Transcript Breast Cancer Survivorship

Treatment, Survivorship and
the Breast Cancer Patient
Michelle Melisko, MD and Hope Rugo, MD
UCSF Helen Diller Family Comprehensive
Cancer Center
Breast Cancer Mortality in US
and UK
WHO Mortality and UN Population Estimates
Breast Cancer Incidence by Age
Ravdin P, et al: N Engl J Med 2007
Breast Cancer Incidence by ER-Status
Ravdin P, et al: N Engl J Med 2007
Progress in the Treatment of
Breast Cancer
• What do we know?
– New chemotherapy regimens, new schedules have resulted in
incremental benefits in DFS and OS
•
•
•
•
Addition of taxanes to anthracycline based regimens
Dose dense better than every three week, but only for paclitaxel?
Longer therapy is better than shorter?
Unclear what the addition of yet more chemotherapy agents will
provide
– Biologic subset may be critical
• Non chemotherapy agents to alter milieu
• The role of DNA repair, instrinsic subtypes, race…..
– New hormone agents have improved outcome in ER+ disease
• We have no idea who benefits the most
– Biologic subtypes are the key to selecting appropriate therapy
• We are better at defining the population who benefit more or less, than
we are at finding ways to circumvent resistance
Cancer Survivors 2009 (U.S.)
Jemal et al. CA Cancer J Clin 2009; 59:225
High Rates of Long-term Survival
Among Breast Cancer Survivors
There are an estimated 2.5 million breast cancer survivors in
the United States
Patients Alive (%)
100
90
81
80
74
60
40
20
0
5
10
15
Years After Diagnosis
Horner MJ et al (eds). National Cancer Institute. http://seer.cancer.gov/csr/1975_2006. Accessed July 21, 2009.
US Cancer Prevalence: 10 Million+
Approximately one-fourth are breast cancer survivors
22%
17%
Female breast
Prostate
Colorectal cancer
3%
Gynecologic
6%
Other genitourinary
Hematologic
8%
19%
6%
Melanoma
Lung
9%
10%
Surveillance Epidemiology and End Results (SEER) Program (www.seer.cancer.gov). Prevalence
database: US Estimated Complete Prevalence Counts on 1/1/2004. NCI, DCCPS, released
April 2007, based on the November 2006 SEER data submission.
Other
No Clear Agreement Among Health Care
Professionals (HCPs) on a Survivorship Definition
How do you define a cancer survivor? (n=144)
Following the completion
of active treatment
2.1% Not sure
7.6%
From diagnosis to the
point of recurrence 11.1%
37.5%
From the moment of
diagnosis and for the 38.9%
balance of life
2.8%
Disease-free
after 5 years
Disease-free after
2 to 3 years
Breast Cancer Survivorship Alliance. Health Care Professional Survey: Assessment of Survivorship Awareness and
Educational Needs. Conducted at: 30th Annual San Antonio Breast Cancer Symposium; December 13-17, 2007; San
Antonio, TX.
The Definition of a Cancer Survivor
(National Coalition for Cancer Survivorship1
“A ‘Cancer Survivor’ is defined by the
National Coalition for Cancer Survivorship
as anyone with a history of cancer, from
the time of diagnosis and for the
remainder of life, whether that is days or
decades.”2
1. Rowland JH et al. J Clin Oncol. 2006;24:5101-5104. 2. Clark EJ. You have the right
to be hopeful. 2004.
http://www.canceradvocacy.org/resources/publications/hopeful.pdf.
Challenges of Cancer Survivorship
• Survivors are at risk for a wide range of late
physical effects of their primary treatment
• Compared with matched controls, cancer
survivors have a substantially increased burden
of illness:
– Days lost from work, inability to work
– General health perception
– Need for help with daily activities
Ganz PA. J Clin Oncol. 2006;24:5105-5111. American Society of Clinical Oncology. Cancer Advances Information
From the Experts: Cancer Survivorship – Increasing Survival, Improving Lives. December 2004.
Three Seasons of Survivorship
Acute
Diagnosis
Selection of
treatment
Fear and anxiety
Confrontation with
mortality
Mullan F. N Engl J Med. 1985;313:270-273.
Extended
Permanent
Disease
stabilization
Surveillance
Remission
Consolidation of
therapies
Late side effects of
therapy
Recurrence anxiety
Long-term risks
Thoughts of
returning to normal
CANADA
• 968 early-stage breast cancer patients
who had completed adjuvant treatment
were randomized to follow up in a cancer
center or with their own family physician
– No differences in number of recurrences,
deaths, recurrence related serious clinical
events
– No difference in patient reported healthrelated quality of life
Grunfeld E, Levine MN, Julian JA, et al. Randomized trial of long-term followup for early-stage breast cancer: a comparison of family physician versus
specialist care. J Clin Oncol 2006;24(6):848-55.
ASCO Treatment Plan and Summary
 Name, age, contact information
 Breast cancer diagnosis
 Surgery (type/dates)
 Patient history, including comorbid conditions
 Adjuvant chemotherapy/radiation therapy (planned
and received)
– Details on agents/doses prescribed (dates
initiated/completed)
– Toxicities (anticipated, experienced)
 Overview of page 2 (not shown)
– Hormonal therapy (agent, duration, date to be
initiated)
– Trastuzumab (dates, ejection fraction)
– Provider contacts (including referrals)
– Pre- and posttreatment comments (eg, baseline
assessments, patient counseling, follow-up
recommendations)
Reproduced with permission from the American Society of Clinical Oncology.
Breast Cancer Adjuvant Treatment Plan and Summary. http://www.asco.org/ASCOv2/Practice+%26+Guidelines/
Quality+Care/Quality+Measurement+%26+Improvement/Chemotherapy+Treatment+Plan+and+Summary. Accessed
June 10, 2009.
ASCO Survivorship Care Plan
N/A=not applicable. Breast Cancer Survivorship Care Plan. v1.0 09/07.
http://www.asco.org/ASCO/Downloads/Cancer%20Policy%20and%20
Clinical%20Affairs/Quality%20of%20Care/
Breast%20Cancer%20Survivorship%20Plan%209.07.doc. Accessed
May 27, 2009.
Follow-Up Care
Providers to Contact
Medical history and physical
examination
• First 5 years
• Year 6+
Posttreatment
mammography
• First 5 years
• Year 6+
Breast self-examination
• N/A
Pelvic examination
Ob/gyn
Coordination of care
• First 5 years
• Year 6+
Genetic counseling
If indicated, based on risk
factors
Follow-Up Care
Visit Frequency
Medical history and physical
examination
• Years 1 to 3: every 3 or 6
months (including key notes for
1st-year visits)
• Years 4 to 5: every 6 or 12
months
Mammography
• Every 6 or 12 months as
indicated
Notes
• May include any relevant
patient notes and/or
recommendations
Essential Components
of Survivorship Care
Recurrence, new
cancers, late effects
Treating the consequences
of cancer and its
treatments
Hewitt M, et al. eds. From Cancer Patient to Cancer Survivor: Lost in Transition.
Washington DC; The National Academies Press; 2005.
Recurrence, second cancers,
and assessing medical and
psychosocial late effects
Interdisciplinary
coordination between
PCPs and specialists
56 year old postmenopausal woman is
diagnosed with a Stage I estrogen receptor
positive HER2 negative breast cancer. She
is treated with a lumpectomy, SLND, and
radiation to the breast. She has recently
started on an aromatase inhibitor.
She comes to see her primary care MD for
routine health care and is extremely
worried about breast cancer recurrence.
She wants to have lab tests and scans to
“make sure her cancer hasn’t come back”.
What are the chances that this
patient will die of breast cancer
in the next 10 years?
1. < 5%
2. 10-20%
3. 20-40%
Should you order any lab tests or
scans to follow up on her cancer?
Breast Cancer Follow Up:
What to do and What NOT to do
• American Society of Clinical Oncology 2006 Update
of the Breast Cancer Follow-Up and Management
Guidelines in the Adjuvant Setting (JCO Nov 1 2006:
5091-5097)
– Routine labs, CT scans, bone scans are not
necessary or indicated
• American Society of Clinical Oncology 2007 Update
of Recommendations for the Use of Tumor Markers
in Breast (JCO Nov 20 2007: 5287-5312)
– TUMOR MARKERS ARE NOT RECOMMENDED
Breast Imaging Recommendations
• NCCN, ACSO, and ACS guidelines recommend follow up
mammograms every 6-12 months for affected breast in the
setting of breast conserving surgery
• Breast MRI only indicated for the following:
– Pts with equivocal mammographic and/or PE findings
– Pts presenting with malignant axillary adenopathy and unknown site of
primary tumor
– Patient with extensive or locally advanced cancer undergoing
chemotherapy
– Screening of women at increased ( 20% to 25%) lifetime risk
• Known BRCA1 or BRCA2 gene mutation carrier
• Pt with first-degree relative with a BRCA1 or BRCA2 gene mutation who
has not had genetic testing themself
• Radiation therapy to the chest between the ages of 10-30 yo
• Genetic disease such as Li-Fraumeni or Cowden syndrome or one of
these syndromes in first-degree relatives
Orel S, JCO Feb 2008
Symptom/Side-Effect Management
Spectrum of Potential Side Effects
Depression
Weight gain
Cardiovascular effects
Hot flashes/night sweats
Cognitive
dysfunction
Early breast cancer
treatments including:
Radiation therapy
Chemotherapy
Monoclonal antibody
Hormonal therapy
Chronic fatigue
Genitourinary symptoms
Sexual dysfunction
Other 2nd-malignancy
(ie, endometrial cancer)
Hayes DF. N Engl J Med. 2007;356:2505-2513.
Arthralgia/joint symptoms
Osteoporosis/
bone fractures
Tamoxifen
• Tamoxifen has been shown to decrease disease
recurrence and increase overall survival
• Remains the standard of care for pre-menopausal
breast cancer patients
• CYP2D6 pharmacogenetics varies and results in
different levels of therapeutic efficacy
– Certain antidepressants should be avoided in patients
on tamoxifen
• Tamoxifen use has been associated with
endometrial cancer and thromboembolism
EBCTG. Lancet. 1998;351:1451-1467 (A); Johnston et al. Nat Rev Cancer. 2003;3:821-831(B);
Knox et al. Presented at: American Society of Clinical Oncology Annual Meeting; June 2-6,
2006; Atlanta, Ga (A).
Thrombotic Effects of
Breast Cancer Treatment
• Tamoxifen increases the risk of thromboembolic events
and cerebrovascular disease by approximately
threefold1,2
• Increased risk in women with additional risk factors1,2
• A meta-analysis indicated a 29% increase in risk of
stroke in women randomized to tamoxifen vs placebo or
other therapies3
• Concurrent combination of chemotherapy and tamoxifen
has been associated with a further increased risk of
thromboembolism4
1. Hayes DF. N Engl J Med. 2007;356:2505-2513. 2. Mrozek MD, Shapiro CL. Clin Adv Hematol Oncol.
2005;3:211-222. 3. Bushnell CD, Goldstein LB. Neurology. 2004;63:1230-1233. 4. Pritchard KI, et al. J Clin Oncol.
1996;14:2731-2737.
Aromatase Inhibitors
• AIs have been shown to decrease disease
recurrence compared with tamoxifen
• Several regimens have been shown to be
more effective than 5 yrs of tamoxifen alone
– 5 yrs of adjuvant AI therapy
– 2 to 3 yrs of tamoxifen, followed by 2 to 3 yrs of
an AI
– 5 yrs of tamoxifen, followed by 5 yrs of AI
Winer et al. J Clin Oncol. 2005;23:619-629 (A).
Your breast cancer patient comes in to see
you three months later and is complaining of
pain in her right hip and also stiffness in her
hands. She says she has tried
acetominophen without relief. What should
you do?
1. Reassure patient that joint pains are a
common side effect of the aromatase
inhibitors.
2. Order plain films of her hands and/or hip
3. Order a bone scan
4. Suggest she try NSAIDS and exercise
Musculoskeletal Events:
Bone Health
• During treatment, aromatase inhibitors (AIs):
– Reduce estrogen
– Are associated with a decline in BMD and an increased risk of
fracture
– Exacerbate the normal progressive loss of BMD in
postmenopausal women
• In contrast, tamoxifen may preserve BMD
• Osteoporosis/increased fracture risk are serious health issues for
breast cancer survivors
• Patients with osteopenia/osteoporosis prior to initiation of AI
therapy may be at the greatest risk
BMD=bone mineral density.
Chien AJ, Goss PE. J Clin Oncol. 2006;24:5305-5312; Gralow JR. J Clin Oncol. 25:1-4; Hilner BE et al. J Clin Oncol. 2003;21:4042-4057; Grey AB, et al.
Am J Med. 1995;99:636-641; Marttunen MB, et al. J Clin Endocrinol Metab. 1998;83:1158-1162; Eastell R, et al. J Clin Oncol. 2008;26:1051-1058.
Aromatase Inhibitors and Bone
Loss – What can be done?
• IV bisphosphonates may decrease AI-associated
bone loss
– Z-FAST study evaluated 36-month safety and
efficacy of upfront vs delayed IV ZA in
decreasing AI-associated bone loss in
postmenopausal women with early breast cancer
Brufsky A, et al. SABCS 2007. Abstract 27.
Monitoring of bone density while
on an aromatase inhibitor
• Most patients should have a bone density tested within one year of
starting an AI
• Recommend patients with normal BMD at baseline to take calcium,
vit D, and pursue weight bearing exercise
• Patients with osteopenia should have BMD rechecked one year later
to assess change
• Patients with osteoporosis at baseline or during follow up should
consider bisphosphonate therapy
• Osteoporosis is not a contraindication to taking
an aromatase inhibitor
Musculoskeletal Events:
Joint Symptoms
• AIs are associated with significantly higher rates
of joint symptoms/arthralgias vs tamoxifen1
– Typical onset within 2 months of treatment
initiation1
– Symptoms may resolve over time2
– The true etiology and the optimal treatment is
not known1
1. Burstein HJ. Breast. 2007;16:223-234. 2. Buzdar AU, for the ATAC Trialists’ Group. Presented at: 42nd Annual Meeting of the American
Society of Clinical Oncology; June 2-6, 2006; Atlanta, GA. Abstract 551.
ATAC Substudy: Risk Factors
for Developing Joint Symptoms
Risk Factor
Joint Symptoms, n
(%)
Multivariate OR (95%
P Value
CI)
Anastrozole
1040 (37.2)
1.31 (1.16-1.47)
< .001
Previous HRT
840 (42.3)
1.52 (1.35-1.72)
< .001
Chemotherapy
485 (38.9)
1.20 (1.04-1.38)
.01
HR negative
130 (27.7)
0.76 (0.61-0.85)
.02
• UK
563 (30.2)
1.19 (1.01-1.37)
.04
• North America
803 (47.7)
2.1 (1.81-2.43)
< .001
BMI > 30 kg/m2 (vs <
25)
555 (39.3)
1.36 (1.17-1.57)
< .001
Region of origin
(vs rest of world)
•
Use of previous HRT led to greater difference in joint symptoms between
patients on anastrozole vs tamoxifen
Sestak I, et al. SABCS 2007. Abstract 2071.
Estrogen Deprivation:
Vasomotor Symptoms
• Chemotherapy can induce ovarian failure
• Hormone therapy can exacerbate vasomotor
symptoms
• Hot flashes and sleep disturbances are common
• May lead to additional physical and psychosocial
symptoms including mood lability
1. Hayes DF. N Engl J Med. 2007;356:2505-2513; 2. Barton DL, et al. Supportive Cancer Therapy. 2006;3:91-7. 3. Mrozek MD, Shapiro CL.
Clin Adv Hematol Oncol. 2005;3:211-222.
Mean Hot Flash Score Reduction
Randomized Studies
100
% Reduction (Mean)
Black Cohosh (n=58)
Placebo (n=420)
Soy (n=78)
Vitamin E (n=53)
Clonidine (n=75)
Fluoxetine (n=36)
80
60
Ven (vs MPA) (n=94)
Venlafaxine (n=48)
40
MPA 400 mg (n=94)
20
Megestrol (n=74)
0
0
1
2
3
Week
4
5
6
Hot Flash Severity
Change from baseline
in hot flash severity
0
-2
-4
-6
Placebo
-8
Gabapentin 300 mg
-10
Gabapentin 900 mg
-12
-14
Baseline
Week 4
Week 8
Pandya KJ et al. Lancet 2005;366:818–824.
Estrogen Deprivation:
Sexual Dysfunction Symptoms
• 40% to 100% of cancer survivors report some form of sexual
dysfunction (ie, vaginal dryness, painful intercourse)1
• Multiple dimensions2:
– Psychological/body image
– Hormonal treatment effects
• After primary treatment with mastectomy and chemotherapy3:
– 34% of women lacked sexual interest
– ~25% of women report difficulty with arousal, orgasm, or
lubrication
1. Krychman ML, et al. Oncology. 2006;71:18-25. 2. Hayes DF. N Engl J Med. 2007;356:2505-2513. 3. Ganz PA,
et al. J Natl Cancer Inst. 2004;96:376-387. 4. Ganz PA. J Clin Oncol. 2006;24:5105-5111.
Vaginal Dryness
• Non-estrogenic vaginal lubricants
• Vaginal estrogens (Cream or ESTRING)
• Pilocarpine
• Vaginal Testosterone Cream
“Vaginal estradiol appears to be
contraindicated in postmenopausal women
on adjuvant aromatase inhibitors”
• Serum estradiol, FSH, and LH levels were followed in 7 postmenopausal
women using vaginal estrogen preparations while on AIs for breast
cancer
– Serum was analysed for estradiol, FSH and LH at baseline then 2, 4, 7-10
and 12 weeks since commencement of vaginal estradiol
– Estradiol was measured on an assay specifically developed for measuring
low levels in postmenopausal women
• Serum estradiol levels rose from baseline levels < or = 5 pmol/l
consistent with AI therapy to a mean 72 pmol/l at 2 weeks
• By 4 weeks this had decreased to < 35 pmol/l in the majority (median 16
pmol/l) although significant further rises were seen in two women
• Vagifem significantly raised estradiol levels, at least in the short term
“This reverses the estradiol suppression achieved by aromatase inhibitors in
women with breast cancer and is contraindicated”
Kendall et al, Annals Oncol 2006
Transdermal Testosterone in Female Cancer
Survivors with Decreased Libido –
NCCTG N02C3
4 weeks
4 weeks
Testosterone*
10 mg/day
Placebo**
Placebo**
Testosterone*
10 mg/day
R
*In Vanicream
** Vanicream
JCO 24:469S, 2006 ASCO abstract #8507
Libido Change from Baseline
9
8
7
6
5
placebo
testosterone
4
3
2
1
0
1st Period
2nd Period
P=0.58
P=0.71
Mean Change from baseline:
Free testosterone concentrations
2
T
e
s
t
1
o
s
t
e ng/dl
0
r
o
n
e
-1
placebo
testosterone
P<.0001
1st
period
2nd
Period
(Norms: 0.3-1.9 ng/dl)
UCSF Trial - A Phase II Study of Vaginal
Testosterone Cream vs. the ESTRING for
Vaginal Dryness or Decreased Libido in Early
Breast Cancer Patients Treated with AIs
• Objectives:
– To evaluate the safety, based on serial estradiol
levels, of intravaginal testosterone cream or the
ESTRING administered for relief of vaginal dryness
and/or decreased libido related to AI therapy in early
breast cancer patients
– To document the systemic estradiol and testosterone
levels in early breast cancer patients on AIs being
treated with intravaginal testosterone cream or the
ESTRING
PI: Melisko
TREATMENT / EVALUATION
Patients randomized to a 12 week course of either:
• Testosterone Cream 1% micronized in velvachol - 0.5 gm of
cream vaginally 3 x/wk for 12 wks
OR
• Estring 2mg ring inserted vaginally once every 12 weeks
• Serum estradiol at baseline, week 4 and week 12
• Serum testosterone at baseline, week 4 and week 12 in
testosterone cream arm
• Repeat estradiol at week 6-8 if week 4 estradiol is elevated
outside post-menopausal range or >10pg/ml above baseline
Potential Impact of Lifestyle Factors
on Survivorship
Diet and
Weight
• Weight and weight gain may be associated with higher rates of
breast cancer recurrence and mortality, especially in1
– Those who have never smoked
– Premenopausal women
– Women who were normal weight at diagnosis
– Women with early stage cancers
• Some studies have shown that a diet high in fat may be
associated with an increased risk of recurrence2
Exercise
• Regular moderate exercise may improve survival, particularly in
women with hormone receptor–positive tumors3
Alcohol
• Limited alcohol consumption is recommended by the NCCN to
promote a healthy lifestyle4
1. Kroenke CH et al. J Clin Oncol. 2005;23:1370-1378 2. Chlebowski RT et al. J Natl Cancer Inst. 2006;98:1767-1775
3. Holmes MD et al. JAMA. 2009;293:2479-2486. 4. National Comprehensive Cancer Network. Breast Cancer Risk
Reduction-v.2.2009. http://www.nccn.org/professionals/physician_gls/PDF/breast_risk.pdf. Accessed September 15,
2009.
Insulin and Breast Cancer Prognosis
3.5
3
2.5
Death p=0.001
HR
2
Distant Recurrence p=0.007
1.5
1
0.5
0
< 27
27-35.3
35.3-51.9
> 51.9
Insulin Quartiles (pmol/L)
Goodwin PJ et al. J Clin Oncol 2002;20:42-51
Metformin and Cancer – Clinical Studies
I. In early breast cancer, metformin:
– lowers insulin by 22% (p=0.02)
– improves insulin sensitivity by 26% (p=0.02)
– has no adverse effects on HRQOL
– is associated with significant GI toxicity in 12%
Goodwin PJ Breast Ca Res Treat 2006; 100(suppl):A2085
II. Metformin is associated with enhanced response to neoadjuvant therapy in breast cancer
2529 patients received neoadjuvant RX (MD Anderson)
pCR
2374
Non-diabetic
68
Diabetic
receiving
metformin
87
Diabetic
NOT receiving
metformin
16%
24%
8%
p=0.02
p=0.007
p=0.04
p=0.10
Jiralerspong S JCO 2009; 27:3297-3302
Mechanisms of Action of Metformin.
Gonzalez-Angulo A M , Meric-Bernstam F Clin Cancer Res
2010;16:1695-1700
©2010 by American Association for Cancer Research
NCIC CTG MA.32
T1–3*, N0-3,M0 invasive breast cancer
surgically removed within 1 year
Radiotherapy, chemotherapy**,
endocrine therapy, trastuzumab,
biologics, bisphosphonates
* If pT1C, ≥ 1 adverse prognostic factor
** CXT must be completed
STUDY SCHEMA
R
A
N
D
O
M
I
Z
E
Metformin
850 mg po bid X 5 years
(includes 4-week ramp-up
of 850mg po daily)
Identical Placebo
One caplet po bid X 5 years
(includes 4 week ramp-up
of one caplet po daily)
Primary Outcome:
Invasive cancer free survival
Secondary Outcome:
Overall survival, Distant Disease-Free Survival, Breast Cancer Free Interval,
Adverse Events, Hospitalization (CV, diabetes), QOL (888 subjects)
Embedded Correlative:
Weight, Fasting Insulin (baseline, 6 months, 5 years), Tumor Blocks
Sample Size:
3,582 (431 events) – 5 year IDFS 0.85 (placebo), HR =0.76, α=0.05 β=0.20
2 interim analyses (benefit, futility) at 144 and 288 events
Planned subset analyses (α=0.10, 2 sided; β=0.80) in ER/PgR neg (HR 0.65)
and Triple negative (HR 0.55)
Mature Analysis From the Women’s Intervention Nutrition Study
(WINS) Evaluating Dietary Reduction and Breast Cancer
Outcomes
Eligibility Criteria:
 Women 48-79 years
 Early breast cancer
 Primary surgery ± RTx
 Systemic therapy (ER+:
tamoxifen/chemotherapy;
ER–: chemotherapy)
 Dietary fat intake > 20% of
calories
R
A
N
D
O
M
I
Z
E
(n = 2437)
Dietary intervention:
reduced fat intake
(n = 975)
Control
(n = 1462)
Primary Endpoint: Relapse-free survival
Randomization 60:40 within a
year from primary surgery
Chlebowski RT, et al. Breast Cancer Res Treat 2006; 100(suppl 1):S16 (abstract 32).
Change in BMI and Weight by Group
Diet Minus Control Group
Variable
Year 1
BMI (kg/m2)
-0.80
Weight (LBS)
Year 3
-0.77
Year 5
(-1.3
-1.1
(-1.3 to -0.3)
to -0.2)
(-1.9 to -0.4)
-5.0
-3.9
-6.0
(-8.0 to -2.1)
(-6.9 to -0.5)
(-9.9 to -1.9)
All values, P < .005 versus control
BMI = Body Mass Index
All values for weight, P = .005, intervention versus control Information on weight and BMI was
available for all 975 and 1462 women in the dietary intervention group and the control group,
respectively, at baseline; for 854 and 1310 at year 1; 698 and 1044 at year 3; and 386 and 998 at
year 5.
Chlebowski RT, et al. Breast Cancer Res Treat 2006; 100(suppl 1):S16 (abstract 32).
Relapse-Free Survival (All)
HR 0.79; 95% CI, 0.62-1.00
Follow-up 5.8 years, median
Solid line – Diet; Dashed line ---- Control
Relapse-Free Survival (ER+, PgR+)
HR 0.92; 95% CI, 0.71-1.19
Solid line – Diet; Dashed line ---- Control
Relapse-Free Survival (ER–, PgR–)
HR 0.46; 95% CI, 0.26-0.80
Solid line – Diet; Dashed line ---- Control
Study Design
Postmenopausal, T1-3, N0-2, M0
ER and/or PgR +ive on letrozole
n=2150
R
Education Arm
-Mailings annually x 2 years
-Subscription to Canadian Health Magazine
Education plus Telephone-based Weight
Loss Intervention x 2 years
*REMOTE DELIVERY OF INTERVENTION
IN ENGLISH, FRENCH *
Follow-up 4-6 years
Primary:
DFS
Secondary:
1. OS
2. Distant disease-free surival
3. Weight
4. QOL
5. Non-cancer outcomes (DM, CVD, arthritis)
6. Biomarkers – insulin (Substudy)
7. Compliance
* Coordinated by Ontario Clinical Oncology Group *
Courtesy of Goodwin
Factors Associated with Reduction
In Breast Cancer Mortality
Early Detection
Mammography
LR Therapy
Surgery
XRT
Treatment of
Advanced Disease
Hormonal Therapy,
Chemotherapy,
Trastuzumab
Adjuvant Systemic
Therapy
Hormonal Therapy
and Chemotherapy