The n e w e ng l a n d j o u r na l of m e dic i n e

Cl inic a l Decisions
Interactive at nejm.org

Contralateral Prophylactic Mastectomy

This interactive feature addresses the approach to a clinical issue. A case vignette is followed by specific options, neither of which
can be considered either correct or incorrect. In short essays, experts in the field then argue for each of the options. Readers can
participate in forming community opinion by choosing one of the options and, if they like, providing their reasons.

C a s e V igne t t e died of metastatic breast cancer at 55 years of

A Woman Considering
Contralateral Prophylactic
Mastectomy
Ramya Ramaswami, M.B., B.S., M.P.H.
Ms. Markes is a 51-year-old woman who has
recently received a diagnosis of breast cancer,
and she comes to you to seek your opinion about
her surgical options. Three weeks earlier, she had
undergone mammography and magnetic reso-
nance imaging to evaluate a mass in the left
breast. She has been told that she has a 3-cm
triple-negative (i.e., negative for estrogen and
progesterone receptors and for overexpression of
human epidermal growth factor receptor type 2
[HER2]) invasive ductal carcinoma of the left
breast. The breast cancer is at clinical stage IIA
or T2N0M0 (i.e., the tumor is >2 cm and <5 cm
in the greatest dimension and has not spread to
the lymph nodes or to distant sites). Ms. Markes
has no history of medical or surgical issues.
Menarche was at 11 years of age, and she had an
elective termination of pregnancy when she was
22 years old.
Ms. Markes is anxious and fearful, especially
since she has a family history of breast cancer.
Her sister received a diagnosis of breast cancer
at 37 years of age. Ms. Markes tearfully recollects
her experiences of caring for her mother, who
age. Ms. Markes does not know whether any
other family members have a history of cancer.
She underwent testing for BRCA1 and BRCA2
mutations, and the results were negative. On
examination today, you note breast asymmetry
and palpate a 3-cm mass in her left breast. There
are no palpable lymph nodes. She has participat-
ed in many support groups, and after discussion
with other women who have undergone breast-
cancer surgery, she has been encouraged to con-
sider contralateral prophylactic mastectomy and
bilateral breast reconstruction. Ms. Markes asks
you whether you would recommend a contralat-
eral prophylactic mastectomy in her case.
T r e atment O p t i ons
Which of the following strategies would you
choose for this patient?
1. Recommend contralateral prophylactic mas-
tectomy.
2. Do not recommend contralateral prophylactic
mastectomy.
To aid in your decision making, each of these
approaches is defended in a short essay by an
expert in the field. Given your knowledge of the
patient and the points made by the experts, which
option would you choose? Make your choice, vote,
and offer your comments at NEJM.org.

O p t i on 1
unacceptably high. There are no alternative risk-
Recommend Contralateral reduction strategies available to Ms. Markes, who
Prophylactic Mastectomy has triple-negative breast cancer and a strong
family history. Although Ms. Markes tested nega-
Monica Morrow, M.D. tive for BRCA1 and BRCA2 mutations, her risk of
Contralateral prophylactic mastectomy is a pro- a contralateral breast cancer is substantially high-
cedure that a woman chooses to reduce a risk of er than that in the average woman with unilat-
contralateral breast cancer that she considers eral breast cancer, and, therefore, contralateral

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 Clinical Decisions
prophylactic mastectomy is a reasonable consid-
eration. In a study involving women who were
known not to have BRCA1 and BRCA2 mutations,
those in whom unilateral breast cancer was diag-
nosed before they were 55 years of age and who
had a family history of breast cancer in a first-
degree relative had a 10-year cumulative risk of
contralateral breast cancer of 6.7%.1 Early age at
diagnosis in the affected relative, as was the
case with Ms. Markess sister, further increased
the risk of a second breast cancer. Ms. Markess
risk may actually be even greater, since she has
two affected relatives and triple-negative breast
cancer. In patients with estrogen-receptorposi-
tive breast cancer, endocrine therapy, which is part
of treatment, reduces the risk of contralateral
breast cancer by approximately 50%,2 but the
same benefit is not seen with the cytotoxic
chemotherapy Ms. Markes will receive for her
triple-negative disease.
Although Ms. Markes does not have a BRCA1
or BRCA2 mutation, she may have another muta-
tion that confers a predisposition to breast can-
cer; such a mutation could be identified with
panel testing. Other genes such as PALB2 have
been found to be mutated in patients with triple-
negative breast cancer,3 but little is known about
the risk of contralateral breast cancer associated
with these mutations. Testing will be more use-
ful to inform care for Ms. Markess relatives than
to assist her with her decision about undergoing
contralateral prophylactic mastectomy.
The majority of metastases of triple-negative
breast cancer occur within 5 years after diagno-
sis,4 so some might counsel Ms. Markes to delay
contralateral prophylactic mastectomy to decrease
the likelihood that it will have been performed
unnecessarily. However, a delay in undergoing
the procedure will limit her reconstructive op-
tions, since abdominal tissue can be used to
reconstruct two breasts simultaneously but not
sequentially, owing to disruption of the blood
supply during the initial procedure. In addition,
a delayed contralateral prophylactic mastectomy
procedure would subject Ms. Markes to two
separate operations and recovery periods and to
anxiety about cancer development during the
observation period factors that could nega-
tively affect her quality of life.
Desire for peace of mind drives many women
to proceed with contralateral prophylactic mas-
tectomy, and in a study involving women with
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unilateral breast cancer and a family history of
breast cancer who were surveyed 20 years after
they had undergone contralateral prophylactic
mastectomy, 90% were satisfied or very satisfied
with their decision to undergo the procedure.5
For women who are at increased risk for contra-
lateral breast cancer, a discussion of contralateral
prophylactic mastectomy to make them aware of
the option and of the risks and benefits associ-
ated with it is important. The more common
scenario encountered in practice today is the pa-
tient who is not at increased risk for contralateral
breast cancer but wishes to undergo contralat-
eral prophylactic mastectomy. A discussion of
risk associated with the procedure and of the
lack of a survival benefit with contralateral pro-
phylactic mastectomy in such patients and a
recommendation against the procedure by the
surgeon are effective in reducing the use of con-
tralateral prophylactic mastectomy in patients who
have a low likelihood of benefit.6 In a patient
such as Ms. Markes, contralateral prophylactic
mastectomy is an appropriate consideration.
Disclosure forms provided by the author are available with the
full text of this article at NEJM.org.
From the Breast Service, Department of Surgery, Memorial
Sloan Kettering Cancer Center, New York.
O p t i on 2
Do Not Recommend
Contralateral Prophylactic
Mastectomy
Reshma Jagsi, M.D., D.Phil.
Ms. Markes has good reason to consider carefully
whether she wishes to pursue contralateral pro-
phylactic mastectomy. It is one of several options
that patients at high genetic or familial risk
should discuss with their physicians. The deci-
sion to proceed with contralateral prophylactic
mastectomy requires that Ms. Markes understand
both the expected benefits and the risks. Although
contralateral prophylactic mastectomy is an op-
tion that is consistent with National Comprehen-
sive Cancer Network guidelines for women at high
genetic or familial risk for breast cancer, it is not
routinely recommended in such cases.7 Multiple
factors must be considered to ensure that the
patient makes an informed decision that also
takes her personal preferences into consideration.
1289
 The n e w e ng l a n d j o u r na l
The benefits of contralateral prophylactic mas-
tectomy relate to the absolute reduction in the
risk of subsequent contralateral primary cancer.
Ms. Markes needs to understand that the main
threat to her survival comes not from a future
new breast cancer that might be prevented with
contralateral prophylactic mastectomy but from
her current diagnosis of triple-negative cancer
and its substantial potential for metastasis to
distant organs. To better estimate her risks of
a future primary cancer, I would recommend
multiplex panel testing of genes beyond BRCA1
and BRCA2 that are associated with her per-
sonal and family history of cancer (e.g., PALB2,
BARD1, and RAD51C), and I would estimate her
familial risk with the use of mathematical mod-
els. Still, she should understand that the benefit
expected is primarily in preventing a subsequent
cancer and not in improving her survival from
the cancer she has. As noted in the Society for
Surgical Oncology consensus statement on pro-
phylactic mastectomy, evidence overall does not
support a substantial survival benefit, nor would
one be expected because an individual must
survive the first cancer, develop a contralateral
cancer, and then succumb to the contralateral can-
cer in order to have had a survival benefit from
[contralateral prophylactic mastectomy].8
The risks of bilateral mastectomy are sub-
stantial and must also be weighed carefully. Bi-
lateral mastectomy, especially when combined
with breast reconstruction, as it usually is, con-
stitutes a considerably more involved surgical
procedure than the simple outpatient unilateral
lumpectomy for which Ms. Markes is most likely
a candidate. Evidence indicates that breast-con-
serving therapy, including adjuvant radiotherapy,
yields equivalent, if not better, local control than
mastectomy for triple-negative disease.9 Compli-
cation rates are higher with contralateral pro-
phylactic mastectomy than with unilateral mas-
tectomy or breast-conserving therapy, especially
when the mastectomy is combined with recon-
struction; potential complications include those
related to bleeding, wound healing, and infec-
tion.8 If nodal involvement is found on pathologi-
cal evaluation after mastectomy, radiotherapy will
then be recommended, which would magnify the
differential risk of mastectomy as compared with
breast-conserving therapy. Moreover, although
most studies suggest high satisfaction with the
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of m e dic i n e
decision to undergo contralateral prophylactic
mastectomy, the procedure can deleteriously af-
fect body image and sexuality.5
More-extensive surgical procedures can delay
the initiation of adjuvant chemotherapy, and a
delay may be particularly detrimental to patients
who have aggressive subtypes such as triple-
negative disease, for which systemic therapy is
critical.10 To avoid this concern, I would recom-
mend that Ms. Markes initiate chemotherapy in
the neoadjuvant setting. Sequencing chemotherapy
before surgery is a good idea in such a case be-
cause it may also facilitate breast conservation and
provide additional time for the patient to undergo
genetic testing and deliberate on the complex
risks and benefits of her surgical options.
Because contralateral prophylactic mastectomy
is not expected to meaningfully reduce Ms.
Markess risk of recurrence of the current cancer
or improve her overall survival, her case requires
a multimodal approach, and the option of uni-
lateral breast-conserving therapy is an option she
should consider. Still, given her risk of a subse-
quent cancer if she survives this cancer, contra-
lateral prophylactic mastectomy is also an option
she should consider. Ms. Markess case contrasts
with the more common situation of a patient
who has hormone-receptorpositive cancer and
no indication of a hereditary syndrome, for whom
many physicians would recommend against con-
tralateral prophylactic mastectomy.6 Nevertheless,
the physicians role here should be to ensure that
Ms. Markes fully understands the nature and
likelihood of the benefits and risks in various
scenarios, so that she can then apply her own
values, priorities, and preferences to select the
approach that is right for her.
Disclosure forms provided by the author are available with the
full text of this article at NEJM.org.
From the Department of Radiation Oncology and Center for
Bioethics and Social Sciences in Medicine, University of Michi-
gan, Ann Arbor.
1. Reiner AS, John EM, Brooks JD, et al. Risk of asynchronous
contralateral breast cancer in noncarriers of BRCA1 and BRCA2
mutations with a family history of breast cancer: a report from
the Womens Environmental Cancer and Radiation Epidemiology
Study. J Clin Oncol 2013;31:433-9.
2. Early Breast Cancer Trialists Collaborative Group (EBCTCG).
Relevance of breast cancer hormone receptors and other factors
to the efficacy of adjuvant tamoxifen: patient-level meta-analysis
of randomised trials. Lancet 2011;378:771-84.
3. Afghahi A, Telli ML, Kurian AW. Genetics of triple-negative
breast cancer: implications for patient care. Curr Probl Cancer
2016;40:130-40.
 Clinical Decisions

4. Millar EK, Graham PH, OToole SA, et al. Prediction of local
recurrence, distant metastases, and death after breast-conserving
therapy in early-stage invasive breast cancer using a five-bio-
marker panel. J Clin Oncol 2009;27:4701-8.
5. Frost MH, Hoskin TL, Hartmann LC, Degnim AC, Johnson
JL, Boughey JC. Contralateral prophylactic mastectomy: long-
term consistency of satisfaction and adverse effects and the sig-
nificance of informed decision-making, quality of life, and per-
sonality traits. Ann Surg Oncol 2011;18:3110-6.
6. Jagsi R, Hawley ST, Griffith KA, et al. Contralateral prophy-
lactic mastectomy decisions in a population-based sample of
patients with early-stage breast cancer. JAMA Surg 2017;152:
274-82.
7. National Comprehensive Cancer Network (NCCN). NCCN
clinical practice guidelines in oncology genetic/familial
high-risk assessment: breast and ovarian (https://w
ww.nccn.org/
professionals/physician_gls/f_guidelines.asp).
8. Hunt KK, Euhus DM, Boughey JC, et al. Society of Surgical
Oncology Breast Disease Working Group statement on prophylac-
tic (risk-reducing) mastectomy. Ann Surg Oncol 2017;24:375-97.
9. Abdulkarim BS, Cuartero J, Hanson J, Deschnes J, Lesniak
D, Sabri S. Increased risk of locoregional recurrence for women
with T1-2N0 triple-negative breast cancer treated with modified
radical mastectomy without adjuvant radiation therapy compared
with breast-conserving therapy. J Clin Oncol 2011;29:2852-8.
10. Gagliato DdeM, Gonzalez-Angulo AM, Lei X, et al. Clinical
impact of delaying initiation of adjuvant chemotherapy in patients
with breast cancer. J Clin Oncol 2014;32:735-44.
DOI: 10.1056/NEJMclde1708293
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