GRALOW Tanzania Systemic Therapy 9-14 short.ppt

GRALOW Tanzania Systemic Therapy

1. Women’s Empowerment Cancer Advocacy Network (WE
CAN) Conference
Treatment Options for Breast Cancer:
Adjuvant and Metastatic Systemic Therapy
Dar esSalaam, Tanzania, September 2014
Julie R. Gralow, M.D.
Jill Bennett Endowed Professor of Breast Cancer
Director, Breast Medical Oncology
Professor, Global Health
University of Washington School of Medicine
Fred Hutchinson Cancer Research Center
Seattle Cancer Care Alliance

2. Why Tanzania Has a Special
Place in My Heart
Summit of Mt. Kilimanjaro
19,340 feet
February 7, 2009

3. Importance of Pathology: 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 critical in selecting therapy
in both early stage and metastatic breast cancer

4. •Young onset breast cancer
•High grade (aggressive) tumors
•High proliferative tumors
•ER negative tumors
•“Triple negative” (ER-/PR-/HER2-)
tumors
African Women More Likely to
Have:

5. Breast Cancer Systemic Therapies
•Drug treatments that can attack
cancer cells throughout the body
–Endocrine therapy
–Chemotherapy
–Biologically-targeted therapy

6. WHO Essential Medicine List for
Adults 18
th
Edition (April 2013)
•Antineoplasticsrelevant to treatment of
breast/cervical cancer
–Tamoxifen
–Doxorubicin (Adriamycin)
–Cyclophosphamide (Cytoxan)
–Paclitaxel (Taxol)
–Docetaxel(Taxotere)
–Fluorouracil (5-FU)
–Methotrexate
–Carboplatin
–??Trastuzumab(Herceptin) –proposed for addition

7. Treatment of Early Stage Breast
Cancer
•Breast cancer most curable when detected early
–Micrometastases(undetectable) can exist at time
of diagnosis in many patients, leading to
eventual recurrence
•Multidisciplinary care 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

8. No surgery
mastectomy
chemotherapy + endocrine therapy
chemotherapy + endocrine therapy +
HER2 targeted therapy
Incremental Benefit of Adjuvant
Treatments in Early Stage Breast
Cancer in USA
Survival

9. Treatment of Metastatic
Breast Cancer
•Metastatic breast cancer is not curable,
but can be very treatable
•Goals:
–Control and regression of disease
–Prolongation of life
–Improvement in symptoms and
quality of life

10. Choices in the Treatment of
Metastatic Breast Cancer
•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

11. Metastatic Breast Cancer Survival
in USA: Impact of New Agents
Giordano S et al, Cancer 100:44-52, 2004

12. Endocrine Therapy in Breast Cancer
Estrogen
Cell
Growth
and
Division
Estrogen
Receptor
SERMS (tamoxifen),
SERDS Aromatase inhibitors,
ovarian suppression
Endocrine therapy effective only in ER-positive breast cancer
ER/PR staining: CRITICAL IN SELECTING THERAPY!

13. Adjuvant (Early Stage) Endocrine Therapy
in Breast Cancer
•Tamoxifen has substantial clinical efficacy, less cost, and
several decades of use throughout world
–Still the standard for premenopausal
–Reasonable for many postmenopausal
–Longer duration (> 5 years) may benefit many patients
•Adjuvant aromatase inhibitors: small differences in
recurrences (and in some trials deaths)
–Side effects different
•Ovarian suppression effective as a sole treatment
–Still unclear whether it adds to chemo/tamoxifen

14. Early Breast Cancer Trialists’ Collaborative Group
Clinical Trials of Tamoxifen in Early Stage
Breast Cancer: Disease-free Survival
ER Negative ER Positive
Adjuvant tamoxifen
significantly reduces
recurrence in ER positive
breast cancer
tamoxifen
control
Tamoxifen effective in both pre-and postmenopausal women
Adjuvant tamoxifen
doesn’t impact
recurrence in ER
negative breast cancer

15. Endocrine Therapy for Metastatic
Breast Cancer
•Endocrine therapy is the preferred choice for ER+
metastatic breast cancer
–Less side effects than chemotherapy
•Exceptions:
–Concern or proof of endocrine resistance
–Need for fast response (location, symptoms)

16. Chemotherapy

17. Adjuvant (Early stage) Chemotherapy
in Breast Cancer
•Adjuvant chemotherapy reduces recurrences and
deaths
–Reducing dose from that proven to be effective in
clinical trials reduces benefit
–Chemotherapy drugs have significant side effects
•For unselected patients/tumors:
–anthracyclinesbetter than CMF regimens
–taxanes add to anthracyclines –expensive
•Not all patients/tumors benefit from chemotherapy!
•ER-negative, high grade, HER-2+ tumors get most
benefit from chemotherapy

18. Chemotherapy Dose Matters
Adjuvant Chemotherapy -20 Year Follow-up
Milan Study
BonadonnaG et al, N EnglJ Med 332: 901-6,1995
0.9
1.0
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
5 10 15 20
Years after Mastectomy
Disease-free survival
Probability of Relapse
-
free Survival
5 10 15 20
Years after Mastectomy
0.9
1.0
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
Overall survival
Probability of Overall Survival
>85% of dose
<65% of dose
Control
65-84% of dose
If chemotherapy is given, it should be given at full dose

19. European School of Oncology Guideline:
Chemotherapy for Metastatic Breast
Cancer
CardosaF et al, J NatlCancer Inst101:1174-1181, 2009
•Sequential single agent chemotherapy generally
preferred choice
–Less toxicity than combination chemo
–No data to support optimal sequence
•Combination chemotherapy reserved for patients
with:
–rapid clinical progression
–life-threatening visceral metastases
–need for rapid symptom/disease control
•Chosen regimen should be evidence-based, with
proven efficacy and acceptable toxicity

20. Biologically-Targeted
Therapy

21. Four US FDA-Approved Drugs with HER-2
as a Target
cell division
HER-2
nucleus
cancer cell
Trastuzumab (Herceptin)
Anti-HER-2 Antibody
Lapatinib (Tykerb)
Dual HER-1/HER-2
Tyrosine Kinase Inhibitor
Pertuzumab
Anti-HER-2 Antibody
T-DM1
Antibody-Drug
Conjugate
20-25% of breast
cancers
overexpress HER2
Only effective for HER2+
breast cancer

22. Adjuvant (Early Stage) HER-2
Targeted Therapy
•Anti-HER2 monoclonal antibody trastuzumab
(Herceptin) for 1 year is standard
–Reduces recurrence by 1/2 & deaths by 1/3 when
added to chemo in early stage breast cancer
–Trastuzumabgoing off patent soon, and prices
will drop
•All regimens include chemotherapy in addition to
HER2 targeting therapy

23. European School of Oncology
Guideline: HER2 Targeted Therapy
for Metastatic Breast Cancer
CardosaF et al, J NatlCancer Inst101:1174-1181, 2009
•Anti-HER2 therapy should be offered earlyto all
HER2+ metastatic breast cancer patients unless
contraindicated (or unavailable)
•Optimal duration of anti-HER2 therapy for
metastatic breast cancer (when to stop) unknown

24. Complications of Breast Cancer
Bone Metastases
Pain
Spinal cord
compression
Radiation
therapy
Orthopedic
surgery
Hypercalcemia
Fractures
The bone is the initial site of recurrence in 35-40% of
breast cancer patients

25. European School of Oncology Guideline:
Bone Metastases in Breast Cancer
CardosaF et al, J NatlCancer Inst101:1174-1181, 2009
•Bone modifying agents should be routinely used in
combination with other systemic therapy in patients
with bone metastases
–Bisphosphonates (pamidronate, zoledronicacid)
–RANK ligand inhibitor (denosumab)
•Agents should be started early, if possible before
onset of bone symptoms
•Should be continued even in presence of disease
progression

26. Systemic Treatment of Breast
Cancer: Summary
•Main principles of modern oncology
–Multidisciplinary treatment
–Evidence-based medicine
–Individualized (tailored) therapy
•Keep in mind 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