Transcript Biology and treatment of breast cancer

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
Breast Cancer Biology: Not all Breast
Cancers are the Same!!
HER-2 +
20-25% of
Breast Cancer
Estrogen
Receptor (ER) +
75% of Breast
Cancer
Tumor ER and HER2 status are CRITICAL in selecting
therapy in both early stage and metastatic breast
cancer!
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
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
Breast Cancer Treatment:
A Multidisciplinary Team Approach
•Radiology
•Pathology
•Surgery
•Radiation
Oncology
•Medical
Oncology
Fighting the Crab – Kiev, Ukraine
Breast Cancer Systemic Therapies
• Drug treatments that can attack
cancer cells throughout the body
–Endocrine (hormonal) therapy
–Chemotherapy
–Targeted therapy
Estrogen Receptor as a Target for
Therapy
Aromatase inhibitors,
ovarian suppression
Estrogen
SERMS (tamoxifen),
SERDS
Estrogen
Receptor
Cell
Growth
and
Division
Endocrine therapy is effective only in ER-positive breast cancer
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
http://www.who.int/medicines/publications/essentialmedicines/en/
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)
http://www.who.int/medicines/publications/essentialmedicines/en/
HER-2 as a Target for Therapy
Pertuzumab
Anti-HER-2 Antibody
HER-2
Trastuzumab
Anti-HER-2 Antibody
cancer cell
nucleus
T-DM1
Ado-trastuzumab
emtansine
Antibody-Drug cell division
Conjugate
Lapatinib
Dual HER-1/HER-2
Tyrosine Kinase Inhibitor
WHO Model List of Essential Medicines
19th Edition (April 2015)
Antineoplastic drugs relevant to breast cancer
• Targeted Therapy
– Trastuzumab (Herceptin)
http://www.who.int/medicines/publications/essentialmedicines/en/
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)
Targeting the Cancer Environment:
Bone Inhibition
cancer cells
osteoclasts
osteoblasts,
macrophages
Drugs that block bone destruction:
• Bisphosphonates (zoledronic acid, pamidronate)
• RANK ligand inhibitor (denosumab)
Goals in the Treatment of Breast
Cancer Vary by Stage
Non-Metastatic Breast Cancer
Cancer confined to the breast and local lymph node
areas
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
Metastatic Breast Cancer
Cancer that has spread beyond the breast and local
lymph node areas
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
Treatment of Metastatic Breast
Cancer: A Balancing Act
Balancing treatment efficacy and toxicity is a
major objective
Quantity
of
Life
Quality
of
Life
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
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
Biology and Treatment of Breast
Cancer: The Future
• Cancer care is set to change dramatically in the next
10-20 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
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 symptomrelated interventions
• Include patient preferences and active participation
– Patients, families and caregivers should be invited to
participate in decision-making