)

14. Goals in the Treatment of Breast Cancer Vary by Stage

15. Non-Metastatic Breast Cancer
Cancer confined to the breast and local lymph node areas

16. Treatment of Non-Metastatic Breast Cancer
Goal: Cure
Breast cancer is most curable when detected early
Micrometastases (undetectable) can exist at time of diagnosis in many patients, leading to eventual recurrence
Multidisciplinary care is critical for best outcomes
Surgery
Radiation therapy
Adjuvant systemic (drug) therapy
Reduces risk of recurrence and death
Should be tailored to the patient and tumor

17. Metastatic Breast Cancer
Cancer that has spread beyond the breast and local lymph node areas

18. Treatment of Metastatic Breast Cancer
Goals:
Control and regression of disease
Prolongation of life
Improvement in symptoms and quality of life
Metastatic breast cancer is not currently usually curable, but is treatable

19. Quantity of Life Quality of Life
Treatment of Metastatic Breast Cancer: A Balancing Act Balancing treatment efficacy and toxicity is a major objective
Quantity of
Life
Quality of
Life

20. Choices in the Treatment of Metastatic Breast Cancer
Treatment is mainly with drug therapy that can attack cancer throughout the body
Radiation can be important (ie for pain control)
Surgery uncommon
Choice of treatment is based on many factors:
Patient age, menopausal status, general health and functional status
Tumor ER status, HER-2 status
Previous treatments
Extent and sites of disease
Available therapies in the patient’s country

21. Biology and Treatment of Breast Cancer: Challenges
Despite important progress to date, cancer remains one of the world’s most serious health problems
Disparities in cancer care and survival remain significant
Worldwide, new cancer cases and deaths continue to rise

22. Biology and Treatment of Breast Cancer: The Future
Cancer care is set to change dramatically in the next years
Advances in technology and a deeper understanding of cancer biology will transform cancer care
Continued investments in cancer research required to translate scientific breakthroughs into new and affordable treatments

23. Biology and Treatment of Breast Cancer: Summary
Main principles of modern oncology
Multidisciplinary treatment
Evidence-based medicine
Individualized (tailored) therapy
Primary goals of therapy
Adjuvant: curative intent
Metastatic: incurable but treatable
Include psychosocial and supportive care and symptom-related interventions
Include patient preferences and active participation
Patients, families and caregivers should be invited to participate in decision-making