# Invasive Breast Cancer after Mastectomy and Autologous  Breast Reconstruction

Authors: Shaheen Zakaria; Jennifer L. Herrick; Carol Reynolds; Nho V. Tran; John H. Donohue; Judy C. Boughey
Journal: Scholarly Research Exchange
 (2009)

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## Abstract

Recurrence or new breast cancer after mastectomy and autologous breast reconstruction is a rare occurrence. We present a case series of four patients with this rare phenomenon and describe their presentation, workup, and surgical and adjuvant therapy. We discuss the possible physiologic mechanisms leading to tumor recurrence in a reconstructed breast along with literature review.  A new palpable mass in a reconstructed breast mound warrants tissue diagnosis to avoid delay in treatment. The surgical options for breast cancer in tissue reconstructions depend on the location and extent of the tumor, involvement of the vascular pedicle, stage of disease, and adjuvant therapy options.


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## Body

## 1. Introduction

Mastectomy
and immediate breast reconstruction (IBR) have been shown to be oncologically
safe for women with early stage breast cancer [1, 2]. Options for IBR include
tissue expander placement and autologous flaps. Recurrence or the development
of a new primary breast cancer after mastectomy and autologous breast
reconstruction is rare. We present four patients with this unusual phenomenon
and discuss their surgical management, adjuvant treatment, and outcomes.


## 2. Case Presentations

### 2.1. Case A

A 53-year-old woman underwent left skin-sparing mastectomy (SSM) with immediate
free transverse rectus abdominis myocutaneous (TRAM) flap reconstruction with
anastomosis to internal mammary vessels for a 1.9 cm area of ductal carcinoma
in situ (DCIS), intermediate nuclear grade, estrogen (ER), and progesterone
receptor (PR)
positive.Six years later, she noticed a mass in
the medial aspect of the same breast. Examination revealed two masses, 2 cm
each, located in the upper inner and lower outer quadrants of the reconstructed
breast mound (Figure1). Diagnostic mammography revealed an area of increased
density within the central portion of the reconstructed breast and four
satellite nodular densities. Ultrasound revealed an irregular 1.4 cm mass in
the central breast and a 1.5 cm mass in the upper inner quadrant. Core needle biopsy
of these lesions showed moderately differentiated invasive ductal carcinoma
(IDC). An F18DG-PET scan revealed four foci of increased metabolic
activity within the left breast and one in the left axilla. Breast MRI revealed
enlarged axillary lymph nodes and five contrast-enhancing masses suspicious for
malignancy in the left breast, the largest being a 4.0 cm mass invading the
TRAM flap pedicle (Figure 2).Figure 1
Outlined areas of palpable tumor in the upper inner and lower outer quadrant.Figure 2
Breast MRI showing TRAM flap pedicle involvement with tumor.SSM with excision of the entire TRAM
flap, partial excision of underlying pectoralis muscle, and complete axillary
lymph node dissection were performed with immediate subpectoral tissue expander
placement with AllodermR (Figure 3). Five foci of poorly
differentiated IDC, ER/PR positive, Her2/neu negative, were identified; the largest
focus measured 4.7 cm (Figure 4). No angiolymphatic invasion was seen. The
malignant glands were present within adipose tissue containing adnexal
structures consistent with subcutaneous tissue. No residual breast tissue was
identified histologically. One of twenty-six axillary lymph nodes was positive
for metastatic carcinoma without extranodal extension.Figure 3
Involvement of the vascular pedicle (black arrow) of TRAM flap by the
recurrent tumor.Figure 4
Gross examination of mastectomy specimen.She received adriamycin, cyclophosphamide,
and paclitaxel chemotherapy, chest wall radiation, and hormonal therapy and is
doing well at 6 months of follow-up.


### 2.2. Case B

A 44-year-old woman underwent right breast wide local excision for poorly
differentiated multifocal IDC, basal subtype (triple negative), the largest
focus measuring 2.3 cm. One sentinel lymph node was removed, which was benign. She
received adjuvant chemotherapy (adriamycin, cyclophosphamide, and paclitaxel). Eight
months later, she was diagnosed with local recurrence in the ipsilateral breast
and underwent a right SSM and contralateral (left) risk reduction SSM followed
by immediate bilateral deep inferior epigastric perforator (DIEP) flap
reconstruction. Pathology revealed a 0.8 cm poorly differentiated IDC, basal
subtype (triple negative), with two negative sentinel lymph nodes.Five years later, she noted a lump in
the lower outer quadrant of the contralateral reconstructed left breast (risk
reduction side). Breast MRI revealed a 4.5 cm irregular mass within the left breast
mound. The patient expressed a strong desire for preservation of the breast
mound, and therefore, wide local excision of the DIEP flap in the area of the
tumor was performed with concurrent left sentinel lymph node biopsy. Pathology revealed
a 5.0 cm poorly differentiated IDC, basal subtype, with angiolymphatic invasion.
Two axillary sentinel lymph nodes were negative for metastasis. No residual
breast tissue was identified in the resected specimen. A stagingF18DG-PET
scan (Figure 5) performed postoperatively revealed two foci of intense uptake
within the left breast suspicious for residual cancer and a hypermetabolic
internal mammary lymph node.Figure 5
PET scan showing hypermetabolic foci in the reconstructed breast and
internal mammary nodal chain.She then received chemotherapy consisting
of adriamycin and cyclophosphamide followed by paclitaxel. The internal mammary
lymph node resolved on chemotherapy; however, the two breast masses progressed,
necessitating a complete takedown of the DIEP flap five months later. Pathology
revealed four foci of poorly differentiated IDC, ranging in size from 0.4 to 1.4 cm. She completed (6000cGy) radiation to the left chest wall including the left
supraclavicular region and the internal mammary nodal chain.


### 2.3. Case C

A 62-year-old woman was treated with wide local excision for a 0.8 cm moderately
differentiated ER/PR positive IDC of the right breast. One sentinel lymph
node was negative for metastatic carcinoma. She declined adjuvant radiation and
presented three years later with a mass in the ipsilateral breast which proved
to be IDC on core biopsy. She underwent total mastectomy and pathology revealed
a 0.8 cm moderately differentiated, ER/PR positive, Her2/neu negative IDC with a
single negative lymph node. No lymphovascular invasion was identified. She
received adjuvant anastrozole and underwent delayed DIEP flap reconstruction of
the ipsilateral breast six months later.One year later after her
reconstruction, she presented with a mass in the scar from her original primary
tumor, which proved to be carcinoma on core biopsy. Wide local excision of the DIEP
flap in this area down to and including the pectoral muscle revealed a 1.4 cm
moderately differentiated ER/PR positive, Her2/neu negative IDC confined to
the skin. No residual breast tissue was identified in the resected flap. She
has completed radiation to the reconstructed breast and declined systemic
therapy.


### 2.4. Case D

A 45-year-old woman underwent skin-sparing modified radical mastectomy for 0.7 cm, well differentiated IDC associated with a surrounding 4 cm area of DCIS.
Four of twenty-seven axillary lymph nodes were positive for metastatic carcinoma.
Immediate reconstruction was performed using free TRAM flap. She then received
adjuvant chemotherapy (adriamycin, cyclophosphamide followed by paclitaxel) and
hormonal therapy (Aromasin).Routine examination three years later
revealed a mass over the lateral aspect of the TRAM flap. Diagnostic mammogram
revealed a focus of microcalcifications, which were malignant on core biopsy.
Wide local excision of the TRAM flap was performed. Pathology revealed a 0.5 cm
moderately differentiated ER positive, PR negative, Her2/neu negative IDC associated
with extensive DCIS. There was no lymphovascular invasion, and no residual
breast tissue was identified. She is completing radiation to the breast and
supraclavicular area and is taking Aromasin.


## 2.1. Case A

A 53-year-old woman underwent left skin-sparing mastectomy (SSM) with immediate
free transverse rectus abdominis myocutaneous (TRAM) flap reconstruction with
anastomosis to internal mammary vessels for a 1.9 cm area of ductal carcinoma
in situ (DCIS), intermediate nuclear grade, estrogen (ER), and progesterone
receptor (PR)
positive.Six years later, she noticed a mass in
the medial aspect of the same breast. Examination revealed two masses, 2 cm
each, located in the upper inner and lower outer quadrants of the reconstructed
breast mound (Figure1). Diagnostic mammography revealed an area of increased
density within the central portion of the reconstructed breast and four
satellite nodular densities. Ultrasound revealed an irregular 1.4 cm mass in
the central breast and a 1.5 cm mass in the upper inner quadrant. Core needle biopsy
of these lesions showed moderately differentiated invasive ductal carcinoma
(IDC). An F18DG-PET scan revealed four foci of increased metabolic
activity within the left breast and one in the left axilla. Breast MRI revealed
enlarged axillary lymph nodes and five contrast-enhancing masses suspicious for
malignancy in the left breast, the largest being a 4.0 cm mass invading the
TRAM flap pedicle (Figure 2).Figure 1
Outlined areas of palpable tumor in the upper inner and lower outer quadrant.Figure 2
Breast MRI showing TRAM flap pedicle involvement with tumor.SSM with excision of the entire TRAM
flap, partial excision of underlying pectoralis muscle, and complete axillary
lymph node dissection were performed with immediate subpectoral tissue expander
placement with AllodermR (Figure 3). Five foci of poorly
differentiated IDC, ER/PR positive, Her2/neu negative, were identified; the largest
focus measured 4.7 cm (Figure 4). No angiolymphatic invasion was seen. The
malignant glands were present within adipose tissue containing adnexal
structures consistent with subcutaneous tissue. No residual breast tissue was
identified histologically. One of twenty-six axillary lymph nodes was positive
for metastatic carcinoma without extranodal extension.Figure 3
Involvement of the vascular pedicle (black arrow) of TRAM flap by the
recurrent tumor.Figure 4
Gross examination of mastectomy specimen.She received adriamycin, cyclophosphamide,
and paclitaxel chemotherapy, chest wall radiation, and hormonal therapy and is
doing well at 6 months of follow-up.


## 2.2. Case B

A 44-year-old woman underwent right breast wide local excision for poorly
differentiated multifocal IDC, basal subtype (triple negative), the largest
focus measuring 2.3 cm. One sentinel lymph node was removed, which was benign. She
received adjuvant chemotherapy (adriamycin, cyclophosphamide, and paclitaxel). Eight
months later, she was diagnosed with local recurrence in the ipsilateral breast
and underwent a right SSM and contralateral (left) risk reduction SSM followed
by immediate bilateral deep inferior epigastric perforator (DIEP) flap
reconstruction. Pathology revealed a 0.8 cm poorly differentiated IDC, basal
subtype (triple negative), with two negative sentinel lymph nodes.Five years later, she noted a lump in
the lower outer quadrant of the contralateral reconstructed left breast (risk
reduction side). Breast MRI revealed a 4.5 cm irregular mass within the left breast
mound. The patient expressed a strong desire for preservation of the breast
mound, and therefore, wide local excision of the DIEP flap in the area of the
tumor was performed with concurrent left sentinel lymph node biopsy. Pathology revealed
a 5.0 cm poorly differentiated IDC, basal subtype, with angiolymphatic invasion.
Two axillary sentinel lymph nodes were negative for metastasis. No residual
breast tissue was identified in the resected specimen. A stagingF18DG-PET
scan (Figure 5) performed postoperatively revealed two foci of intense uptake
within the left breast suspicious for residual cancer and a hypermetabolic
internal mammary lymph node.Figure 5
PET scan showing hypermetabolic foci in the reconstructed breast and
internal mammary nodal chain.She then received chemotherapy consisting
of adriamycin and cyclophosphamide followed by paclitaxel. The internal mammary
lymph node resolved on chemotherapy; however, the two breast masses progressed,
necessitating a complete takedown of the DIEP flap five months later. Pathology
revealed four foci of poorly differentiated IDC, ranging in size from 0.4 to 1.4 cm. She completed (6000cGy) radiation to the left chest wall including the left
supraclavicular region and the internal mammary nodal chain.


## 2.3. Case C

A 62-year-old woman was treated with wide local excision for a 0.8 cm moderately
differentiated ER/PR positive IDC of the right breast. One sentinel lymph
node was negative for metastatic carcinoma. She declined adjuvant radiation and
presented three years later with a mass in the ipsilateral breast which proved
to be IDC on core biopsy. She underwent total mastectomy and pathology revealed
a 0.8 cm moderately differentiated, ER/PR positive, Her2/neu negative IDC with a
single negative lymph node. No lymphovascular invasion was identified. She
received adjuvant anastrozole and underwent delayed DIEP flap reconstruction of
the ipsilateral breast six months later.One year later after her
reconstruction, she presented with a mass in the scar from her original primary
tumor, which proved to be carcinoma on core biopsy. Wide local excision of the DIEP
flap in this area down to and including the pectoral muscle revealed a 1.4 cm
moderately differentiated ER/PR positive, Her2/neu negative IDC confined to
the skin. No residual breast tissue was identified in the resected flap. She
has completed radiation to the reconstructed breast and declined systemic
therapy.


## 2.4. Case D

A 45-year-old woman underwent skin-sparing modified radical mastectomy for 0.7 cm, well differentiated IDC associated with a surrounding 4 cm area of DCIS.
Four of twenty-seven axillary lymph nodes were positive for metastatic carcinoma.
Immediate reconstruction was performed using free TRAM flap. She then received
adjuvant chemotherapy (adriamycin, cyclophosphamide followed by paclitaxel) and
hormonal therapy (Aromasin).Routine examination three years later
revealed a mass over the lateral aspect of the TRAM flap. Diagnostic mammogram
revealed a focus of microcalcifications, which were malignant on core biopsy.
Wide local excision of the TRAM flap was performed. Pathology revealed a 0.5 cm
moderately differentiated ER positive, PR negative, Her2/neu negative IDC associated
with extensive DCIS. There was no lymphovascular invasion, and no residual
breast tissue was identified. She is completing radiation to the breast and
supraclavicular area and is taking Aromasin.


## 3. Discussion

We have presented four diverse cases of breast carcinoma recurrence after autologous
tissue reconstruction (Table1), which highlight the challenges and management
options for these patients. Our report also illustrates how implant-based breast
reconstruction can be used when the entire tissue flap requires removal.Table 1
Summary of the four cases.
CaseInitial tumorInitial reconstructionRecurrenceSurgical treatment of recurrenceAdjuvant treatmentOutcomeADCISSSM with immediate free TRAM flapIDCSSM, complete TRAM excision, implant-based reconstructionChemotherapy, hormonal therapy and local radiationAlive without evidence of diseaseBNone (Prophylactic mastectomy)SSM with immediate DIEP flapIDCInitial WLE followed by complete DIEP excisionChemotherapy, locoregional radiationAlive with recurrenceCIDC (0.8 cm)SSM with Delayed DIEP flapIDCWLELocal radiationAlive without evidence of diseaseDIDC (0.7 cm)SSM with immediate free TRAM flapIDCWLELocoregional radiation and hormonal therapyAlive without evidence of diseaseWomen undergoing skin-sparing
mastectomies with immediate breast reconstruction (IBR) for small tumors (T1 or
T2) have recurrence rates similar to those patients with delayed or no
reconstruction [1–3]. The
overall incidence of locoregional recurrence after mastectomy ranges from 2–15% at five years
[4–6]. Tissue transfer procedures are an oncologically safe option for breast reconstruction
[7, 8]. A 4–6% prevalence of
skin flap or chest wall recurrences following autologous breast reconstruction
using TRAM flaps has been reported [3, 9] and regional nodal recurrences occur
in up to 15% of patients after TRAM flap reconstruction [10, 11].Limited assessment of the factors
associated with local recurrences after SSM and IBR exist. In a study by Kroll
et al. [4] local recurrence (LR) rates were lower in patients with T1 tumors
compared to T2 tumors (6% versus 9%), but this difference was not statistically
significant. A trend was also identified for a high nuclear grade being associated
with a higher risk of LR. Another study of 173 patients by Medina-Franco et al.
[6], in which the majority of patients (92%) had tissue reconstruction, identified
tumor stage II or III, tumor size greater than 2.0 cm, node positivity and poor
tumor differentiation to be associated with increased LR. Local recurrence was
an independent predictor of reduced survival after SSM and IBR, as were primary
tumor stage, poor tumor differentiation, and absence of treatment with hormone
therapy. In this study, 75% of patients who developed LR within a median
follow-up of 73 months developed distant metastases and died of disease within
a mean of 21 months. Other reports of patients with recurrent breast cancer
after mastectomy have shown that approximately 70% of LRs occur in the first 36
months [12, 13],
while 90% are detected within five years of initial diagnosis [14].
Although several studies have reported worse prognosis with LR after mastectomy
than after breast conservation therapy [8, 14–16], this more
adverse impact of LR on survival after mastectomy has not been supported by
others [3]. In a study
by Gilliland et al. all patients with LR developed distant metastases between
1.2 and 4.2 years and all died of disease between 2.5 and 7.2 years [14]. Other
reports with longer term follow-up of up to 10 years among patients with LR after
mastectomy have reported overall survival rates of 18–42% [14, 17]
and 10-year disease-free survival of 7–17% after the
diagnosis of LR [15, 16]. In contrast, the MD Anderson experience of 23 patients
with LR after SSM and IBR revealed 61% of patients alive with no evidence of
disease at a median follow-up of 26 months [3]. However, survival after breast
cancer has been consistently shown to be associated with stage and grade of the
primary tumor [6, 14, 17, 18], and therefore, distant relapse seen synchronously
with LR can mostly be attributed to tumor biology rather than type of surgical
treatment performed. However, not all local recurrences are equal. Patients
with subcutaneous tissue recurrences have a better survival, decreased
incidence of distant metastases, and greater chance of remaining disease free
than those with true chest wall recurrences [19].The possible
mechanisms of development of LR or a new cancer after mastectomy and IBR are
not well elucidated. Possible explanations include residual cancer, benign
residual breast tissue progressing to cancer, tumor spillage at the time of the
initial operation, and hematogenous tumor spread. All forms of mastectomy,
whether radical, modified radical, or skin-sparing, leave some residual breast
tissue. Concerns have been raised about the increased residual breast tissue
remaining after SSM because of the length of the skin flaps and retention of
the inframammary fold. Carlson et al. used computer image analysis to examine
the inframammary fold tissue retained with a SSM [20]. Residual breast tissue was identified
in 13 of 24 specimens but was correlated to only 0.02% of the total tissue
volume removed. Barton et al. demonstrated equivalent amounts of residual
glandular breast tissue remaining on the anterior chest walls of 27 patients
who had undergone SSM compared to 28 patients following total mastectomy, based
on multiple chest wall biopsies [21]. The fact that histologic examination of LR
rarely shows identifiable breast tissue has been highlighted by others [20]. Some
researchers have proposed that skin and subcutaneous recurrences may be a
result of residual tumor cells that were separate from an adequately resected
cancer [19]. Displacement of tumor cells can occur after core needle biopsies
of breast tumors [22]. Although it is not conclusive that displacement of tumor
cells leads to recurrence, it is recommended that needle biopsy exit sites be
excised at the time of definitive surgery. However, incorporating these biopsy
sites in a SSM
incision can be technically challenging. Reassuringly though, despite changes
in surgical approaches over time, the LR rate after total mastectomy for breast
cancer has remained relatively constant. It is, therefore, plausible that factors
found to be associated with LRs, that is, stage and grade of primary tumor,
also dictate distant failures and prognosis.The issue of routine screening of the
reconstructed breast is unsettled and routine mammography is not generally recommended.
However, some researchers recommend routine mammograms after SSM and IBR in
patients initially presenting with multifocal or multicentric primary tumors [23].
Most recurrences after SSM and IBR are superficial subcutaneous nodules, which
are easily appreciable on physical examination.However
mammography should be performed after a recurrence is suspected, as well as a
breast ultrasonography if indicated [3].
MRI can discern between benign and malignant findings in patients with
palpable abnormalities or pain after TRAM flap reconstruction [24]. Some
researchers recommend patients undergoing TRAM flap reconstruction to be
followed with a baseline MRI within six months after the surgical procedure and
annually thereafter. If the patient has a BI-RADS category 3 lesion in the TRAM
flap or contralateral breast, follow-up imaging at four to six months is recommended.
For patients with BI-RADS category 4 or 5 lesions in the TRAM flap or
contralateral breast, a biopsy is indicated [25]. The role of vigilant and regular physical
examination cannot be over emphasized. All patients undergoing mastectomy,
including prophylactic mastectomy, should be counseled of the continued risk of
breast cancer after mastectomy.A new palpable mass in a reconstructed
breast mound warrants imaging evaluation and, where appropriate, a tissue
diagnosis, preferably with a core biopsy to avoid a delay in treatment. All four
of our patients had subcutaneous disease, a more common presentation than true
chest wall recurrences. Case A had
pectoralis invasion from the bulky subcutaneous cancer that was not diagnosed
early.The surgical options for breast cancer
in patients with tissue reconstruction depend on the location and extent of the
tumor, involvement of the vascular pedicle of the flap, stage of disease, and
adjuvant therapy options. An evaluation for distant metastatic disease should
be undertaken which should include complete blood count, liver function tests,
CT scan of abdomen and pelvis as well as a bone scan. In cases of LR only,
excellent disease control without sacrificing the reconstructed breast mound
can be achieved in most patients. The goal of surgical treatment is to achieve
clear resection margins. However, excision of a TRAM flap should be strongly
considered in patients with multifocal or multicentric recurrences. This
treatment is necessary if the recurrence involves the TRAM flap pedicle. Excision alone for
patients with LR after mastectomy is associated with failure rates of up to 75%
[26]. Adjuvant radiation therapy to the residual TRAM flap or the chest wall is
recommended. Adjuvant systemic therapy should also be considered for these
patients as LR is a manifestation of aggressive primary disease and these
patients are at significant risk for systemic failure.Nodal evaluation in patients with LR
after mastectomy with reconstruction is dependent on individual patient
factors. The accuracy of sentinel lymph node (SLN) surgery in these patients is
unknown. Reports of SLN in patients with recurrent breast cancer have included
a few case reports of successful lymphatic mapping after mastectomy [27, 28]. Currently
SLN surgery in this setting has not been validated and therefore should only be
performed with concomitant axillary lymph node dissection. In patients where
the axilla has already been dissected, SLN mapping may be helpful to identify
residual nodal tissue in the axilla or extraaxillary sites at risk for
metastases. The use of lymphoscintigraphy is especially important in these
situations. Sentinel node mapping in our patients showed localization to the
ipsilateral axilla, despite prior mastectomy and TRAM reconstruction. The
importance of axillary staging in LR is questionable. Historically, the
majority of these patients had undergone complete axillary lymph node
dissection at the time of initial surgical resection of the primary breast
tumor. In the current age of SLN surgery, we are encountering patients with
recurrent breast cancer with residual axillary lymph nodes. The majority of
patients with LR receive chemotherapy and radiation regardless of the nodal
evaluation and a multidisciplinary evaluation of these patients is important.Local recurrence after mastectomy and
autologous tissue reconstruction is fortunately a rare phenomenon. Any new
subcutaneous mass warrants evaluation and a biopsy if the workup is
suspicious for recurrent cancer. Local control rates and patient survival are
high, even after a diagnosis of LR especially in low risk patients with early
stage breast cancer. These results can often be achieved while maintaining most
of the reconstructed breast mound.



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