Transcript Wishing on a STAR:

Wishing on a STAR: Primary
Prevention of Breast Cancer
Kristin Steffen, MD
Primary Care Conference
March 14, 2007
I have no financial disclosures.
Objectives
• Identify the only SERM approved for
primary prevention of breast cancer in
premenopausal and postmenopausal women
• Identify potential future medications for
primary prevention of breast cancer
• Identify the potential benefits and risks of
the SERMs tamoxifen and raloxifene
Case
SS is a 65 yo F who is highly motivated to pursue
preventive health measures of all sorts. She comes
in to discuss a medication she read about recently
as a breast cancer preventive measure (plus 9 other
issues).
PMH: s/p hysterectomy at age 33, osteoporosis,
metatarsal fx age 58, atrophic vaginitis,
fibromyalgia+ many others (no DVT/PE)
FH: No breast cancer
SH: Married, nonsmoker
Meds:Estring, Actonel, Lipitor, Prilosec, + more
Tamoxifen
• FDA approved
• Only SERM with proven efficacy in premenopausal women
• 50% incidence of invasive and noninvasive
breast cancer
•  risk of endometrial cancer predominantly in
women ages 50+
•  risks of stroke, PE, DVT more frequently in
women 50+
Raloxifene
• FDA approval expected for breast cancer
prevention in postmenopausal women based on
STAR trial findings
• MORE: 76% invasive breast cancer risk
• CORE: 69% invasive breast cancer risk
• RUTH: 44% invasive breast cancer risk
(12/10,000)
•  risks stroke (49%, 7/10,000), VTE (44%,
12,10,000) in RUTH
• NO increased risk of endometrial cancer
STAR trial/STAR QOL study
• Objective:
Compare relative effects and safety of
raloxifene and tamoxifen on developing
invasive breast cancer and other disease
outcomes
STAR: Design and Setting
• Prospective double blind RCT in nearly 200
centers in North America
• 19,747 postmenopausal women, mean age
58.5 years with increased 5 year breast
cancer risk (per Gail Model)
STAR: Intervention
• Trial: Oral tamoxifen 20 mg daily or
raloxifene 60 mg daily over 5 years
• Study: 36 item symptom checklist, Medical
Outcomes Study Short form(SF-36), Center
for Epidemiologic Studies-depression
(CES-D), Medical Outcomes Study Sexual
Activity Questionnaire
STAR: Outcome Measures
• Trial: incidence of invasive breast cancer,
incidence of noninvasive breast cancer,
bone fractures, thromboembolic events
• Study: SF-36 physical and mental
component summaries
STAR: Results
• Tamoxifen=Raloxifene:
–
–
–
–
Rates of invasive cancer
Rates of CV events (include stroke)
Rates of osteoporotic fracture
Pt reported outcomes for physical and mental
health (ie minimal difference in adverse effect
burden and QOL but see below)
STAR: Results
• Tamoxifen differed in:
– Fewer noninvasive (lobular CA in situ, ductal
CA in situ), but uncertain clinical significance
– vasomotor symptoms
– leg cramps
– bladder control problems
STAR Results
• Raloxifene differed in:
– 30%  risk VTE
– 38%  risk endometrial cancer, (BUT not
statistically significant)
– 84%  risk endometrial hyperplasia
– 56% risk hysterectomy
– 20%  risk cataract/cataract surgery
–  MSK problems, dyspareunia, weight gain
Issues to Ponder
•
•
•
•
•
•
•
NNT estimates 55-126 for invasive breast CA
Risk/benefit ratio for an individual
Patient acceptance
Physician acceptance
“Side benefit” of therapy for osteoporosis
Length of therapy unknown
Pts will look to primary care providers for
guidance
Case Patient SS
• Discuss her preferences, adverse risks, potential
benefits
• Consider dual role for osteoporosis treatment, she
has taken Actonel > 5 years and the debate on
length of bisphosphonate therapy
• Postmenopausal and s/p hysterectomy: both
addition of Tamoxifen, or addition/substitution of
Raloxifene (when FDA approved) could be
considered
The Future
• Breast cancer prevention trials comparing
raloxifene to aromatase inhibitor and
aromatase inhibitor to placebo are ongoing
References
• Barrett-Connor E, et al. Effects of
raloxifene on cardiovascular events and
breast cancer in postmenopausal women.N
Engl J Med 2006; 355:125-137.
• Cummings SR et al. The effect of raloxifene
on breast cancer in postmenopausal
women:results from the MORE randomized
trial.JAMA 1999;281:2189-2197.
Reference, cont
• Fisher B et al. Tamoxifen for prevention of breast
cancer:report of the National Surgical Adjuvant
Breast and Bowel Project P-1 Study.J Natl Cancer
Inst 1998;90:1371-1388.
• Fisher B et al.Tamoxifen for the prevention of
breast cancer: current status of the National
Surgical Adjuvant Breast and Bowel Project P-1
Study.J Natl Cancer Inst 2005;97:1652-1662.
References, cont.
• Land SR et al. Patient-reported symptoms and
quality of life during treatment with tamoxifen or
raloxifene for breast cancer prevention: the
NSABP Study of Tamoxifen and Raloxifene
(STAR) P-2 trial.JAMA 2006;295:2742-2751.
• Vogel VG et al. Effects of Tamoxifen and
Raloxifene on the risk of developing invasive
breast cancer and other disease outcomes: the
NSABP Study of Tamoxifen and Raloxifene
(STAR) P-2 trial.JAMA 2006;295:2727-2741.