B27

1
Alison Stopeck, M.D. Director, Breast Cancer
Program
2
Breast Cancer Statistics 2009
New Cases 194,280 1,910 192,370
Deaths 40,610 440 40,170
Survival 79.1 77.0 79.1
All Men Women
A woman in the U.S. has a 1 in 8 chance of
developing invasive breast cancer during her
lifetime
Over 2.5 million women living in the United
States who have been diagnosed with breast cancer
3
Female Deaths From Cancer
4
Breast Cancer Update November 2009Topics for
Today

• Better tests for determining therapy
• Personalized medicine
• Targeted Therapies
• New advances in hormonal therapy
• Anti-angiogenicsAre they for everyone?
• Bone Health and Osteoclast Targeted Therapies
• Bisphosphonates

5
Breast Cancer Treatment PlanningNot Optimized

• Many women are offered chemotherapy, knowing that
  few will benefit
• Guidelines assume all patients benefit equally
• Some patients are under-treated, many others are
  over-treated

6
Accepted Prognostic Factors

• Age (very old or very young)
• Tumor size
• Axillary node status
• Histologic tumor type
• Pathologic grade
• Proliferative rate
• Hormonal-receptor status
• Her-2 status

NIH Consensus Conference 11/00
7
Better Tests for Determining Who Will Benefit
From Chemotherapy, especially in Patients with HR
and/or LN Negative Disease
8
My RS is 30, What is the chance of recurrence
within 10 yrs?
9
Oncotype DX Technology Final Gene Set
PROLIFERATION Ki-67 STK15 Survivin Cyclin B1 MYBL2
ESTROGEN ER PGR Bcl2 SCUBE2
HER2 GRB7 HER2
GSTM1
REFERENCE Beta-actin GAPDH RPLPO GUS TFRC
CD68
INVASION Stromelysin 3 Cathepsin L2
BAG1
10
Oncotype DX TechnologyAlgorithm and Recurrence
Score (RS)
11
Multi-Gene Recurrence Score Assay for Predicting
Recurrence Paik S et al, San Antonio 2003,
abstract 16
B-14 Validation Set Distant Recurrence Rates by
Subgroup LN-, ER patients treated with tamoxifen
Risk Group of 10-yr
Rate 95 CI Patients
Recurrence Low (RSlt18) 51 6.8
4.0, 9.6 Intermediate (RS 18-30) 22
14.3 8.3, 20.3 High (RS31)
27 30.5 23.6, 37.4
Do patients with a high recurrence score benefit
from chemotherapy?
12
Chemotherapy Benefit and Oncotype DX
NSABP B-20 Chemo Benefit Study in N-, ER Pts
Tam MF

• Objective Determine the magnitude of the
  chemotherapy benefit as a function of 21 gene
  Recurrence Score assay

Randomized
Tam CMF
Tam
SABCS 2004 Abstract 24
13
B-20 Results

• Tam vs Tam Chemo All 651 Pts

1.0
0.9
0.8
4 5 overall benefit -small benefit for many or
large benefit for a small subset
0.7
0.6
DRFS
0.5
0.4
0.3
0.2
N Events 424 33 227
31
All Patients
Tam Chemo
0.1
p 0.02
Tam
0.0
0
2
4
6
8
10
12
Years
14
B-20 Results

• Tam vs Tam Chemo Low Risk (RS lt 18)

10yr
1.0
96
95
0.9
0.8
0.7
0.6
DRFS
0.5
0.4
0.3
N Events 218 11 135
5
0.2
Low Risk Patients (RS lt 18)
Tam Chemo
p 0.76
0.1
Tam
0.0
0
2
4
6
8
10
12
Years
Years
SABCS 2004 Abstract 24
15
B-20 Results

• Tam vs Tam Chemo Int Risk (RS 1830)

10yr
1.0
89
0.9
90
0.8
0.7
0.6
DRFS
0.5
0.4
0.3
N Events 89 9 45
8
0.2
Int Risk Patients (RS 18 - 30)
Tam Chemo
p 0.71
0.1
Tam
0.0
0
2
4
6
8
10
12
Years
SABCS 2004 Abstract 24
16
B-20 Results
Tam vs Tam Chemo High Risk (RS 31)
10yr
1.0
0.9
88
0.8
0.7
60
0.6
DRFS
0.5
0.4
0.3
N Events 117 13 47
18
0.2
High Risk Patients (RS 31)
Tam Chemo
p 0.001
0.1
Tam
0.0
0
2
4
6
8
10
12
Years
SABCS 2004 Abstract 24
17
Several Components of the RS Have Been Associated
with Variable Benefit to Chemotherapy or Hormonal
Therapy
PROLIFERATION Ki-67 STK15 Survivin Cyclin B1 MYBL2
ESTROGEN ER PR Bcl2 SCUBE2
HER2 GRB7 HER2
18
Recurrence Score Assay vs. Guidelines as Applied
to NSABP B-14Paik S et al, San Antonio 2004,
abstract 104
19
Overall Goal
To determine whether the Oncotype DX test is
prognostic in the tamoxifen and anastrozole arms
of ATAC
NB (i) aromatase inhibitor treated group
(ii) more contemporary population (iii)
all postmenopausal (iv) UK population
Dowsett et al., SABCS 2008, Abstract 53
20
ATAC Anastrozole, Tamoxifen, Alone or in
Combination
RANDOM IZE
Anastrozole
9366 postmenopausal patients with breast cancer
following local treatment (N9366) 84 HR
Tamoxifen
Anastrozole tamoxifen
Primary end point DFS, defined as time to
earliest occurrence of local or distant
recurrence, new primary contralateral breast
cancer, or death from any cause
HR hormone receptorpositive DFS
disease-free survival. Update of Howell et al.
Breast Cancer Res Treat. 200488(suppl 1)S7.
Abstract 1. Howell et al. Lancet. 200536560.
21
Primary Analysis

• Is there a significant relationship between
• the rate of DISTANT recurrence (TTDR DRFI) and
  the Recurrence Score (RS)
• in N-, HR, no chemotherapy patients from
  tamoxifen and anastrozole arms?

ATAC
Tamoxifen Arm
RS
HR Breast Cancer No Adjuvant Chemotherapy
Anastrozole Arm
RS
Tamoxifen Anastrozole Arm
Not examined
Dowsett et al., SABCS 2008, Abstract 53
22
Time to Distant Recurrence in ATACHR patients,
100 month median follow-up
ATAC trialists, Lancet Oncology 2008
23
Results TTDR by Recurrence Score Group Node
Negative, Both Treatment Arms
n872
Dowsett et al., SABCS 2008, Abstract 53
24
Results TTDR by Recurrence Score Group Node
Positive, Both Treatment Arms
n306
Dowsett et al., SABCS 2008, Abstract 53
25
Results For Any Recurrence Score the Rate of
Distant Recurrence Increases with the Number of
Positive Nodes
100
4 Positive Nodes
90
80
70
60
9-Years Risk of Distant Recurrence ()
50
1-3 Positive Nodes
40
Node Negative
30
20
10
0
0
5
10
15
20
25
30
35
40
45
50
Recurrence Score
Dowsett et al., SABCS 2008, Abstract 53
26
Results Percent with Distant Recurrence at 9
Years Node Negative
of events
20
All Patients, Low RS (n513)
24
All Patients, Int. RS (n229)
28
All Patients, High RS (n130)
72
All Patients (n872)
8
Tamoxifen, Low RS (n245)
12
Tamoxifen, Int. RS (n117)
21
Tamoxifen, High RS (n70)
41
All Tamoxifen (n432)
12
Anastrozole, Low RS (n268)
12
Anastrozole, Int. RS (n112)
7
Anastrozole, High RS (n60)
31
All Anastrozole (n440)
0
10
20
30
40
50
60
70
Dowsett et al., SABCS 2008, Abstract 53
Percent with Distant Recurrence at 9 Years
27
Results Recurrence Score vs. Adjuvant! Online
Correlation

• RS and Adjuvant! Online each
• - Highly significant
• Independent
• In both node negative (shown in table) and node
  positive patients
• Similar results for mortality

• RS and Adjuvant! correlate weakly (Spearman
  R0.234)

Predicted rate of distant recurrence at 10 yrs
from RS Predicted rate of relapse at 10 yrs
from Adjuvant!
Dowsett et al., SABCS 2008, Abstract 53
28
Phase III SWOG 8814 (TBCI 0100) Postmenopausal,
N, ER

• RANDOMIZE

n 1477
tamoxifen x 5 yrs
CAF x 6, then tamoxifen
CAF x 6, with concurrent tam
(n 361)
(n 566)
(n 550)
Superior Disease-Free Survival (DFS) and Overall
Survival (OS) over 10 Years
Albain, SABCS 2007, Abstract 10Albain, et al.
Breast Cancer Res Treat 2005
29
SWOG 8814/TBCI 0100 21-Gene Recurrence Score is
Prognostic for DFS and OS in Tamoxifen Arm
10-yr 60, 49, 43
10-yr 77, 68, 51
Albain, SABCS 2007, Abstract 10
30
Albain, SABCS 2007, Abstract 10
31
CAF Benefit Greatest in Higher RS for Both Nodal
Subsets, with No Benefit in Lower RS
Albain, SABCS 2007, Abstract 10
32
Taylor Ex
33
Schema TAILORx
Node-Neg, ER-Pos Breast Cancer
Register Specimen banking
Oncotype DX Assay
RS 11-25 Randomize Hormone Rx vs Chemotherapy
Hormone Rx
RS lt10 Hormone Therapy Registry
RS gt25 Chemotherapy Hormone Rx
Primary study group
34
Physicians of the future
Chemotherapy? What is this, the dark ages?
paraphasing Bones McCoy, Star Trek IV The
Voyage Home
35
Targeted Therapy

• Exploit specific characteristics of the tumor
• Define a specific molecular or biologic process
  that is crucial to the tumor
• Establish a therapy that specifically targets
  that critical process or pathway
• Validate the therapy in clinical trials

36
Ideal Target
DNA
RNA
Blood Vessels (angiogenesis)
PROTEIN
Estrogen receptor Her2/neu receptor
Epidermal Growth Factor receptor
37
Recurrence Hazard Rates for Breast Cancer After
Primary Therapy
0.3
0.2
Recurrence hazard rate
0.1
0
0
1
2
3
4
5
6
7
8
9
10
11
12
Years
Number at risk
3585 3226 2786 2443 2188 1972 1739 1426 1085 801
527 328
Saphner et al. J Clin Oncol. 1996142738.
38
NSABP B-14No Benefit of Extending Tamoxifen
5 y Tam 10 y Tam (N593) (N579) P Value
Disease-free
survival 82 78 0.03 Overall survival 94 91 0.
07
Standard of Care is to stop Tamoxifen after 5
years of therapy
Fisher et al. J Natl Cancer Inst. 200193684.
39
Study Design JMA.17 Trial
5187 Postmenopausal women who had received
previous tamoxifen therapy lasting 4.5 6 years
Localized breast cancer (no evidence of
metastatic disease) Estrogen and/or progesterone
receptor positive
Letrozole x 5 years
Placebo
40
MA17 Switching to letrozole after tamoxifen
therapy DFS by treatment duration
NNT Number needed to treat
Adapted from Goss et al, Proc ASCO 2004 A6044
41
Why switch therapy?

• Many patients relapse within the first 5 years
  of diagnosis
• Resistance can occur as early as 12 to 18 months
  after starting tamoxifen
• tamoxifen may act as an agonist
• Serious side-effects of tamoxifen
• endometrial cancer TE
• Benefit to bone mineral density
• tamoxifen increases BMD
• pre-treatment might lessen osteopenia caused by
  AIs

42
BIG 1-98 Trial Design
R A N D O M I Z E
Tamoxifen
A
n2459
Letrozole
B
n2463
8010 pts
Tamoxifen
Letrozole
C
n1548
Letrozole
Tamoxifen
D
n1540
Years
0
2
5

• 8028 randomized (18 withdrew consent)
• Primary core analysis (circles) compares
  tamoxifen vs letrozole monotherapy, including
  arms C D prior to the switch at 2 years
• Median follow-up 25.8 months (n4007 tamoxifen
  n4003 letrozole)

Update of Thürlimann et al. J Clin Oncol.
200523(16S)6S. Abstract 511. Thürlimann et
al. N Engl J Med. 20053532747.
43
BIG 1-98 Sequential Treatment Disease-Free
Survival
44
Sequential Treatment ComparisonsMedian Follow-up
71 months
Tam?Let vs. Let
Let?Tam vs. Let
45
Breast Cancer EventsTam?Let vs. Let
Overall
By Nodal Status
42 of the population is node positive 58 node
negative
46
Breast Cancer EventsLet?Tam vs. Let
Overall
By Nodal Status
42 of the population is node positive 58 node
negative
47
Conclusions

• Updated results of BIG 1-98 suggest superior
  overall survival with letrozole compared with
  tamoxifen
• Adjuvant endocrine therapy should start with
  letrozole especially for patients at higher risk
  for early recurrence
• Patients commenced on letrozole can be switched
  after 2 years to tamoxifen.
• Improved therapeutic approaches beyond five years
  are required to control late relapses

48
Targeting Angiogenesis in Cancer

• Starve the tumor
• Block pathway for metastases
• Improve or normalize blood flow ? increase
  delivery of chemotherapy agents
• Target is a normal endothelial cell
• no genetic instability
• Fewer pathways of resistance

49
Primary Role of Vascular Endothelial Cell Growth
Factor (VEGF) in Tumor Induced Angiogenesis

• Most tumors produce VEGF
• Find VEGF associated with areas of angiogenesis
  in tumors
• Tumor blood vessels express VEGF receptors
• Increased VEGF levels in blood and urine of
  cancer patients
• Hypoxia increases VEGF
• Inhibitors of VEGF protein or VEGF receptors
  inhibit tumor growth in animal models

50
Agents Targeting the VEGF Pathway
Anti-VEGF antibodies (bevacizumab)
Soluble VEGFRs (VEGF-TRAP)
VEGF
Anti-VEGFR antibodies (IMC-1121b)
VEGFR-1
VEGFR-2
Endothelial cell
Small-moleculeVEGFR inhibitors (PTK787,
SU11248, ZD6474, BAY 43-9006)
Podar and Anderson. Blood. 20051051383
51
Bevacizumab (Avastin)Recombinant Humanized
Monoclonal Antibody to VEGF-A
FDA-approved for therapy of metastatic
colorectal, renal cell, lung and most recently
breast cancer in combination with chemotherapy
52
E2100 Study Design

• Stratify
• DFI lt 24 mos. vs. gt 24 mos.
• lt 3 vs. gt 3 metastatic sites
• Adjuvant chemotherapy yes vs. no
• ER vs. ER- vs. ER unknown

RANDOMI ZE
Paclitaxel Bevacizumab (N 350)
Paclitaxel (N 332)
28-day cycle Paclitaxel 90 mg/m2 D1, 8 and
15 Bevacizumab 10 mg/kg D1 and 15
Miller K et al, SABCS 2005 A 3
53
Response
34.3
28.2
16.4
14.2
236
250
316
330
Miller K et al, SABCS 2005 Abstract 3
54
Progression Free Survival
HR 0.51 (0.43-0.62) Log Rank Test plt0.0001
484 events reported
Miller K et al, SABCS 2005 Abstract 3
55
Overall Survival
1.0
0.8
0.6
Survival Probability
0.4
HR 0.84 (0.64-1.05) Log Rank Test p0.12
0.2
0.0
0
6
12
18
24
30
36
Months
275 events reported
Miller K et al, SABCS 2005 Abstract 3
56
Miller K et al. NEJM 2007
57
E2100Paclitaxel Versus Paclitaxel/Bevacizumab
plt.0001 p.02 p.002 p.05
Miller K et al, SABCS 2005 Abstract 3
58
Phase III AVADO Study Docetaxel Bevacizumab
for Locally Recurrent or Metastatic Breast Cancer
Docetaxel 100 mg/m2 Placebo q 3 weeks

• Eligibility criteria
• HER2 disease
• First-line treatment
• Locally recurrent or metastatic breast cancer
• Stratify by
• Region
• Prior taxane
• Time to relapse since adjuvant chemotherapy
• Measurable disease
• Hormone receptor status

Docetaxel 100 mg/m2 Bevacizumab 7.5 mg/kg q 3
weeks
Docetaxel 100 mg/m2 Bevacizumab 15 mg/kg q 3 weeks
(n 705)
Patients were allowed to cross over to
bevacizumab following disease progression
Primary endpoint Progression-free
survival Secondary endpoints Overall response
rate, duration of response, time to treatment
failure, overall survival, quality of life
Miles, ASCO 2008, abstract LBA1011.
59
AVADO Results
Median F/U 10.2 mos (range 0 -18mo)? most
benefit in pts who had received prior adjuvant
therapy
Ref Miles et al. LBA 1011 ASCO 2008
60
AVADO PFS subgroup analysis(ITT population)
Favors bevacizumab
Favors placebo
0.25 0.5 1 2 4
mg/kg q3w
Miles, ASCO 2008, abstract LBA1011
61
Insights from MBC Trials

• Choice of chemotherapy may be important
• Drug specific synergy
• What is a clinically meaningful improvement in
  PFS?
• 350,000/YOL
• Improved efficacy in patients previously treated
  with chemotherapy?
• Relative resistance to prior chemotherapy
  obviated by normalization of vessels
• Agents do have significant toxicities
• Dose response not observed

We dont know how to use these agents effectively
62
Predictive Biomarkers

• Identify responsive patients
• Optimize dose/schedule of agents
• Determine therapeutic efficacy
• Identify when to discontinue therapy
• Particularly important as we move these agents
  into the adjuvant and neoadjuvant setting

63
Superior median overall survival was seen for
patients in E2100 who experienced grade 3 or 4
hypertension or no hypertension
Schneider, B. P. et al. J Clin Oncol
264672-4678 2008
64
Osteoclast-Targeting Agents in Breast Cancer
Bisphosphonates
65
All AIs Increase Fracture Risk
IES2 (58 months)
BIG 1-983 (26 months)
MA.174 (30 months)
AI Aromatase inhibitor. 1. Howell A, et al.
Lancet. 200536560-62 2. Coleman RE, et al.
Lancet Oncol. 20078119-127 3. Thurlimann B, et
al. N Engl J Med. 20053532747-2757 4. Goss
PE, et al. J Natl Cancer Inst. 2005971262-1271.
66
BMD Loss With Cancer Therapies
Normal men1
Late menopausal women1
Early menopausal women1
Aromatase inhibitor (AI) therapy 2
Bone marrow transplant3
Cancer treatment induced bone loss
Androgen deprivation therapy4
AI therapy plus gonadotropin-releasing hormone
agonist 5
Ovarian failure secondary to chemotherapy6
1. Kanis JA. Osteoporosis. Blackwell Healthcare
Communications Ltd199722-55. 2. Eastell R et
al. J Bone Miner Res. 200217(suppl 1)S165. 3.
Lee WY et al. J Clin Endocrinol Metab.
200287329-335. 4. Maillefert JF et al. J Urol.
19991611219-1222. 5. Gnant M. San Antonio
Breast Cancer Symposium, 2002. 6. Shapiro CL et
al. J Clin Oncol. 2001193306-3311.
67
Bisphosphonates

• Potent inhibitors of bone resorption
• Analogs of endogenous pyrophosphate
• Strongly bind to hydroxyapatite on bone surface
• Differences in side chains produce differences in
  anti-resorptive potency and toxicities
• Main effects are on osteoclasts
• Direct apoptotic effect, inhibit differentiation
  and maturation
• Also exert influences on macrophages,
  osteoblasts, tumor cells

68
Bisphosphonates

• Proven efficacy in treatment of osteoporosis,
  diseases with accelerated bone resorption
• Roles of bisphosphonates in cancer
• Treatment of hypercalcemia
• Treatment of bone metastases
• Reduction in skeletal-related events
• Improvement in pain, QOL
• Preservation of bone mineral density
• Prevention of metastases?

69
Z/ZO-FAST Design
IMMEDIATE
EligibilityER/PgR early breast
cancerPostmenopausal T score 2
Stratification Adjuvant CT T score Established
vs recent postmenopausal
Letrozole 2.5 mg/d
R A N D O M I Z E
Zoledronic acid 4 mg IV q6mo
DELAYED
Letrozole 2.5 mg/d
Add zoledronic acid ifBMD T score below ?2 or
clinical or asymptomatic fracture at 36 months
5 years

• 1065 pts in 128 centers in Asia Pacific, Central
  and South America, Egypt, and Europe in ZO-FAST

602 randomized pts in Z-FAST (US)
70
ZO-FAST Update-36 mo F/U
HR 0.588, p.03
SABCS 2008, Ab 44
71
ABCSG-12 Trial of Endocrine Therapy With or
Without Zoledronic Acid Study Design
Tamoxifen 20 mg/day

• Eligibility criteria
• Premenopausal
• Stage I/II breast cancer
• lt 10 positive nodes
• ER and/or PgR disease
• No adjuvant chemotherapy

(n 452)
RANDOMI ZE
Tamoxifen 20 mg/day Zoledronic acid 4 mg q 6
months
(n 449)
Anastrozole 1 mg/day
Surgery plus radiation therapy
Goserelin 3.6 mg q 28 days
(n 450)
(n 1803)
Anastrozole 1 mg/day Zoledronic acid 4 mg q 6
months

• Primary Disease-free survival
• Secondary Recurrence-free survival, overall
  survival, safety
• Exploratory Bone metastasisfree survival
• Median follow-up 60 months

(n 449)
Gnant et al. ASCO 2008 abstract LBA4.
72
ABCSG-12 Bone Substudy 2007 Change From Baseline
in Lumbar Spine BMD
No Zoledronic Acid
Zoledronic Acid
Tamoxifen
Tamoxifen
Anastrozole
Anastrozole
6
4
2
0
-2
Percent Change BMD From Baseline in g/cm2
-4
-4.5
-6
-8
-7.8
-10
-9.0
P.003
-12
Plt.0001
-14
-13.6
Plt.0001
Adapted with permission from Gnant M et al.
Presented at SABCS 2007.
73
Primary Endpoint Disease-Free SurvivalABCSG-12
36 reduction in recurrences with addition of
Zoledronic acid
Number at risk
904
838
735
565
441
265
161
60
No ZOL
899
851
744
573
434
270
131
59
ZOL
Gnant et al. ASCO 2008 abstract LBA4.
74
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75
Mechanism of Metastases in Breast Cancer

• Tumor cell dormancy
• Bone may serve as a reservoir for malignant cells
  early in the metastatic process
• Tumor cell seeding
• Circulating cells have affinity for bone
  chemotactic responses to areas of bone resorption
  (Orr FW et al, Science 203, 1979)
• Metastatic growth
• Interaction between tumor cells and bone
  microenvironment contributes to tumor cell growth
  and development of metastases

76
SWOG 0307 Study Design
RANDOMIZE
Zoledronic acid 4 mg IV monthly for 6 mo then Q
3 mo for 30 mo
Clodronate 1600 mg orally QD x 36 mos
Ibandronate 50 mg orally QD x 36 mos
111
Treatment x 3 yrs Follow-up x 7 yrs 10 yrs
total
Patient Population N4500 BrCa stage
I/II/IIIa f/u 6 mo for recurrence
then Q yr Std adj systemic therapy X 10 yr for
survival
77
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78
Study Design International, Randomized,
Double-Blind, Active-Controlled Study
Denosumab 120 mg SC and Placebo IV every 4
weeks (N 1026)

• Key Inclusion
• Adults with advanced breast cancer and confirmed
  bone metastases
• Key Exclusion
• Current or prior intravenous bisphosphonate
  administration

Supplemental Calcium and Vitamin D
Zoledronic acid 4 mg IV and SC
placebo every 4 weeks (N 1020)
IV product dose adjusted for baseline creatinine
clearance and subsequent dose intervals
determined by serum creatinine (per Zometa label)
79
Time to First On-Study SRE
HR 0.82 (95 CI 0.71, 0.95)P 0.01
(Superiority)
1.00
0.75
Proportion of Subjects Without SRE
0.50
KM Estimate ofMedian Months
0.25
Denosumab
Not reached
Zoledronic acid
26.5
0
0
3
6
9
12
15
18
21
24
27
30
Months
Subjects at risk
Adjusted for multiplicity
80
Bone Modulation in Cancer Patients-reduction in
SREs-improvement in pain and QOL
Potential Roles of Osteoclast-Targeting Agents in
Cancer
Preventing metastases?
Preserving bonemineral density
Agent/Schedule/Dose?
81
The Future in Breast Cancer

• Treat only those who need treatment ? spare the
  other 70
• Treat with targeted therapies whenever possible?
  higher efficacy and lower toxicity
• Limit surgery and radiation whenever possible to
  avoid lymphedema/arm disabilities
• Better screening with breast MRI, digital
  mammograms
• Screen for osteoporosis, lipids, cardiac risk
  factors (long-term toxicities of therapy)
• Maintain ideal body weight

82
Trends in 5 year Breast Cancer Survival by Year
of Diagnosis
74 76
83 85
92 97
83
Personalized Medicine?
84
Thank you for your attention