Download Prophylactic Mastectomy And Prophylactic Bilateral Oophorectomy

MEDICAL POLICY
POLICY TITLE
PROPHYLACTIC MASTECTOMY AND PROPHYLACTIC BILATERAL
OOPHORECTOMY
POLICY NUMBER
MP- 1.036
Original Issue Date (Created):
10/11/2002
Most Recent Review Date (Revised):
5/31/2016
Effective Date:
11/22/2016
POLICY
RATIONALE
DISCLAIMER
POLICY HISTORY
I.
PRODUCT VARIATIONS
DEFINITIONS
CODING INFORMATION
DESCRIPTION/BACKGROUND
BENEFIT VARIATIONS
REFERENCES
POLICY
Prophylactic Mastectomy
Prophylactic mastectomy may also be considered medically necessary in patients at high
risk of breast cancer. (For definitions of risk levels, see policy guidelines, below.)
Prophylactic mastectomy may be considered medically necessary in patients with such
extensive mammographic abnormalities (i.e., calcifications) that adequate biopsy or
excision is impossible.
Prophylactic mastectomy is considered investigational for all other indications, including
but not limited to contralateral prophylactic mastectomy in women with breast cancer who
do not meet high risk criteria. There is insufficient evidence to support a conclusion
concerning the health outcomes or benefits associated with this procedure.
Policy Guidelines
It is strongly recommended that all candidates for prophylactic mastectomy undergo
counseling regarding cancer risks from a health professional skilled in assessing cancer
risk other than the operating surgeon and discussion of the various treatment options,
including increased surveillance or chemoprevention with tamoxifen or raloxifene.
There is no standardized method for determining a woman’s risk of breast cancer that
incorporates all possible risk factors. There are validated risk prediction models, but they
are based primarily on family history.
Some known individual risk factors confer a high risk by themselves. The following list
includes factors known to indicate a high risk of breast cancer:
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MEDICAL POLICY
POLICY TITLE
PROPHYLACTIC MASTECTOMY AND PROPHYLACTIC BILATERAL
OOPHORECTOMY
POLICY NUMBER
MP- 1.036

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lobular carcinoma in situ or
a known BRCA1 or BRCA2 mutation or
another gene mutation associated with high risk, e.g., TP53 (Li-Fraumeni
syndrome), PTEN (Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome),
CDH1, and STK11 or
high risk (lifetime risk about 20% or greater) of developing breast cancer as
identified by models that are largely defined by family history or
received radiotherapy to the chest between 10 and 30 years of age.
A number of other factors may increase the risk of breast cancer but do not by themselves
indicate high risk. It is possible that combinations of these factors may be indicative of high
risk, but it is not possible to give quantitative estimates of risk. As a result, it may be
necessary to individualize the estimate of risk taking into account numerous risk factors. A
number of risk factors, not individually indicating high risk, are included in the National
Cancer Institute Breast Cancer Risk Assessment Tool, also called the Gail Model. Risk
factors in the model can be accessed online
(http://www.cancer.gov/bcrisktool/Default.aspx).
Prophylactic Oophorectomy
Prophylactic bilateral oophorectomy may be considered medically necessary for women
with the following conditions:


Two or more first-degree relatives (e.g., parent, sibling, offspring) with a diagnosis
of ovarian cancer; or
Women with known BRCA1 or BRCA2 mutations associated with breast-ovarian
cancer syndrome.
Cross-references
MP-2.211 Genetic Testing for Hereditary Breast and/or Ovarian Cancer Syndrome
(BRCA1/BRCA2)
MP-2.235 Assays of Genetic Expression in Tumor Tissue as a Technique to Determine
Prognosis in Patients with Breast Cancer
II. PRODUCT VARIATIONS
Top
This policy is applicable to all programs and products administered by Capital BlueCross
unless otherwise indicated below.
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POLICY TITLE
PROPHYLACTIC MASTECTOMY AND PROPHYLACTIC BILATERAL
OOPHORECTOMY
POLICY NUMBER
MP- 1.036
FEP PPO*
*The FEP program dictates that all drugs, devices or biological products approved by the U.S.
Food and Drug Administration (FDA) may not be considered investigational. Therefore, FDAapproved drugs, devices or biological products may be assessed on the basis of medical
necessity.
III. DESCRIPTION/BACKGROUND
Top
Prophylactic Mastectomy
Prophylactic mastectomy (PM) is defined as the surgical removal of the breast in the absence of
malignant disease to reduce the risk of breast cancer occurrence.
Prophylactic mastectomies may be considered in women thought to be at high risk of developing
breast cancer, either due to a family history, presence of genetic mutations such as BRCA1 or
BRCA2, having received radiation therapy to the chest, or the presence of lesions associated with
an increased cancer risk such as lobular carcinoma in situ (LCIS). LCIS is both a risk factor for
all types of cancer, including bilateral cancer, and in some cases, a precursor for invasive lobular
cancer. For those who develop invasive cancer, up to 35% may have bilateral cancer. Therefore,
bilateral PM may be performed to eliminate the risk of cancer arising elsewhere;
chemoprevention and close surveillance are alternative risk reduction strategies. Prophylactic
mastectomies are typically bilateral but can also describe a unilateral mastectomy in a patient
who has previously undergone or is currently undergoing a mastectomy in the opposite breast for
an invasive cancer. (i.e., contralateral prophylactic mastectomy [CPM]). The use of CPM has
risen in recent years in the United States. An analysis of data from the National Cancer Data
Base found that the rate of CPM in women diagnosed with unilateral stage I-III breast cancer
increased from approximately 4% in 1998 to 9.4% in 2002.(1)
The appropriateness of a PM is a complicated risk-benefit analysis that requires estimates of a
patient’s risk of breast cancer, typically based on the patient’s family history of breast cancer
and other factors. Several models are available to assess risk, such as the Claus model and the
Gail model. Breast cancer history in first- and second-degree relatives is used to estimate breast
cancer risk in the Claus model. The Gail model uses the following 5 risk factors: age at
evaluation, age at menarche, age at first live birth, number of breast biopsies, and number of
first-degree relatives with breast cancer.
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POLICY TITLE
PROPHYLACTIC MASTECTOMY AND PROPHYLACTIC BILATERAL
OOPHORECTOMY
POLICY NUMBER
MP- 1.036
Prophylactic Oophorectomy
Prophylactic oophorectomy is the preventive, surgical removal of the ovaries. The goal of
prophylactic oophorectomy is to prevent the development of ovarian cancer and/or reduce the
risk of breast cancer in women who are at high risk for these diseases.
Ovarian epithelial carcinoma is one of the most common gynecologic malignancies and the
leading cause of death due to gynecologic malignancy. Most women are diagnosed after the age
of 50, with the greatest risk of ovarian cancer occurring in women over the age of 70. The
lifetime risk of developing ovarian cancer is 1.7% for the general population. Due to the
inadequacies of existing screening techniques, which include pelvic examination, transvaginal
ultrasound, and serum CA-125 testing, most cases of ovarian cancer go undiagnosed until the
disease is well advanced and survival rates for ovarian cancer are very poor. The etiology of
ovarian cancer is uncertain but increased age, nulliparity, and a family history of the disease
confer an increased risk, with family history being the strongest risk factor.
There are three major ovarian cancer syndromes: hereditary breast and ovarian cancer (HBOC),
which is caused by mutations in the breast cancer susceptibility genes BRCA1 and BRCA2, sitespecific ovarian cancer syndrome, and Lynch II Syndrome (a combination of breast, ovarian,
endometrial, gastrointestinal, and genitourinary cancers), which is associated with hereditary
nonpolyposis colorectal cancer (HNPCC). Autosomal dominant inheritance has been shown in
some of these mutations, and the lifetime risk for ovarian cancer associated with these
syndromes ranges from 5% to over 60%, depending on the population studied. Women who have
these gene mutations are at risk for other cancers, and the lifetime risk of breast cancer among
women with a mutation in BRCA1 or BRCA2 approaches 90%. While screening measures for
breast cancer generally detect tumors at earlier stages than do ovarian cancer screening measures,
no screening test for either breast or ovarian cancer has been shown to decrease cancer risk.
IV. RATIONALE
TOP
Prophylactic Mastectomy
Most recently, the literature was searched through January 7, 2016. Following is a summary of
the key literature.
Prophylactic Mastectomy
The evidence review was initially based on a 1999 TEC Assessment that concluded prophylactic
mastectomy (PM) met the TEC criteria for patients with a family history of breast cancer.2 The
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PROPHYLACTIC MASTECTOMY AND PROPHYLACTIC BILATERAL
OOPHORECTOMY
POLICY NUMBER
MP- 1.036
Assessment largely focused on a 1999 retrospective cohort analysis that found approximately 13
moderate-risk women would have to have PM to prevent 1 cancer. For those at high risk of
breast cancer, reduction in breast cancer incidence ranged from 90% to 94%. Four to 8 high-risk
women would need to undergo PM to prevent 1 occurrence of breast cancer.
As of 2014, the National Comprehensive Cancer Network guideline recommends that PM should
only be considered in high-risk women, defined as having a BRCA1 or BRCA2 mutation or
another gene mutation associated with increased risk (e.g., PTEN [Cowden and Bannayan-RileyRuvalcaba syndromes], TP53 [Li-Fraumeni syndrome], CDH1, STK11), a compelling family
history, and possibly in women with lobular carcinoma in situ (LCIS) or prior thoracic
radiotherapy before 30 years of age.3 In patients who received radiotherapy to the chest between
the ages of 10 and 30 years of age, the increased risk of breast cancer can reach almost 30% by
age 55 years.4 Patients with LCIS, which is usually identified incidental to breast biopsy, are also
at increased risk of cancer. In 2011, Oppong and King reported that, compared with the general
population, women with LCIS face an 8- to 10-fold increased risk of cancer, equaling 26% after
20 years in 1 study.5
A 2010 Cochrane review examined the impact of PM on mortality and other health outcomes.6
The authors did not identify any randomized controlled trials (RCTs). Thirty-nine observational
studies with some methodologic limitations were identified in the literature search. The studies
presented data on 7384 women with a wide range of risk factors for breast cancer who underwent
PM. Studies on the incidence of breast cancer and/or disease-specific mortality reported
reductions after bilateral PM, particularly for those with BRCA1 or BRCA2 mutations. The
authors concluded that, while the available observational data suggested bilateral PM reduces the
rate of breast cancer mortality, more rigorous studies (ideally RCTs) were needed, and that
bilateral PM should only be considered among patients at very high risk of disease.
Section Summary: Prophylactic Mastectomy
Evidence from systematic reviews found that reduction in breast cancer incidence is reduced and
breast cancer survival is increased in women at high risk of breast cancer, especially those with
BRCA1 or BRCA2 and selected other mutations and those with a compelling family history.
Contralateral Prophylactic Mastectomy
Incidence of Second Primary Breast Cancer
The potential for CPM to impact survival is related to its association with a reduced risk of
subsequent primary breast cancer in the other breast (i.e., contralateral breast cancer [CBC]). In
general, according to data from the U.S. Surveillance, Epidemiology and End Results (SEER)
database, annual rates of CBC were stable between 1975 and 1985, after which rates declined
about 3% per year (95% confidence interval [CI], 2.7% to 3.5%).7 Beginning in 1990, the annual
decline in CBC rates was only in women with estrogen receptor‒positive cancer, with no
decrease in women with estrogen receptor‒negative cancer. The investigators suggested that the
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POLICY TITLE
PROPHYLACTIC MASTECTOMY AND PROPHYLACTIC BILATERAL
OOPHORECTOMY
POLICY NUMBER
MP- 1.036
decrease in CBC rates after estrogen receptor‒positive cancer may be attributed at least in part to
the increased availability of adjuvant hormone therapies.
Studies were sought on the risk of CBC in women who meet high-risk criteria versus averagerisk criteria. In 2014, Molina-Montes et al published a systematic review of studies on the risk of
a second primary breast cancer in women with and without BRCA1 or BRCA2 mutations.8
Twenty studies were included; 12 retrospective cohort studies, 2 prospective cohort studies, and
6 case-control studies. Most studies included only women who had undergone genetic testing; it
is likely that even those who tested negative had other risk factors that motivated testing. A
meta-analysis found that the cumulative risk of a second primary breast cancer at 5 years after
initial diagnosis was 14% (95% CI, 9% to 19%) in BRCA1 or BRCA2 mutation carriers and 3%
(95% CI, 2% to 5%) in noncarriers. Cumulative risks of a second primary cancer at 10 years
after initial diagnosis was 22% (95% CI, 18% to 27%) in BRCA1 or BRCA2 mutation carriers
and 5% (95% CI, 3% to 7%) in noncarriers.
Survival
As is the case for bilateral PM, no RCTs evaluating the effect of CPM on health outcomes have
been published. There are a number of observational studies, including some with large sample
sizes, and a systematic review of observational studies. Observational studies have attempted to
control for potential confounders, but not all relevant factors were measured, and the possibility
of selection bias remains.
A systematic review and meta-analysis of studies on CPM was published in 2014 by Fayanju et
al.9 The authors searched for published studies that compared the incidence of CBC in women
with unilateral disease who did and did not undergo CPM. Fourteen observational studies met
eligibility criteria and were included in the meta-analysis. In a meta-analysis of 4 studies,
mortality from breast cancer was lower in the group that had CPM (relative risk [RR], 0.69; 95%
CI, 0.56 to 0.85). Moreover, in a meta-analysis of data from 6 studies, overall survival (OS) was
significantly higher in patients who underwent CPM (n=10,666) than those who had no CPM
(n=145,490) (RR=1.09; 95% CI, 1.06 to 1.11). The authors also conducted a subgroup analysis
by risk level. Studies in which all patients were BRCA mutation carriers and studies in which all
patients had a family history of breast cancer (4 studies) were categorized as indicating higher
familial/genetic risk. Together, the studies included 618 patients who had CPM and 1318
patients who did not. In a meta-analysis limited to these 4 studies, neither OS nor mortality from
breast cancer differed significantly among women who had or did not have CPM. The relative
risk of breast cancer mortality with and without CPM was 0.66 (95% CI, 0.27 to 1.64). For OS
with and without CPM, the relative risk was 1.09 (95% CI, 0.97 to 1.24). The absolute reduction
in the risk of metachronous breast cancer did not differ in women with and without CPM when
data from all 8 studies were analyzed (risk difference [RD], -18.0%; 95% CI, -42.0% to 5.9%,
but was significantly lower in women with CPM in the 4 studies exclusively enrolling women at
increased familial/genetic risk (RD = -24.0%; 95% CI, -35.6% to -12.4%). Commenting on the
totality of findings, the authors stated that the improvement in survival after CPM in the general
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PROPHYLACTIC MASTECTOMY AND PROPHYLACTIC BILATERAL
OOPHORECTOMY
POLICY NUMBER
MP- 1.036
breast cancer population was likely not due to a decreased incidence of contralateral breast
cancer, but rather was secondary to selection bias (e.g., CPM recipients may be otherwise
healthier and have better access to health care).
Studies in the Fayanju meta-analysis were published between 1997 and 2005. More recent large
observational analyses are described below.
Other analyses have also suggested that the association between CPM and reduced mortality
identified in some data analyses can be attributed at least in part to selection of a healthier cohort
of women for CPM.10,11 In particular, a 2014 analysis by Kruper et al of a large dataset from the
SEER database looked at CBC and survival outcomes.10 The investigators conducted a casecontrol analysis including 28,015 CPM patients and 28,015 unilateral mastectomy patients,
matched on age group, race/ethnicity, extent of surgery, tumor grade, tumor classification, node
classification, estrogen receptor status, and propensity score. The investigators were not able to
match for BRCA or other mutation status. When all matched patients were included, diseasespecific survival (DSS) and OS were significantly lower in women who underwent unilateral
mastectomy compared with CPM. For DSS, the hazard ratio (HR) was 0.83 (95% CI, 0.77 to
0.90); for OS, it was 0.77 (95% CI, 0.73 to 0.82). Presumably, CPM would increase survival by
lowering the risk of CBC. The authors conducted another analysis excluding women diagnosed
with CBC; the remaining sample was still large (25,924 women with unilateral mastectomy and
26,299 women with CPM). In the analysis excluding women with CBC, DSS and OS remained
significantly lower in women who had unilateral mastectomy versus CPM. For DSS, the HR was
0.87 (95% CI, 0.80 to 0.94); for OS, it was 0.76 (95% CI, 0.71 to 0.81). The investigators
suggested that the survival benefits found in CBC patients was not due to prevention of CBC, but
instead to selection bias (e.g., healthier women choosing CBC). A limitation of the analysis was
the inability to control for risk factors including gene mutation status, family history, and a
history of radiotherapy to the chest between ages 10 and 30 years.
In 2013, Yao et al evaluated OS after CPM by analyzing data from the National Cancer Data
Base.1 The database collects data from 1450 Commission of Cancer‒accredited cancer programs.
The analysis included 219,983 women who had mastectomy for unilateral breast cancer; 14,994
(7%) of these women underwent CPM at the time of their mastectomy surgery. The investigators
did not report risk factors such as known genetic mutations. The 5-year OS rate was 80%. In an
analysis adjusting for confounding factors, the risk of death was significantly lower in women
who had CPM than in women who did not. The adjusted HR for OS was 0.88 (95% CI, 0.83 to
0.93). The absolute risk of death over 5 years with CPM was 2.0% lower than without CPM. In
subgroup analyses, there was a survival benefit after CPM for individuals ages 18 to 49 years
and aged 50 to 69 years, but not for those 70 years or older. There was also a survival benefit for
women with stage I and II tumors, but not stage III tumors.
A subsequent study by Pesce et al, published in 2014, focused on the subgroup of patients who
were young (<45 years old) with stage I or II breast cancer.12 A total of 4338 (29.7%) of 14,627
women in this subgroup had CPM at the time of mastectomy surgery. Median follow-up was 6.1
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MP- 1.036
years. In a multivariate analysis controlling for potentially confounding factors, OS did not differ
significantly among patients who underwent unilateral mastectomy and those who also had CPM
(HR=0.93; 95% CI, 0.79 to 1.09). Moreover, among women younger than 45 years with estrogen
receptor‒negative cancer, there was no significant improvement in OS in those who had CPM
versus unilateral mastectomy (HR=1.13; 95% CI, 0.90 to 1.42).
There are risks and benefits associated with CPM. In particular, several analyses have found
higher rates of surgical complications in women undergoing CPM (bilateral mastectomy) versus
unilateral mastectomy. Besides morbidity associated with these complications, surgical
complications may delay receiving adjuvant therapy.
In 2015, Silva et al published a large multicenter study including 20,501 women with unilateral
breast cancer from the American College of Surgeons National Surgery Quality Improvement
Program (NSQIP) database.13 A total of 13,268 (64.7%) women underwent unilateral
mastectomy and 7233 (35.3%) had bilateral mastectomy. The analysis did not report on high-risk
factors such as BRCA mutation status or family history. All women had breast reconstruction; a
higher proportion of women who had unilateral mastectomy (19.5%) than bilateral mastectomy
(8.9%) had autologous reconstruction; the remainder had implant-based reconstruction. The
authors conducted analyses controlling for confounding variables (i.e. age, race smoking,
diabetes, chronic pulmonary disease, hypertension) and stratifying by type of implant. The rate
of overall complications was significantly higher for women who had a bilateral versus unilateral
mastectomy, regardless of reconstruction type. Among women with implant reconstructions,
overall complication rates were 10.1% after bilateral mastectomy and 8.8% after unilateral
mastectomy (adjusted odd ratio [OR], 1.20; 95% CI, 1.08 to 1.33). In women with autologous
reconstructions, overall complication rates were 21.2% after bilateral mastectomy and 14.7%
after unilateral mastectomy (adjusted OR=1.60; 95% CI, 1.28 to 1.99). The most common
complication was reoperation within 30 days, followed by surgical site complications.
Transfusion rates were also significantly higher (p<0.001) in women with bilateral versus
unilateral mastectomies who had either type of reconstruction. The rates of medical
complications were relatively lowapproximately 1% of women who had implant
reconstructions and 3% of women who had autologous reconstructions experienced a medical
complication (i.e., pneumonia, renal insufficiency or failure, sepsis, urinary tract infection,
venous thromboembolism)and did not differ significantly for unilateral versus bilateral
mastectomies.
Several single-center studies have also found significantly higher surgical complication rates
after bilateral than unilateral mastectomy. For example, in a 2013 study by Miller et al, which
included 600 women with unilateral breast cancer, CPM remained associated with a significantly
higher risk of any complication (OR=1.53; 95% CI, 1.04 to 2.25) and a significantly higher risk
of major complications (OR=2.66; 95% CI, 1.37 to 5.19) than unilateral mastectomy.14
Moreover, in a 2014 study by Eck et al, which assessed 352 women with unilateral breast cancer,
94 (27%) women had complications, 48 (14%) in the unilateral mastectomy group and 46 (13%)
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POLICY NUMBER
MP- 1.036
in the bilateral mastectomy group.15 The difference between groups was not statistically
significant (p=0.11), but this study may have been underpowered. Moreover, the Eck study
found a significant delay in adjuvant therapy after surgical complications. Women with
complications waited longer before receiving adjuvant therapy than those without complications
(49 days vs 40 days, p<0.001).
Section Summary: Contralateral Prophylactic Mastectomy
Large observational studies have had mixed findings on the survival benefit of CPM in women
with unilateral breast cancer who do not otherwise meet high-risk criteria. Researchers have
suggested that improvement in survival after CPM in the general breast cancer population found
in some studies is due at least in part to selection bias. Moreover, there are risks (e.g., surgical
risks) of CPM.
Ongoing and Unpublished Clinical Trials
A search of ClinicalTrials.gov in January 2016 did not identify any ongoing or unpublished trials
that would likely influence this review.
Summary of Evidence
The evidence for prophylactic mastectomy (PM) in women who have high risk of breast cancer
or extensive mammographic abnormalities precluding incision or biopsy includes a TEC
Assessment and systematic review of observational studies. Relevant outcomes are overall
survival, disease-specific survival, functional outcomes, and treatment-related morbidity. The
studies found that PM reduces breast cancer incidence and increases survival in select patients.
The evidence is sufficient to determine qualitatively that the technology results in a meaningful
improvement in the net health outcome.
The evidence for contralateral prophylactic mastectomy (CPM) in women who have unilateral
breast cancer but are not otherwise at high risk includes observational studies. Relevant
outcomes are overall survival, disease-specific survival, functional outcomes, and treatmentrelated morbidity. Available studies do not clearly demonstrate a survival benefit in women
without high-risk criteria. Moreover, there are potential risks (e.g., surgical risks) associated with
CPM. National guidelines, including those from the National Comprehensive Care Network, do
not recommend that CPM be considered other than for certain high-risk women. The evidence is
insufficient to determine the effects of the technology on health outcomes.
Clinical Input Received From Physician Specialty Societies and Academic Medical Centers
While the various physician specialty societies and academic medical centers may collaborate
with and make recommendations during this process, through the provision of appropriate
reviewers, input received does not represent an endorsement or position statement by the
physician specialty societies or academic medical centers, unless otherwise noted.
In response to requests, focused clinical input was received from 6 academic medical centers and
1 specialty society while this policy was under review in 2016. The focused clinical input
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addressed the issue of CPM in women with unilateral breast cancer who are not otherwise at high
risk for developing breast cancer in the contralateral breast. Clinical input was mixed. Clinicians
offered suggestions for modifying high-risk criteria but there was no consensus on potential
additional risk factors.
Practice Guidelines and Position Statements
National Comprehensive Cancer Network
 Breast Cancer Risk Reduction (v.2.2015): “Risk-reduction mastectomy should
generally be considered only in women with a genetic mutation conferring a high risk
history for breast cancer (See NCCN guidelines for Genetic/Familial High-Risk
Assessment: Breast and Ovarian,16 Table on GENE-2*), compelling family history, or
possibly with LCIS [lobular carcinoma in situs] or prior thoracic radiation therapy at
< 30 years of age. The value of risk-reduction mastectomy in women with deleterious
mutations in other genes associated with a 2-fold or greater risk for breast cancer
(based on large epidemiologic studies) in the absence of a compelling family history
of breast cancer is unknown.”3
 Breast cancer (v.2.2015): Except for certain high-risk situations (noted in the risk
reduction guideline previously discussed), CPM is discouraged.17 The guideline
states: “the small benefits from contralateral prophylactic mastectomy for women
with unilateral breast cancer must be balanced with the risk of recurrent disease from
the known ipsilateral breast cancer, psychological and social issues of bilateral
mastectomy, and the risks of contralateral mastectomy. The use of a prophylactic
mastectomy contralateral to a breast treated with breast-conserving therapy is very
strongly discouraged.”
* Genes that confer more than 20% risk of breast cancer include BRAC1, BRCA2, ATM, CDH1,
CHEK2, PALB2, PTEN, STK11, and TP53.
Society of Surgical Oncology
The Society of Surgical Oncology developed a position statement on PM in 1993 and updated it
in 2007.18 The position statement states that bilateral PM is potentially indicated in patients with:



known BRCA 1 or 2 mutations or other genes that convey strong increased
susceptibility to breast cancer,
a history of multiple first-degree relatives with a history of breast cancer history or
family history of multiple successive generations with breast and/or ovarian cancer,
or
biopsy-confirmed, high-risk histology such as LCIS or atypical ductal or lobular
hyperplasia.
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MP- 1.036
The position statement also stated that CPM may be potentially indicated in patients:


with high risk (as previously defined) of contralateral breast cancer,
in whom surveillance would be difficult such as with dense breast tissue or diffuse
indeterminate microcalcifications, or to improve symmetry.
National Cancer Institute
The National Cancer Institute issued a fact sheet in 2012 on surgery to reduce the risk of breast
cancer.19 The fact sheet provided the following information: “Prophylactic surgery to remove
both breasts (called bilateral prophylactic mastectomy) can reduce the risk of breast cancer in
women who have a strong family history of breast and/or ovarian cancer, who have a deleterious
(disease-causing) mutation in the BRCA1 gene or the BRCA2 gene, or who have certain breast
cancer-associated mutations in other genes, such as TP53 and PTEN.”
U.S. Preventive Services Task Force Recommendations
No U.S. Preventive Services Task Force recommendations for PM have been identified.
Medicare National Coverage
There is no national coverage determination (NCD).
Prophylactic Oopherectomy
Professional Societies/Organizations
American College of Obstetricians and Gynecologists (ACOG): According to the ACOG
guidelines for prophylactic hysterectomy, prophylactic oophorectomy should be considered for
select women at high risk of inherited ovarian cancer. Hormone replacement therapy should be
considered for women undergoing prophylactic oophorectomy, and patients should be counseled
about the risks and benefits of hormone replacement therapy prior to undergoing surgery.
Compliance with hormone replacement therapy is important in women undergoing prophylactic
oophorectomy to reduce the risk of future morbidity (ACOG, 1999).
Summary
Despite the lack of randomized controlled trials (RCT), the published peer-reviewed medical
literature indicates that prophylactic oophorectomy should be considered for premenopausal (age
35 or older), high-risk women (i.e., women known to carry the BRCA1 and/or BRCA2 mutation
or to have a lineage familial cancer), and only after completion of childbearing. The literature
also suggests that a hysterectomy should be performed in conjunction with prophylactic
oophorectomy in women from families with Lynch syndrome. For premenopausal women with
early breast cancer, ovarian ablation by oophorectomy is a therapeutic option. It is imperative
that women undergoing prophylactic oophorectomy with or without hysterectomy understand
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that this surgery does not completely eliminate the risk of developing cancer. Counseling
regarding the risks and benefits of the procedure is equally important for women considering this
preventive measure. Specifically, such women should be educated about the increased risk of
cardiovascular disease and osteoporosis as a result of surgically-induced menopause after
undergoing oophorectomy with or without hysterectomy (American College of Medical Genetics
[ACMG], 1999).
V. DEFINITIONS
Top
BRCA1 refers to a breast cancer gene that is found in a small percentage of patients with this
malignancy and carried by some individuals who will develop breast cancer later in life.
BRCA2 refers to a breast cancer gene found in a small number of patients with breast and
ovarian cancers, and carried by some individuals who will develop breast cancer later in life.
FIRST-DEGREE RELATIVE refers to a parent, sibling, or child.
GENE is the basic unit of heredity, the code for a specific protein.
HYPERPLASIA refers to excessive proliferation of normal cells in the normal tissue arrangement
of an organ.
IN SITU means in position, localized.
MUTATION is an unusual change in genetic material occurring spontaneously or by induction.
OVARIAN CANCER is an abnormal, malignant growth located in the ovaries.
P53 GENE is a tumor suppressor gene that normally inhibits the growth of tumors. This gene is
altered in many types of cancer.
PTEN GENE is a tumor suppressor gene that normally inhibits the growth of tumors. This gene is
altered in many types of cancer.
PROPHYLACTIC OOPHORECTOMY refers to the elective surgical removal of ovaries, before
cancer develops, in women at high risk for ovarian cancer due to a family history of the disease.
SECOND-DEGREE RELATIVE refers to aunt, uncle, niece, nephew, or grandparent.
THIRD-DEGREE RELATIVE refers to a great aunt/uncle, first cousin or great
grandmother/grandfather.
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MEDICAL POLICY
POLICY TITLE
PROPHYLACTIC MASTECTOMY AND PROPHYLACTIC BILATERAL
OOPHORECTOMY
POLICY NUMBER
MP- 1.036
VI. BENEFIT VARIATIONS
Top
The existence of this medical policy does not mean that this service is a covered benefit
under the member's contract. Benefit determinations should be based in all cases on the
applicable contract language. Medical policies do not constitute a description of benefits.
A member’s individual or group customer benefits govern which services are covered,
which are excluded, and which are subject to benefit limits and which require
preauthorization. Members and providers should consult the member’s benefit information
or contact Capital for benefit information.
VII. DISCLAIMER
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Capital’s medical policies are developed to assist in administering a member’s benefits, do not constitute
medical advice and are subject to change. Treating providers are solely responsible for medical advice and
treatment of members. Members should discuss any medical policy related to their coverage or condition
with their provider and consult their benefit information to determine if the service is covered. If there is a
discrepancy between this medical policy and a member’s benefit information, the benefit information will
govern. Capital considers the information contained in this medical policy to be proprietary and it may only
be disseminated as permitted by law.
VIII. CODING INFORMATION
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Note: This list of codes may not be all-inclusive, and codes are subject to change at any time. The
identification of a code in this section does not denote coverage as coverage is determined
by the terms of member benefit information. In addition, not all covered services are
eligible for separate reimbursement.
Covered when medically necessary:
CPT Codes®
19303
19304
58661
58940
Current Procedural Terminology (CPT) copyrighted by American Medical Association. All Rights Reserved.
ICD-10-CM
Diagnosis
Codes
D05.01
D05.02
R92.1
Z15.01
Z15.02
Z15.89
Description
Lobular carcinoma in situ of right breast
Lobular carcinoma in situ of left breast
Mammographic calcification found on diagnostic imaging of breast
Genetic susceptibility to malignant neoplasm breast
Genetic susceptibility to malignant neoplasm of ovary
Genetic susceptibility to other disease
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MEDICAL POLICY
POLICY TITLE
PROPHYLACTIC MASTECTOMY AND PROPHYLACTIC BILATERAL
OOPHORECTOMY
POLICY NUMBER
MP- 1.036
ICD-10-CM
Diagnosis
Codes
Z40.01
Z40.02
Z80.3
Z80.41
Description
Encounter for prophylactic removal of breast
Encounter for prophylactic removal of ovary
Family history of malignant neoplasm of breast
Family history of malignant neoplasm of ovary
*If applicable, please see Medicare LCD or NCD for additional covered diagnoses.
IX. REFERENCES
1.
2.
3.
4.
5.
6.
7.
8.
9.
Top
Prophylactic Mastectomy
Yao K, Winchester DJ, Czechura T, et al. Contralateral prophylactic mastectomy and
survival: report from the National Cancer Data Base, 1998-2002. Breast Cancer Res Treat.
Dec 2013;142(3):465-476. PMID 24218052
Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). Bilateral
prophylactic mastectomy in women with an increased risk of breast cancer. TEC
Assessments. 1999; Volume 14:Tab 14.
National Comprehensive Cancer Network. Breast Cancer Risk Reduction. V.2. 2015
http://www.nccn.org/professionals/physician_gls/pdf/breast_risk.pdf. Accessed July 13,
2015.
Saslow D, Boetes C, Burke W, et al. American Cancer Society guidelines for breast screening
with MRI as an adjunct to mammography. CA Cancer J Clin. Mar-Apr 2007;57(2):75-89.
PMID 17392385
Oppong BA, King TA. Recommendations for women with lobular carcinoma in situ (LCIS).
Oncology (Williston Park). Oct 2011;25(11):1051-1056, 1058. PMID 22106556
Lostumbo L, Carbine NE, Wallace J. Prophylactic mastectomy for the prevention of breast
cancer. Cochrane Database Syst Rev. 2010(11):CD002748. PMID 21069671
Nichols HB, Berrington de Gonzalez A, Lacey JV, Jr., et al. Declining incidence of
contralateral breast cancer in the United States from 1975 to 2006. J Clin Oncol. Apr 20
2011;29(12):1564-1569. PMID 21402610
Molina-Montes E, Perez-Nevot B, Pollan M, et al. Cumulative risk of second primary
contralateral breast cancer in BRCA1/BRCA2 mutation carriers with a first breast cancer: A
systematic review and meta-analysis. Breast. Dec 2014;23(6):721-742. PMID 25467311
Fayanju OM, Stoll CR, Fowler S, et al. Contralateral prophylactic mastectomy after
unilateral breast cancer: a systematic review and meta-analysis. Ann Surg. Dec
2014;260(6):1000-1010. PMID 24950272
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MEDICAL POLICY
POLICY TITLE
PROPHYLACTIC MASTECTOMY AND PROPHYLACTIC BILATERAL
OOPHORECTOMY
POLICY NUMBER
MP- 1.036
10. Kruper L, Kauffmann RM, Smith DD, et al. Survival analysis of contralateral prophylactic
mastectomy: a question of selection bias. Ann Surg Oncol. Oct 2014;21(11):3448-3456.
PMID 25047478
11. Jatoi I, Parsons HM. Contralateral prophylactic mastectomy and its association with
reduced mortality: evidence for selection bias. Breast Cancer Res Treat. Nov
2014;148(2):389-396. PMID 25301088
12. Pesce C, Liederbach E, Wang C, et al. Contralateral prophylactic mastectomy provides no
survival benefit in young women with estrogen receptor-negative breast cancer. Ann Surg
Oncol. Oct 2014;21(10):3231-3239. PMID 25081341
13. Silva AK, Lapin B, Yao KA, et al. The effect of contralateral prophylactic mastectomy on
perioperative complications in women undergoing immediate breast reconstruction: a
NSQIP analysis. Ann Surg Oncol. Oct 2015;22(11):3474-3480. PMID 26001862
14. Miller ME, Czechura T, Martz B, et al. Operative risks associated with contralateral
prophylactic mastectomy: a single institution experience. Ann Surg Oncol. Dec
2013;20(13):4113-4120. PMID 23868655
15. Eck DL, Perdikis G, Rawal B, et al. Incremental risk associated with contralateral
prophylactic mastectomy and the effect on adjuvant therapy. Ann Surg Oncol. Oct
2014;21(10):3297-3303. PMID 25047470
16. National Comprehensive Cancer Network. NCCN Guidelines Version 2, 2015.
Genetic/Familial High-Risk Assessment: Breast and Ovarian.
www.nccn.org/professionals/physician_gls/pdf/genetics_screening.pdf. Accessed July 13,
2015.
17. National Comprehensive Cancer Network. Breast Cancer. V.2.2015.
http://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Accessed July 13, 2015.
18. Giuliano AE, Boolbol S, Degnim A, et al. Society of Surgical Oncology: position statement
on prophylactic mastectomy. Approved by the Society of Surgical Oncology Executive
Council, March 2007. Ann Surg Oncol. Sep 2007;14(9):2425-2427. PMID 17597344
19. National Cancer Institute. Fact Sheet: Surgery to Reduce the Risk of Breast Cancer. 2012,
reviewed in 2013; http://www.cancer.gov/cancertopics/factsheet/Therapy/risk-reducingsurgery. Accessed July 13, 2015.
Other Sources:
1. Mosby's Medical, Nursing & Allied Health Medical Dictionary, 6th edition.
Prophylactic Oophorectomy
1. Kerlikowske K, Brown JS, Grady DG. Should women with familial ovarian cancer
undergo prophylactic oophorectomy?. Obstet Gynecol. 1992;80(4):700-707.
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MEDICAL POLICY
POLICY TITLE
PROPHYLACTIC MASTECTOMY AND PROPHYLACTIC BILATERAL
OOPHORECTOMY
POLICY NUMBER
MP- 1.036
2. Averette HE, Nguyen HN. The role of prophylactic oophorectomy in cancer prevention.
Gynecol Oncol. 1994;55(3):S38-S41.
3. Meijer WJ, van Lindert CM. Prophylactic oophorectomy. Eur J Obstet Gynecol Reprod
Biol. 1992;47(1):59-65.
4. van Eijkeren MA, de Graaff J, van Etten FHPM. Familial ovarian cancer. Eur J Obstet
Gynecol Reprod Biol. 1992;47(3):263-266.
5. Evans DGR, Ribiero G, Warrell D, et al. Ovarian cancer family and prophylactic
choices. J Med Genetics. 1992;29(6):416-418.
6. Schwartz PE. The role of prophylactic oophorectomy in the avoidance of ovarian cancer.
Int J Gynecol Obstet. 1992;39(3):175-184.
7. National Institutes of Health. NIH Consensus Development Conference on Ovarian
Cancer: Screening, Treatment, and Follow-up. Bethesda, MD: NIH; 1994;12(3):4-9.
8. American College of Obstetricians and Gynecologists (ACOG). Prophylactic
oophorectomy. ACOG Technical Bulletin No. 111. Washington, DC: ACOG; 1987.
9. Kerlikowske K, Brown JS, Grady DG. Should women with familial ovarian cancer
undergo prophylactic oophorectomy: An editorial reply. Obstet Gynecol. 1993;81(2):315316.
10. Speroff T, Dawson NV, Speroff L, Haber RJ. A risk-benefit analysis of elective bilateral
oophorectomy: Effect of changes in compliance with estrogen therapy on outcome. Am J
Obstet Gynecol. 1991;164(1 Pt 1):165-174.
11. Nguyen HN, Averette HE, Janicek M. Ovarian carcinoma. Cancer. 1994;74(2):545-555.
12. Sightler SE, Bioke GM, Estape RE, Averettte HE. Ovarian cancer in women with prior
hysterectomy: A 14-year experience at the University of Miami. Obstet Gynecol.
1992;78(4):681-684.
13. Reiter RC, Gambone JC. Editorial reply to Ovarian cancer in women with prior
hysterectomy: A 14-year experience at the University of Miami. Obstet
Gynecol.1992;79(2):317-319
14. Lu KH Garber JE, Cramer DW, et al. Occult ovarian tumors in women with BRCA1 or
BRCA2 mutations undergoing prophylactic oophorectomy. J Clin Oncol.
2000;18(14):2728-2732.
15. Gotlieb WH, Baruch GB, Friedman E. Prophylactic oophorectomy: clinical
considerations. Semin Surg Oncol. 2000;19(1):20-27.
16. Farghaly SA. Current status of management of hereditary ovarian-breast cancer
syndrome. Obstet Gynecol. 2000;95(4 Suppl 1):S51.
17. Berchuck A, Schildkraut JM, Marks JR, Futreal PA. Managing hereditary ovarian cancer
risk. Cancer. 1999;86(11 Suppl):2517-2524.
18. Eisinger F, Alby N, Bremond A, et al. Inserm ad hoc committee: Recommendations for
the management of women with a genetic risk for developing cancer of the breast and/or
the ovary. Bull Cancer. 1999;86(3):307-313.
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MEDICAL POLICY
POLICY TITLE
PROPHYLACTIC MASTECTOMY AND PROPHYLACTIC BILATERAL
OOPHORECTOMY
POLICY NUMBER
MP- 1.036
19. Rebbeck TR. Prophylactic Oophorectomy in BRCA1 and BRCA2 mutation carriers. J
Clin Oncol. 2000;18(90001):100S-103S.
20. Eisen A, Rebbeck TR, Wood WC, Weber BL. Prophylactic surgery in women with a
hereditary predisposition to breast and ovarian cancer. J Clin Oncol. 2000;18(9):19801995.
21. Rebbeck TR, Levin AM, Eisen A, et al. Breast cancer risk after bilateral prophylactic
oophorectomy in BRCA1 mutation carriers. J Natl Cancer Inst. 1999;91(17):1475-1479.
22. Kauff ND, Satagopan JM, Robson ME, et al. Risk-reducing salpingo-oophorectomy in
women with a BRCA1 or BRCA2 mutation. N Engl J Med. 2002;346(21):1609-1615.
23. Rebbeck TR, Lynch HT, Neuhausen SL, et al. Prophylactic oophorectomy in carriers of
BRCA1 or BRCA2 mutations. N Engl J Med. 2002;346(21):1616-1622.
24. Haber D. Prophylactic oophorectomy to reduce the risk of ovarian and breast cancer in
carriers of BRCA mutations. N Engl J Med. 2002;346(21):1660-1662.
25. Tice JA. Prophylactic oophorectomy - what is the effect on breast and ovarian cancer for
BRCA+ women? Technology Assessment. San Francisco, CA: California Technology
Assessment Forum; October 8, 2003.
[Website]:http://ctaf.org/sites/default/files/assessments/565_file_Prophylactic_Oophorect
omy_What_is_the_effect_on_Breast_and_Ovarian_Cancer_for_BRCA_Women.pdf
Accessed March 14, 2016.
26. Parker WH, Broder MS, Liu Z, et al. Ovarian conservation at the time of hysterectomy
for benign disease. Obcstet Gynecol. 2005;106(2):219-226.
27. Schmeler KM, Lynch HT, Chen LM, et al. Prophylactic surgery to reduce the risk of
gynecologic cancers in the Lynch syndrome. N Engl J Med. 2006;354(3):261-269.
28. Agostini A, Vejux N, Bretelle F, et al. Value of laparoscopic assistance for vaginal
hysterectomy with prophylactic bilateral oophorectomy. Am J Obstet Gynecol.
2006;194(2):351-354.
29. Parker WH, Shoupe D, Broder MS, et al. Elective oophorectomy in the gynecological
patient: When is it desirable? Curr Opin Obstet Gynecol. 2007;19(4):350-354.
30. Metcalfe KA. Oophorectomy for breast cancer prevention in women with BRCA1 or
BRCA2 mutations. Womens Health (Lond Engl). 2009;5(1):63-68.
31. Parker WH. Bilateral oophorectomy versus ovarian conservation: Effects on long-term
women's health. J Minim Invasive Gynecol. 2010;17(2):161-166.
32. Berek JS, Chalas E, Edelson M, et al; Society of Gynecologic Oncologists Clinical
Practice Committee. Prophylactic and risk-reducing bilateral salpingo-oophorectomy:
Recommendations based on risk of ovarian cancer. Obstet Gynecol. 2010;116(3):733743.
33. Rebbeck TR, Kauff ND, Domchek SM. Meta-analysis of risk reduction estimates
associated with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 mutation
carriers. J Natl Cancer Inst. 2009;101(2):80-87.
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MEDICAL POLICY
POLICY TITLE
PROPHYLACTIC MASTECTOMY AND PROPHYLACTIC BILATERAL
OOPHORECTOMY
POLICY NUMBER
MP- 1.036
34. American College of Obstetricians and Gynecologists (ACOG). Hereditary breast and
ovarian cancer syndrome. ACOG Practice Bulletin No. 103. Washington, DC:
American College of Obstetricians and Gynecologists (ACOG); April 2009.
35. Domchek SM, Friebel TM, Singer CF, et al. Association of risk-reducing surgery in
BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. JAMA.
2010;304(9):967-975.
36. Muto MG. Risk-reducing bilateral salpingo-oophorectomy in women at high risk of
epithelial ovarian and fallopian tubal cancer. Updated Septemeber 17, 2015..
[Website]: http://www.uptodate.com. [online serial]. Waltham, MA Accessed March
14, 2016.
37. American College of Obstetricians and Gynecologists (ACOG). Elective and riskreducing salpingo-oophorectomy. Washington (DC): American College of
Obstetricians and Gynecologists (ACOG); 2008 Jan. 11 p. (ACOG practice bulletin;
no. 89).Updated March 7, 2014. . [Website]:
http://www.guideline.gov/content.aspx?id=12190. Accessed March 14, 2016.
X. POLICY HISTORY
MP 1.036
Top
CAC 10/29/02
CAC 1/28/03
CAC 1/27/04
CAC 2/22/05
CAC 3/28/06
CAC 3/27/07
CAC 5/27/08
12/12/08 Definition Change
CAC 9/29/09 Policy criteria for prophylactic mastectomy revised with additional
indications (PTEN and p53 mutations)
CAC 11/30/10 Consensus Review
CAC 11/22/11 Consensus Review
04/05/2013- Deleted codes removed from policy
7/24/13 Admin coding review complete
CAC 9/24/13. Minor review. For prophylactic mastectomy. Definition of high risk
clarified and medically necessary indication for those at moderately increased risk
of breast cancer removed, except for women with extensive mammographic
abnormalities. New investigational statement added for contralateral prophylactic
mastectomy among women with cancer in the other breast who do not meet one of
the medically indicated conditions. No change to prophylactic oophorectomy policy
statements.
Page 18
MEDICAL POLICY
POLICY TITLE
PROPHYLACTIC MASTECTOMY AND PROPHYLACTIC BILATERAL
OOPHORECTOMY
POLICY NUMBER
MP- 1.036
CAC 9/30/14 Consensus review. References updated; rationale added. No changes
to the policy statements.
CAC 6/2/15 Minor review. Added other gene mutations associated with increased
risk to policy guidelines. (e.g., PTEN, TP53, CDH1, and STK11). Updated
rationale and references. Coding reviewed.
CAC 5/31/16 Minor revision. Medically necessary statement on lobular carcinoma
in situ removed and added to high-risk criteria in the policy guidelines. Also in the
policy guidelines, “20% to 25%” changed to “20%”, revised bullet points on high
risk mutations in relatives with genetic syndromes and added wording on
characteristics that may increase risk in combination with other factors. Guidelines,
rationale, and references updated. Coding reviewed.
Administrative Update 11/22/16 -Variation reformatting 10/21/16.
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Health care benefit programs issued or administered by Capital BlueCross and/or its subsidiaries, Capital Advantage
Insurance Company®, Capital Advantage Assurance Company® and Keystone Health Plan® Central. Independent
licensees of the BlueCross BlueShield Association. Communications issued by Capital BlueCross in its capacity as
administrator of programs and provider relations for all companies
Page 19