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of Surgeons of Edinburgh and Irelandwww.thesurgeon.net

Chest wall resection and reconstruction for locallyrecurrent breast cancer: From technical aspects tobiological assessment

Francesco Petrella a,*, Davide Radice b, Alessandro Borri a,Domenico Galetta a, Roberto Gasparri a, Monica Casiraghi a,Adele Tessitore a, Alessandro Pardolesi a, Piergiorgio Solli a,Giulia Veronesi a, Stefania Rizzo c, Stefano Martella d, Mario Rietjens d,Lorenzo Spaggiari a,e

aDepartment of Thoracic Surgery, European Institute of Oncology, ItalybDepartment of Epidemiology and Biostatistics, European Institute of Oncology, ItalycDepartment of Radiology, European Institute of Oncology, ItalydDepartment of Plastic and Reconstructive Surgery, European Institute of Oncology, ItalyeUniversity of Milan School of Medicine, Italy

a r t i c l e i n f o

Article history:

Received 14 October 2013

Received in revised form

22 February 2014

Accepted 3 March 2014

Available online xxx

Keywords:

Breast cancer

Chest wall resection

Chest wall reconstruction

* Corresponding author. Department of Thora0257489362; fax: þ39 0294379218.

E-mail addresses: francesco.petrella@ieo

Please cite this article in press as: PetrellFrom technical aspects to biological asse

http://dx.doi.org/10.1016/j.surge.2014.03.0011479-666X/ª 2014 Royal College of SurgeonsPublished by Elsevier Ltd. All rights reserved

a b s t r a c t

Introduction: Breast cancer is the leading cause of cancer death among women in the

industrialized countries. The incidence of local recurrences after mastectomy and breast-

conserving therapy varies between 5% and 40% depending on risk factors and primary

therapy.

Methods: From April 1999 to April 2011, 40 patients underwent chest wall resection and

reconstruction for locally recurrent breast carcinoma with chest wall invasion. The main

goal of surgery was local disease control to palliate clinical symptoms.

Results: Local radical resection was achieved in 26 patients (65%). One, 2 and 5 year overall

survival rates were 94.4%, 82.0% and 68.5%; 1, 2 and 5 year disease-free survival rates were

94.4%, 73.6% and 45.5% respectively.

Univariate analysis indicated age (p ¼ 0.002) and synchronous distant metastases

(p ¼ 0.020) as factors having a negative impact on overall survival; multivariate analysis

disclosed age (p ¼ 0.052) and synchronous metastases (p ¼ 0.059) as factors with a slight

negative impact on overall survival. Older age was associated with improved overall

survival.

Univariate analysis indicated synchronous distant metastases (p ¼ 0.029) and the need

of post resectional additional treatments (p ¼ 0.022) as factors adversely conditioning

disease-free survival or time to progression; multivariate analysis disclosed the need of

post resectional additional treatments (p ¼ 0.036) as the only factor adversely conditioning

disease-free survival or time to progression.

cic Surgery, European Institute of Oncology, Via Ripamonti, 435, 20141 Milan, Italy. Tel.: þ39

.it, [email protected] (F. Petrella).

a F, et al., Chest wall resection and reconstruction for locally recurrent breast cancer:ssment, The Surgeon (2014), http://dx.doi.org/10.1016/j.surge.2014.03.001

of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland..

mailto:[email protected]

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http://dx.doi.org/10.1016/j.surge.2014.03.001



t h e s u r g e on x x x ( 2 0 1 4 ) 1e72

Please cite this article in press as: PetrellaFrom technical aspects to biological asse

Conclusions: Chest wall resection and reconstruction for locally recurrent breast cancer is a

feasible and safe procedure providing adequate local disease control and an excellent

palliation of very disabling symptoms in a selected group of patients.

ª 2014 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and

Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.

Introduction

Breast cancer is the leading cause of cancer death among

women in the industrialized countries.1 The incidence of local

recurrences after mastectomy and breast-conserving therapy

varies between 5% and 40% depending on risk factors and

primary therapy.2

The first-line treatments in recurrent breast cancer are

endocrine therapy for patients with estrogen or progesterone

receptor positive cancer, and chemotherapy for patients with

receptor-negative cancers.3e5 However, local therapies such

as radiotherapy or surgery may be required in selected cases

for local disease control and palliation of disabling symptoms

like pain, bleeding, ulceration, malodorous secretion, infec-

tion and fungating lesions.6,7

On the one hand, locoregional recurrence of breast cancer

following breast surgery may be a systemic disease and in

many patients it tends to occur at the same time as distant

metastases, making the indication for surgical resection

questionable.8,9 On the other, although the primary goal of

chest wall resection is to achieve local tumor control, it may

lead to long-termpalliation and even cure for a small subset of

patients with isolated chest wall recurrence of breast cancer

after multimodal treatment failure.10

Early detection of locoregional recurrence and small tumor

size predicted a better prognosis.11e13 Options for local treat-

ment of locoregional recurrence include wide local excision

and/or radiotherapy whether or not in combination with hy-

perthermia14; however, for small lesions, the type of local

treatment did not affect the final outcome.15

Whether complete resection of local recurrence offers a

merely palliative or possibly curative approach or a major

prolongation of survival remains unsettled.16 The aim of this

study was to define the role of chest wall resection for locally

recurrent breast cancer as a salvage treatment for a selected

group of symptomatic patients.

Methods

The present study was conducted in accordance with the

Declaration of Helsinki.17 Written informed consent was ob-

tained from all subjects before any procedure was done. The

investigators explained all the planned procedures verbally to

all subjects who received and signed a subject information

sheet to acquaint themselves with details of the planned

therapeutic schedule. All patients authorized the in-

vestigators to use their data anonymously only for scientific

purposes according to Italian legislation (law no. 675/1996).

F, et al., Chest wall resssment, The Surgeon (2

Data were collected prospectively and entered into our

institutional general thoracic database at the point of care.

The database was reviewed retrospectively.

From April 1999 to April 2011, 40 patients underwent chest

wall resection and reconstruction for locally recurrent breast

carcinoma with chest wall invasion proven by routine pre-

operative chest computed tomography (CT) or by chest wall

magnetic resonance imaging (MRI) in selected cases. Themain

goal of surgical therapy was local disease control to palliate

clinical symptoms like pain, cutaneous ulceration and

discomfort related to chest wall deformity. For this reason a

distant metastasis was not a contraindication. Selection

criteria for surgery weremultimodal treatment failure and life

expectancy of more than 6 months.

The surgical approach involved soft tissue resection with

broad margins and chest wall resection with total or partial

sternectomy and resection of one or more ribs. In case of

major tissue defect following resective surgery reconstruction

was performed using different types of prostheses covered by

a vascularized pedicle muscle flap.

Technical aspects of demolition and reconstructive pro-

cedures were reviewed (sternectomy, ribs resection, soft tis-

sue resection, endothoracic organ resection, type of

prosthesis, type of flap and technical complications) together

with oncologic history including previous type and date of

breast operation, histology and biology of breast and thoracic

surgical specimens (Ki67%, Her2 neu expression, estrogen and

progesterone receptor expression), and the interval between

breast and thoracic surgery.

Patients were defined as triple negative if estrogen, pro-

gesterone and Her2 neu expression were negative; otherwise,

they were defined as non-triple negative.10

Recurrence was defined as the return of cancer after

treatment and after a period of time during which the cancer

could not be detected. Local recurrence was defined as the

reappearance of disease in locoregional lymph nodes or in the

chest wall adjacent to the site of thoracic excision. Distant

recurrence was defined as distant sites of visceral disease,

including malignant pleural effusions or implants.

Progression was defined as cancer growthwithout a period

of time duringwhich the cancer could not be detected. Distant

progression was defined as cancer spreading to distant sites;

locoregional progression was defined as cancer worsening

close to the surgical field.

A complete resection (R0) was defined as pathologic

demonstration of negative tissue margins and an assessment

by the operating surgeon that all detectable disease had been

removed. Microscopically incomplete resection (R1) was

defined as complete macroscopic resection with positive

margins found on final pathologic review. Macroscopically

ection and reconstruction for locally recurrent breast cancer:014), http://dx.doi.org/10.1016/j.surge.2014.03.001



Table 1b e Clinico-pathological features of the studypopulation.

t h e s u r g e on x x x ( 2 0 1 4 ) 1e7 3

incomplete resection (R2) was defined as gross residual dis-

ease after attempted resection.18

Statistical analysis

Patient characteristics were summarized and tabulated using

either counts and percentage or counts, mean, standard de-

viation (SD), median, min and max for the categorical or

continuous variables, respectively. Overall survival (OS) and

disease-free survival (DFS) were defined as the time from

surgery to the last follow-up date or death and to the last

follow-up date or recurrence date respectively, then esti-

mated and plotted using the KaplaneMeier method. Univar-

iate and multivariate hazard ratios (HR) for the OS and DFS

were estimated using the Cox proportional hazards model

and tabulated alongside their 95% confidence Intervals. The

statistical analyses were conducted using SAS Software 9.2

(NC, USA).

%

Median age 59 (30e83)

Sternectomy required 21/40 52.5

Median ribs resected 2.5 (1e5)

Endothoracic

organ resection

4/40 10

Mean tumor size 5.4 cm (1.3e18)

Synchronous metastases

at CWRRa

15/40 37.5%


(lymph nodes)

5/15 33.3%


(distant sites)

10/15 66.6%

Treatments before CWRRa

(combined)

Chemotherapy 31/40 77.5

Radiotherapy 23/40 57.5

Hormone therapy 23/40 57.5

Target therapy 4/40 10

None 4/40 10

Treatments after CWRRa

(combined)

Chemotherapy 22/40 55

Radiotherapy 6/40 15

Hormone therapy 25/40 62.5

Target therapy 5/40 12.5

Results

With regard to initial non-surgical treatment, at the time of

breast cancer diagnosis 11 patients (27.5%) received

chemotherapyþ hormone therapy; 7 patients (17.5%) received

chemotherapy alone; 6 patients (15%) received hormone

therapy þ radiotherapy; 5 patients (12.5%) received

chemotherapy þ radiotherapy; 4 patients (10%) received hor-

mone therapy alone; 2 patients (5%) received radiotherapy

alone; 1 patient (2.5%) did not receive any treatment; 4 pa-

tients (10%) received other combined treatments (e.g.,

chemotherapy þ hormone therapy þ target therapy or

chemotherapy þ hormone therapy þ radiotherapy).

Surgical aspects

The study population consisted of 40 patients with a median

age of 59 years (range 30e83 years) at chest wall resection. The

median interval between breast and chest wall operationswas

59 months (range 0e402).

Chest wall resection included total or partial sternectomy

in 21/40 cases (52.5%). 34/40 patients (85%) received at least 1

Table 1a e Technical aspects of the procedures.

Variable Subgroup %

Prosthesis Polypropylene mesh þresinous material

76.4

Polyglactin knitted mesh 8.9

Polypropylene mesh alone 8.9

Titanium bars 5.8

Flap Latissimus dorsi 40

Pectorialis major 20

TRAM 30

Fascio e cutaneous 3.4

Cyclopization 6.6

Surgical

complication

Flap ischemia 5

Prosthesis infection 7.5

Bleeding 2.5

Operative mortality 0

Please cite this article in press as: Petrella F, et al., Chest wall resFrom technical aspects to biological assessment, The Surgeon (2

rib resection and among them a median of 2.5 ribs were

removed (range 1e5). Three out of 40 patients (7.5%) received

extended soft tissue resection involving periostium removal

but without complete chest wall resection. Four out of 40 pa-

tients (10%) received endothoracic organ resection as follows:

left lung in 2 cases, pericardium in 1 case, pericardium plus

left innominate vein in 1 case.

Local radical resection was achieved in 26/40 patients

(65%). Microscopic residual disease was left in 13/40 patients

(32.5%). Macroscopic residual disease was left in 1 patient

(2.5%).

A prosthesis was used in 34/40 patients (85%): 26/34 (76.4%)

received monofilament polypropylene mesh plus resinous

None 1/40 2.5

Outcome after

salvage therapy

Disease control 30/40 75

Toxicity 8/40 20

Previous breast

surgery

Mastectomy 62.5

Quadrantectomy 32.5

Ductal resection 2.5

Bilateral mastectomy 2.5

Previous breast

histology

Ductal carcinoma 52.5

Papillary carcinoma 5

Medullary carcinoma 2.5

Mucinous carcinoma 2.5

Lobular carcinoma 2.5

Combined lobular

and ductal carcinoma

2.5

Phyllodes tumor 2.5

NOSb histology 30

a CWRR: Chest wall resection and reconstruction.b NOS: Not otherwise specified.




Table 2 e Clinical characteristics of deceased patients.

N. Age atdiagnosis

Age atrecurrence

Cause ofdeath

Her2neu/Er/Pr/ Adjuvanttherapy

DFI(months)

R status atresection

Distant diseaseat time of treatment

1 37 39 Rec �/�/� No NA Not radical No

2 57 59 Rec �/�/� C 21 Not radical Yes

3 49 52 Rec �/þ/þ C/H/R 13 Radical Yes

4 58 61 Rec �/�/� H 19 Radical No

5 53 55 Rec �/�/� C 10 Radical Yes

6 51 53 Rec �/�/� C 1 Radical Yes

7 30 31 Prog �/�/� C/T 5 Radical Yes

8 52 54 Prog �/�/� C 16 Not radical Yes

9 34 34 Prog �/�/� C NA Radical Yes

Table legend: DFI ¼ disease-free interval; Rec ¼ recurrence; Prog ¼ progression; C ¼ chemotherapy; H ¼ hormone therapy; R ¼ radiotherapy;

T ¼ target therapy; NA ¼ not applicable.

t h e s u r g e on x x x ( 2 0 1 4 ) 1e74

material (Bard* Mesh, Bard Davol Inc., Cranston, RI, USA;

Cranioplastic, Codman & Shurtleff, Inc. Raynham, MS, USA);

3/34 (8.8%) received adsorbable polyglactin knitted mesh

(Vicryl knittedmesh, Ethicon Inc., New Brunswick, NJ, USA); 3/

34 (8.8%) received monofilament polypropylene mesh alone

(Bard * Mesh, Bard Davol Inc., Cranston, RI, USA) and 2/34

patients (5.8%) received titanium bars.

Thirty out of 40 (75%) patients received a flap to complete

chest wall reconstruction: latissimus dorsi muscle flap was

used in 12/30 cases (40%); pectorialis major muscle flap was

used in 6/30 cases (20%); transposition of rectus abdominis

muscle (TRAM) was used in 9/30 cases (30%); a fascio-

cutaneous sliding flap was used in 1/30 case (3.3%); cyclop-

ization was used in 2/30 cases (6.6%).

Six out of 40 patients (15%) had postoperative surgical

complications requiring a re-do operation: The operative

mortality rate was 0% (Table 1).

Specimen biological assessment

Biological assessment on chest wall specimens disclosed a

Ki67mean value of 49.9%; Her2 neumean expression of 17.2%,

evaluated as percentage of neoplastic cells showing mem-

brane immunoreactivity to the Dako polyclonal antiserum

(Dako Denmark A/S, Glsotrup, Denmark); estrogen and pro-

gesterone receptors expression of 49.2% and 12.1%

respectively.

With regard to the hormonal status of chest wall speci-

mens we observed estrogen and progesterone receptors

both positive in 12 patients (30%); both negative in 15 pa-

tients (37.5%). We observed 7 triple-negative patients

(17.5%).

Follow-up

After a median follow-up of 30.6 months 15/40 patients

(37.5%) were alive and disease-free; 15/40 patients (37.5%)

were alive with disease; 9/40 patients (22.5%) had died from

disease; 1/40 (2.5%) patient was lost to follow-up.

Age at diagnosis, age at recurrence, cause of death, hor-

monal patterns, adjuvant therapies and disease-free interval

of deceased patients are summarized in Table 2.


Multimodality treatments

Following chest wall resection 22/40 patients (55%) received

chemotherapy, 25/40 patients (62.5%) received hormone ther-

apy, 6/40 patients (15%) received radiotherapy, 5/40 patients

(12.5%) received target therapy. Only 1/40 patient (2.5%) did not

receiveanyadditional treatment following chestwall resection;

in all cases additional treatments were proposed on clinical,

histological and biological bases, without any fixed algorithm.

Overall and disease-free survival

One, 2 and 5 year overall survival rates were 94.4%, 82.0% and

68.5%; 1, 2 and 5 year disease-free survival rates were 94.4%,

73.6% and 45.5% respectively. After a median follow-up of 30.6

months themedian overall survival (OS) was not reached. The

median disease-free survival was 49.1 months (Fig. 1a and b).

Univariate analysis indicated age (p ¼ 0.002) and synchro-

nous distant metastases (p ¼ 0.020) as factors adversely

impacting on overall survival; multivariate analysis disclosed

age (p ¼ 0.052) and synchronous metastases (p ¼ 0.059) as

factors with a slight negative impact on overall survival.

Univariate analysis indicated synchronous distant metas-

tases (p ¼ 0.029) and the need for post-resectional additional

treatments (p ¼ 0.022) as factors adversely impacting on

disease-free survival or time to progression. Multivariate

analysis disclosed the use of post-resectional additional

treatments (p ¼ 0.036) as the only factor with an adverse

impact on disease-free survival or time to progression.

Discussion

Despite major therapeutic advances, recurrent breast cancer

is still a lethal disease in most patients.5,19 Isolated local re-

currences are thought to represent about 20% of all re-

currences, while local disease, in combination with either

regional or distant recurrences, represents a further 3%.20

The majority of locoregional recurrences occur as isolated

chest wall disease, and only a small proportion present with

concurrent systemic disease or following distant metasta-

ses.21,22 In our series 15 patients (37.5%) presented with con-

current systemic disease: 10 patients (66.6%) presented with




Fig. 1 e a) Overall survival b) disease-free survival.

t h e s u r g e on x x x ( 2 0 1 4 ) 1e7 5

distant metastases (pleura or distant bone), while 5 patients

(33.4%) presented with regional nodal involvement (internal

mammary chain or axillary lymph nodes). We never observed

true distant soft tissue metastases, probably because of the

local invasive biology of the original breast disease.

Although palliation rather than prolongation of survival is

usually the main aim of chest wall resection, some studies

found that a small subset of patients would have a long

disease-free interval and possibly cure after chest wall

resection and reconstruction.23,24

Our results confirm existing evidence that surgery is indi-

cated in patients who have isolated breast cancer recurrence,

even when surgery means chest wall resection. Moreover,

adjuvant radiotherapy and e for estrogen receptor positive

tumors e adjuvant hormone therapy is indicated.11 On the

contrary, although it is well-known that the longer the

disease-free interval, the better the survival outcome, our uni

and multivariate analysis disclosed that the interval between

breast and thoracic surgery had no impact on overall survival,

probably due to the small number of patients.

As peripheral osteomuscular structures are the major

target sites of recurrence, macroscopic radical resection was

Fig. 2 e CT scan disclosing chest wall recurrence following

left mastectomy, involving the left hemimanubrium of the

sternum and the 2nd chondro-costal joint.


very often possible Fig. 2. Microscopic infiltration of the

resection margins was observed in some isolated cases,

whereas macroscopic residual disease was anecdotal.

The vast majority of our patients required prosthetic

reconstruction of the chest wall because of the large tissue

defect following resective surgery Figs. 3. Our preferred

reconstruction technique comprises a prosthesis (mono-

filament polypropylenemesh plus resinousmaterial) followed

by latissimus dorsi muscle flap. This combination offers a

stable assessment of the chest wall, allowing adequate

ventilation. In addition, the procedure is relatively faster than

other reconstruction techniques (e.g. TRAM) and gives rise to

fewer postoperative complications.

We assume that our good overall and disease-free survival

rates are only partially due to surgical resection itself. We

believe these patients benefit from an ideal pre and post-

operative multimodality treatment and from strict candidate

selection that led us to operate on less than one-third of the

patients referred to us with this indication; the need of post

resection treatments is probably a surrogate for presence of

systemic disease; in fact all patients but one required addi-

tional treatment following chest wall resection. However, due

to the small number of enrolled patients and the non-ran-

domized retrospective design of our study, further studies are

required to confirm our results.

Conclusions

Chest wall resection and reconstruction for locally recurrent

breast cancer is a feasible and safe procedure providing

adequate local disease control and an excellent palliation of

very disabling symptoms. This approachmay be advocated as

an effective palliative procedure in selected patients.

Competing interest and disclosure

The authors declare that they have no competing interests

and anything to disclose.




Fig. 3 e Intra operative view: a) Chest wall recurrence b) Post resectional view c) Latissimus dorsi pedicled muscle flap d)

Final view.

t h e s u r g e on x x x ( 2 0 1 4 ) 1e76

Acknowledgment

The authors thank Anne Collins for editing the English text.

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