Transcript Slide 1

BREAST CANCER RISK REDUCTION
Clinical Practice Guideline Update
www.asco.org/guidelines/ © American Society of Clinical Oncology®. All rights reserved.
Introduction
• ASCO published its first breast cancer risk reduction (BCRR)
guideline in 1999
• ASCO Guidelines are updated at intervals by an Update
Committee of the original Expert Panel
• BCRR updates published in 2002 and 2009
www.asco.org/guidelines/ © American Society of Clinical Oncology®. All rights reserved.
Guideline Methodology:
Systematic Review
• Literature review focused on available systematic reviews and
meta-analyses of published phase III randomized controlled
trials (RCTs) on breast cancer risk reduction from June 2007
through June 2012
• MEDLINE
• Cochrane Collaboration Library
www.asco.org/guidelines/ © American Society of Clinical Oncology®. All rights reserved.
Clinical Questions
• Which pharmacologic interventions reduce the risk of
developing breast cancer in women not previously
diagnosed with breast cancer?
www.asco.org/guidelines/ © American Society of Clinical Oncology®. All rights reserved.
Recommendations: Tamoxifen
• Should be discussed as an option to reduce the risk of invasive
BC, specifically estrogen (ER)-positive breast cancer, in
premenopausal women who are ≥ 35 years of age with a 5-year
projected absolute BC risk ≥ 1.66%, or with LCIS. Risk reduction
benefit continues for at least 10 years.
• Should be discussed as an option to reduce the risk of invasive
BC, specifically estrogen (ER)-positive breast cancer, in
postmenopausal women who are ≥ 35 years of age with a 5year projected absolute BC risk ≥ 1.66%, or with LCIS. Risk
reduction benefit continues for at least 10 years.
www.asco.org/guidelines/ © American Society of Clinical Oncology®. All rights reserved.
Recommendations: Tamoxifen
• Is not recommended for use in women with a history of deep
vein thrombosis, pulmonary embolus, stroke, transient ischemic
attack, or during prolonged immobilization.
• Is not recommended in combination with hormone therapy.
• Is not recommended for women who are pregnant, women
who may become pregnant, or nursing mothers.
• Follow-up should include a timely work-up of abnormal vaginal
bleeding.
• Discussions with patients and health care providers should
include both the risks and benefits of tamoxifen in the
preventive setting.
• DOSAGE: 20 mg/d orally for 5 years.
www.asco.org/guidelines/ © American Society of Clinical Oncology®. All rights reserved.
Results from SERM Trials:
Tamoxifen vs. placebo
NSABP-P1
IBIS-I
ITALIAN
ROYAL MARSDEN
7 (mean 6.2)
10 (median 8.0)
13 (median, 11.2)
20 (median, 13.2)
TAM
6597
3579
2700
1238
PLA
6610
3575
2708
1233
Follow-up (years)
BREAST CANCER INCIDENCE
Sample size*
All breast cancers
Invasive
TAM
NR
142
62
96
PLA
NR
195
74
113
NR
RR, 0.73 (0.58 to 0.91)
RR, 0.84 (0.60 to 1.17)
HR, 0.84 (0.64 to 1.10)
TAM
145
124
53
82
PLA
250
168
66
104
RR, 0.57 (0.46 to 0.70)
RR, 0.74 (0.58 to 0.94)
RR, 0.80 (0.56 to 1.15)
HR, 0.78 (0.58 to 1.04)
TAM
70
87
40
53
PLA
182
132
52
86
RR, 0.38 (0.28 to 0.50)
RR, 0.66 (0.50 to 0.87)
RR, 0.77 (0.51 to 1.16)
HR, 0.61 (0.43 to 0.86)
TAM
56
35
21
24
PLA
42
35
19
17
RR, 1.31 (0.86 to 2.01)
RR, 1.00 (0.61 to 1.65)
RR, 1.10 (0.59 to 2.05)
HR, 1.4 (0.7 to 2.6)
TAM
60
NR
9
NR
PLA
93
NR
6
NR
RR, 0.63 (0.45 to 0.89)
NR
RR, 1.50 (0.53 to 4.20)
NR
TAM
NR
NR
NR
NR
PLA
NR
NR
NR
NR
NR
NR
NR
NR
TAM
NR
17
NR
14
PLA
NR
27
NR
9
All
ER+
ER-
Noninvasive
All
LCIS
DCIS
www.asco.org/guidelines/ ©
rights reserved.
NRAmerican Society of Clinical Oncology®.
RR, 0.63 (0.32 toAll
1.20)
NR
NR
Adverse Events/ Side Effects:
Tamoxifen vs. placebo
NSABP-P1
Follow-up (years)
Death
VTE
IBIS-I
7 (mean 6.2)
All
DVT
PE
ITALIAN
10 (median 8.0)
ROYAL MARSDEN
13 (median, 11.2)
20 (median, 13.2)
TAM
126
65
36
54
PLA
114
55
38
54
RR, 1.10 (0.85 to 1.43)
RR, 1.18 (0.81 to 1.73)
HR, 0.96 (0.61 to 1.52)
HR, 0.99 (0.68 to 1.44)
TAM
NR
117
44
8c
PLA
NR
68
28
3c
NR
RR, 1.72 (1.27 to 2.36)
RR, 1.63 (1.02 to 2.62)
NR
TAM
49
68
NR
NR
PLA
34
37
NR
NR
NR
NR
NR
NR
13
NR
NR
RR, 2.15 (1.08 to 4.51)
NR
NR
TAM
RR, 1.44 (0.91 to 2.30)
RR, 1.84 (1.21 to
28
(see DVT)
2.82)b
PLA
Cardiovascular
Stroke
TIA
TAM
113
NR
NR
10c
PLA
109
NR
NR
12c
RR, 1.03 (0.79 to 1.36)
NR
NR
NR
TAM
71
15
6
7c
PLA
50
12
2
9c
RR, 1.42 (0.97 to 2.08)
RR, 1.25 (0.55 to 2.93)
RR, 3.11 (0.63 to 15.4)
NR
TAM
31
17
6
NR
PLA
34
22
5
NR
RR, 0.91 (0.54 to 1.52)
RR, 0.77 (0.39 to 1.52)
RR, 1.24 (0.38 to 4.08)
NR
www.asco.org/guidelines/ © American Society of Clinical Oncology®. All rights reserved.
Adverse Events/Side Effects:
Tamoxifen vs. placebo
NSABP-P1
Follow-up (years)
Endometrial
Cancer
Fracture
Cataract
IBIS-I
7 (mean 6.2)
ITALIAN
10 (median 8.0)
ROYAL MARSDEN
13 (median, 11.2)
20 (median, 13.2)
TAM
53
17
NR
13c
PLA
17
11
NR
5c
RR, 3.28 (1.87 to 6.03)
RR, 1.55 (0.68 to 3.65)
NR
NR
TAM
116
240
NR
19c
PLA
80
235
NR
22c
RR, 0.68 (0.51 to 0.92)
RR, 1.02 (0.86 to 1.21)
NR
NR
TAM
NR
67
NR
NR
PLA
NR
54
NR
NR
RR, 1.21 (1.10 to 1.34)
RR, 1.24 (0.87 to 1.77)
NR
NR
*Sample size included in analyses; aShen et al, JNCI, 2008; bDVT and PE combined
Abbreviations: NSABP-P1, National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial P1; IBIS-I, International Breast
Intervention Study; Italian, Italian Randomized Tamoxifen Prevention Trial; Royal Marsden, Royal Marsden Tamoxifen Trial; TAM, tamoxifen; PLA,
placebo; NR, not reported in published literature; NA, not applicable; LCIS, lobular carcinoma in situ; AH, atypical hyperplasia; DCIS, ductal
carcinoma in situ; VTE, venous thromboembolism; DVT, deep vein thrombosis; PE, pulmonary embolism; TIA, transient ischemic attack; (xx to xx),
95% confidence interval.
www.asco.org/guidelines/ © American Society of Clinical Oncology®. All rights reserved.
Recommendations: Raloxifene
• Should be discussed as an option to reduce the risk of invasive
BC, specifically estrogen (ER)-positive breast cancer, in
postmenopausal women who are ≥ 35 years of age with a 5year projected absolute BC risk ≥ 1.66%,a or with LCIS.
• May be used longer than 5 years in women with osteoporosis,
in whom BC risk reduction is a secondary benefit.
• Should not be used for BC risk reduction in premenopausal
women.
www.asco.org/guidelines/ © American Society of Clinical Oncology®. All rights reserved.
Recommendations: Raloxifene
• Is not recommended for use in women with a history of deep
vein thrombosis, pulmonary embolus, stroke, or transient
ischemic attack, or during prolonged immobilization.
• Discussions with patients and health care providers should
include both the risks and benefits of raloxifene in the
preventive setting.
• DOSAGE: 60 mg/d orally for 5 years.
www.asco.org/guidelines/ © American Society of Clinical Oncology®. All rights reserved.
Results from Other SERM Trials
Follow-up
(years)
CORE
MORE
RUTH
STAR
PEARL
GENERATIONS
4 + time in
MORE trial
(median, 7.9)
4
(median, 3.4)
7
(median, 5.6)
8
(median, 6.75)
5
(median, 4.96)
4
(median, NR)
BREAST CANCER INCIDENCE
RAL: 5129
Sample size*
PLA: 2576
All breast cancers
events
Invasive
All
ER+
ER-
RAL: 5111
PLA: 2571
RAL: 5044
PLA: 5057
RAL: 9754
TAM: 9736
RAL: 56
PLA: 65
HR, 0.42 (0.29 to
0.60)
RAL: NR
PLA: NR
RR, 0.38 (0.24 to
0.58)
RAL: 52
PLA: 76
RAL: NR
TAM: NR
NR
RAL: 37
PLA: 55
HR, 0.33 (0.21 to
0.49)
RAL: NR
PLA: NR
RR, 0.28 (0.17 to
0.46)
RAL: 40
PLA: 70
HR, 0.56 (0.38 to 0.83)
RAL: 310
TAM: 247
RR, 1.24 (1.05 to
1.47)
RAL: NR
PLA: NR
RR, 0.16 (0.09 to
0.30)
RAL: 25
PLA: 55
HR, 0.45 (0.28 to 0.72)
RAL: 109
TAM: 115
RR, 0.94 (0.72 to
1.24)
RAL: NR
PLA: NR
NR
RAL:13
PLA: 9
HR, 1.44 (0.61 to 3.36)
RAL: 51
TAM: 44
RR, 1.15 (0.75 to
1.77)
RAL: 22
PLA: 44
HR, 0.24 (0.15 to
0.40)
RAL: 15
PLA: 7
HR, 1.06 (0.43 to
2.59)
HR, 0.67 (0.47 to 0.96)
www.asco.org/guidelines/ © American Society of Clinical Oncology®. All rights reserved.
LAS (.25mg): 2729
LAS (.5mg): 2745
PLA: 2740
LAS (.25mg): 20
HR, 0.82 (0.45 to 1.49)
LAS (.5mg): 5
HR, 0.21 (0.08 to 0.55)
PLA: 24
LAS (.25mg):16
HR, 0.79 (0.41 to 1.52)
LAS (.5mg): 3
HR, 0.15 (0.04 to 0.50)
PLA: 20
LAS (.25mg): 9
HR, 0.50 (0.22 to 1.11)
LAS (.5mg): 3
HR, 0.17 (0.05 to 0.57)
PLA: 18
LAS (.25mg): 8
HR, 2.55 (0.67 to 9.65)
LAS (.5mg): 1
HR, 0.35 (0.04 to 3.34)
PLA: 3
ARZ: 4676
PLA: 4678
ARZ: NR
PLA: NR
NR
ARZ: 1%
PLA: 2.3%
HR, 0.44 (0.26 to
0.76)
ARZ: NR
PLA: NR
NR
ARZ: NR
PLA: NR
NR
Results from Other SERM Trials
Follow-up
(years)
CORE
MORE
RUTH
STAR
PEARL
GENERATIONS
4 + time in
MORE trial
(median, 7.9)
4
(median, 3.4)
7
(median, 5.6)
8
(median, 6.75)
5
(median, 4.96)
4
(median, NR)
BREAST CANCER INCIDENCE
Noninvasive
RAL: 16
All PLA: 7
HR, 1.12 (0.46 to
2.73)
LCIS
DCIS
RAL: NR
PLA: NR
NR
RAL: NR
PLA: NR
NR
RAL: NR
PLA: NR
NR
RAL:NR
PLA: NR
NR
RAL: NR
PLA: NR
NR
RAL: NR
PLA: NR
NR
RAL: NR
PLA: NR
NR
RAL: NR
PLA: NR
NR
RAL: 137
TAM: 111
RR, 1.22 (0.95 to
1.59)
RAL: 34
TAM: 33
RR, 1.02 (0.61 to
1.70)
RAL: 86
TAM: 70
RR, 1.22 (0.88 to
1.69)
www.asco.org/guidelines/ © American Society of Clinical Oncology®. All rights reserved.
LAS (.25mg): NR
LAS (.5mg): NR
PLA: NR
LAS (.25mg): NR
LAS (.5mg): NR
PLA: NR
LAS (.25mg): 4
HR, 1.00 (0.25 to
3.99)
LAS (.5mg): 2
HR, 0.50 (0.09 to
2.73)
PLA: 4
ARZ: NR
PLA: NR
NR
ARZ: NR
PLA: NR
NR
ARZ: NR
PLA: NR
NR
Adverse Events/Side Effects:
Other SERM Trials
CORE
ADVERSE EVENTS/SIDE EFFECTS
Death
RAL: 47
PLA: 29
P=.27
MORE
DVT
RAL: 554
PLA: 595
HR, 0.92 (0.82 to
1.03)
RAL: 202
TAM: 236
RR, 0.84 (0.70 to
1.02)
RAL: 47
PLA: 13
P=.094
RAL: NR
PLA: NR
NR
RAL: 103
PLA: 71
HR, 1.44 (1.06 to
1.95)
RAL: 154
TAM: 202
RR, 0.75 (0.60 to
0.93)
RAL: 31
PLA: 10
P=.32
RAL: NR
PLA: NR
P=.002
RAL: 65
PLA: 47
HR, 1.37 (0.94 to
1.99)
RAL: 86
TAM: 118
RR, 0.72 (0.54 to
0.95)
RAL: 17
PLA: 2
P=.05
RAL: NR
PLA: NR
HR, 3.97 (0.91 to
17.3)
RAL: 36
PLA: 24
HR, 1.49 (0.89 to
2.49)
RAL: 68
TAM: 84
RR, .080 (0.57 to
1.11)
RAL: 7
PLA: 4
P=.75
RAL: NR
PLA: NR
HR, 0.69 (0.22 to
2.18)
RAL: 21
PLA: 27
P=.53
RAL: 37
TAM: 65
RR, 0.55 (0.36 to
0.83)
PE
Endometrial
Cancer
STAR
RAL: NR
PLA: NR
HR, 0.61 (0.36 to
1.03)
VTE
All
RUTH
www.asco.org/guidelines/ © American Society of Clinical Oncology®. All rights reserved.
PEARL
LAS (.25mg): 90
HR, 1.38 (1.00 to 1.89)
LAS (.5mg): 73
HR, 1.12 (0.80 to 1.56)
PLA: 65
LAS (.25mg): 48
HR, 2.67 (1.55 to 4.58)
LAS (.5mg): 37
HR, 2.06 (1.17 to 3.61)
PLA: 18
LAS (.25mg): NR
LAS (.5mg): NR
PLA: NR
NR
LAS (.25mg): 12
HR, 5.98 (1.34 to 26.7)
LAS (.5mg): 9
HR, 4.49; 0.97 to 20.8
PLA: 2
LAS (.25mg): 3
LAS (.5mg): 2
PLA: 3
NR
GENERATIONS
ARZ: 105
PLA: 98
P=.62
ARZ: 63
PLA: 27
P<.001
ARZ: 26
PLA: 9
P=.004
ARZ: 16
PLA: 7
P=.06
ARZ: 9
PLA: 4
P=.16
Adverse Events/Side Effects:
Other SERM Trials
CORE
MORE
RUTH
STAR
PEARL
GENERATIONS
ADVERSE EVENTS/SIDE EFFECTS
Cardiovascular
RAL: NR
PLA: NR
NR
RAL: NR
PLA: NR
NR
RAL: NR
PLA: NR
NR
RAL: 126
TAM: 114
RR, 1.10 (0.85 to
1.43)
Stroke
RAL: NR
PLA: NR
NR
RAL: NR
PLA: NR
HR, 0.68 (0.43 to
1.07)
RAL: NR
PLA: NR
HR, 1.10 (0.92 to
1.32)
RAL: 51
TAM: 53
RR, 0.96 (0.64 to
1.43)
TIA
RAL: NR
PLA: NR
NR
RAL: NR
PLA: NR
NR
RAL: NR
PLA: NR
NR
RAL: 50
TAM: 41
RR, 1.21 (0.79 to
1.88)
www.asco.org/guidelines/ © American Society of Clinical Oncology®. All rights reserved.
LAS (.25mg): 73
HR, 0.76 (0.56 to 1.03)
LAS (.5mg): 65
HR, 0.68 (0.50 to 0.93)
PLA: 95
LAS (.25mg): 31
HR, 0.61 (0.39 to 0.96)
LAS (.5mg): 32
HR, 0.64 (0.41 to 0.99)
PLA: 50
LAS (.25mg): 19
HR, 1.35 (0.68 to 2.69)
LAS (.5mg): 14
HR, 1.00 (0.48 to 2.09)
PLA:14
ARZ: 116
PLA: 113
P=.88
ARZ: 47
PLA: 42
P=.59
ARZ: NR
PLA: NR
NR
Adverse Events/Side Effects:
Other SERM Trials
CORE
ADVERSE EVENTS/SIDE EFFECTS
Fracture
RAL: NR
PLA: NR
P<.05
Cataract
RAL: NR
PLA: NR
NR
MORE
RUTH
STAR
RAL: 64
PLA: 97
RAL: V 64; NV 428
PLA: V 97; NV 438
RAL: 96
TAM: 104
RR, 0.66 (0.55 to
0.81)
V: HR, 0.65 (0.47
to 0.89); NV: HR,
0.96 (0.84 to
1.10)
RR, 0.92 (0.69 to
1.22)
RAL: 374
PLA: 391
P=.56
RAL: 603
TAM: 739
RR, 0.80 (0.72 to
0.89)
RAL: NR
PLA: NR
NR
PEARL
LAS (.25mg):
V: 189/2734
HR, 0.69 (0.57 to 0.83)
NV: 269/2852 HR, 0.90 (0.76
to 1.06)
LAS (.5mg):
V: 156/2748
HR, 0.58 (0.47 to 0.70)
NV: 230/2852
HR, 0.76 (0.64 to 0.91)
PLA:
V: 262/2744 (HR, NR)
NV: 296/2852 (HR, NR)
LAS (.25mg): NR
LAS (.5mg): NR
PLA: NR
NR
GENERATIONS
ARZ:
V: 109/4192
NV: 334/4192
PLA:
V: 179/4162
NV: 354/4162
V: RR, 0.61 (0.48 to
0.77); NV: RR, 0.94 (0.81
to 1.10)
ARZ: NR
PLA: NR
NR
Abbreviations: TAM, tamoxifen; RAL, raloxifene; PLA, placebo; LAS, lasofoxifene; ARZ, arzoxifene; NR, not reported in published literature; V, vertebral
fractures; NV, nonvertebral fractures; (xx to xx), 95% confidence interval; CORE, Continuing Outcomes Relevant to Evista; MORE, Multiple Outcomes of
Raloxifene Evaluation; RUTH, Raloxifene Use for the Heart; STAR, National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial P2; PEARL,
Postmenopausal Evaluation and Risk-Reduction with Lasofoxifene; GENERATIONS, Generations Trial; LCIS, lobular carcinoma in situ; AH, atypical hyperplasia;
DCIS, ductal carcinoma in situ; DVT, deep vein thrombosis; PE, pulmonary embolism; TIA, transient ischemic attack.
www.asco.org/guidelines/ © American Society of Clinical Oncology®. All rights reserved.
Recommendations: Exemestane
• Should be discussed as an alternative to tamoxifen and/or
raloxifene to reduce the risk of invasive breast cancer,
specifically estrogen (ER)-positive breast cancer, in
postmenopausal women who are ≥ 35 years of age with a 5year projected absolute BC risk ≥ 1.66%, or with LCIS or atypical
hyperplasia.
• Should not be used for BC risk reduction in premenopausal
women.
• Discussions with patients and health care providers should
include both the risks and benefits of exemestane in the
preventive setting.
• DOSAGE: 25 mg/d orally for 5 years.
www.asco.org/guidelines/ © American Society of Clinical Oncology®. All rights reserved.
Results from Aromatase Inhibitor Trials:
MAP.3
Follow-up (years)
BREAST CANCER INCIDENCE
Sample size*
3 (median): range 0 to 63.4 months
All breast cancers
Invasive
All
ER+
ER-
Noninvasive
All
LCIS
DCIS
EXE:2285, PLA:2275
EXE: 20
PLA: 44
HR, 0.47 (0.27 to 0.79 )
EXE: 11, PLA: 32
HR, 0.35 (0.18 to 0.70)
EXE: 7
PLA: 27
HR, 0.27 (0.12 to 0.60)
EXE: 4
PLA: 5
HR, 0.80 (0.21 to 2.98)
NR
EXE: 4
PLA: 11
HR, 0.36 (0.11 to 1.12)b
EXE: 9
PLA: 14
HR, 0.65 (0.28 to 1.51)
www.asco.org/guidelines/ © American Society of Clinical Oncology®. All rights reserved.
Results from Aromatase Inhibitor Trials:
MAP.3
Follow-up (years)
ADVERSE EVENTS/SIDE EFFECTS
Sample Size
3 (median): range 0 to 63.4 months
Death
VTE
All
DVT
PE
Cardiovascular
Stroke
TIA
Endometrial Cancer
Fracture
Cataract
EXE: 2240
PLA: 2248
EXE: 19
PLA: 19
NR
EXE: 11
PLA: 7
NR
NR
NR
EXE: 106
PLA: 111
P=.78
EXE: 13
PLA: 11
NR
(see stroke)
EXE: 5
PLA: 8
NR
EXE: 149
PLA: 143
P=.72
NR
*Sample size included in analyses; aOnly results from cognitive subprotocol available (Jenkins et al, Lancet Oncol, 2008). Abbreviations: EXE, exemestane;
ANA, anastrozole; PLA, placebo; NR, not reported in published literature; IBIS-II, International Breast Intervention Study (II) ; LCIS, lobular carcinoma in
situ; AH, atypical hyperplasia; DCIS, ductal carcinoma in situ; VTE, venous thromboembolism; DVT, deep vein thrombosis; PE, pulmonary embolism; TIA,
transient ischemic attack.
bResults for incidence of atypical ductal hyperplasia, atypical lobular hyperplasia, and LCIS combined
www.asco.org/guidelines/ © American Society of Clinical Oncology®. All rights reserved.
Patient and Clinician Communication
Key Discussion Points
• Assessment and discussion of individual risk of developing
breast cancer
• Options for reducing the risk of developing breast cancer (nonpharmacologic and pharmacologic)
• Potential impact of specific chemoprevention agents on the
incidence of both invasive and noninvasive breast cancers
• Potential risks and side effects of chemoprevention agents
www.asco.org/guidelines/ © American Society of Clinical Oncology®. All rights reserved.
Patient and Clinician Communication
Key Discussion Points
• Long-term effectiveness of the chemoprevention agents
• Chemoprevention studies were not powered to detect
differences in mortality as it was considered that a reduction in
incidence was itself an important clinical endpoint.
• Accessibility - cost/insurance coverage
• Resources/materials for consideration (e.g. www.cancer.net)
• Plan for follow-up.
www.asco.org/guidelines/ © American Society of Clinical Oncology®. All rights reserved.
Health Disparities
• Challenges to minimizing health disparities include:
• Equal access to health care
• Racially diverse participation in clinical trials
• Improved risk assessment models
• Racial, ethnic, and socioeconomic status may affect health
outcomes and/or create barriers to access and use of
chemoprevention agents for BCRR
• In addition to age and comorbidities, race is important
when considering risk-benefit profiles, so race-specific
estimates should be considered and incorporated in
discussions between patients and clinicians
www.asco.org/guidelines/ © American Society of Clinical Oncology®. All rights reserved.
Future Directions
• Need for:
• Research to address poor uptake of BCRR in high-risk
women
• Effective tools and approaches to educate providers on
chemoprevention
• Efficacious interventions that communicate to eligible
women the risks and benefits of specific chemoprevention
agents
• Tools that more accurately identify women at increased risk
• Greater understanding of what disparities and barriers exist
with regard to chemoprevention use among high-risk
women
www.asco.org/guidelines/ © American Society of Clinical Oncology®. All rights reserved.
The Bottom Line
• Intervention
•
Pharmacologic interventions for breast cancer risk reduction, including selective
estrogen receptor modulators and aromatase inhibitors
• Target Audience
•
Medical Oncologists, Surgical Oncologists, Gynecologists, Primary Care
Physicians, General Practitioners
• Key Recommendations
• Tamoxifen (20 mg/d orally for 5 years) should be discussed as an option to
reduce the risk of invasive breast cancer, specifically estrogen (ER)-positive
breast cancer, in premenopausal or postmenopausal women ≥ 35 years of age at
increased risk of breast cancer, or with lobular carcinoma in situ (LCIS).
Tamoxifen is not recommended for use in women with a history of deep vein
thrombosis, pulmonary embolus, stroke, transient ischemic attack, during
prolonged immobilization, in women who are pregnant or who may become
pregnant, or nursing mothers. Tamoxifen is not recommended in combination
with hormone therapy.
www.asco.org/guidelines/ © American Society of Clinical Oncology®. All rights reserved.
The Bottom Line
• Key Recommendations
• Raloxifene (60 mg/d orally for 5 years) should be discussed as an option to
reduce the risk of invasive breast cancer, specifically ER-positive breast cancer, in
postmenopausal women ≥ 35 years of age at increased risk of breast cancer, or
with LCIS. It should not be used for breast cancer risk reduction in
premenopausal women. Raloxifene is not recommended for use in women with
a history of deep vein thrombosis, pulmonary embolus, stroke, transient
ischemic attack, or during prolonged immobilization.
• Exemestane (25 mg/d orally for 5 years) should be discussed as an alternative to
tamoxifen or raloxifene to reduce the risk of invasive breast cancer, specifically
ER-positive breast cancer, in postmenopausal women ≥ 35 years of age at
increased risk of breast cancer, or with LCIS or atypical hyperplasia. Exemestane
should not be used for breast cancer risk reduction in premenopausal women.
• For tamoxifen and raloxifene, the most favorable risk-benefit profile is seen in
women at greatest risk of developing breast cancer.
www.asco.org/guidelines/ © American Society of Clinical Oncology®. All rights reserved.
The Bottom Line
• Key Recommendations (con’t)
• Discussions with patients and health care providers should include both the risks
and benefits of each agent under consideration.
• NOTE1: Refer to Table 1 for the complete recommendations.
• NOTE2: Increased risk is defined as a 5 year projected absolute risk of breast
cancer ≥1.66% on the NCI Breast Cancer Risk Assessment Tool or an equivalent
measure.
• NOTE3: Trials were not designed to assess mortality and the impact of the agent
on overall survival or breast cancer-specific survival has not been demonstrated
in 10 years of follow-up.
• Methods
•
A systematic review of randomized controlled trials and meta-analyses
published from June 2007 through June 2012 was completed using MEDLINE
and the Cochrane Collaboration Library. An Update Committee reviewed the
evidence to determine whether the 2009 ASCO clinical practice guideline
www.asco.org/guidelines/ © American Society of Clinical Oncology®. All rights reserved.
recommendations needed to be updated.
Additional Resources
• A Data Supplement and clinical tools and resources can be
found on ASCO’s Web site at:
• http://www.asco.org/guidelines/bcrr
• Patient information is also available at:
• http://www.asco.org/guidelines/bcrr
• http://www.cancer.net/publications-and-resources/whatknow-ascos-guidelines/what-know-ascos-guideline-drugslower-breast-cancer-risk
• www.cancer.net/bcriskinfo
www.asco.org/guidelines/ © American Society of Clinical Oncology®. All rights reserved.
Update Committee Panel Members
UPDATE COMMITTEE MEMBER
Kala Visvanathan, MD, MHS, CoChair
Scott M. Lippman, MD,
Co-Chair
AFFILIATION
Johns Hopkins Medical Institutions, Baltimore, MD
Nananda Col, MD, MPH
Moores Cancer Center, University of California, San
Diego, CA
Johns Hopkins Medicine and Sidney Kimmel
Comprehensive Cancer Center, Baltimore, MD
MD Anderson Cancer Center, University of Texas,
Houston, TX
University of New England, Biddeford, ME
Jack Cuzick, PhD
Queen Mary University of London, UK
Nancy E. Davidson, MD
Andrea De Censi, MD
University of Pittsburgh Cancer Institute and UPMC
CancerCenter, Pittsburgh, PA
E.O. Ospedali Galliera, Italy
Carol Fabian, MD
University of Kansas Medical Center, Kansas City, KS
Elissa Bantug, MHS
Powel Brown, MD, PhD
www.asco.org/guidelines/ © American Society of Clinical Oncology®. All rights reserved.
Update Committee Panel Members
UPDATE COMMITTEE MEMBER
AFFILIATION
Leslie Ford, MD
National Cancer Institute, Bethesda, MD
Judy Garber, MD, MPH
Dana Farber Cancer Institute, Boston, MA
Maria Katapodi, PhD, RN, FAAN
University of Michigan School of Nursing, Ann Arbor,
MI
National Cancer Institute, Bethesda, MD
Barnett Kramer, MD, MPH
Monica Morrow, MD
Barbara Parker, MD
Carolyn Runowicz, MD
Victor Vogel III, MD
James L. Wade, MD
Memorial Sloan Kettering Cancer Center, New York,
NY
Moores Cancer Center, University of California, San
Diego, CA
Herbert Wertheim College of Medicine, Florida
International University, Miami, FL
Geisinger Medical Center Cancer Institute, Danville,
PA
Cancer Care Specialists of Central Illinois, Decatur, IL
www.asco.org/guidelines/ © American Society of Clinical Oncology®. All rights reserved.
ASCO Guidelines
The clinical practice guidelines and other guidance published herein are
provided by the American Society of Clinical Oncology, Inc. (“ASCO”) to assist
practitioners in clinical decision making. The information therein should not be
relied upon as being complete or accurate, nor should it be considered as
inclusive of all proper treatments or methods of care or as a statement of the
standard of care. With the rapid development of scientific knowledge, new
evidence may emerge between the time information is developed and when it
is published or read. The information is not continually updated and may not
reflect the most recent evidence. The information addresses only the topics
specifically identified therein and is not applicable to other interventions,
diseases, or stages of diseases. This information does not mandate any
particular course of medical care. Further, the information is not intended to
substitute for the independent professional judgment of the treating physician,
as the information does not account for individual variation among patients.
Recommendations reflect high, moderate or low confidence that the
recommendation reflects the net effect of a given course of action.
www.asco.org/guidelines/ © American Society of Clinical Oncology®. All rights reserved.
ASCO Guidelines
[Cont’d] The use of words like “must,” “must not,” “should,” and “should not”
indicate that a course of action is recommended or not recommended for
either most or many patients, but there is latitude for the treating physician to
select other courses of action in individual cases. In all cases, the selected
course of action should be considered by the treating physician in the context
of treating the individual patient. Use of the information is voluntary. ASCO
provides this information on an “as is” basis, and makes no warranty, express or
implied, regarding the information. ASCO specifically disclaims any warranties
of merchantability or fitness for a particular use or purpose. ASCO assumes no
responsibility for any injury or damage to persons or property arising out of or
related to any use of this information or for any errors or omissions.
www.asco.org/guidelines/ © American Society of Clinical Oncology®. All rights reserved.