Ann Thorac Surg 2008;85:1894-1900. doi:10.1016/j.athoracsur.2008.02.012
© 2008 The Society of Thoracic Surgeons
Original Articles: General Thoracic
Full-Thickness Resection With Myocutaneous Flap Reconstruction for Locally Recurrent Breast Cancer
Godehard Friedel, MD, FETCSa,*,
Thomas Kuipers, MDb,
Jürgen Dippon, PhDc,
Fawaz Al-Kammash, MDd,
Thorsten Walles, MDa,
Thomas Kyriss, MDa,
Stefanie Veit, MDa,
Michael Greulich, MDb,
Volker Steger, MDa
a Department of Thoracic Surgery, Schillerhöhe Hospital at Robert Bosch Hospital, Gerlingen, Germany
b Department of Plastic Surgery, Marienhospital, Stuttgart, Germany
c Department of Mathematics, Universität Stuttgart, Stuttgart, Germany
d Department of Thoracic Surgery, King Hussein Medical Center, Amman, Jordan
Accepted for publication February 5, 2008.
* Address correspondence to Dr Friedel, Klinik Schillerhoehe at Robert Bosch Hospital, Solitudestr 18, Gerlingen, D-70839, Germany (Email: godehard.friedel{at}klinik-schillerhoehe.de).
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Abstract
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Background: Despite available recommendations, therapeutic procedures of locally recurrent breast cancer are very different. This retrospective study presents the possibilities and results of complete, full-thickness chest wall resection.
Methods: Between 1985 and 2006, 63 women (mean age, 58 years) with local recurrence of breast cancer invading the chest wall underwent chest wall resection with myocutaneous flap coverage and are included in this study. Adequate lung, cardiovascular, renal, and hepatic functions were additional eligibility requirements for inclusion. Preoperative known extrapulmonary metastases, pleural dissemination, and Eastern Cooperative Oncology Group (ECOG) status 3 or 4 were exclusion criteria. Survival rates were calculated by the Kaplan-Meier method. Univariable and multivariable Cox regression analysis was used for relative risk factors.
Results: The median interval between operation for the primary tumor and of the local recurrence was 89 months, with median follow-up at 28 months. In the total collective, cumulative 5-, 10- and 15-year survival rates were 46%, 29%, and 22%, respectively, with a median survival of 56 months. R0 resection was associated with a 5-year survival of 50.4%. Prognostic factors were patient age at the time of the primary operation and tumor invasion of bony structures. Mortality was 1.6% and morbidity was 25%.
Conclusions: Full-thickness chest wall resection of locally recurrent breast cancer performed by a team of thoracic and plastic surgeons provides the best survival rates, with low mortality and morbidity. An earlier application of this method may lead to further improvement of these results.
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Introduction
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The incidence of local recurrences after mastectomy and breast-conserving therapy varies between 5% and 40%, depending on risk factors and primary therapy [1]. No standard therapy for local recurrences has been defined, however. The current recommendation is to excise the visible tumor, with subsequent radiation therapy. In many cases, irradiation or chemotherapy is the primary or only therapy. Surgical therapy for local recurrences or chest wall metastases of breast cancer is either not performed at all or, if surgical intervention does occur, a sufficient safety margin is not achieved. Local recurrences are often misjudged as the first indication of a systemic dissemination of the disease and a curative approach is therefore abandoned [2].
Certainly, some patients with chest wall recurrence have evidence of metastatic growth, but reports have demonstrated long-time survival. Even today, large ulcerated chest wall tumors may develop. These local wounds can be difficult to care for, can be personally demoralizing, and may lead to social isolation for patients late in life [2]. Whether complete resection of local recurrence offers a palliative or curative approach, or a major prolongation of survival, continues to be unclear. Moreover, chest wall resection is often regarded as a mutilating intervention with high morbidity and mortality. The possibility of chest wall resection with plastic coverage for complete resection of chest wall recurrences is largely unknown. There are very few reports on the results of full-thickness complete chest wall resections for locally recurrent breast cancer with a sufficient safety margin.
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Patients and Methods
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Between 1985 and 2006, 63 women with local recurrence of breast cancer invading the chest wall underwent complete, full-thickness chest wall resection with myocutaneous flap coverage. The term "local recurrence" is defined as a relapse of tumor after a breast-conserving procedure in the mammary region, after radical surgical therapy in the chest wall region, the covering skin, scar tissue, and the remaining glandular tissue. A local recurrence also includes the involvement of ipsilateral lymph nodes in the area of the tumor.
All patients meeting this definition of local recurrence requiring chest wall resection with flap coverage and who were advised and accepted at our tertiary referral center for plastic and thoracic surgery are included in this study. Preoperative known extrapulmonary metastases, pleural dissemination, and Eastern Cooperative Oncology Group (ECOG) status 3 or 4 were exclusion criteria. Eligibility requirements also included adequate lung, cardiovascular, renal, and hepatic functions. All operations were intended to be curative at the time of inclusion.
Patient data were obtained retrospectively from medical records. The study was approved by the local Ethics Committee of the University of Tübingen, which also waived the need for patient consent to this study. The present condition of the patients was documented by regular outpatient follow-up or by obtaining information from the family physician, the patient, or from relatives. Descriptive data on patients who had primary tumor treatment are listed in Table 1.
A complete resection (R0) was defined as a complete resection of any visible tumor material with a pathologic demonstration of negative resection margins. Resection was performed according to the following standards: The visible tumor was resected with a lateral safety margin of at least 2 cm; if tumor invasion of a rib was assumed, the cranial and caudal ribs were resected as well. In case of any doubt about the extension of the tumor, frozen sections of the margins were performed.
Duration of survival was calculated using the Kaplan-Meier method, with the impact on survival determined for the different univariable factors by means of the log-rank test. Calculation was started at the time of chest wall resection and included postoperative death. Relative risk and multivariable analyses were calculated by Cox regression analysis. To check the proportional hazards assumption, log-log survival probabilities were plotted against log time. In addition, possible colinearities and interdependencies were considered in the multivariable model. The factors included in the analysis were presence or absence of bone infiltration, metastases, and multilocular chest wall recurrence; disease free interval (
4 years or > 4 years); tumor diameter ( 2 cm or > 2 cm); and age at primary resection ( 45 years or > 45 years). The 95% confidence intervals (CI) were calculated. Statistical analyses were computed using R software (www.r-project.org).
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Results
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General
At the time of surgical intervention of local recurrences, the median patient age was 58 years. The median interval between surgery of the primary tumor and that of the local recurrence was 89 months. Mean follow-up was 44 months, with a mean follow-up of survivors at 49 months. All interventions were performed by a team of 1 thoracic and 1 plastic surgeon, and all patients were in good general condition (ECOG grade 0 or 1). Surgical data are detailed in Table 2. A mean of 3.3 ribs were resected in 58 (92%) patients. In all cases, the chest wall local recurrence was completely resected. One patient had to undergo a second sternal resection with R1 situation after final histologic review 10 days later. A complete resection could not be achieved in 8 patients: 6 had pleural carcinosis that was not detected in preoperative procedures and 2 had involvement of deep mediastinal lymph nodes.
Hospital mortality was 1.6% after 1 patient died postoperatively from pulmonary complications. Complications were observed in 16 patients (25%), and reoperations had to be performed in 11 (17%; Table 3).
At the time of follow-up, 36 patients (57.1%) were still alive, and 32 (89%) had no evidence of disease. Of the 27 deceased, 19 (70%) died of progressive disease. The cumulative 5-year survival for the total collective was 46.3% (CI, 32% to 66%); 10-year survival was 29.2% (CI, 16% to 52%); and, 15-year survival was 21.9% (CI, 9% to 49%). The median survival was 56 months (CI, 46 to 154 months).
Survival
The 5- and 10-year survival of the 55 patients who had complete resection was 50.5% (CI, 35.4% to 71.7%) and 34.7% (CI, 19.8% to 60.6%), respectively, with a 61-month median survival. This contrasts with the 9 patients with incomplete resections whose 5- and 10-year survival was 23.3% (CI, 4.7% to 100%) and 0%, with a 14-month median survival (p = 0.007). The descriptive data on the apparent prognostic relevant variables of the following subgroup analyses are in Table 4. For the 39 patients in whom the recurrence did not invade bony structures, 5- and 10-year survival was 57.4% (CI, 39.9% to 82.6%) and 41.0% (CI, 22.6% to 72.2%), with a median survival of 86 months. In the 24 patients with histologically proven bone invasion, 5-year survival was 29.0% (CI, 12.4% to 67.7%) and 10-year survival was 9.7% (CI, 1.5% to 59.2%) with a 46-month median survival. This survival difference is significant (p = 0.03; Fig 1).
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Fig 1. Cumulative survival concerning bone infiltration (dashed line) vs no bone infiltration (solid line) of the chest wall. (Dotted lines represent 95% confidence intervals; log-rank comparison of both survival curves, p = 0.0024).
| Patients at Risk |
0 m |
60 m |
120 m |
180 m |
240 m |
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| No bone infiltration |
30 |
11 |
6 |
3 |
3 |
| Bone infiltration |
25 |
4 |
2 |
2 |
. . . |
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Factors Related to Survivability
In the 10 patients in whom additional metastases of lung, pericardium, or diaphragm were resected, 5- and 10-year survival was 40% (CI, 14.7% to 100%) and 20% (CI, 36.3% to 100%) with a median survival of 56 months. The 53 patients without metastases had a 5- and 10-year survival of 47.5% (CI, 32.5% to 69.3%) and 30.8% (CI, 16.4% to 57.9%), respectively, with a median survival of 57 months (p = 0.66). Also, the 21 patients who required multivisceral resections had no difference in survival compared with those with only chest wall resection, with 5-year survival of 46.5% vs 46%.
A tumor size of 2 cm and below (n = 15) was associated with a 5- and 10-year survival of 56.4% (CI, 33.6% to 94.6%), with a size above 2 cm (n = 48) resulting in respective survivals of 43.4% (CI, 27.8% to 67.5%) and 19.8% (CI, 7.8% to 49.9%). A median survival rate was not determined for the first group and was 56 months for the second group (p = 0.29).
When considering the interval between primary operation and reoperation with a cutoff date of 48 months, we did not find any statistical significant difference (p = 0.09). In the 47 patients with an interval exceeding 48 months, 5- and 10-year survival was 53.6% (CI, 37.0% to 77.6%) and 28.9% (CI, 13.8% to 60.4%), with a median survival of 61 months, compared with a 28.1% (CI, 11.2% to 70.6%) 5- and 10-year survival, with a median survival of 30 months if the disease-free interval (DFI) was less than 48 months (n = 16; Fig 2).
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Fig 2. Cumulative survival concerning disease free interval (DFI) exceeding 48 months (solid line) vs DFI of 48 months or less (dashed line). (The dotted lines represent 95% confidence intervals; log-rank comparison of both survival curves, p = 0.0024).
| Patients at Risk |
0 m |
60 m |
120 m |
180 m |
240 m |
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| DFI > 48 m |
47 |
12 |
5 |
5 |
5 |
| DFI 48 m |
16 |
5 |
5 |
2 |
. . . |
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Another important factor is patient age at the time of the primary operation. The 24 patients younger than 45 years at the time of primary therapy for breast cancer had a better prognosis, with a 5- and 10-year survival of 74% (CI, 54.7% to 100%) and 46.6% (CI, 24.9% to 87.4%), and a median survival of 92 months. In contrast, the 39 women older than 45 years at the time of primary therapy had a 5- and 10-year survival of 23.2% (CI, 9.7% to 55.0%) and 15.5% (CI, 4.7% to 50.2%), with a median survival of 30 months (p = 0.002; Fig 3).
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Fig 3. Cumulative survival for aged 45 years or younger (solid line) or older than 45 years (dashed line) at the time of primary treatment. (The dotted lines represent 95% confidence intervals; log-rank comparison of survival curves, p = 0.0024).
| Patients at Risk |
0 m |
60 m |
120 m |
180 m |
240 m |
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| Age 45 y |
24 |
11 |
5 |
4 |
4 |
| Age > 45 y |
39 |
4 |
3 |
. . . |
. . . |
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Considering expected prognostic factors, only bone invasion and age group reveal an influence on survival (p = 0.04 and p = 0.005, respectively). Risk ratios of univariable Cox analysis are reported in Table 5. The bone invasion and age at the time of primary therapy factors were analyzed additionally using multivariable Cox analysis. Only bone invasion and age at the time of primary therapy show demonstrative p values of 0.04 and 0.002, respectively, as well as a risk of premature death, which is 2.2- and 4.9-fold higher for patients with bone invasion and age older than 45 years at the time of primary treatment, respectively (Table 6).
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Comment
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Complete resection with free margins is recommended as first choice for treatment in recurrent breast cancer. In most cases, however, local excision of superficial tissue is performed, which then often proves to be a R1 or R2 resection and safety margins are hardly ever sufficient. In a study of 130 patients with local recurrence and different therapeutic modalities, including systemic therapy, surgical resection of different extent, radiation therapy, or a combination of these procedures, Chagpar and colleagues [3] found that radiation therapy was of great importance. This is not astonishing, because resection procedures suggesting a complete resection were only applied in 25% of the patients in the study. Complete chest wall resection is usually performed only after all other procedures have been exhausted [4].
Veronesi and colleagues [5] and Fortin and associates [6] demonstrate that the incidence of metastases increases both after manifestations of a local recurrence and after therapy for a primary tumor. In both cases, there is a peak after about 2 years, with a subsequent decrease in the incidence of new metastases [5, 6]. Thus, local recurrence has to be regarded as a repeated episode of a disease with an increased risk of subsequent metastases and not vice versa. The curve of metastatic incidence might be flattened or reduced markedly by a radical resection with sufficient safety margins. Furthermore, Fortin and colleagues showed that resection of the primary tumor with an insufficient safety margin always bears a high risk for the manifestation of local recurrence. Additional radiation therapy does not decrease the risk for these patients unless they were operated on with sufficient safety margins [6]. If local recurrence is treated with soft tissue resection only, without including the whole chest wall, the risk of re-recurrence is between 45% and 62% [7]. This risk after exclusive radiation therapy increases up to 83% [8].
Mortality after chest wall resection is reported to be 3.5% to 4.5% [9]. Hospital mortality in our collective was 1.6%, and a similar rate of 1.6% was reported by Henderson and colleagues [10] in 61 patients. Mansour and colleagues [11] presented a 30-day mortality of 7% and morbidity of 24%. Morbidity has been reported to be 20% to 50% in various studies. Faneyte and colleagues [4] described a complication rate of 40% in their collective, with surgical revision necessary for 22%. A complication rate of 41% was reported by Kluiber and colleagues [12] in a study of 12 patients. The City of Hope Hospital reported a complication rate of 32% in 22 patients [9]. The morbidity was 25% in our group, with a 17% rate of reinterventions; however, after a learning curve, we have had no need for reinterventions during the last 10 years.
For the expected prognostic factors of disease free interval, additional metastases, multilocular manifestation of the recurrence, and largest tumor diameter, we have not seen an impact on prognosis (Table 5).
As reported by Fortin and colleagues [6], risk factors affecting long-term survival were diameter of the local recurrence (> 1.5 cm), disease-free interval (< 2 years), skin invasion, and initial tumor stage T2 or positive lymph nodes [6]. We have not seen differences within 4 years of disease-free survival. There have been only some indications of worse prognosis associated with tumors exceeding 2 cm in diameter. Faneyte and colleagues [4] found age at the time of primary resection and the disease-free interval to be prognostic factors. The 5-year survival in their cohort was 45%; after R0 resection without additional metastases, 58%; and in the palliative setting, still 21%. Patients who were younger than 35 years at the time of primary therapy had significantly lower survival rates after the resection of a chest wall recurrence; however, this group consisted of only 4 patients, and a 5-year survival rate was not provided [4].
In our investigation, the distinction between younger and older patients was determined to be 45 years, which corresponds with the average time of the onset of menopause. We detected a significant difference, however, with an improved long-term survival for the younger group, which was the most significant factor in our group. In contrast to the common prognosis, younger patients achieved a better prognosis by surgical therapy for the local recurrence than older patients. Whether this is actually due to the therapeutic procedure or the generally decreased life expectancy of older patients should be the subject of a more detailed investigation. We have not, however, found any influence of postoperative complications or reoperations. We had 25% reinterventions within the younger group and 13% in the older group. The difference in long-term survival was not significant between patients who required reoperation and those who did not. Morbidity had no major influence on survival between these groups.
Miyauchi and colleagues [13] reported 5-year survival of 48% in 23 patients. Prognostic factors were disease-free interval and positive mediastinal lymph nodes. Henderson and colleagues [10] reported a 5-year survival of only 24%; however, the incidence of incomplete resections in this group was 26%, and the only prognostic factor was the presence of additional metastases. Thoracic surgeons at the Memorial Sloan-Kettering Cancer Center reported a 5-year survival of 18% [2]. If patients with additional metastases were excluded, 5-year survival was 35%; however, this group had an astonishingly high incidence of R1 and R2 resections. Downey and colleagues [2] concluded that chest wall resection primarily represented a palliative approach. Our data do not support those results. Patients with metastases who underwent complete resection had 5-year survival of 40%. Besides that, we do not consider the additional resection of metastases per se to be a palliative intervention. Several reports have shown that metastatic resection indeed offers long-term survival in the treatment of breast cancer [14–17].
Even in cases of multilocular metastases, resection of local recurrence with palliative intent may contribute to markedly improved quality of life. Palliative resections are mostly applied in primarily irradiated patients with a re-recurrence. Some of the tumors are ulcerated or the patients have severe pain. The improvement in quality of life by an extended resection of the tumor is obvious [2]. Even if resection was only palliative (ie, if tumor tissue was left in place), 5-year survival was 23.3%. These data are confirmed by Faneyte and colleagues [4], who reported a 5-year survival of 21% in this setting.
Research of the literature has revealed that complete chest wall resection is only performed in rare cases. Besides our report with 63 patients, the largest cohort reported in the last 20 years included 69 patients and resection was not so extensive [18]. In our opinion, there are major therapeutic shortcomings in this field. If, as in our collective, the surgical intervention is performed by a team of experienced thoracic and plastic surgeons, and the necessary preoperative, intraoperative, and postoperative infrastructure for the treatment of these diseases is available, almost any local recurrence can be resected with low morbidity and mortality. Unfortunately, many patients are only referred to such a team after multiple previous therapeutic procedures, and few patients come on their own initiative. In our group, 27 patients received a mean of 2.1 therapeutic procedures before a final resection. Two patients had undergone five and six surgical interventions previously.
The results and procedures of cited references are detailed in Table 7
[19–22]. Considering that the incidence of chest wall recurrence varies between 5% and 40%, we can conclude without any doubt that only a minority of patients receive correct treatment.
In conclusion, radical resection of the chest wall with reconstruction can offer long-term palliation and even cure to a significant proportion of patients with isolated chest wall recurrence. Surgical resection is recommended as first-line treatment in all guidelines. Therefore, locally recurrent breast cancer with a suspected invasion of the chest wall should be presented to a team of thoracic and plastic surgeons for consideration of complete resection.
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Acknowledgments
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We thank Liza Bacchus, MD, and Don McClellan for the review of the manuscript and language editing.
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References
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- Downey RJ, Rusch V, Hsu FI, et al. Chest wall resection for locally recurrent breast cancer: is it worthwhile? J Thorac Cardiovasc Surg 2000;119:420-428.[Abstract/Free Full Text]
- Chagpar A, Kuerer HM, Hunt KK, Strom EA, Buchholz TA. Outcome of treatment for breast cancer patients with chest wall recurrence according to initial stage: implications for post-mastectomy radiation therapy Int J Radiat Oncol Biol Phys 2003;57:128-135.[Medline]
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- Veronesi U, Marubini E, Del Vecchio M, et al. Local recurrences and distant metastases after conservative breast cancer treatments: partly independent events J Natl Cancer Inst 1995;87:19-27.[Abstract/Free Full Text]
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Invited Commentary
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Ann. Thorac. Surg. 2008 85: 1900.
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P. L. Camp and Y. L. Colson
Invited Commentary
Ann. Thorac. Surg.,
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Abstract
Introduction
