healthmedicinet

Assessment of the patient requesting CRRM

These guidelines have been formulated to aid clinicians dealing with requests for
CRRM. Where possible, a level of evidence has been assigned from the designations
set by the Centre of Evidence-Based Medicine. There are several steps in the process
of preoperative assessment and counselling that are clinically important before an
informed consent to CRRM can be given. These can be summarised as follows:

Step 1 Taking a history

Step 2 Calculating the risk of contralateral breast cancer

Step 3 Cooling off period whenever possible

Step 4 Multi-disciplinary team (MDT) discussion

Step 5 Patient consent

Step 1: Taking a history

The first element of history taking is to determine the reasons behind a patient’s
request to discuss CRRM. For the majority of women, the decision to request contralateral
surgery is based on factors other than inherited genetic risk 11]. Women with breast cancer may have complex, multi-factorial reasons for requesting
CRRM, and so the history should typically begin with open-ended questions to let the
patient discuss her reasoning, objectives, hopes and fears. Objective assessment of
this is challenging, with only a few reports in the literature 11].

Table 1 lists the main reasons patients request CRRM 12] and is verified by our own study of clinical practice in England 9]. Patients list fear of a second diagnosis, fear of chemotherapy and anxiety about
their children’s future as the main drivers, followed by gene mutation status and
family history—whereas surgeons rank gene mutation and family history as the main
reasons to offer CRRM 9].

The breast cancer patient requesting CRRM is different to the patient considering
BRRM. Although the latter may have experience of a family member’s breast cancer journey,
they would not have had the personal experience of breast cancer, and their reasons
for choosing risk-reducing mastectomy may vary significantly 11], 13], 14]. Fear of developing another breast cancer is a frequently expressed concern, but
not necessarily related to whether or not this would influence life expectancy 15]. For some women, fear of having repeated chemotherapy is their main concern. For
others, it is mistrust of annual mammographic surveillance particularly if their first
breast cancer was mammographically occult, or if they have had a stressful ‘recall’
following a surveillance mammogram. Greater confidence in good outcomes following
breast reconstruction may prompt a discussion of whether better symmetry might be
obtained by bilateral rather than unilateral mastectomy, a factor that may also explain
the ‘Angelina Jolie’ effect of increased interest in BRRM 16]. For women whose primary motive is better long-term survival, a simple explanation
that CRRM will not achieve this in those who do not carry a gene mutation may stop
the discussion going further. However, women may have strongly held motivations for
CRRM quite independent of any effect on survival chances, and these need to be understood
and recorded.

The clinical history also needs to assess the index breast cancer and highlight any
potential poor prognostic indicators. It may be useful to objectively assess this
risk using one of several validated predictive tools readily available. In addition,
any co-morbidities should be identified that would influence further surgery and in
particular reconstructive surgery. In step 5 of the process, a more detailed discussion
is required of their expectations around breast reconstruction including a discussion
of the risks and benefits of the reconstructive options in their case.

Step 2: Calculating the risk of contralateral cancer

Women being considered for CRRM should have an objective assessment made of their
risk of developing CBC, as well as an explanation of whether CRRM would or would not
influence survival prospects. It is well documented that many women overestimate their
personal risk of CBC and the survival benefit of CRRM and at the same time underestimate
the adverse effects of the additional surgery 15], 17]. A significant proportion of breast cancer patients will undergo CRRM despite knowing
there is no survival advantage in non-mutation carriers 17] with only a small proportion understanding the limited survival benefit in non-mutation
carriers 17].

CBC risk is multi-factorial as seen in Table 2. It is important to calculate an individualised lifetime risk of CBC to stratify
patients into different risk-groups, prior to consent for CRRM. This will facilitate
the counselling process and provide a useful standard so that practices throughout
can be audited.

The risk of CBC in patients with known BRCA gene mutations is approximately 2–3 % per annum, and likely higher in TP53 mutation carriers 18]. The baseline risk of CBC in patients with no family history is approximately 0.5 %
per annum 19]. The use of anti-endocrines is associated with a 50–70 % risk reduction, with a greater
reduction in risk from aromatase inhibitors 8]. These baseline risks can be modified by certain factors listed in Table 2. Patients diagnosed with unilateral breast cancer requesting CRRM and who have a
strong family history should ideally have formal assessment of risk and genetic testing
carried out by a clinical geneticist. In other cases, a useful objective assessment
of risk of CBC can be calculated as follows.

Life expectancy at birth for women varies within the UK (range 78.5 years—Glasgow
to Purbeck 86.6 year—Source ONS) 20], and we have used 80 years as the average life expectancy. Thus, to obtain the number
of years of CBC risk, we can simply use the following calculation:

We can then use the quoted annual incidence of CBC at 0.5 % per year as a guide to
the background risk for CBC in women diagnosed with breast cancer. To obtain a life-time
risk based on this, we can use the following calculation (this assumes good life expectancy
from the ipsilateral primary and typically would only apply to stage 1 cancers):

Once this value has been calculated, we can modify the risk based on patient’s personal
risk profile as follows:

Estrogen receptor (ER)-positive disease and on anti-endocrine treatment—multiply
by 0.5 (50 % risk reduction)

Gene carriers—multiply by 4 (2 % annual incidence of CBC)

Oophorectomy under 40 years (surgical, chemotherapy induced or natural)—multiply
by 0.5 (50 % reduction)

Family history—multiply by 2 (unpublished data based on our own family history clinic)

Note: where numerous factors are being considered, the multiplicative interaction
of factors is not known. For those patients with a known genetic mutation and a family
history, consider modifying risk based on gene mutations (i.e. multiply by 4) only.
Anti-endocrine treatment in those who have had oophorectomy under the age of 40 years,
consider risk reduction by one factor (i.e. multiply by 0.5) as there is no data to
our knowledge on whether the relationship is additive.

The quoted baseline annual incidence of CBC of 0.5 % per annum is reduced in ER-positive
tumours by 50 % after 5 years of adjuvant tamoxifen but even more by an aromatase
inhibitor.

Unilateral ductal carcinoma in situ (DCIS) is associated with an increased risk of
developing a contralateral invasive cancer or DCIS. This annual risk is estimated
at 0.6 % 21] and may be used in the above formula.

These calculations are of course only a guide, but they are useful to stratify risk
into clinically relevant risk categories such as the following:

Low risk

10 % remaining life-time risk of CBC

Above average risk

10–20 % remaining life-time risk of CBC

Moderate risk

20–30 % remaining life-time risk of CBC

High risk

30 % remaining life-time risk of CBC

The use of risk categories has proved invaluable in the context of BRRM, and there
are several validated tools now to calculate breast cancer risk based on family history
and lifestyle factors for women without a cancer diagnosis 22] (i.e. Manchester Score, Tyrer-Cuzick, BOADICEA). At present, there are no validated
tools to calculate CBC risk in the context of CRRM. Our experience of using the above
method has been previously presented in abstract form and is a useful clinical tool
for validation in future studies 10].

Step 3: Cooling off period whenever possible

The decision-making process around BRRM is characterised by several months of pre-
and post-test counselling. In contrast, women who request CRRM may do so within a
few hours or days from their diagnosis of breast cancer. Nationally defined targets
for prompt treatment following a diagnosis of breast cancer may impact on the shared
decision-making process by limiting the time available for careful consideration of
the pros and cons of CRRM.

For the majority of patients, it is probably in their best clinical interest to defer
any decision about CRRM until after their primary cancer treatment has been completed.
This “cooling off period” minimises the risk that they make a decision for CRRM as
a knee-jerk reaction at a time when they are emotionally vulnerable. There are exceptions
to this recommendation however. These include the patient with a known BRCA mutation
who may have made a decision many months or years previously to undergo bilateral
mastectomies for therapeutic and risk-reducing reasons in the event of a cancer being
diagnosed. Non-mutation carriers in the high-risk group defined in step 2, such as
those with a significant family history or previous mantle radiotherapy, may also
decide on CRRM as part of their primary treatment on diagnosis of a unilateral cancer
and again may not benefit from a cooling off period.

Overall, the majority of women are satisfied with their decision of CRRM up to a decade
following surgery [Ref. Frost et al., JCO 2005]. However, it is not known whether
timing of this decision impacts on the level of satisfaction. Where feasible, this
step allows women to carefully consider the various options available to them in a
non-time constrained manner. However, this is not always possible as the need to treat
the affected side and possible reconstructive options will influence the decision-making
process and the speed at which happens.

Patients considering an immediate transverse rectus abdominus muscle/deep inferior
epigastric artery perforator (TRAM/DIEP) flap reconstruction for their primary therapeutic
mastectomy are also an important possible exception and are discussed further in step
5.

Step 4: MDT discussion

Given the complexity of the decision-making process, all women considering CRRM should
be assessed in a multi-disciplinary setting—surprisingly, this is not universally
practised in the UK 9]. The core members of the team should include breast care nurse, breast surgeon, oncologist,
radiologist and pathologist and where possible, an oncoplastic-reconstructive surgeon
familiar with the various reconstructive options including free TRAM/DIEP. For patients
with a family history, discussion with a clinical geneticist of their risk of CBC
and the possibility of genetic testing should be offered during the patients cooling
off period. Often, the breast care nurse will have developed a close relationship
with the patient and is the patient’s advocate at the MDT meeting. She should have
the option of requesting additional psychology assessment if she feels necessary,
but we would not regard this as mandatory. The patients’ reasons for requesting CRRM
should be discussed at the MDT in the light of her objective risk of CBC, influence
on survival chances, risks and benefits of the additional surgery, and the alternative
options around surveillance and imaging. Additionally, it is useful to review the
imaging, as some women may be particular challenging to offering radiological surveillance
on the contralateral side.

The main benefit of a multi-disciplinary approach is that requests for CRRM can be
scrutinised across various specialties and facilitate shared decision-decision making
23]. A recent report showed that introduction of this approach resulted in almost a third
of requests for CRRM being declined, mainly due to a low risk of CBC in light of a
high risk of systemic relapse. There is good evidence across various specialties supporting
this form of collaborative working 24]. Our own approach enables the MDT process to consider each request for CRRM on an
individual basis prior to making a consensus-led decision with the option of patient-led
appeal for extenuating circumstances.

Step 5: Patient consent

Each of the steps above is part of the consent process, commencing with a clear discussion
of the benefits that the patient hopes to achieve with CRRM, and a clear explanation
of the objective risk of CBC and whether or not any survival advantage can be achieved.
Particularly for the non-gene carrier where no survival advantage exists, the conclusion
that CRRM is appropriate and has the support of the MDT meeting should be recorded
in the clinical notes. The next step is to explore the various reconstruction options
available to the patient if that is what she wishes, combined with a clear explanation
of the limitations of such surgery, its risks and complications. Unrealistic expectations
of a perfect outcome and no postoperative complications should be addressed if present.
The final step is the signing of a formal consent form, on which there is only sufficient
space for the recording of a brief summary of the risks and benefits; all of these
prior discussions should be recorded within the clinical notes prior to the actual
signing of the form.

A particularly challenging situation is the patient who requests CRRM at the same
time as her therapeutic mastectomy as part of her primary treatment. This puts the
surgeon under time pressure to go through a complex consent process. For patients
in the high-risk group defined in step 2, the situation may be fairly straightforward
as often the patient will have had considered bilateral mastectomy as her preferred
option long before the actual diagnosis. For patients undergoing primary neo-adjuvant
systemic therapy, the situation is also more straightforward because a period of several
months of “cooling off” between those first discussions and the final decision to
proceed give the surgeon and his/her MDT time to complete the above steps. For the
patient requiring a therapeutic mastectomy as her first treatment, and who chooses
an immediate TRAM/DIEP flap as her preferred reconstruction, the decision has to be
made within a few days, as otherwise the option of bilateral symmetrical reconstruction
is lost forever. In these circumstances, there may be no time to proceed to a formal
genetic assessment or to offer a cooling off period. The opportunity for CRRM should
probably not be denied to the patient in those circumstances, as long as the risks
and benefits are clearly explained and approved by the MDT, and recorded in the clinical
notes.

Currently, there is not enough provision in the UK for every MDT to have an oncoplastic
surgeon who can offer free TRAM/DIEP recon as a core member. Many MDTs in the UK have
to refer out with to an extended MDT member (usually a plastic surgeon) which causes
time delays and lengthens the decision-making process for patients and anxiety levels.
Ideally, all MDTs should include an oncoplastic surgeon familiar with the various
reconstructive options.

Women who are deemed not suitable for CRRM are currently offered annual mammography
surveillance for 5 years or up to the age of 50 years—whichever is longer.