The American Journal of Surgery (2013) 206, 894-899

Southwestern Surgical Congress

Neoadjuvant therapy and breast cancer surgery: a closer

look at postoperative complications
Erin M. Garvey, M.D.a, Richard J. Gray, M.D.a, Nabil Wasif, M.D.a,
William J. Casey, M.D.b, Alanna M. Rebecca, M.D.b, Peter Kreymerman, M.D.b,
Deborah Bash, M.D.b, Barbara A. Pockaj, M.D.a,*

a
Division of Surgical Oncology, Department of Surgery, Mayo Clinic Arizona, 5777 East Mayo Boulevard, Phoenix, AZ
85054, USA; bDivision of Plastic Surgery, Department of Surgery, Mayo Clinic Arizona, Phoenix, AZ, USA

KEYWORDS: Abstract
Neoadjuvant; BACKGROUND: Neoadjuvant therapy is important in the treatment of advanced breast cancer.
Breast cancer surgery; METHODS: Postoperative complications in neoadjuvant patients were analyzed.
Postoperative RESULTS: One hundred forty patients underwent 148 breast cancer surgeries after neoadjuvant ther-
complications apy: 28% breast-conserving therapy procedures, 36% mastectomies, 28% mastectomies with immedi-
ate reconstruction, and 8% mastectomies with delayed reconstruction. Forty-seven patients (34%)
suffered 59 complications: 18% of those undergoing breast-conserving therapy, 30% of those undergo-
ing mastectomy, 44% of those undergoing mastectomy with immediate reconstruction, and 67% of
those undergoing mastectomy with delayed reconstruction. Major complications occurred in 18% of
patients. Skin loss occurred in 6% of patients. One patient had partial nipple necrosis. Three patients
suffered implant loss. One patient had deep inferior epigastric artery perforator flap loss. Eleven hema-
tomas and 5 infectious complications required reoperation.
CONCLUSIONS: Surgery after neoadjuvant therapy is safe, but careful counseling is warranted given
that 18% of patients experienced major complications. Complications rates are higher with reconstruc-
tion, but feared complications of skin, nipple, implant, or flap loss were infrequent.
Ó 2013 Elsevier Inc. All rights reserved.

Neoadjuvant therapy plays an important role in treating
advanced breast cancer. Initially indicated for inoperable
tumors or inflammatory breast cancer, the indication for
neoadjuvant therapy has been expanded to include oper-
able tumors.1–5 Multiple studies have shown no difference
in overall or disease-free survival between patients under-
going neoadjuvant or adjuvant therapy.6–10 However,
The authors declare no conflicts of interest.
* Corresponding author. Tel.: 11-480-301-2849; fax: 11-480-342-
2170.
E-mail address: pockaj.barbara@mayo.edu
Manuscript received March 17, 2013; revised manuscript September 5,
2013
fewer studies have focused on the adverse surgical out-
comes associated with neoadjuvant therapy, especially
with respect to breast reconstruction. The most common
complication associated with breast surgery has been
reported to be wound infection.11 Given that cytotoxic
chemotherapy is known to cause neutropenia,12 it has
been hypothesized that neoadjuvant chemotherapy may
lead to increased infectious complications. However, a re-
cent American College of Surgeons National Surgical
Quality Improvement Program study showed no associa-
tion between neoadjuvant chemotherapy and postopera-
tive wound complications.13 Oh et al14 provided an
up-to-date, concise review of the plastic surgery literature
with respect to the effects of neoadjuvant and adjuvant

0002-9610/$ - see front matter Ó 2013 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.amjsurg.2013.09.004
E.M. Garvey et al. Surgical complications after neoadjuvant therapy
chemotherapy on the outcomes of breast reconstruction,
citing studies that show no increase in postoperative com-
plications with the use of adjuvant or neoadjuvant therapy.
The caveats of this review were that most studies were
small, underpowered, and not designed to directly analyze
the relationship between neoadjuvant therapy and postop-
erative complications. The purpose of this study was to
determine the rates of all postoperative complications in
patients treated with neoadjuvant therapy with respect to
the type of breast surgery performed (breast-conserving
therapy [BCT] vs mastectomy vs mastectomy with recon-
struction) and to the timing of reconstruction (immediate
vs delayed).
Methods
A prospective breast cancer database at a single insti-
tution was reviewed, identifying all patients aged .18
years who were treated with neoadjuvant therapy before
breast cancer surgery from January 2000 through May
2012. At our institution, neoadjuvant therapy is recom-
mended for all patients with inflammatory breast cancer
and all patients with inoperable breast cancer and is
considered in patients who present with large primary
tumors (T2 disease or greater). All patients received
preoperative antibiotics. For those patients who underwent
reconstruction and had drains in place, postoperative
antibiotics were continued until the drains were removed.
All patients also received venous thrombosis prophylaxis.
All patients received thromboembolism deterrent hose and
sequential compressive devices, while patients who under-
went inpatient procedures also received preoperative and
postoperative subcutaneous heparin. All patients were
stratified into groups on the basis of type of surgical
procedure: BCT; mastectomy; mastectomy with immediate
reconstruction (Mast1IRecon), defined as reconstruction
taking place at the time of the breast cancer surgery; and
mastectomy with delayed reconstruction (Mast1DRecon),
defined as reconstruction taking place after the index breast
cancer surgery. Further subgroups for patients who
underwent reconstruction were created on the basis of
mastectomy type: skin-sparing mastectomy (SSM), nipple-
sparing mastectomy (NSM), modified radical mastectomy,
and total mastectomy. Postoperative complications in-
cluded seromas, hematomas, wound infections, tissue
expander or implant rupture or loss, skin necrosis, nipple
loss, and flap loss. A major complication was defined as any
complication requiring unplanned repeat surgical interven-
tion. Complication rates were calculated with respect to the
number of patients who experienced a complication. Insti-
tutional review board approval was obtained.
Results
Of the 2,643 patients with breast cancer over the
12.5-year study period, 140 (5%) underwent 148 breast
895
cancer surgeries after completing neoadjuvant therapy.
All patients were female, and the average age was 55
years (range, 24 to 90 years). The majority of patients
(86%) were Caucasian, with the remaining as follows: 6%
Hispanic, 4% African American, 3% Native American,
and 1% Asian. Ninety patients (64%) were postmenopau-
sal. The majority of patients (114 [81%]) underwent
neoadjuvant chemotherapy, 12 (9%) had only neoadjuvant
hormonal therapy, 10 (7%) had combinations of neo-
adjuvant biologic and chemotherapy, 3 (2%) had combi-
nations of neoadjuvant hormonal and chemotherapy, and
1 (1%) had only neoadjuvant radiation therapy.
Thirty-nine patients (28%) underwent 41 BCT proce-
dures, 50 (36%) underwent 53 mastectomies, 39 (28%)
underwent 42 Mast1IRecon procedures, and 12 (8%)
underwent 12 Mast1DRecon procedures. Of the 101
patients who underwent mastectomies, 34 (34%) under-
went contralateral prophylactic mastectomies.
Types of reconstruction included 30 tissue expander/
implants, 16 deep inferior epigastric artery perforator
(DIEP) flaps, 4 transverse rectus abdominis myocutaneous
(TRAM) flaps, and 4 other flaps, including 1 superficial
inferior epigastric artery, 1 superior gluteal artery perfo-
rator, and 2 latissimus dorsi flaps. One tissue expander/
implant patient was ultimately converted to a DIEP flap
because of complications and therefore was counted as a
tissue expander/implant patient. Of the 42 Mast1IRecon
procedures, 3 (7%) were total mastectomies, 7 (17%)
were modified radical mastectomies, 22 (52%) were SSM
procedures, and 10 (24%) were attempted NSM proce-
dures, with 1 patient requiring conversion to SSM
(counted as SSM in Table 1).
Forty-seven patients (34%) suffered 59 complications,
including 7 of 39 (18%) of those who underwent BCT, 15 of
50 (30%) of those who underwent mastectomy, 17 of 39
(44%) of those who underwent Mast1IRecon, and 8 of 12
(67%) of those who underwent Mast1DRecon (Table 1).
Major complications, defined as those requiring repeat sur-
gical intervention, occurred in 25 of 140 patients (18%): 5
of 50 mastectomy patients (10%), 15 of 39 Mast1IRecon
patients (38%), and 5 of 12 Mast1DRecon patients
(42%). There were no major complications in BCT pa-
tients. Skin loss requiring operative debridement occurred
in 8 of 140 patients (6%): 1 of 50 mastectomy patients
(2%), 4 of 39 Mast1IRecon patients (10%), and 3 of 12
Mast1DRecon patients (25%). One of the 9 NSM patients
(11%) had partial nipple necrosis requiring operative de-
bridement. Three of the 20 skin-sparing Mast1IRecon pa-
tients (15%) suffered implant loss after 2 infections and
1 rupture. Two of the 16 DIEP flap patients (13%) required
early operative revision because of venous congestion, both
of which occurred after skin-sparing Mast1IRecon. One
of the 16 DIEP flap patients (6%) had flap loss after Mast1
DRecon secondary to a postoperative hematoma and
venous thromboses. There were 11 hematomas (8%) and
1 infected seroma that required reoperation. There were
11 infectious complications (8%), 5 of which were major:
896 The American Journal of Surgery, Vol 206, No 6, December 2013

Table 1 Number and percentage of patients with complications by type of procedure performed
Variable BCT Mastectomy SSM1IR NSM1IR MRM1IR TM1IR Mast1DRecon Total
Procedures 41 53 23 9 7 3 12 148
Patients 39 50 20 9 7 3 12 140
Any complication 7 (18%) 15 (30%) 10 (50%) 5 (56%) 2 (29%) d 8 (67%) 47 (34%)
Major complication d 5 (10%) 10 (50%) 3 (33%) 2 (29%) d 5 (42%) 25 (18%)
Skin loss d 1 (2%) 3 (15%) d 1 (14%) d 3 (25%) 8 (6%)
Nipple loss (partial) d d d 1 (11%) d d d 1 (.7%)
Flap loss d d d d d d 1 (8%) 1 (.7%)
Implant loss d d 3 (15%) d d d d 3 (2%)
Major infection d 1 (2%) 4 (20%) d d d d 5 (4%)
BCT 5 breast-conserving therapy; IR 5 immediate reconstruction; Mast1DRecon 5 mastectomy plus delayed reconstruction; MRM 5 modified radical
mastectomy; NSM 5 nipple-sparing mastectomy; SSM 5 skin-sparing mastectomy; TM 5 total mastectomy.

1 in a mastectomy patient and the other 4 in patients who
underwent skin-sparing Mast1IRecon. Other minor com-
plications included 9 seromas managed conservatively, 8
seromas requiring aspiration, 6 hematomas managed con-
servatively, and 6 wound infections treated with antibiotics.
Lymphedema occurred in 14% of patients.
Overall, 103 of 140 patients (74%) underwent postop-
erative radiation therapy, including 30 BCT patients,
38 mastectomy patients without reconstruction, 25
Mast1IRecon patients, and 10 Mast1DRecon patients.
Thirty-seven of the 47 patients (79%) who experienced
complications were treated with adjuvant radiation. The
1 patient who received neoadjuvant radiation therapy
did not experience a complication. Three of the 12
patients (25%) who received only neoadjuvant hormonal
therapy experienced complications: 1 major infection,
1 infection treated with antibiotics, and 1 seroma managed
conservatively.
Comments
Breast cancer surgery, although generally well toler-
ated, is not without its complications. A 2007 study
determined wound infection to be the most common
complication after breast cancer surgery and found an
incidence of 4.3% in mastectomy patients versus 1.97% in
BCT patients,11 while other studies have cited a range of
3% to 19% for wound infection.15 Our overall infectious
complication rate was 8%, and all patients received preop-
erative antibiotics. Seroma, epidermolysis, and hematoma
can also complicate breast cancer procedures, with
reported rates of 29% for seroma in mastectomy versus
18% in BCT and 18% for epidermolysis in mastectomy
versus 0% in BCT and overall rates of hematoma in breast
cancer surgery ranging from 2% to 10%.16,17 In our series,
the rates of seroma and hematoma were 11.6% each, and
2% of mastectomy patients without reconstruction had
epidermolysis.
The addition of reconstruction to the breast cancer
procedure creates the potential for more postoperative
complications. Breast reconstruction can be achieved
through a variety of procedures, each with its own set
of medical and cosmetic complications. The risks associ-
ated with tissue expander and implant reconstruction
include infection, malposition, deflation, implant expo-
sure or extrusion, and seroma and hematoma formation,
with long-term risks further including capsular contrac-
ture and wrinkling of the implant.18 The use of postoper-
ative radiation therapy often exacerbates implant-related
complications, with some sources citing reconstruction
failure in 24% to 37% versus 8% in patients not treated
with radiation, capsular contraction in 32.5%, and an
overall complication rate of 53% to 68% versus 31% in
patients not treated with radiation.19–22 The majority of
our patients who had complications, regardless of recon-
struction or timing, underwent postoperative radiation
therapy. The above studies, and our present study, high-
light the important relationship between postoperative
radiation and the risk for postoperative complications;
the risk for postoperative radiation therapy should not
be underestimated. Interestingly, our 1 patient who re-
ceived neoadjuvant radiation, who later underwent mas-
tectomy without reconstruction, did not experience a
postoperative complication.
The alternative to implant-based reconstruction is an
autologous pedicled or free perforator tissue flap. In 1 study,
a pedicled, compared to a free, TRAM flap was associated
with a 12% versus 18% risk for infection, a 4% versus 4.5%
to 9% risk for hematoma or seroma, a 16% versus 15% risk
for partial flap loss, a 1% versus 1.5% risk for total flap loss,
and an 8% versus 12% long-term risk for abdominal wall
laxity or hernia, while another study showed total flap loss
for free TRAM flaps as low as .18%.23,24 Only 1 of our 4
TRAM flap patients experienced a complication, but it was
a major complication: wound breakdown requiring operative
debridement. Compared with pedicled TRAM flaps, DIEP
flaps initially were thought to have a higher risk for total
flap loss, but more recent studies have shown no difference
in flap failure rates, with a rate of 3.1% for DIEP flaps.25,26
Another study showed lower rates of flap loss at 2.5% for
partial flap loss and .5% for total flap loss.27 Other DIEP
E.M. Garvey et al. Surgical complications after neoadjuvant therapy
complications include a 12.5% rate of hematoma or seroma
and a 12.5% rate of infection.26 Only 1 of our 16 DIEP flap
patients failed, but 2 required early reoperation for salvage.
Superficial inferior epigastric artery flaps are associated with
a 2% to 2.9% risk for flap loss and a 17.4% risk for venous
thrombosis.24,28 Superior or inferior gluteal artery perforator
flaps can have sciatic nerve complications and high rates of
flap loss at 6.5% for inferior gluteal artery perforator
flaps.18,29 Latissimus dorsi flaps often have complications
at the donor site, namely seroma, with rates reported as
high as 56%.30 Our 1 patient with a superior gluteal artery
perforator flap required operative debridement for wound
breakdown, but our 1 patient with a superficial inferior epi-
gastric artery flap and 2 with latissimus dorsi flaps did not
have any complications.
Special consideration must also be given to the added
risks of SSM and NSM, mainly skin and nipple necrosis.
Skin necrosis in SSM, however, was reported at 10.7%
versus 11.2% in non-SSM.31 Skin loss requiring operative
debridement occurred in 8 of our 140 patients (6%), only
3 of whom were SSM patients and none of whom under-
went NSM. The rates of nipple necrosis are generally
reported in the 2% to 13% range.32–36 Skin and nipple
necrosis are thought to be related to the type of skin inci-
sion, surgical dissection, flap length, and breast size, all fac-
tors that are unlikely to be influenced by neoadjuvant
chemotherapy.32 Partial nipple necrosis requiring operative
debridement occurred in 1 of our 9 NSM patients (11%).
Despite all of the literature on breast cancer surgery and
reconstruction complications, the impact of neoadjuvant
therapy on such outcomes has been less well studied. The
2012 National Surgical Quality Improvement Program
study looked at a large number of patients and found no
association between neoadjuvant chemotherapy and post-
operative wound complications at a rate of 3.4% in those
treated with neoadjuvant therapy versus 3.1% for those who
were not; however, there was a trend toward an increase in
wound complications in neoadjuvant patients undergoing
mastectomy with reconstruction.13 One study cited compli-
cation rates in neoadjuvant patients of 1.9% for wound in-
fection, 9.3% for seroma formation, and 14.8% for skin flap
necrosis.37 The majority of the currently sparse neoadjuvant
literature relates to breast reconstruction outcomes. Tissue
expander and implant use has been cautioned against in
neoadjuvant patients on the basis of a 32% tissue expander
loss, mostly due to infection and extrusion.38 Our rate of
tissue expander/implant loss was 3 of 30 patients (10%):
2 infections and 1 rupture. A high complication rate
(55%) has been noted after neoadjuvant therapy in patients
undergoing reconstruction with a pedicled TRAM or free
TRAM flap.39 Our complication rate for TRAM reconstruc-
tion was 1 of 4 patients (25%). One small study reported
rates of 7.4% total and 14.8% partial DIEP flap loss after
neoadjuvant therapy.40 Our rate of total DIEP flap loss
was 1 of 16 patients (6%). Our complication rate of 44%
for neoadjuvant patients who underwent immediate recon-
struction is higher than prior data from our prospectively
897
maintained breast cancer database, which demonstrated a
30% postoperative complication rate for patients who
underwent immediate breast reconstruction.
The main limitation of our study was the small, hetero-
geneous sample size. Neoadjuvant therapy is 1 of many
factors that may contribute to the development of a postop-
erative complication. Age, comorbidities, body mass index,
tobacco use, and radiation therapy, for example, must be
taken into consideration. A larger sample size with multi-
variate analysis could help better define the relationship
between the above factors and postoperative complications.
Conclusions
Surgery after neoadjuvant therapy is safe, but careful
counseling is warranted given that 18% of patients expe-
rienced major complications. Complications rates were
higher in those patients undergoing reconstruction, but
feared complications of skin, nipple, implant, and flap loss
were infrequent.
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Discussion
Anees Chagpar, M.D. (New Haven, CT): I have the
privilege of discussing this paper. To begin with, I’d like
to congratulate the authors on presenting their work exam-
ining postoperative complication rates after neoadjuvant
therapy. Often times I think such data are not reported sim-
ply because none of us like to admit that we have any
complications. So I am glad to see that the folks at Mayo
Arizona have the integrity to present these data which
will help us to better present the risks of surgery after sys-
temic therapy to our breast cancer patients. I do have sev-
eral questions for the authors. First, you point out that the
overall rate of complications was 34%, ranging from 18%
for breast conserving surgery to 67% for those who had a
mastectomy with delayed reconstruction. In your last slide
or next to last slide, you had pointed out that your data
aligned with the literature and historically other studies
have not found a difference between those who had neoad-
juvant therapy and those who did not. What were the rates
of complications in patients not treated with neoadjuvant
therapy at your institution? This would help us to put these
data into better context. Second, you note that 74% of the
patients in your cohort underwent radiation therapy postop-
eratively and you correctly mentioned this often is also as-
sociated with a higher complication rate. But it makes it
difficult to sort out what proportion of the complication
rate you found in your population was attributed to the neo-
adjuvant systemic therapy and what proportion was attrib-
utable to postoperative radiation therapy. Did you do a
factor analysis or a multivariate model or some way to
give us a sense of the respective rates of each of these?
And finally, while it is good to be able to tell our patients
about what complication rates they can expect, it is even
better if we can determine how to lower these. Did you
look at potential techniques that may influence complica-
tion rates, for example closing cavities or using drains
to prevent seromas, using hemostatic agents to prevent
E.M. Garvey et al. Surgical complications after neoadjuvant therapy
hematomas or perhaps varying antibiotic regimens preoper-
atively to prevent infection or heparin for venous conges-
tion to prevent the complication that you showed us. I
realize that the sample size may limit the inferences that
you may be able to make, but I would be remiss if I at least
didn’t ask.
I thank the authors once again for a fine presentation and
for the Congress the opportunity to discuss it.
Erin M. Garvey, M.D. (Phoenix, AZ): Thank you. I’ll
begin with your first question. You asked about the rates
of complications and non-neoadjuvant patients at our insti-
tution. We are currently in the process of comparing this
current data to our large cohort of 2,600 patients to specif-
ically stratify non-neoadjuvant and neoadjuvant. However,
prior studies that we have done at our institution, specifi-
cally in a skin-sparing mastectomy cohort, had the follow-
ing results. Thirty percent of our skin-sparing mastectomy
patients had no complications, 35% had a minor complica-
tion, and 35% had a major complication. So that is not a
perfect 1-to-1 comparison, but that gives us something to
reflect back on with our non-neoadjuvant patients at
Mayo. I do agree with you that there would be more value
in being able to perform that multivariant analysis in the
full cohort and that is our ongoing process that we are
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working with right now, at which point I think we will
have the data to run a meaningful multivariant analysis in
order to be able to evaluate multiple factors, especially ra-
diation as a potential contributor to the increased risk of
complications. With that said, once we do have that full co-
hort of data, I think that may point to certain techniques or
certain things that we can focus on as surgeons to hopefully
prevent complications. As the general surgeon, I think our
focus, especially when doing skin or nipple sparing needs
to be on meticulous flap creation not compromising the
blood flow in order to attempt to prevent the skin necrosis
or even infections. In terms of what our plastic surgeons do
at this time, they do routinely use drains and we have a
standardized protocol for antibiosis. But perhaps once we
have our full analysis, we will be able to better address
things and alter our techniques accordingly.
Dr Chagpar: Did you look at smokers versus non-
smokers or diabetics versus nondiabetics, patient related
factors that may influence your complication rate?
Dr Garvey: I think that will be incredibly important in
the next step that we have; just the few demographic pieces
of data I shared with you is what we mainly looked at for
this small cohort, but diabetics and smokers will certainly
be evaluated.