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CURRENT
OPINION The renaissance of endocrine therapy in
breast cancer
Nicole Williamsa
and Lyndsay N. Harrisa,b
Purpose of review
Endocrine therapy for breast cancer has been the cornerstone of treatment for over a century since the
discovery of the regressive effect of oophorectomy on ‘cancer of the mamma’ in 1896 by Beatson. Studies
in the prevention and treatment of both early and metastatic breast cancer will be reviewed with a focus on
recent large randomized clinical trials that may be practice changing.
Recent findings
Data from pivotal clinical trials that looked at the duration of adjuvant tamoxifen therapy in premenopausal
women will be discussed. In addition, several recent clinical trials that address the optimal sequence of
endocrine therapy and advances in the treatment of endocrine-resistant metastatic disease will be reviewed.
New findings from molecular studies that demonstrate targets in the endocrine axis and the role of
aromatase inhibitors in the prevention setting will be highlighted.
Summary
Overall, these clinical trials show the benefit of aromatase inhibitors in the prevention setting, longer
duration of tamoxifen in the adjuvant setting for premenopausal women, and new biologic agents with
hormonal therapies.
Keywords
androgen receptors, aromatase inhibitors, endocrine therapy, mTOR inhibitors, tamoxifen
INTRODUCTION
Hormone-receptor-positive breast cancer is the most
common breast cancer subtype in developed
countries, regardless of the age or stage at presen-
tation. Approximately 60% of breast cancers diag-
nosed in premenopausal women and 75–80% of
breast cancers found in postmenopausal women
are hormone receptor positive. Recent guidelines
from the College of American Pathologist re-defined
hormone-receptor-positive breast cancer as express-
ing estrogen receptor or progesterone receptor at at
least 1% by immunohistochemistry [1]. Although
not agreed upon by all of the academic community,
these guidelines recognize the fact that even at very
low levels of estrogen receptor expression, benefit is
observed from antiestrogen therapy.
Endocrine therapy for breast cancer has been the
cornerstone of treatment for over a century since the
discovery of the regressive effect of oophorectomy
on ‘cancer of the mamma’ by Beatson in 1896 [2].
Despite its central role in treatment, and although it
is indeed the first ‘targeted therapy’, few advances
have been made until very recently. Decades of
research on endocrine resistance and discovery of
new genomic targets have led to new hormonal
targets, combinations of hormonal therapy with
biologic agents, and with duel hormonal therapies.
This is indeed a ‘hormonal renaissance’ for breast
cancer, and not a moment too soon as much prog-
ress has been made in other breast cancer subtypes.
This review will address the recent studies in the
prevention and treatment of hormone-receptor-
positive breast cancer and their impact on clinical
practice.
a
Seidman Cancer Center, University Hospitals of Case Western Cleve-
land and b
Division of Hematology/Oncology, Department of Medicine,
Case Western Reserve School of Medicine, Cleveland, Ohio, USA
Correspondence to Lyndsay N. Harris, MD, Lakeside 1127, 11100 Euclid
Avenue, Cleveland, OH 44106, USA. Tel: +1 216 286 4414; e-mail:
lyndsay.harris@case.edu
Curr Opin Obstet Gynecol 2014, 26:41–47
DOI:10.1097/GCO.0000000000000039
1040-872X ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins www.co-obgyn.com
REVIEW

2. Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
ENDOCRINE TREAMENT OF METASTATIC
BREAST CANCER
Endocrine therapy is considered the first-line treat-
ment for women with estrogen receptor and pro-
gesterone receptor positive breast cancer for both
premenopausal and postmenopausal women, pro-
vided the pace or burden of disease does not indicate
the need for chemotherapy. There are differences in
the treatment of premenopausal and postmeno-
pausal patients, as the endocrine environment in
the menopausal state leads to variability in drug
activity. The following paragraphs describe the
standard and new approaches for each type of
patient.
Endocrine therapy in metastatic
postmenopausal women
Aromatase inhibitors such as anastrozole, letrozole,
and exemestane are considered the first-line endo-
crine treatment for postmenopausal women because
of their proven superiority over tamoxifen [3–5].
Fulvestrant is an analog of estradiol that down-
regulates the estrogen receptor by disrupting the
estrogen receptor dimerization and accelerating
degradation of the unstable fulvestrant–estrogen
receptor complex. It is typically used after aromatase
inhibitor therapy, although newer studies suggest
an earlier line may be reasonable [6,7].
Several studies have evaluated the timing of
single and combination therapies in the first and
second line setting which are reviewed in Table 1. It
should be noted that in many of these trials, the
patients who experience the most benefit had not
received prior endocrine therapy or had de novo
metastatic disease. On the basis of the results of
these studies, the optimal order of exposure to hor-
monal agents in the advanced setting still needs to
be determined as well as the true benefit of combi-
nation endocrine therapy in the first-line metastatic
setting.
Endocrine therapy in premenopausal women
For premenopausal women with estrogen receptor
and progesterone receptor positive metastatic breast
cancer, a luteinizing hormone releasing hormone
(LHRH) agonist plus tamoxifen remains the stand-
ard of care based on trials showing a survival
advantage for the combination [14]. This practice
has not changed significantly in the recent years.
Patients then are typically treated as postmeno-
pausal upon progression. It should be noted there
is no evidence that using an aromatase inhibitor
with a LHRH agonist is superior to tamoxifen with a
LHRH agonist and should be reserved for pro-
gression of disease.
Novel targeted therapies for metastatic
breast cancer
Unfortunately, not all patients will have a response
to first-line endocrine therapy (de novo resistance)
and patients who respond will eventually progress
(acquired resistance). In the last 2 decades, there
have been major efforts to better understand the
various biological mechanisms responsible for the
development of endocrine resistance with the aim
of identifying new therapeutic strategies. Preclinical
data show a benefit in blocking the mammalian
target of rapamycin (mTOR) pathway in endo-
crine-resistant tumors because the mTOR complex
has the ability to directly active the estrogen recep-
tor. Bolero-2 (Breast Cancer Trials of Oral Everoli-
mus) was a randomized phase 3 trial comparing
everolimus and exemestane vs. exemestane and
placebo in 724 patients with hormone-receptor-
positive advanced breast cancer that had a recur-
rence or progression while receiving therapy with a
nonsteroidal aromatase inhibitor in the adjuvant or
advanced disease setting [15
&&
]. Everolimus com-
bined with an aromatase inhibitor improved pro-
gression-free survival (PFS) in patients previously
treated with nonsteroidal aromatase inhibitors
(10.6 vs. 4.1 months; 95% confidence interval
0.35–0.54; P < 0.001). The results of this study was
also supported by, Tamoxifen plus Everlimus, a
KEY POINTS
Two large randomized trials (ATLAS and aTTom) have
shown that 10 years of adjuvant tamoxifen therapy is
superior to 5 years in premenopausal women.
The combination of inhibition of the mTOR pathway
with everolimus and estrogen receptor blockage results
in improved progression-free survival after progression
on a nonsteroidal aromatase inhibitor.
The FIRST trial showed improved progression-free
survival with the first-line fulvestrant in postmenopausal
hormone-receptor-positive women with metastatic breast
cancer when compared with a nonsteroidal aromatase
inhibitor.
Combination endocrine therapy with fulvestrant and
exemestane in the first-line setting in postmenopausal
women with hormone-receptor-positive metastatic breast
cancer was superior to single-agent therapy in women
with no prior endocrine therapy.
The MAP-3 trial demonstrated that exemestane reduced
the incidence of invasive breast cancers with 3 years of
follow-up reported.
Breast cancer
42 www.co-obgyn.com Volume 26 Number 1 February 2014

3. Copyright © Lippincott Williams Wilkins. Unauthorized reproduction of this article is prohibited.
phase 2 randomized study involving 111 postme-
nopausal women with estrogen-receptor-positive
advanced breast cancer previously treated with an
aromatase inhibitor [16
]. The combination of ever-
olimus and tamoxifen was associated with improved
PFS (8.6 vs. 4.5 months, P ¼ 0.002) and with signifi-
cantly improved overall survival (OS). These studies
suggests that everolimus plays a role in the treat-
ment of patients with endocrine-resistant disease.
New endocrine targets for therapy
Two novel endocrine targets currently being studied
in the clinical trial setting are the androgen receptor
and the LHRH receptor. The androgen receptor (AR)
is expressed in 70–90% of all breast cancers [17].
During the first half of the 20th century, postme-
nopausal women were treated with androgen
therapy. However, in the 1970s, the use of androgen
therapy stopped with the development of tamox-
ifen. Emerging data suggest that the androgen
receptor may play a role in breast cancer pathogen-
esis and may serve as a potential therapeutic target,
especially in more difficult-to-treat triple-negative
breast cancers [18]. A recent study conducted in AR-
positive, estrogen-receptor-negative metastatic
breast cancer patients treated with bicalutamide
(an oral antiandrogen therapy) showed a clinical
benefit of 21%, making this an interesting potential
therapeutic target especially for patients with endo-
crine-resistant disease or triple-negative breast can-
cer [19].
The LHRH also known as gonadotropin-releas-
ing hormone (GnRH) was identified in the early
1970s. LHRH binds to its specific receptor, known
today as type 1 LHRH receptor. Approximately 40–
50% of breast cancer expresses the LHRH receptor,
suggesting that it may be a useful therapeutic target.
AEZS-108 is a LHRH agonist–cytotoxic hybrid drug
with doxorubicin. In preclinical studies, AEZS-108
was found to inhibit breast cancer in mouse models
with minimal side-effects. Currently, there is a
Table 1. First and second line endocrine therapies for metastatic postmenopausal hormone receptor positive breast cancer
Robertson,
2012 (FIRST) [8
]
Mehta, 2012
(SWOG S0226) [9
]
Bergh, 2012
(FACT) [10
]
Chia, 2008
(EFECT) [11]
First line First line First line Second line
Ana Ful Ana Ana þ Ful Anas Ana þ Ful Exe Ful
n 103 102 345 349 258 256 342 351
CBR 67% 72.5% 70% 73% 55% 55.10% 31.50% 32.20%
PFS (months) 13.1 23.4Ã 13.5 15Ã 10.2 10.8Ã 3.7 3.7Ã
OS (months) NR NR 41.3 47.7 38.2 37.8 NR NR
Significanceà HR 0.66; 95% CI
0.47–0.92;
P ¼ 0.01
HR 0.80; 95% CI
0.68–0.94;
P ¼ 0.007
HR 0.99; 95% CI
0.81–1.20;
P ¼ 0.91
HR 0.93; 95% CI
0.819–1.133;
P ¼ 0.65
Johnston, 2013 (SoFEA) [12
] Di Leo, 2010 (CONFIRM) [13] Howell, 2002 [6]
Second line Second line Second line
Ana þ Ful Ful Exe Ful 500 mg Ful 250 mg Ana Ful
n 243 231 249 362 374 229 222
CBR 34% 32% 27% 45.60% 39.60% 45% 44.60%
PFS (months) 4.4Ã 4.8 3.4 6.5Ã 5.5 5.1 5.5Ã
OS (months) 20.2 19.4 21.6 25.1 22.8 NR NR
SignificanceÃ
(primary endpoint)
HR 1; 95% CI 0.83–1.21;
P ¼ 0.98
HR 0.80; 95% CI 0.68–0.94;
P ¼ 0.006
HR 0.98; 95% CI
0.80–1.21; P ¼ 0.84
à primary endpoint; Ana, anastrozole; CBR, clinical benefit rate; CI, confidence interval; Exe, exemestane; Ful, fulvestrant; HR, hazard ratio; NR, not reported;
OS, overall survival; PFS, progression-free survival; FIRST, Fulvestrant First-line study Comparing Endocrine Treatment; SWOG SO226, Combination Anastrozole
and Fulvestrant in Metastatic Breast Caner; FACT, Fulvestrant and Anastrozole Combination Therapy; EFECT, The Evaluation of Faslodex versus Examestane;
SoFEA, Study of faslodex with or without concomitant arimidex vs exemestane following progression on non-steroidal aromatase inhibitors; CONFIRM,
Comparison of Faslodex in Recurrent or Metastatic Breast Cancer. The updated FIRST trial shows a PFS benefit with first-line fulvestrant. A high proportion of
patients enrolled in this trial were treatment naı¨ve (71.6% in the fulvestrant arm and 77.7% in the anastrozole arm). The SWOG S0226 trial examined the role of
combination therapy with anastrozole and fulvestrant vs. anastrozole alone, and found an improved PFS and OS which in contrast to the results of the FACT trial
showed no improvement in PFS and OS with combination anastrozole and fulvestrant. It should be noted that there was a large proportion of patients with de
novo metastatic disease (38.9%) in the SWOG S0228 trial and a higher proportion of patients in the FACT trial had prior exposure to tamoxifen (67 vs. 40%).
Several studies including Howell et al. showed that fulvestrant had similar PFS compared with anastrozole after prior endocrine therapy. The CONFIRM trial
showed that 500 mg dose was superior to the 250 mg dose. Also, the EFECT trial showed similar benefits with exemestane or fulvestrant in the second-line setting
therapy. The SoFEA trial showed that combination therapy offered no additional benefit in the second-line setting when compared to single agent therapy.
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phase II clinical trial examining the benefit of
AEZS-108 in chemotherapy-resistant triple-negative
breast cancer that expresses the LHRH receptor
[20
].
ENDOCRINE THERAPY FOR EARLY-STAGE
BREAST CANCER
Endocrine therapy in the adjuvant setting can con-
sist of treatment with tamoxifen, ovarian suppres-
sion, or aromatase inhibitors. Again, variability in
menopausal hormone environment leads to differ-
ent indicated treatment.
Tamoxifen
The benefits of adjuvant tamoxifen therapy have
been repeatedly demonstrated. The Early Breast
Cancer Trialists’ Collaborative Group (EBCTCG)
published a recent collaborative meta-analysis of
individual patient data from 20 trials with a median
follow-up of 13 years and showed that 5 years of
adjuvant tamoxifen therapy reduced the 15-year
risk of breast cancer recurrence and death [21].
Tamoxifen continues to be the standard of care
for adjuvant hormonal therapy in premenopausal
women as aromatase inhibitors are not active in this
population.
The duration of endocrine therapy remains
an important clinical question. The Adjuvant
Tamoxifen: Longer Against Shorter (ATLAS) trial
assessed the further effects of continuing tamoxifen
to 10 years instead of stopping at 5 years [22
]. This
trial accrued 12 894 women with early breast cancer
who had completed 5 years of treatment with adju-
vant tamoxifen therapy and they were randomly
assigned to continue tamoxifen to 10 years or stop at
5 years. After a median follow-up of 7.6 years, they
found that continuing tamoxifen reduced the risk of
breast cancer recurrence (P ¼ 0.002), reduced breast
cancer mortality (P ¼ 0.01) and reduced overall
mortality (P ¼ 0.01). Ten years of tamoxifen therapy
produced a further reduction in recurrence and
mortality, particularly after year 10. Longer therapy
was associated with an increased risk for pulmonary
embolism, and endometrial cancer, although this
risk was lower in premenopausal women. No
increase in the incidence of stroke was seen with
10 vs. 5 years and a decrease in the incidence of
ischemic heart disease was noted. The UK adjuvant
aTTom (Adjuvant Tamoxifen treatment-to offer
more) trial randomly allocated 7000 women,
most with unknown estrogen receptor status, to
continue tamoxifen to 10 years or stop at 5 years
[23
]. This study confirmed the reduction in recur-
rence and death seen with extended endocrine
therapy. On the basis of the results of the above
studies, a new standard of care for premenopausal
women with estrogen-receptor-positive tumors is
now 10 years of adjuvant tamoxifen therapy.
Ovarian suppression or ablation
Estrogen receptor expression is a powerful positive
predictive factor for antiestrogen therapy. However,
estrogen receptor expression may also be a negative
predictive factor for benefit from chemotherapy.
The EBCTCG examined the effects of ovarian
ablation on recurrence and death and showed that
in women less than 50 years of age, ablation of
functioning ovaries significantly improved the
long-term survival in the absence of chemotherapy
[24].
This led to a number of studies that have eval-
uated ovarian suppression vs. chemotherapy and
combination chemotherapy and ovarian suppres-
sion therapy in estrogen-receptor-positive premeno-
pausal women which are illustrated in Table 2. The
IBCSG (International Breast Cancer Study Group)
II-93, IBCSG VIII, and Austrian Breast and Colorectal
Cancer Study Group trial-12 (ABCSG-12) studies
show that a subset of premenopausal women
have benefit from adjuvant ovarian suppression
without systemic chemotherapy. In addition,
younger women who do not experience chemother-
apy-induced amenorrhea may benefit from ovarian
suppression with goserelin plus tamoxifen as illus-
trated by the INT (Intergroup) 0101 and IBCSG VIII
studies.
A recent Cochrane review examined the role of
LHRH agonists as ovarian suppression treatment for
early breast cancer in premenopausal women and
included 14 randomized trials that involved over
13 000 premenopausal women [32]. They concluded
that LHRH agonists show clinical benefit in the
adjuvant setting for premenopausal women; how-
ever, definitive comparisons against third-gener-
ation chemotherapy regimens and tamoxifen are
required before their place in the adjuvant setting
can be properly defined. Also, the American Society
of Clinical Oncology (ASCO) review panel stated
that ovarian suppression is not recommended either
as addition to systemic therapy or as an alternative
to systemic therapy and reiterated that the difficulty
with the available data is that ovarian function
suppression has not been compared with many
systemic treatment options (anthracycline-based
and taxane-based chemotherapy, aromatase inhibi-
tors) in use today [33]. They stated that ovarian
suppression should be considered only for women
who will not receive systemic treatment (e.g., those
patients who cannot tolerate or refuse systemic
Breast cancer
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therapy). However, if treatment with cyclophospha-
mide, methotrexate, and fluorouracil (CMF) is being
considered, there is available evidence to suggest
that ovarian suppression is a reasonable alternative.
More definitive information will be forthcom-
ing when the results of two ongoing studies are
available. One such trial is the Suppression of Ovar-
ian Function Trial (SOFT) that will assess the role of
ovarian suppression in combination with an aroma-
tase inhibitor (exemestane) compared with ovarian
suppression plus tamoxifen or tamoxifen alone as
adjuvant therapy [34]. The Tamoxifen and EXemes-
tane Trial (TEXT) trial will assess the benefit of an
LHRH agonist with the additional of either tamox-
ifen or exemestane for 5 years from the start of
adjuvant therapy [35]. In the TEXT trial, adjuvant
systemic chemotherapy was optional and lymph
node status was found to be the predominant deter-
minant of chemotherapy use [36]. The results of
both of these trials are anticipated in 2014 and
may greatly impact our current treatment
approaches.
Aromatase inhibitors
Premenopausal women who undergo ovarian func-
tion suppression may be treated with aromatase
inhibitors. The ABCSG-12 (Austrian Breast and
Colorectal Cancer Study Group Trial-12) random-
ized early-stage premenopausal women receiving
goserelin to either anastrozole or tamoxifen with
or without zoledronic acid [27]. At a median follow-
up of 62 months, there was no difference seen in
disease-free survival between patients receiving
anastrozole or tamoxifen, but those on anastrozole
alone had an inferior OS.
Many premenopausal women with early breast
cancer develop amenorrhea after chemotherapy,
Table 2. Role of adjuvant ovarian function suppression/ovarian ablation in premenopausal women
Study Population Intervention Endpoints Significant outcomes
Thurlimann, 2009
IBCSG 11-93 [25]
Node-positive HR þ
premenopausal
women
AC Â 4, OFS T vs.
OFS T
DFS, OS No difference in DFS and OS
between two groups. This trial
had lower risk node-positive
patient and small sample size
IBCSG VIII, 2003 [26] Node-negative pre/
premenopausal
women
CMF vs. Z vs.
CMF ! Z
DFS In HR-positive node-negative
patients, CMF alone and Z
alone had similar results. An
advantage to CMF ! was seen
in women 40
Ghant, 2011
ABCSG-12 [27]
Stage I or II HR þ
premenopausal
Z þ Ana; Z þ T DFS, OS No difference in DFS between
patients receiving Ana and T
overall, but those on Ana alone
had inferior OS
Davidson, 2005 INT
0101 [28]
Node-positive HR þ
premenopausal
women
CAF Â 6 vs. CAF ! Z
vs. CAF ! Z þ T
DFS, OS, TTR CAF-ZT improved TTR and DFS
but not OS but the addition of Z
did not significantly improve
outcome to CAF alone. Women
40 did appear to benefit
from Z
Ejlertsen, 2006 [29] Node positive or
tumors 5 cm
HR þ premenopausal
women
OA vs. CMF Â 6 DFS, OS OA had similar effect to CMF on
disease-free survival and OS
Jonat, 2002
ZEBRA study [30]
Node-positive
premenopausal
women
Z vs. CMF Â 6 DFS, OS In HR-positive patients, Z had
similar outcomes in DFS and
OS
Jakesz, 2002
ABCSG5 [31]
Stage I or II HR þ
premenopausal
Z þ T vs. CMF X6 RFS, OS Z þ T had significantly improved
RFS and trend toward OS
compared with CMF
IBCSG, International Breast Cancer Study Group; ABCSG, Austrian Breast and Colorectal Cancer Study Group; Int, Intergroup; ZEBRA, Zoladex Early Breast
Cancer Research Association; HR, hormone receptor; Ana, anastrozole; AC, adriamycin, cyclophosphamide; CAF, cyclophosphamide, doxorubicin, and
fluorouracil; CMF, cyclophosphamide, methotrexate, and fluorouracil; DFS, disease-free survival; OFS, ovarian function suppression; OA, ovarian ablation; OS,
overall survival; RFS, relapse-free survival; T, tamoxifen; TTR, time to recurrence; Z, goserelin; Zol, zoledronic acid. The ZEBRA, IBCSG VIII, IBCSG 11-93, and
Ejlertsen studies compare ovarian suppression vs. systemic chemotherapy and show that there are no differences between disease-free survival and OS between
the two arms. ABSCGF showed that complete ovarian suppression was better than systemic chemotherapy in relapse-free survival. In INT 0101 and IBCSG VIII,
systemic chemotherapy followed by ovarian suppression was found to be most beneficial in younger women (40 years of age). ABCSG-12 showed no
difference between tamoxifen or anastrozole combined with goserelin in disease-free survival.
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and in the majority of those older than age 40, this
is permanent. Some oncologists have started
extending the use of aromatase inhibitors to
women older than age 40 with chemotherapy-
induced ovarian failure. Aromatase inhibitors
must be used with caution in premenopausal
women who have had chemotherapy-induced
amenorrhea because they can be associated with
return of ovarian function and pregnancy. On the
basis of the results of the available data, we would
recommend continued use of tamoxifen in the
adjuvant setting in premenopausal women. How-
ever, if a premenopausal woman develops amenor-
rhea after chemotherapy and her hormone levels
are reflective of a postmenopausal setting, an
aromatase inhibitor could be used with close
monitoring. The results of the SOFT and the TEXT
trial will provide further recommendations for the
role of aromatase inhibitors in premenopausal
women.
In postmenopausal women, 5 years of adjuvant
aromatase inhibitors when compared with tamox-
ifen significantly lowered the recurrence rates;
however, no clear survival benefit has been demon-
strated until recently. The Breast International
Group (BIG) 1-98 trial was updated with a median
follow-up of 8.1 years and a survival benefit was
noted with letrozole monotherapy [37
].
The optimal duration of adjuvant endocrine
therapy for postmenopausal women is currently
unknown. The MA17 trial examined the effect of
adding an aromatase inhibitor after 5 years of
tamoxifen therapy in postmenopausal women and
benefit has been seen with the addition of an aroma-
tase inhibitor [38]. The results of the ATLAS trial,
discussed earlier, showed a benefit to extended
endocrine therapy using tamoxifen, suggesting that
this strategy may be useful; however, no trial has
evaluated 10 years of aromatase inhibitor therapy.
There are several ongoing studies comparing
extended vs. 5 years of aromatase inhibitor therapy
and results are anxiously awaited! On the basis of the
available data, standard of care is monotherapy with
an aromatase inhibitor for 5 years or sequential
therapy with tamoxifen for 2–5 years followed by
an aromatase inhibitor for 5 years. However, if a
woman is at high risk for relapse, it may be beneficial
to extend aromatase inhibitor therapy beyond the
5-year mark.
ROLE OF ENDOCRINE THERAPY IN
PRIMARY PREVENTION OF BREAST
CANCER
Tamoxifen and raloxifene are currently approved for
risk reduction in women at least 35 years of age at
greater than 1.2-fold increased risk of breast cancer
[39]. In MAP-3 (Mammary Prevention.3 trial),
exemestane was given to postmenopausal women
at risk for developing invasive breast cancer, and
after 3 years of follow-up, exemestane was found to
significantly reduce invasive breast cancer with no
serious toxic side-effects [40]. Results of the Inter-
national Breast Cancer Intervention Study 2 trial
(IBIS-2) evaluating anastrozole in the prevention
setting will be available in 2013.
CONCLUSION
Endocrine therapy continues to be the mainstay of
treatment for hormone-receptor-positive breast can-
cer at all stages and ages. Results of the recent
clinical trials demonstrate the benefit of 10 vs. 5
years of tamoxifen in the adjuvant setting for pre-
menopausal women and have examined the benefit
of combination endocrine therapy in the first-line
and second-line setting. In addition, targeted
therapy has been developed and validated as a useful
approach to overcoming resistance to endocrine
therapy. These studies will lead to practice change
for hormone-receptor-positive breast cancer. They
also pose new clinical questions and will guide
future research in order to determine the optimal
duration of adjuvant endocrine therapy, the most
beneficial sequence of endocrine therapy in the
metastatic setting and how to continue to overcome
endocrine resistance.
Acknowledgements
None.
Conflicts of interest
L.N.H. and N.W. have no conflicts of interest to report.
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Endocrine therapy in breast cancer Williams and Harris
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