NcXHF

SHARI GOLDFARB
KEY POINTS
Breast cancer and its treatment, especially endocrine
therapy, can cause sexual dysfunction, which is often
multifactorial in nature with both a physical and mental
component.
Clinicians should discuss sexual health with all women with
breast cancer and survivors of the disease.
Women with breast cancer often experience premature
menopause, which causes greater intensity and duration of
symptoms than women undergoing natural menopause.
Hot flashes, vaginal dryness, urogenital atrophy,
dyspareunia, decreased libido, and changes in sexual
response have been shown to negatively affect quality of
life, compliance with medication, and overall outcome.
Treatment options for sexual dysfunction in women with
breast cancer depend on the etiology of the problem and
concomitant medical conditions. Some possible treatments
include: lubricants, moisturizers, counseling, sex therapy,
altering contributing medications, physical therapy for
pelvic floor disorders, and mechanical devices/vibrators.
proach 48 hours and exemestane 27 hours) allowing for daily
dosing.
Fulvestrant
Fulvestrant is a selective estrogen receptor degrader that was
FDA approved in April 2002 for the treatment of hormone
receptor–positive metastatic breast cancer. Fulvestrant
downregulates the ER by binding to it and inducing a change
in conformational shape that prevents ER dimerization, resulting
in the loss of cellular ER. 14,15
OVARIAN SUPPRESSION
In premenopausal women with hormone receptor–positive
metastatic breast cancer, estrogen deprivation is a key therapeutic
strategy. Since the ovaries are the predominant sites of
estrogen synthesis in premenopausal women, a patient’s ovaries
must be medically suppressed or surgically ablated via
bilateral oophorectomies as part of her breast cancer treatment.
16,17 Estrogen levels are immediately and permanently
reduced to the postmenopausal range in all women after surgical
castration, whereas medical ablation is slower and may
take several weeks before estrogen is fully suppressed. Medical
ablation is performed by using a luteinizing hormonereleasing
hormone (LHRH) analog, which acts on the
hypothalamic-pituitary-ovarian axis and suppresses circulating
estrogen levels. 18 LHRH analogs include goserelin,
buserelin, triptorelin, and leuprolide and are administered as
either monthly or every 3 month injections. 18 Medical suppression
is reversible once the LHRH agonist is discontinued.
After the initial administration of an LHRH analog, there is a
surge in both estrogen and gonadotropin levels, which may
cause a tumor flare phenomenon.
More recently with the presentation and publication of
data from the Suppression of Ovarian Function Trial (SOFT)
and Tamoxifen and Exemestane trial (TEXT) studies, ovarian
suppression is being considered as adjuvant therapy for
some young premenopausal women with high-risk earlystage
disease. 19 The TEXT trial randomly assigned premenopausal
women with early-stage hormone receptor–positive
breast cancer to receive either 5 years of adjuvant therapy
with triptorelin in combination with tamoxifen or triptorelin
in combination with exemestane. The SOFT trial randomly
assigned premenopausal women with early-stage hormone
receptor–positive breast cancer to receive either ovarian suppression
with exemestane, ovarian suppression with tamoxifen,
or tamoxifen alone for 5 years. In the SOFT trial, ovarian
suppression could be achieved with either triptorelin, ovarian
irradiation, or bilateral oophorectomy.
The original plan was for separate statistical analyses for
the TEXT and SOFT studies followed by a planned combined
analysis of the ovarian suppression plus tamoxifen versus
ovarian suppression plus exemestane cohorts. 19 However, as
a result of low recurrence rates, in 2011 the studies were
amended to make the primary analysis a combined analysis.
The combined analysis had a median follow-up of 68
months. In the ovarian suppression plus exemestane cohort,
disease-free survival at 5 years was 91.1% compared with
87.3% in the ovarian suppression plus tamoxifen arm (hazard
ratio [HR] for disease recurrence, second invasive cancer, or
death, 0.72; 95% CI, 0.60 to 0.85; p 0.001). There was no
signifıcant difference in overall survival between the two
treatment groups (HR for death in the exemestane plus ovarian
suppression group, 1.14; 95% CI, 0.86 to 1.51; p 0.37).
SEXUAL SIDE EFFECTS OF ENDOCRINE THERAPY
In premenopausal women, the primary site of both estrogen
and testosterone synthesis is the ovaries. However, hormones
play essential roles in central and peripheral aspects of female
sexual function, sexuality, and integrity of the urogenital
tract. When premenopausal women undergo either medical
or surgical ovarian ablation for the treatment of breast cancer,
they are abruptly put into menopause. This can also
occur with chemotherapy-induced amenorrhea and menopause,
which may be transient or permanent. Premature
menopause often causes greater intensity and duration of
symptoms than women undergoing natural menopause. Hot
flashes, vaginal dryness, urogenital atrophy, dyspareunia, decreased
libido, and changes in sexual response have been
shown to negatively affect QoL, compliance with medication,
and overall outcome. Iatrogenic menopause often causes
lower steroid levels than natural menopause. For example,
testosterone levels in natural menopause are around 290 pg/
mL, but are 110 pg/mL in iatrogenic menopause, which substantially
worsens sexual function. Likewise, estradiol,
androstenedione, and dehydroepiandrosterone (DHEA) are
present at lower levels as a result of iatrogenic menopause compared
with natural menopause.
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2015 ASCO EDUCATIONAL BOOK | asco.org/edbook