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Review article
OOPHORECTOMY & ITS ROLE IN BREAST CANCER RISK REDUCTION
NORHAN AHMED AHMED HASSAN, EL-MENIAWY
Faculty of medicine-october 6 university

ARTICLE INFO ABSTRACT

Keywords: An oophorectomy is when a surgeon removes one or both ovaries. The ovaries are the
breast cancer
reproductive glands in women that make hormones to control the menstrual cycle and promote
oophorectomy
procedure
bone and heart health. Ovaries also contain and help grow eggs that can lead to pregnancy.
fertility. Owing to the significant breast cancer risk associated with BRCA1 or BRCA2 mutations, women
with these mutations have several options available to them by which to reduce the risk of
breast cancer. These include surgical (prophylactic mastectomy and prophylactic
oophorectomy) and medical (chemoprevention) options. The breast cancer risk reductions
associated with these options range from a 90% risk reduction associated with prophylactic
mastectomy to approximately 50% with oophorectomy or tamoxifen. This article reviews the
efficacy of prophylactic oophorectomy for the prevention of breast cancer in BRCA1 and BRCA2
mutation carriers. The predictors of uptake of the preventive surgery will be discussed, in
addition to the psychosocial implications of the surgery.

c
Copyright 2010 BioMedSciDirect Publications IJBMR - ISSN: 0976:6685. All rights reserved.

Anatomy that covers the ovary is known as the mesovarium.[4[The ovarian

Structure
The ovaries are considered the female gonads.[2] Each ovary is
whitish in color and located alongside the lateral wall of the uterus
in a region called the ovarian fossa. The ovarian fossa is the region
that is bounded by the external iliac artery and in front of the
ureter and the internal iliac artery. This area is about 4 cm x 3 cm x
2 cm in size.[3][4[The ovaries are surrounded by a capsule, and
have an outer cortex and an inner medulla.[4] The capsule is of
dense connective tissue and is known as the tunica
albuginea.[5[Usually, ovulation occurs in one of the two ovaries
releasing an egg each menstrual cycle.The side of the ovary closest
to the fallopian tube is connected to it by infundibulopelvic
ligament,[3] and the other side points downwards attached to the
uterus via the ovarian ligament.Other structures and tissues of the
ovaries include the hilum.
Ligaments
The ovaries lie within the peritoneal cavity, on either side of the
uterus, to which they are attached via a fibrous cord called the
ovarian ligament. The ovaries are uncovered in the peritoneal
cavity but are tethered to the body wall via the suspensory
ligament of the ovary which is a posterior extension of the broad
ligament of the uterus. The part of the broad ligament of the uterus
pedicle is made up part of the fallopian tube, mesovarium, ovarian
ligament, and ovarian blood vessels.[6]
Microanatomy
The surface of the ovaries is covered with membrane
consisting of a lining of simple cuboidal-to-columnar shaped
mesothelium,[7] called the germinal epithelium.Micrograph of
the ovarian cortex from a rhesus monkey showing several round
follicles embedded in a matrix of stromal cells. A secondary follicle
sectioned throughthe nucleus of an oocyte is at the upper left, and
earlier stage follicles are at the lower right. The tissue was stained
with the dyes hematoxylin and eosin.The outer layer is the ovarian
cortex, consisting of ovarian follicles and stroma in between them.
Included in the follicles are the cumulus oophorus, membrana
granulosa (and the granulosa cells inside it), corona radiata, zona
pellucida, and primary oocyte. Theca of follicle, antrum and liquor
folliculi are also contained in the follicle. Also in the cortex is the
corpus luteum derived from the follicles. The innermost layer is
the ovarian medulla.[8] It can be hard to distinguish between the
cortex and medulla, but follicles are usually not found in the
medulla.Follicular cells are flat epithelial cells that originate from
surface epithelium covering the ovary. They are surrounded by
granulosa cells that have changed from flat to cuboidal and
proliferated to produce a stratified epithelium. The ovary also
contains blood vessels and lymphatics.[9]

* Corresponding Author : NORHAN AHMED AHMED HASSAN

c Copyright 2011. CurrentSciDirect Publications. IJBMR - All rights reserved.

 Norhan Ahmed Ahmed Hassan, El-meniawy/Int J Biol Med Res.12(2):7322-7328
Physiology &Function
At puberty, the ovary begins to secrete increasing levels of
hormones. Secondary sex characteristics begin to develop in
response to the hormones. The ovary changes structure and function
beginning at puberty.[1] Since the ovaries are able to regulate
hormones, they also play an important role in pregnancy and
fertility. When egg cells (oocytes) are released from the Fallopian
tube, a variety of feedback mechanisms stimulate the endocrine
system which cause hormone levels to change.[10] These feedback
mechanisms are controlled by the hypothalamus and pituitary
gland. Messages from the hypothalamus are sent to the pituitary
gland. In turn, the pituitary gland releases hormones to the ovaries.
From this signaling, the ovaries release their own hormones.
Gamete production
The ovaries are the site of production and periodical release of
egg cells, the female gametes. In the ovaries, the developing egg cells
(or oocytes) mature in the fluid-filledThe process of ovulation and
gamete production, oogenesis, in a human ovary.follicles. Typically,
only one oocyte develops at a time, but others can also mature
simultaneously. Follicles are composed of different types and
number of cells according to the stage of their maturation, and their
size is indicative of the stage of oocyte development.[11]:833When
the oocyte finishes its maturation in the ovary, a surge of luteinizing
hormone secreted by the pituitary gland stimulates the release of the
oocyte through the rupture of the follicle, a process called
ovulation.[12] The follicle remains functional and reorganizes into a
corpus luteum, which secretes progesterone in order to prepare the
uterus for an eventual implantation of the embryo.[11]:839
Hormone secretion
At maturity, ovaries secrete estrogen, androgen,[13][14] inhibin,
and progestogen.[15][16][1] In women before menopause, 50% of
testosterone is produced by the ovaries and released directly into the
blood stream. The other 50% of testosterone in the blood stream is
made from conversion of the adrenal pre-androgens ( DHEA and
androstenedione) to testosterone in other parts of the body.
Estrogen is responsible for the appearance of secondary sex
characteristics for females at puberty and for the maturation and
maintenance of the reproductive organs in their mature functional
state. Progesterone prepares the uterus for pregnancy, and the
mammary glands for lactation. Progesterone functions with
estrogen by promoting menstrual cycle changes in the
endometrium.[medical citation needed[3)
Ovarian aging
As women age, they experience a decline in reproductive
performance leading to menopause. This decline is tied to a decline
in the number of ovarian follicles. Although about 1 million oocytes
are present at birth in the human ovary, only about 500 (about
0.05%) of these ovulate, and the rest are wasted. The decline in
ovarian reserve appears to occur at a constantly increasing rate with
age,[17] and leads to nearly complete exhaustion of the reserve by
about age 52. As ovarian reserve and fertility decline with age, there
is also a parallel increase in pregnancy failure and meiotic errors
resulting in chromosomally abnormal conceptions.
The ovarian reserve and fertility perform optimally around
20–30 years of age.[18] Around 45 years of age, the menstrual cycle
begins to change and the follicle pool decreases significantly.[18] The
7323
events that lead to ovarian aging remain unclear. The variability of
aging could include environmental factors, lifestyle habits or genetic
factors.[18[women with an inherited mutation in the DNA repair
gene BRCA1 undergo menopause prematurely,[19] suggesting that
naturally occurring DNA damages in oocytes are repaired less
efficiently in these women, and this inefficiency leads to early
reproductive failure. The BRCA1 protein plays a key role in a type of
DNA repair termed homologous recombinational repair that is the
only known cellular process that can accurately repair DNA double-
strand breaks. Titus et al.[20] showed that DNA double-strand
breaks accumulate with age in humans and mice in primordial
follicles. Primordial follicles contain oocytes that are at an
intermediate (prophase I) stage of meiosis. Meiosis is the general
process in eukaryotic organisms by which germ cells are formed, and
it is likely an adaptation for removing DNA damages, especially
double-strand breaks, from germ line DNA (see Meiosis and Origin
and function of meiosis).[citation needed] Homologous
recombinational repair is especially promoted during meiosis. Titus
et al.[20] also found that expression of 4 key genes necessary for
homologous recombinational repair of DNA double-strand breaks
(BRCA1, MRE11, RAD51 and ATM) decline with age in the oocytes of
humans and mice. They hypothesized that DNA double-strand break
repair is vital for the maintenance of oocyte reserve and that a
decline in efficiency of repair with age plays a key role in ovarian
aging.A variety of testing methods can be used in order to determine
fertility based on maternal age. Many of these tests measure levels of
hormones FSH, and GnrH. Methods such as measuring AMH (anti-
mullerian) hormone levels, and AFC (antral follicule count) can
predict ovarian aging. AMH levels serve as an indicator of ovarian
aging since the quality of ovarian follicles can be determined.[21]
The history behind the procedure
The relationship between breast cancer and the presence of
functional ovaries was first observed by a British doctor, Thomas
William Nunn. He reported breast cancer regression in a woman 6
months after she had reached menopause. Based on Mr. Nunn's
observation, a German surgeon, Albert Schinzinger, was the first to
propose removal of the ovaries as a potential therapy for breast
cancer. This procedure was subsequently done for the first time in
1895 by a British physician, George Thomas Beatson. While some
success was reported, it was largely unpopular at first, because it was
associated with a high degree of morbidity.It was not until the mid
20th century that large oophorectomy trials focusing on its role in
breast cancer were studied and reintroduced into the mainstream of
breast cancer treatment. Studies by reputable bodies, such as the
Early Breast Cancer Trialist's Collaborative Group, showed
compelling evidence for the procedure. These studies suggested that
the removal of the ovaries had a large positive effect on disease-free
survival as well as on the overall survival of patients with early breast
cancer. Advancements in medicine, and our understanding of breast
cancer, however, has affected the practice of oophorectomy. These
advancements include using chemotherapy, targeting hormone
receptors and alternative ways to suppress ovarian function without
the removal of these key organs.
Types of oophorectomy
The types of oophorectomy procedures include:
Bilateral oophorectomy is removal of both of the ovaries.
Unilateral oophorectomy is removal of only one of the ovaries.
 Norhan Ahmed Ahmed Hassan, El-meniawy/Int J Biol Med Res.12(2):7322-7328
7324
Other surgical procedures that may be performed
Hysterectomy is the removal of a woman's uterus. The uterus is a
pear-shaped organ in the lower abdominal (pelvic) area where a
baby grows during pregnancy.
Salpingectomy is the removal of one or both fallopian tubes, which
connect the ovaries to the uterus. Salpingectomy is often combined
with oophorectomy. If one fallopian tube is removed with one ovary,
the surgery is a unilateral salpingo-oophorectomy. If both fallopian
tubes are removed with both ovaries, it is a bilateral salpingo-
oophorectomy.
Indication of oophorectomy
A surgeon may remove one or both of your ovaries for several
reasons, including
• A disease known as endometriosis, when cells from inside the
womb (uterus) travel and grow elsewhere.
• Benign (non-cancerous) growths known as cysts.
• Preventative surgery for patients with a high risk of cancer of the
breast or ovaries.
• Cancer of the ovary.
• A condition known as torsion of the ovary. This condition
happens when the ovary twists around the blood supply, causing
severe pain.
• An infection of the ovary or the area around it, also known as
pelvic inflammatory disease (PID) or a tubo-ovarian abscess (TOA).
Women who possess BRCA1 and BRCA2 genetic mutations have
a greater risk of developing ovarian and breast cancer.Those who
have completed their families and have a genetic predisposition to
the development of these malignant conditions are prime candidates
for the procedure. It may also be performed prophylactically in
those who have a strong family history of ovarian and breast
cancer. Studies show that the risk of developing breast cancer in
women with a BRCA mutation may be halved by bilateral
oophorectomy. The chances of developing ovarian cancer in such
women may be reduced by up to 90% by this procedure.Important
to note that is that the total risk varies depending on several factors,
such as the lifestyle choices of the women (including their weight
management and alcohol consumption), and their family history.
Hence, oophorectomy may be of immense benefit in some women,
but not in others. In the latter, the risks associated with the
procedure and the possible side effects outweigh the benefit due to
the reduction in cancer propensity. While the surgical procedure is
generally safe, the associated risks include injury to internal organs,
intestinal blockage and infection. Moreover, the premature
reduction of sex hormones may lead to problems, such as
osteoporosis (or bone thinning) and an increased risk of heart
disease.
Procedures of the operation
Abdominal oophorectomy (open oophorectomy) is the removal
of the ovaries through a five to seven inch incision in the lower part of
your belly. The incision may be vertical or horizontal. A horizontal
incision (bikini cut) is placed very low on the abdomen so it is not
easily visible. Open surgery allows your doctor to directly see and
access the surgical area. Open surgery generally involves a longer
recovery and more pain than minimally invasive surgery. Open
surgery requires a larger incision and more cutting and
displacement of muscle and other tissues than minimally invasive
surgery. Despite this, open surgery may be a safer or more effective
method for certain patients.
Laparoscopic oophorectomy is the removal of the ovaries and
fallopian tubes through several small incisions in your abdomen.
Your doctor inserts a small tube fitted with a special camera and
other surgical instruments through the small incisions to remove the
ovaries. The camera transmits pictures of the inside of your body to a
video screen. Your doctor sees the inside of your abdomen on the
screen while performing surgery. Minimally invasive surgery
generally involves a faster recovery and less pain than open surgery.
This is because it causes less trauma to tissues and organs. A vaginal
approach can also be performed, especially when combined with
hysterectomy.
Types of anasethia that may be used
General anesthesia is generally a combination of intravenous
(IV) medications and gases that put you in a deep sleep. You are
unaware of the procedure and do not feel any pain. You may also have
a peripheral nerve block infusion in addition to general anesthesia. A
peripheral nerve block infusion is an injection or continuous drip of a
liquid anesthetic. The anesthetic flows through a tiny tube inserted
near your surgical site to control your pain during and after surgery.
Regional anesthesia is also known as a nerve block. It involves
injecting an anesthetic around certain nerves to numb a large area of
the body. You will likely have sedation with regional anesthesia to
keep you relaxed and comfortable
Risks and complications of the procedure
Oophorectomy is a generally safe procedure that carries a small
risk of complications, including infection, intestinal blockage and
injury to internal organs. The risk of complications depends on how
the procedure is performed.But more concerning is the impact of
losing the hormones supplied by your ovaries. If you have yet to
undergo menopause, oophorectomy causes early menopause. Early
menopause carries many risks, including:
Reducing risk of complication
• Following activity, dietary and lifestyle restrictions and
recommendations before, during and after surgery or treatment
• Informing the patient is nursing or there is any possibility that
may be pregnant
• Losing weight if there is overweight. This will help to keep
patient as healthy as possible and may reduce risk of heart disease
and of bone fractures.
• Notifying doctor immediately of any concerns after surgery, such
as bleeding, fever, increase in pain, or wound redness, swelling or
drainage
• Stopping smoking. This can help reduce the risk of osteoporosis
and heart disease.
• Taking medications exactly as directed
Managing side effects of prophylactic oophorectomy
Non-hormonal treatments
The side effects of oophorectomy may be alleviated by medicines
other than hormonal replacement. Non-hormonal biphosphonates
(such as Fosamax and Actonel) increase bone strength and are
available as once-a-week pills. Low-dose selective serotonin
 Norhan Ahmed Ahmed Hassan, El-meniawy/Int J Biol Med Res.12(2):7322-7328
reuptake inhibitors such as Paxil and Prozac alleviate vasomotor
menopausal symptoms, i.e., "hot flashes".[42]
Hormonal treatments
In general, hormone replacement therapy is somewhat
controversial due to the known carcinogenic and thrombogenic
properties of estrogen; however, many physicians and patients feel
the benefits outweigh the risks in women who may face serious
health and quality-of-life issues as a consequence of early surgical
menopause. The ovarian hormones estrogen, progesterone, and
testosterone are involved in the regulation of hundreds of bodily
functions; it is believed by some doctors that hormone therapy
programs mitigate surgical menopause side effects such as increased
risk of cardiovascular disease,[43] and female sexual
dysfunction.[44[Short-term hormone replacement with estrogen
has negligible effect on overall mortality for high-risk BRCA
mutation carriers. Based on computer simulations, overall mortality
appears to be marginally higher for short-term HRT after
oophorectomy or marginally lower for short-term HRT after
oophorectomy in combination with mastectomy.[45] This result can
probably be generalized to other women at high risk in whom short-
term (i.e., one- or two-year) treatment with estrogen for hot flashes
may be acceptable.
Ooprhorectomy impact on chances of fertility
Removing one ovary will not significantly change your chances of
becoming pregnant, assuming your other ovary and fallopian tube
are working normally. Removing both tubes and ovaries will mean
that the person will no longer be able to become pregnant on their
own. Young women who are told they need to undergo removal of
both tubes and ovaries should see an infertility doctor to talk about
storing eggs before the procedure.(23)
Relation of oophorectomy to menopause
Ovaries produce estrogen and progesterone, both of which help
control the menstrual cycle. Removing both ovaries will cause
menopause to begin immediately. It is important to be aware that
this will happen before the procedure. Even if patient is no longer
considering having children, it is important to be prepared for
symptoms after surgery. In addition to no longer having periods,
menopause can cause (19)
· Hot flashes
· Vaginal dryness
· Depression
· Memory loss
· Loss of sexual drive
· Memory problems
· Osteoporosis
Consideration of prophylactic oophorectomy
Prophylactic oophorectomy is usually reserved for those with:
Inherited gene mutations. People with a significantly increased
risk of breast cancer and ovarian cancer due to an inherited mutation
in the BRCA1 or BRCA2 gene — two genes linked to breast cancer,
ovarian cancer and other cancers who have completed childbearing
may consider this procedure. People with other inherited gene
mutations that increase the risk of ovarian cancer, including those
with Lynch syndrome, might also consider this procedure.
7325
Strong family history. Prophylactic oophorectomy may also be
recommended if you have a strong family history of breast cancer
and ovarian cancer but no known genetic alteration. It might also be
recommended if you have a strong likelihood of carrying the gene
mutation based on your family history but choose not to proceed
with genetic testing.(15)
Role of oophprectomy in breast cancer risk reduction
Clinical genetic testing for BRCA1 and BRCA2 mutations has
been available since 1995. Based on a large combined analysis, for
women who are identified as having a mutation in BRCA1 the risk of
breast cancer is 65% and the risk of ovarian cancer is 39%; for
women with a BRCA2 mutation, the risk for breast cancer is 45% and
the risk for ovarian cancer is 11% [1]. These cancer risks can be
compared with the general population risks of 11 and 1.4% for
breast and ovarian cancer, respectively. In addition to these
increased risks, women with BRCA1 or BRCA2 mutations are often
diagnosed at younger ages than women in the general
population.There are differences in the breast cancer phenotypes
observed in BRCA1 compared with BRCA2 mutation carriers.
Estrogen receptor status has been demonstrated to be different in
these two groups of women. Only 10–24% of BRCA1-associated
breast cancers are ER-positive, compared with 65-79% of BRCA2-
associated breast cancers [2,3]. This may have implications for the
ways in which BRCA breast cancers are treated and the effectiveness
of breast cancer risk-reduction strategies.
Prophylactic salpingo-oophorectomy
A prophylactic salpingo-oophorectomy (PSO) involves the
removal of both the ovaries and fallopian tubes. It is important that
the fallopian tubes are removed since they have become recognized
as an important site of occult cancer in BRCA1 and BRCA2 mutation
carriers who have undergone prophylactic oophorectomy [10–13].
Currently, PSO is the most effective option available to women with
BRCA1 or BRCA2 mutations by which to prevent ovarian cancer
[8,14[.Although it was recognized that PSO would reduce the risk of
ovarian cancer in BRCA1 and BRCA2 mutation carriers, it was
unclear if the procedure would also reduce the risk of breast cancer
in this group of high-risk women. In 2002, the first two studies
investigating the breast cancer risk reduction associated with
prophylactic oophorectomy in BRCA1 and BRCA2 mutation carriers
were reported [8,15]. Kauff et al. followed 170 BRCA1 and BRCA2
mutation carriers over the age of 35 years for a mean time of 24.2
months [15]. Of the 98 women who underwent PSO, three (3%)
developed breast cancer compared with eight of 72 women (11%)
who chose surveillance. Similar findings were reported by Rebbeck
et al. in a retrospective study of 99 women who had undergone PSO
compared with 142 matched controls [8]. The follow-up period was
greater than 8 years. Of the 99 women who had undergone PSO, 21
(21%) developed breast cancer compared with 60 (42%) in the
control group (hazard ratio [HR] = 0.47; 95% CI: 0.29–0.77). This
suggested that PSO was associated with a 53% breast cancer risk
reduction. In both of these early studies, there were no specific
analyses undertaken to examine the effectiveness of PSO in the
prevention of breast cancer specifically for BRCA1 versus BRCA2.In
2005, Eisen et al. presented a large, international, retrospective
study of 1439 women with breast cancer and 1866 matched controls
[6]. They reported that a previous history of oophorectomy was
associated with a significant 56% reduction in the breast cancer risk
for BRCA1 mutation carriers (odds ratio [OR] = 0.44; 95% CI:
0.29–0.66) and a 46% risk reduciton for BRCA2 mutation carriers
(OR = 0.57; 95% CI: 0.28–1.15). The protective effect was evident for
 Norhan Ahmed Ahmed Hassan, El-meniawy/Int J Biol Med Res.12(2):7322-7328
7326
15 years post-oophorectomy. This study suggested that PSO may be
more effective in preventing breast cancer in BRCA1 mutation
carriers compared with BRCA2 mutation carriers.In contrast to this
finding, Kauff et al. reported on 579 women without breast cancer
(368 BRCA1 and 229 BRCA2) in a prospective follow-up study [7].
Women self-selected PSO or observation. During a 3-year follow-
up period, PSO was associated with a 39% breast cancer risk
reduction in BRCA1 mutation carriers (HR = 0.61; 95% CI:
0.30–1.22; p = 0.16) and a 72% risk reduction in BRCA2 mutation
carriers (HR = 0.28; 95% CI: 0.08–
0.92; p = 0.04). These results suggested that PSO was more
effective for BRCA2 mutation carriers than BRCA1 mutation carriers.
Although the results of these two studies differ in the effectiveness of
PSO in BRCA1 versus BRCA2 mutation carriers, they both support
the hypothesis that estrogen deprivation reduces the risk of breast
cancer. This has also been supported by research on tamoxifen
(antiestrogen) and breast cancer risk (both bilateral and
contralateral) [9,16]. All research published to date suggests that
PSO is effective at reducing the risk of breast cancer in women with a
BRCA1 or BRCA2 mutation (between 39 and 72%) (Table 1).
For PSO to be effective at reducing the risk of breast cancer in
BRCA1 and BRCA2 mutation carriers, the procedure must be carried
out at an earlier age than when breast cancers are first observed in
this group of women. This suggests that the procedure should be
ideally performed between 40 and 45 years of age. In addition,
research has shown that the level of breast cancer risk reduction is
associated with age at PSO, probably owing to the amount of
estrogen production. Although women may want to wait until the
onset of menopause to have a PSO because of the side effects
associated with the surgery, research suggests that PSO should be
carried out earlier for maximum breast cancer risk reduction. In the
large, international study of BRCA1 and BRCA2 mutation carriers by
Eisen et al., age at oophorectomy was found to be associated with
breast cancer risk reduction [6]. Women with oophorectomy under
the age of 40 years gained the greatest breast cancer risk reduction of
67% (OR = 0.33; 95% CI: 0.15–0.73; p = 0.006). Having the
preventive surgery between the ages of 41 and 50 years also offered
a significant breast cancer risk reduction (OR = 0.43; 95% CI:
0.25–0.72; p = 0.001). However, having the surgery after the age of 50
years did not significantly reduce a woman's breast cancer risk (OR =
0.64; 95% CI: 0.35–1.17; p = 0.14). It is unclear if there are age
differences for BRCA1 mutation carriers compared with BRCA2
mutation carriers. There have been no other studies conducted with
a sample size this large that would enable subanalyses on age groups.
Although this study suggests that a younger age of PSO is beneficial
in terms of breast cancer prevention, other issues including family
planning and premature estrogen deficiency must also be
considered.
other study should be considered that Of 170 women who met
the criteria for entry, 98 elected to undergo risk-reducing salpingo-
oophorec- tomy a median of 3.6 months after receiving the re- sults
of genetic testing, and 72 chose surveillance for ovarian cancer.
There was no significant difference be- tween the two groups in
terms of mean age, percent- age with BRCA1 or BRCA2 mutations,
mean num- ber of first- and second-degree relatives with breast,
ovarian, fallopian-tube, or primary peritoneal cancer, and
percentage with a history of breast cancer, sys- temic chemotherapy,
or oral-contraceptive use. More women in the salpingo-
oophorectomy group than in the surveillance group (29 of 98 women
[30 percent] vs. 10 of 72 women [14 percent]) had undergone bi-
lateral mastectomy before the start of follow-up (P= 0.02). There was
no significant difference in the num- ber of women who underwent
bilateral mastectomy during a mean of 24.2 months of follow-up.
Com- plete demographic information for the two groups is
summarized in Table 2. (46)
Psychosocial implications
Although PSO offers a significant breast and ovarian cancer risk
reduction in BRCA1 and BRCA2 mutation carriers, there are side
effects that should be considered when making decisions about
breast cancer prevention. When a premenopausal woman has an
oophorectomy, she is immediately placed into menopause and as a
result, experiences menopausal symptoms. Although this is not the
focus of this paper, the effects of premature surgical menopause on
overall health need to be carefully considered. Hormone therapy
(HT) is an option for women who experience menopausal
symptoms. However, there has been concern that HT use would
increase a woman's risk of developing breast cancer. In a recent
large, matched case–control study, Eisen et al. reported that among
postmenopausal women with a BRCA1 mutation, HT was not
associated with an increased risk of breast cancer [24[.Menopausal
symptoms may influence psychosocial functioning in women who
undergo prophylactic oophorectomy. There is limited research
describing the psychosocial impact of having a prophylactic
oophorectomy. Elit et al. conducted a retrospective study of 40
women who had undergone a prophylactic oophorectomy for a
family history of ovarian cancer [25]. The mean age of the women at
time of oophorectomy was 50 years and the mean age at the time of
questionnaire completion was 55 years. Standardized psychosocial
questionnaires were used to measure various psychosocial
attributes. Women in the study had a good quality of life and a
significant decrease in cancer risk perception as a result of the
surgery. However, they experienced menopausal symptoms and
compromised sexual functioning. A larger study of 846 Dutch
women who had undergone prophylactic oophorectomy had similar
findings [26]. Compared with gynecologic screening, women with an
oophorectomy had fewer breast and ovarian cancer worries (p <
0.001) and more favorable cancer risk perception (p < 0.05).
However, the oophorectomy group reported significantly more
endocrine symptoms (p < 0.001) and worse sexual functioning (p <
0.05) than the screening group.The impact of PSO on cancer-related
anxiety has also been studied. In an Australian study, Tiller et al.
conducted a prospective study of 95 women who were initially
assessed at a familial cancer clinic and followed-up 3 years later [27].
There was a higher decrease in cancer-related anxiety for women
who had undergone prophylactic oophorectomy compared with
those who had not (Z = −2.19; p = 0.03(.The research to date suggests
that PSO offers both psychosocial risks and benefits. Women
generally have lower cancer risk perception and lower cancer-
related anxiety. However, the sexual side effects associated with the
surgery and resulting menopause are also evident. In the majority of
studies that have examined psychosocial implications of PSO, the
average age of subjects has been approximately 50 years, which is
close to the age of natural menopause. However, PSO is generally
recommended to BRCA1 and BRCA2 mutation carriers at an age
younger than 50 years. Therefore, it is unclear if psychosocial
implications after PSO in younger women would be the same as
those reported previously. More research is needed in this area.
 Norhan Ahmed Ahmed Hassan, El-meniawy/Int J Biol Med Res.12(2):7322-7328
Table 1. Summary of studies on breast cancer risk reduction
and prophylactic oophorectomy.
Conclusion
Prophylactic salpingo-oophorectomy is effective at preventing
both breast and ovarian cancer in women with BRCA1 or BRCA2
mutations. For maximum breast cancer risk reduction, PSO should
be conducted around the age of 40 years. However, older age has
been shown to be associated with uptake of PSO. In addition,
women with a family history of ovarian cancer, those with a BRCA1
mutation and those with a personal history of breast cancer have
the highest uptake rates of PSO. As with any preventive option,
there are psychosocial implications associated with the
procedure; however, more research is needed in this area. Many
women with BRCA1 and BRCA2 mutations are electing for a PSO.
Research has shown that it significantly reduces a woman's risk of
developing breast cancer, especially if it is carried out at a young
age (before 50 years of age). However, there is little research
addressing the psychosocial implications of PSO on women when
they are having this surgery carried out prior to menopause.
Future research is needed in this area.
7327
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