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8 Applied Aspects ofSystemic Therapy inBreast Oncoplasty andReconstruction
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61
to perform CBE prior to each cycle of neoadjuvant therapy and only if there is suspicion of progression, imaging is done. The indication and
type of imaging modality performed after NAT
may also depend upon the modality used at baseline or requirements of the surgical planning
team [12]. Indeed, imaging before surgery is not
required in patients who will anyway undergo
mastectomy (patient decision, multicentric disease, presence of other contraindications of
breast conservation). USG is more accurate in
determining response in axillary lymph nodes.
MRI has better accuracy than CBE or conventional imaging for determining the extent of local
residual disease and in surgical planning, with
the best correlation with surgical pathology specimen. MRI is less accurate for a dendritic pattern
of tumor shrinkage, non-mass breast cancers like
inltrative lobular carcinoma or tumors with
extensive DCIS component. Further, MRI may
both underestimate and overestimate the extent
of residual disease often resulting in superuous
mastectomies [23, 24]. Positron emission tomography (PET) scans are not used in the routine
assessment of response to NAT in non-metastatic
disease due to their low sensitivity, poor availability, and high costs.
Pathological response assessment is the gold
standard and pCR has the most robust evidence
supporting its role in assessing the efcacy of
NAT. pCR has been dened variously in different
studies but the absence of residual invasive disease in breast or axilla with or without non- invasive
disease is the most used denition [25, 26]. The
most preferred method for assessment of pCR at
present is residual cancer burden (RCB) criteria
which are calculated using the two- dimensional
diameter of the tumor in the surgical specimen,
percentage of tumor cells (both DCIS and invasive tumor cells), and the number of metastatic
nodes and size of lymph node metastasis. The
RCB system is prognostic for disease-free survival and overall survival. There is no evidence to
support the use of blood markers like CA 15-3
and CA 27-29 for monitoring response while the
role of reduced Ki 67% in the residual tumor after
NAT in hormone-positive breast cancer is evolv-
ing and is not recommended outside of clinical
trials.
8.8 Impact ofSystemic Therapy
onWound Healing
Concerns regarding the possibility of higher
wound-related complications due to preoperative
or postoperative systemic therapies have always
persisted among surgeons based on anecdotal
evidence. Alkylating agents (doxorubicin) and
antimetabolites (5-uorouracil, methotrexate,
high dose cyclophosphamide) have been reported
to be associated with reduced wound tensile
strength by impairing initial phases of healing
especially if received within 7–14days of perioperative period [27, 28]. Limited retrospective
data suggest that hormonal agents like tamoxifen
might increase microvascular complications and
delay wound healing during autologous reconstruction procedures [28, 29]. However, clinically meaningful effect on the surgical wound
has not been demonstrated with taxanes, aromatase inhibitors, and trastuzumab. Large retrospective and prospective evidence now suggest that
patients who received neoadjuvant chemotherapy
followed by breast surgery with immediate
reconstruction did not show increased rate of
wound complications like skin ap necrosis,
infection, hematoma, and implant or ap loss as
compared to those who did not receive NACT
[30, 31]. In a recent meta-analysis of more than
eighty-ve thousand patients, NACT in breast
cancer did not affect 30-day morbidity in patients
receiving immediate implant or aps. Breast
reconstruction done immediately or in a delayed
manner may cause a small but signicant delay in
the initiation of adjuvant chemotherapy, but this
delay has not been found to have a signicant
impact on oncological outcomes [31]. If started
at an appropriate time after surgery, adjuvant chemotherapy does not seem to increase woundrelated complications or worsen cosmesis as
most of these happen before the start of systemic
therapy, therefore, more likely related to surgical
factors or other patient-related factors.
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S. Kirar et al.
8.9 Timing ofAdjuvant Systemic
Therapy
The time interval between denitive surgery and
initiation of adjuvant chemotherapy (time to
adjuvant chemotherapy, TTC) affects long-term
outcomes. The lack of data from published randomized studies on the time frame of starting
chemotherapy after curative surgery and the ethical dilemma of conducting a clinical trial to
answer this question have perpetuated the controversy of optimal TTC. A recent meta-analysis
(n= 15,327) reported that each 4-week delay in
initiating adjuvant chemotherapy translates into a
6% increase in the risk of death and an 8%
increase in the risk of recurrence [32]. In another
large retrospective cohort of breast cancer
patients (n=24,843), patients who received adjuvant chemotherapy at 91days or more after surgery had worse overall survival (HR, 1.34;
95%CI 1.15–1.57) and breast cancer-specic survival (HR, 1.27; 95%CI 1.05–1.53), while there
was no evidence of adverse outcomes in the delay
of 31–90 days compared with those receiving
within 31days [33]. Specically, the TNBC subgroup is associated with higher 10-year mortality
when TTC was beyond 30 days, especially in
those who underwent breast conservation surgery
(HR,1.69; 95%CI 1.22–2.34, p=0.002) but not
in those who underwent mastectomy (HR, 1.04;
95%CI 0.84–1.28, p=0.716) [34]. Current breast
cancer guidelines recommend that chemotherapy
should be initiated 6–12weeks after surgery and
excessive delay should be avoided in patients
with locally advanced disease, TNBC, and HER2
positive tumors [12]. Even more complicated is
the determination of the appropriate timing of
initiating adjuvant endocrine therapy, especially
its integration in the treatment plan of patients
who also require adjuvant chemotherapy or
radiotherapy. Major clinical guidelines do not
adequately address this dilemma and recommend
a physician or patient preference [12]. There is no
evidence to support the concern that aromatase
inhibitors given concurrently with RT lead to
increased radiosensitivity related toxicity or detrimental disease control. Retrospective evidence
suggests no impact on the efcacy of concurrent
administration of tamoxifen with radiotherapy;
however, heterogeneous evidence exists for
treatment- related toxicities, specically skin and
lung brosis when tamoxifen is given concurrently with RT.Therefore, in a patient population
with high cure rates, preventing long-term complications by sequential administration is the preferred strategy.
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Perioperative Management
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ofBreast Cancer Patients:
Anesthesiologist Perspectives
NishkarshGupta andSushmaBhatnagar
9
9.1 Introduction
Breast cancer is the most commonly diagnosed
cancer for women all over the world including
India [1]. Anesthesia management of these
patients poses unique challenges to anesthesiologists because of multiple factors involved; variety
of procedures like loco-regional treatment including surgery and radiation therapy. The surgical
treatment may include modied radical mastectomy, simple mastectomy, breast conserving surgery, sentinel lymph node biopsy, breast
reconstruction, etc. In addition, patient may have
received systemic adjuvant therapy in form of
neoadjuvant/adjuvant chemotherapy and adjuvant endocrine therapy. Gaps in perioperative
management have been identied as the single
most important factor for increased perioperative
mortality [2].
Thus it is important to understand the nature
and the magnitude of these risks. The anesthetic
concerns for perioperative management of
patients undergoing breast cancer surgery can be
divided into preoperative, intraoperative, and
postoperative period.
N. Gupta · S. Bhatnagar (*)
Department of Onco-Anaesthesiology and Palliative
Medicine, Dr. B.R. Ambedkar Institute Rotary
Cancer Hospital, AIIMS, New Delhi, India
9.1.1 Preoperative Period
The main aim of pre-anesthesia clinical assessment is to ascertain the anesthetic and surgical
risk and best optimize it before the procedure.
Medical comorbidities are a major source of
adverse perioperative morbidity and can be
reduced by a properly conducted pre-anesthesia
checkup. It is important to ensure that a patient
undergoes a desired surgical intervention with
minimal exacerbation of existing disorders,
avoidance of new morbidities, and prompt recovery from the surgical procedure. For a successful
outcome, it is crucial to provide patients with preoperative counseling, explain the procedure, and
describe potential risks, if any. Preoperative discussion about the procedure between anesthesiologist and surgeon is also important to ensure an
uneventful perioperative course. Sources of perioperative risk may be classied as a risk due to:
1. Anesthetic—anesthesia related risk may be
due to
(a) Anesthetic drugs and interventions
(b) Mechanical and operator error
2. Systemic illness that may affect aesthetic
technique (patient factors)
(a) Cardiac: Many anesthesia induction
agents and inhalational agents are myocardial depressants. Unoptimized patients
with cardiac disease may have accentuated hypotensive response to induction of
© The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023
S. V. S. Deo (ed.), Breast Oncoplasty and Reconstruction,
https://doi.org/10.1007/978-981-99-5536-7_9
65
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N. Gupta and S. Bhatnagar
Fig. 9.1 Specic
concerns in cancer
patient during
preanesthesia evaluation
Malnourishment and Systemic effects of Cancer related pain and
cancer cachexia
anesthesia. The cardiac evaluation and
optimization of breast cancer patients is
based on accepted guidelines as done of
other patients, but the time sensitive
nature of the surgery is considered while
deciding [3].
(b) Autonomic (ANS) neuropathies, such as
diabetic, also accentuate hypotension with
anesthetic induction. In addition, ANS dysfunction has been noted in cancer patients,
more so in advanced cancer. Anti-neoplastic
therapy in the form of chemotherapy (vinca
alkaloids, anthracyclines, paclitaxel) as
well as radiotherapy has been shown to
contribute to ANS dysfunction [4].
Decreased physical activity, psychosocial
stress, sleep disturbances, metabolic
derangements, loss of cardiorespiratory tness that are commonly present in cancer
patients may also adversely impact ANS
function [5]. Resting tachycardia and postural hypotension can be done bedside to
detect ANS dysfunction in these patients.
In select cases formal ANS testing in labs
may improve overall patient outcomes.
(c) Pulmonary: Induction of anesthesia
decreases vital capacity, functional residual capacity, and McCleary clearance.
Also a response to hypoxia and hypercarbia is depressed. The patients with preoperative respiratory dysfunction may have
postoperative respiratory morbidity like
pneumonia, etc. [6].
3. Specic concerns in cancer patient
In addition to the usual concerns regarding
optimization of comorbidities, detection of
undiagnosed illnesses, and alleviating patient
anxiety, cancer patients present specic and
Specific challenges in
cancer patient
chemo and radiotherapy associated medications
unique challenges. A brief discussion of these
conditions is done to keep the anesthetist up to
date regarding these special considerations
and the hazards posed by them (Fig.9.1).
(a) Preoperative chemotherapy may be asso-
ciated with numerous side effects on various organ systems. Anesthetists should
have a detailed knowledge about the
drugs and doses given and should keep a
keen eye for the anticipated adverse
effects during the preoperative assessment of cancer patient. Commonly used
chemotherapy drugs include doxorubicin,
cyclophosphamide, tamoxifen, and
trastuzumab [7].
Anthracyclines like doxorubicin may
lead to cardiac injury which may be progressive from the time of exposure and
continue for months to years. The clinical
manifestations may be classied into
acute (usually reversible, occurring during duration of treatment), sub-acute
(detected within a year of exposure), and
chronic (detected years after exposure)
[8]. A detailed assessment of the patient
(history and systemic examination)
should be done. An ECG is usually nonspecic and sinus tachycardia is most
reported rhythm. We may need to order
specic tests like echocardiography in
case of any cardiac toxicity is expected.
In addition, the chemotherapy drugs may
cause myelosuppression that may lead to
pancytopenia (anemia, neutropenia, and
thrombocytopenia). This may pose a
challenge during surgery and one should
order fresh investigations of the patients
after last chemotherapy.
9 Perioperative Management ofBreast Cancer Patients: Anesthesiologist Perspectives
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67
Preoperative radiation therapy (RT):
Usually RT is given in breast cancer
patients after surgery, but recent reports
have been suggesting role of Rt in preoperative period especially in locally
advanced cancers and early stage disease
as well that may improve overall
outcomes of the patients [9]. Radiation
therapy near heart in patients of breast
cancer may produce a wide array of acute
and chronic cardiovascular adverse
effects like pericarditis with pericardial
effusion (presents within 6 months to
2years after radiation and may be asymptomatic), injury to coronary arteries
(luminal narrowing and coronary artery
disease), valvular dysfunction, myocardial brosis, and brosis of conducting
system of heart [10]. So, a patient with
history of preoperative breast RT for surgery should be thoroughly screened for
above mentioned complications.
(b) Pain in cancer patients: Cancer patient
coming for surgery is often receiving
analgesics to control their pain. A patient
receiving opioid analgesics may have
some degree of tolerance and require
dose escalation in the postoperative
period. A thorough drug history with
details of analgesic use should be elicited
in the preoperative visit [11].
(c) Nutrition in cancer patients:spiepr patient
with cancer coming for surgery may be
malnourished with poor body reserves
and may not tolerate the surgical and perioperative stress. Nutritional deciency
can occur in a cancer patient due to various reasons like metabolic alterations due
to the malignancy per se and hyper-catabolic inammatory state leading to “cancer cachexia” [2, 12].
In addition, side effects of chemotherapy like intractable vomiting, chemotherapy related alterations in taste and smell
lead to loss of appetite [13].
Poor nutritional status may lead to
patient who may have delayed wound
healing, surgical site infections, and
delayed recovery. Thus, assessment of
nutritional status is an integral part of preoperative evaluation of cancer patient
[14].
Indiscriminate use of enteral or parenteral nutrition may be no proven survival
benet in patients undergoing cancer surgery. Some studies have found fewer
operative complications and a shorter
length of hospital stay in severely malnourished patients receiving nutritional
support prior to major surgery for cancers
of the digestive tract and the head and
neck [15].
4. Surgical risk: Various models have been pro-
posed for surgical risk assessment. John
Hopkins Risk classication classies the surgeries into 5 categories based on severity of
surgery and degree of blood loss. Majority of
breast cancer surgery can be classied into
category 1 (the surgery is minimally invasive
and with minimal blood loss and minimal risk
independent to anesthesia) [16].
It is always a dilemma to send the oncosurgery
patients to physician for optimization as any
delay due to optimization of risk factors may lead
to progression of the malignancy, make the tumor
non-respectable, and curable cancer may become
incurable. There are no clear cut guidelines on
target wait times for cancer surgeries. A patient’s
journey from the start of symptoms to the operating table can be understood by Fig.9.2.
As anesthetists we should aim to minimize the
time for preoperative optimization (T2) without
causing undue delay in surgery. One should start
optimization of patient’s right from the rst day
simultaneously with the surgical work-up. This
will save time and patient will not have to wait
for optimization. This means the time before
coming for PAC check-up can be utilized for
screening and control associated comorbidities
and involve any specialist consults if required.
Ontario based study group has come up with
guidelines for target wait times for various cancer surgeries based on patient prole and type
and stage of malignancy [17]. Most of the breast
cancer patients posted for surgery can be catego-
68
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N. Gupta and S. Bhatnagar
Onsetof
symptoms
Fig. 9.2 Key dates in patient’s cancer surgery experience
VisittoSurgicalDecisiont
surgeon workup
rized into category 3 (known or suspected invasive cancer) and we have a maximum of 1month
(4 weeks) for optimization in case the need
arises.
These guidelines provide an overview of the
approximate or the 4 ideal time available to optimize a cancer patient coming for surgery and
may be used as a measure of the quality of care.
9.2 Intraoperative Management
The breast cancer surgery can be done under
standard general anesthesia (GA) only, GA with
regional block technique or regional anesthesia
with sedation only technique. Before initiating
anesthesia, standard monitors should be attached.
One should ensure a good venous access preferably in arm contralateral to the side of surgery. In
addition, one should avoid blood pressure monitoring on the arm that is on the same side of surgery. During positioning one should ensure
adequate padding and prevent overstretching of
arm to prevent brachial plexus injury.
The anesthesia can be standard inhalation
based or total intravenous anesthesia (TIVA)
depending on the availability of drugs/equipment
and anesthetist’s expertise. Generally, we prefer
to secure airway using a supraglottic device like
(I-gel) and we intubate the patients undergoing
prolonged surgeries like ap reconstruction.
These patients are at higher risk for postoperative
nausea vomiting and we prefer to use a combination of drugs to manage it. We usually give 4mg
urgery
operate
T2
Totalpre op time T1 +T2
done
dexamethasone injection at induction and give
injection ondansetron (4–8 mg) thirty minutes
before completion of surgery.
During sentinel lymph node biopsy cardiovascular event may occur due to anaphylactic reaction to dyes used (isosulfan blue and methylene
blue). So, one should be vigilant and be prepared
in case of any eventuality.
In addition, a regional block technique like
Serratus anterior plane block (SAP), thoracic
paravertebral block (TPVB), erector spinae block
(ESPB), PECS 1 and PECS 2 block, and thoracic
epidural block (especially for surgery requiring
ap) may be used [18].
Surgical handling of the tumor may lead to
dispersal of neoplastic cells into the blood and
lymphatic systems. Currently available literature
is limited to animal experiments and retrospective studies. A number of perioperative factors
including anesthetic techniques and surgical factors have been linked to cancer recurrence
(Table9.1).
Regional anesthesia in addition to providing
good analgesia reduces the chances of phantom
breast pain syndrome. In addition, it reduces the
tumor spread by decreasing the neuroendocrine
stress response to surgery, reduces the need of
intravenous or volatile agents or opioids,
decreases inammatory cytokines, and preserves
immune system. Various studies have been done
till now and the results are conicting. Some
studies are favoring regional anesthesia to prevent cancer recurrence and some studies relate
regional anesthesia with tumor recurrence [19].
9 Perioperative Management ofBreast Cancer Patients: Anesthesiologist Perspectives
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Table 9.1 Perioperative factors that have potential for
cancer spread and metastasis
Increased risk Decreased risk
Surgery Regional anesthesia
Hypothermia Propofol
Psychological stress
and anxiety
Intravenous
anesthetic agents
Inhalational agents Beta-blockers
Opioids Statins
Blood transfusion Immunotherapy
Pain Immunonutrition
Anemia Tramadol
Hypotension Thermotherapy
Hypoxia Hyperthermic intra-peritoneal
Hyperglycemia Laparoscopic surgery 2
Midazolam
Alpha-2 agonists
Local anesthetic
Cyclooxygenase inhibitors
chemotherapy (HIPEC)
9.3 Postoperative Management
1. A combination of analgesic drugs like
paracetamol, NSAIDs, and opioids is used to
provide multimodal analgesia. An effective
analgesia also reduces the incidence of postmastectomy pain.
2. A combination of drugs used intraoperatively
to prevent nausea vomiting should be continued in the postoperative period as well.
thermia, early cessation of intravenous uids,
resumption of oral intake, and early ambulation
[21].
9.5 Key Points
• Cancer surgeries are time sensitive and global
data for average waiting time for surgeries
may serve as guidelines for the time available
to optimize a patient.
• Preoperative assessment should be started at
the earliest at the time of visit to the surgeon
using specially developed questionnaires to
avoid unnecessary delays.
• Conduct of safe anesthesia and surgery in a
cancer patient requires a delicate balance
between optimization of comorbidities and
evaluation of specic concerns for a cancer
patient, care must be taken to avoid unnecessary delays, and safe conduct of anesthesia
and surgery should be kept in mind.
• The recent limited clinical evidence suggests
that there is an association between anesthetic
technique and cancer recurrence, but there is
lack of prospective, randomized, clinical trials
to prove this association beyond doubt.
• A comprehensive postoperative care plan
should include multimodal analgesia and
effective management of PONV.
9.4 Enhanced Recovery after
Surgery (Eras) andBreast
Surgery
ERAS protocols have included a standardized
care pathway in the perioperative period and
aim to reduce hospital stay and enhance postoperative recovery [20]. The literature on the
effect of ERAs protocols on patients undergoing breast surgery is limited. The components
of ERAS protocol in breast surgery include preoperative counseling, reduced fasting period,
opioid sparing perioperative analgesia, maintaining intraoperative euvolemia and normo-
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