NcXHF

KATHERINE D. CREW
tion. 24 Despite this evidence, chemoprevention uptake
remains low among these women at high risk. 32
BREAST CANCER CHEMOPREVENTIVE AGENTS
Selective Estrogen Receptor Modulators
Table 2 summarizes results of the major randomized controlled
trials of SERMs and AIs for the primary prevention of
breast cancer. In 1998, the Breast Cancer Prevention Trial
(BCPT) demonstrated that the SERM tamoxifen taken for 5
years reduced breast cancer incidence in women at high risk
by 49% (number needed to treat [NNT] to prevent one invasive
breast cancer was 95 at 5 years and 56 at 10 years). 33,1 The
overall results from three additional randomized controlled
trials confırmed that tamoxifen decreased breast cancer risk
by 30% to 40% compared to placebo. 34-37 In particular, longterm
follow-up data (median of 16 years) from the IBIS-I trial
demonstrated a persistent protective effect of tamoxifen
(NNT was 22 at 20 years). 2 The magnitude of this risk reduction
is comparable to what has been observed with preventive
agents for cardiovascular disease. 38-40
Another SERM, raloxifene, has been shown to reduce the
incidence of breast cancer in postmenopausal women for the
treatment and prevention of osteoporosis. 41,42 Updated analyses
from the Study of Tamoxifen and Raloxifene (STAR)
trial demonstrated that raloxifene had 76% of the effıcacy of
tamoxifen for breast cancer prevention among postmenopausal
women at high risk with a more favorable side effect
profıle. 3 Based on the results of these trials, tamoxifen was
approved by the U.S. Food and Drug Administration (FDA)
for breast cancer risk reduction among women at high risk in
1998 and raloxifene in 2007.
Aromatase Inhibitors
Data from adjuvant trials have proven to be a useful model
for assessing the chemopreventive effects of endocrine therapies,
since results of antiestrogens in the primary prevention
setting closely mirrored those for adjuvant treatment. 37 In
2011, results from the Mammary Prevention Trial-3 (MAP.3)
demonstrated that the AI exemestane given to postmenopausal
women at high risk reduced invasive breast cancer incidence
by 65% compared to placebo (NNT was 26 at 5
years). 4 High-risk criteria included age 60 or older (49%), a
5-year Gail risk score 1.66% or greater (40%), AH or LCIS
(8%), and ductal carcinoma in situ treated with mastectomy
(3%). 4 After a median follow-up of 35 months, 11 invasive
breast cancers occurred in the exemestane arm compared to
32 in the placebo group (annual incidence of 0.19% vs. 0.55%;
p 0.002). 4 In the group comparing exemestane compared
to placebo, more grade 2 or higher arthritis (6.5% vs. 4.0%)
and hot flashes (18.3% vs. 11.9%) were seen. However, overall
quality of life did not differ between the two arms, and no
signifıcant differences in new-onset osteoporosis, clinical
skeletal fractures, cardiovascular events, or other malignancies
were seen.
Another third-generation AI was investigated in the
IBIS-II trial, which randomly assigned postmenopausal
women at high risk, age 40–70, to receive either anastrozole
or placebo for 5 years. 5 With a median follow-up of 5 years,
40 breast cancers (invasive and noninvasive) occurred in the
TABLE 2. Updated Results from Major Randomized Controlled Trials of Selective Estrogen Receptor Modulators
and Aromatase Inhibitors for Breast Cancer Chemoprevention
Trial
No. of
Participants
Eligibility, High-Risk Criteria
for Breast Cancer
BCPT, 2005 1 13,388 Age 35, 5-yr Gail risk
score 1.66% if age 35–59
or 60 or LCIS
IBIS-I, 2014 2 7,154 Age 35–70, 10-fold risk if age
35–39, or 4-fold risk if age
40–44, or 2-fold risk if age
45–70
STAR, 2010 3 19,747 Age 35, postmenopausal,
5-yr Gail risk score 1.66%
MAP.3, 2011 4 4,560 Age 35, postmenopausal,
5-yr Gail risk score 1.66%
if age 35–59 or age 60 or
AH, LCIS, DCIS with
mastectomy
IBIS-II, 2013 5 3,864 Age 40–70, postmenopausal,
4-fold risk if age 40–44, or
2-fold risk if age 45–59, or
1.5-fold risk if age 60–70
Intervention
Tamoxifen 20 mg/d x 5 yrs versus
placebo
Tamoxifen 20 mg/d x 5 yrs versus
placebo
Raloxifene 60 mg/d versus tamoxifen
20 mg/d x 5 yrs
Exemestane 25 mg/d x 5 yrs versus
placebo
Anastrozole 1 mg/d x 5 yrs versus
placebo
Median
Follow-up
(Months)
Breast Cancer
Incidence
Breast Cancer Risk
Reduction RR or
HR (95% CI)
84 3.59 versus 6.29 a 0.57 (0.46–0.70)
192 7.0% versus 9.8% b 0.71 (0.60–0.83)
81 5.02 versus 4.04 a 1.24 (1.05–1.47)
35 0.19% versus 0.55% c 0.35 (0.18–0.70)
60 2% versus 4% b 0.47 (0.32–0.68)
Abbreviations: SERM, selective receptor estrogen modulators; AI, aromatase inhibitor; AH, atypical hyperplasia; BCPT, Breast Cancer Prevention Trial; CI, confidence interval; DCIS, ductal
carcinoma-in-situ; HR, hazard ratio; IBIS, International Breast cancer Intervention Study; LCIS, lobular carcinoma in situ; MAP, Mammary Prevention Trial; RR, relative risk; STAR, Study of
Tamoxifen and Raloxifene.
a Invasive breast cancer incidence rate/1,000 women.
b All breast cancers, invasive and noninvasive.
c Annual incidence of invasive breast cancers.
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