Safety and Effectiveness of Acellular Dermal Matrix in Breast-Conserving Surgery for Breast Cancer: A Single-Institution Study

Article information

J Breast Dis. 2024;12(1):12-18
Publication date (electronic) : 2024 June 30
doi : https://doi.org/10.14449/jbd.2024.12.1.12
Division of Breast, Department of Surgery, Myongji Hospital, Goyang, Korea
Correspondence: Hyuk Jai Shin, M.D., Ph.D. Division of Breast, Department of Surgery, Myongji Hospital, 55 Hwasu-ro 14beon-gil, Deokyang-gu, Goyang 10475, Korea Tel: +82-31-810-6890, Fax: +82-31-810-6163, E-mail: drgsshj@gmail.com
Received 2024 May 14; Revised 2024 June 23; Accepted 2024 June 26.

Abstract

Purpose

As breast-conserving surgery (BCS) has become the most common type of breast surgery, oncoplastic BCS has developed in response to improve cosmetic outcomes. Acellular dermal matrix (ADM) has been used as an adjunct to enhance cosmetic outcomes in partial breast reconstruction. This study aimed to evaluate postoperative complications, cosmetic satisfaction, and oncologic safety over a short-term follow-up period.

Methods

This retrospective study included 26 patients who underwent BCS at Myongji Hospital between April 2019 and April 2021. All procedures were performed by three surgeons. We reviewed demographic data, histologic grades, tumor-node-metastasis stages, treatment modalities, and survival data based on patient medical records.

Results

Of the 26 total patients, 5 developed seromas, which was the most common complication, and one patient experienced red breast syndrome. The incidence of complications per surgeon was less than 25%. The mean satisfaction score for the cosmetic outcome on a 10-point scale was 7.6 (±2.1) as scored by patients and 8.8 (±0.9) as scored by surgeons. Responses regarding cosmetic satisfaction revealed no significant differences among surgeons (p=0.444). Of the 26 patients, four were lost to follow-up, and the mean follow-up period was 35.2 months. Two patients experienced recurrence, both of whom had regional recurrence with no local recurrence.

Conclusion

ADM replacement is a favorable alternative to oncoplastic BCS, in terms of the ease of surgical procedures, minimal complications, and low rates of local recurrence.

INTRODUCTION

The incidence of breast cancer continues to increase, making it the most common cancer among Korean women. According to statistics from the Korean Breast Cancer Society, the number of patients who have undergone breast-conserving surgery (BCS) has continued to increase since 2016, with 68.6% of patients diagnosed with breast cancer undergoing BCS in 2019 [1]. Where BCS is the most common type of surgery, oncoplastic BCS has developed in response to improve cosmetic outcomes [2]. The primary indication for oncoplastic BCS is a large tumor size in patients with small breasts. Oncoplastic BCS can be categorized into volume displacement and volume replacement techniques. For women with small breasts, volume displacement of the breast alone may lead to significant deformity. Volume replacement is the most suitable treatment method for patients with small sized breasts [3]. An acellular dermal matrix (ADM), derived from cadaveric skin using proprietary processing technology, provides the biochemical and structural components of the extracellular matrix and promotes tissue regeneration [4,5]. The safe integration of ADMs into host tissues, attributed to their low antigenicity, avoids issues such as resorption, contracture, and encapsulation [6]. Recently, ADMs have been used as an adjunct to enhance cosmetic outcomes in partial breast reconstruction [7].

Some studies have reported low postoperative ADM-related complications and high cosmetic satisfaction [8-10]. However, there is still inadequate evidence supporting the oncological safety of ADM and defining the associated postoperative complications.

This study aimed to evaluate postoperative complications, cosmetic satisfaction, and oncologic safety of ADM-based oncoplastic BCS among different surgeons within a single institution over a short-term follow-up period.

METHODS

Patients

This retrospective study included 26 patients who underwent BCS with ADM at Myongji Hospital between April 2019 and April 2021. BCS with ADM was performed in patients who had >10% of the total breast volume removed and required level 1 or higher oncoplastic BCS. Level 1 oncoplastic BCS was performed when < 20% of the breast volume was excised.

The follow-up period lasted until December 2023. Four of 26 patients were lost to follow-up. We reviewed patient medical records for demographic data, histologic grades, tumor-node-metastasis stages, treatment modalities, complications, and disease-free survival data. All patients underwent physical examination, mammography, breast ultrasonography, and magnetic resonance imaging. Most patients also underwent chest and abdominopelvic computed tomography or whole-body bone scans to evaluate distant metastases. During the follow-up period, imaging studies were conducted to discriminate between distant metastases, as in the preoperative imaging. Postoperative adjuvant hormone therapy, chemotherapy, and radiation therapy (RT) were administered to patients according to the current guidelines.

Disease-free survival was measured from the date of surgery to the date of any recurrence, last follow-up, or death, as recorded in the Statistics Korea records.

Patients were followed up with at one-month postoperatively to assess short-term complications such as infection, seroma, hematoma, red breast syndrome (RBS), and cosmetic satisfaction. Cosmetic satisfaction was assessed on a 10-point scale using a questionnaire: Scores of 0–4 were classified as dissatisfied, 5–6 as neutral, 7–8 as satisfied, and 9–10 as strongly satisfied.

Type of ADM

In this study, the crosslinked human ADM (Megaderm®, L&C Bio, Seoul, Korea) was derived from donated human skin in United States (US) tissue banks following the guidelines of the American Association of Tissue Banks and the US Food and Drug Administration. After removing epidermal and dermal cells from fresh human cadaver skin, electron beam irradiation was applied to the remaining acellular dermal layer to remove viruses, bacteria, and spores. The product was a 5 × 6 cm square plate with a thickness of 3–5 mm (Figure 1). Three different breast surgeons participated in each surgery.

Figure 1.

Acellular dermal matrix (Megaderm®).

Method of ADM replacement technique

The surgical method used for ADM replacement is shown in Figure 2. If simple primary suturing of the breast parenchyma was difficult or if filling of the surgical site was required after BCS, the ADM was inserted into the subcutaneous area of the tumor resection site.

Figure 2.

Acellular dermal matrix (ADM) replacement. In the procedure of applying breast-conserving surgery using ADM. (A) We removed the tumor from the lesion located at the 3 o’clock of left breast using a circumareolar incision and removed it from the bottom to the top using an energy device. (B) We then applied Megaderm® over the tumor defect site.

Statistical analysis

Differences in clinicopathological characteristics between groups were assessed using the chi-square test, Fisher’s exact test, or Student’s t-test, as appropriate. Summary statistics are presented as numbers (%) for categorical variables. Analyses were performed using R (v4.3.2, R Development Core Team, Vienna, Austria; http://www.R-project.org/). Statistical significance was set at p < 0.05.

Ethics

This study adhered to the ethical tenets of the Declaration of Helsinki and was approved by the Institutional Review Board of Myongji Hospital (IRB no. 2023-12-029). The requirement for informed consent was waived due to the low risk posed by this study.

RESULTS

Patient characteristics

A total of 26 patients were included in the analysis. The clinical characteristics of the patients are summarized in Table 1. The median age was 49.9 years, and the mean body mass index (BMI) was 23.8 kg/m2, with no smoking patients. Invasive ductal carcinoma, the predominant histological type of breast cancer, is hormone receptor-positive and human epidermal growth factor receptor-2-negative, and accounted for 65.4% of cases. Four patients were lost to postoperative follow-up, resulting in the completion of a follow-up period of 22 patients until December 2023. The mean follow-up period was 35.2 months, during which three patients were confirmed to have experienced recurrence.

Clinicopathologic characteristics

Postoperative complications

A comparison of postoperative complications among the different surgeons is shown in Table 2. Complications were observed within the first 30 days postoperatively.

Postoperative complication compared among different surgeons

All procedures were performed by three surgeons, and no significant differences in complications were observed (p = 0.248). Of the 26 total patients, five patients developed seromas, and one patient experienced RBS. Among the six patients with complications, none were smokers and one patient had diabetes mellitus (DM). The incidence of complications per surgeon was < 25%.

Cosmetic satisfaction in patients and surgeons

The mean satisfaction score for the cosmetic outcome on a 10-point scale was 7.6 (± 2.1) as scored by patients and 8.8 (± 0.9) as scored by surgeons (Table 1). Responses regarding cosmetic satisfaction revealed no significant differences among the surgeons (p = 0.444) (Table 3). Images of a patient who underwent follow-up imaging 6 and 12 months after surgery are presented in Figures 3 and 4, respectively. These images show minimal volume defects after surgery.

Cosmetic satisfaction in patients and surgeons

Figure 3.

Follow-up at 6 months after acellular dermal matrix (ADM) insertion. (A) Mammogram demonstrating postoperative distortion and mild parenchymal edema. (B) Ultrasound demonstrating the postoperative state of the ADM insertion with mild parenchymal edema without a focal lesion. (C) Magnetic resonance imaging demonstrating the postoperative state of ADM insertion with mild parenchymal edema and skin thickening.

Figure 4.

Images for follow-up 12 months after acellular dermal matrix (ADM) insertion. (A) Mammogram demonstrating postoperative distortion and fat necrosis with no focal lesion. (B) Ultrasound demonstrating postoperative state of ADM insertion without edema.

Types of recurrence in patients

The types of recurrence are shown in Table 4. Four of the 26 total patients were lost to follow-up, with a mean follow-up period of 35.2 months. Three patients experienced recurrence, two with local recurrence and one with distant recurrence. One patient had supraclavicular lymph node metastasis, the other patient developed distant metastasis following ipsilateral axillary lymph node metastasis, and one patient had pulmonary metastasis as a distant recurrence. No deaths occurred during the follow-up period.

Types of recurrence in patients

DISCUSSION

Complications reported with ADM implantation techniques include skin necrosis, seroma, hematoma, infection, and RBS [11]. The risk factors for complications include a history of DM, obesity, and smoking. RT is a potential contributing factor [12,13].

In this study, we addressed seroma and RBS complications. We defined seroma as aspiration of ≥ 30 cc of fluid. RBS was defined as the development of localized erythema in a predictable pattern on the breast skin over an ADM without systemic infection such as fever, swelling, or tenderness on palpation. Several hypotheses exist regarding the cause of RBS; however, one possibility is a type IV delayed hypersensitivity reaction. We treated the patient with RBS by applying a steroid ointment until the erythema had subsided.

In the present study, the most common complication was seroma, as reported in other studies. However, there was no need for reoperation because of infection. Despite all patients undergoing RT, the incidence of complications did not exceed that reported in previous studies [14,15]. As indicated by our results, none of the patients had a smoking history, and the mean BMI was 23.8 ± 3.3 kg/m2. Only one patient with complications had DM.

ADM was initially used for skin replacement in burn injuries, abdominal wall repair, and other procedures. It was first introduced in breast surgery to correct problems, such as implant rippling, symmastia, and soft tissue defects [16]. The use of ADM is straightforward and simple, leading to the assumption that there are no complications based on the proficiency of surgeons employing ADM [17,18]. It is a simple, safe, and easily learned defect augmentation surgery method to insert a sheet-type ADM between the skin and breast tissues during BCS. We dissected the superficial fascia of the mammary gland to preserve adequate subcutaneous thickness, ensuring sufficient coverage of the ADM. Additionally, we determined the appropriate reconstructive volumes and meticulously calibrated the space for the human ADM to be used as a volume replacement. However, this procedure can be difficult for surgeons [7,19]. Interestingly, our findings are consistent with this assumption because we did not observe any noticeable variation in complication rates among the surgeons. Additionally, there was no statistically significant difference in cosmetic satisfaction related to surgeon experience. Consequently, the learning curve required to use the ADM in the volume replacement procedure appears to be minimal.

Few studies have investigated local recurrence after ADM replacement, with only one study reporting a local recurrence rate of 2.5% at a mean follow-up of 22.8 months [20]. By contrast, our investigation specifically examined the local recurrence rate in patients who underwent ADM replacement. Although the follow-up duration was relatively short (mean follow-up, 35.2 months), we did not observe any local recurrence specifically related to the same breast. However, regional recurrence and distant metastases were reported in our study. Although the limited number of cases in this pilot study precluded robust statistical analysis, we found that ADM insertion did not have a significant impact on local recurrence rates.

This study has some limitations. These findings were based on a small number of patients and should be interpreted with caution. Further research with a larger sample size and longer-term follow-up is necessary to validate these findings.

ADM replacement is a viable alternative to oncoplastic surgery. Our observations indicated minimal complications, notably RBS and seroma formation, with no instances of local recurrence. When >10% of the mammary gland is excised, and oncoplastic BCS becomes imperative, employing a sheet-type ADM has emerged as a safe and convenient method to address breast defects.

Notes

The authors declare that they have no competing interests.

References

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2. Weber WP, Soysal SD, Fulco I, Barandun M, Babst D, Kalbermatten D, et al. Standardization of oncoplastic breast conserving surgery. Eur J Surg Oncol 2017;43:1236–43.
3. Noguchi M, Yokoi-Noguchi M, Ohno Y, Morioka E, Nakano Y, Kosaka T, et al. Oncoplastic breast conserving surgery: volume replacement vs. volume displacement. Eur J Surg Oncol 2016;42:926–34.
4. Kim H, Bruen K, Vargo D. Acellular dermal matrix in the management of high-risk abdominal wall defects. Am J Surg 2006;192:705–9.
5. Lee JH, Kim HG, Lee WJ. Characterization and tissue incorporation of cross-linked human acellular dermal matrix. Biomaterials 2015;44:195–20.
6. Cuomo R. Submuscular and pre-pectoral ADM assisted immediate breast reconstruction: a literature review. Medicina 2020;56:25.
7. Franceschini G, Masetti R. Acellular dermal matrix as filler in breast-conserving surgery: warnings for a careful use. World J Surg Oncol 2021;19:1.
8. Paprottka FJ, Krezdorn N, Sorg H, Könneker S, Bontikous S, Robertson I, et al. Evaluation of complication rates after breast surgery using acellular dermal matrix: median follow-up of three years. Plast Surg Int 2017;2017:1283735.
9. Ortiz JA. Clinical outcomes in breast reconstruction patients using a sterile acellular dermal matrix allograft. Aesthetic Plast Surg 2017;41:542–50.
10. Lewis P, Jewell J, Mattison G, Gupta S, Kim H. Reducing postoperative infections and red breast syndrome in patients with acellular dermal matrix-based breast reconstruction: the relative roles of product sterility and lower body mass index. Ann Plast Surg 2015;74 Suppl 1:S30–2.
11. Podsednik Gardner, Nunez A, De la. Red breast syndrome and acellular dermal matrix. Plast Reconstr Surg Glob Open 2023;11:e5062.
12. Sarkozyova N, Dragunova J, Bukovcan P, Ferancikova N, Breza J, Zilinska JK. Preparation and processing of human allogenic dermal matrix for utilization in reconstructive surgical procedures. Bratisl Med J 2020;121:386–94.
13. Selber JC, Wren JH, Garvey PB, Zhang H, Erickson C, Clemens MW, et al. Critical evaluation of risk factors and early complications in 564 consecutive two-stage implant-based breast reconstructions using acellular dermal matrix at a single center. Plast Reconstr Surg 2015;136:10–20.
14. Valdatta L, Cattaneo AG, Pellegatta I, Scamoni S, Minuti A, Cherubino M, et al. Acellular dermal matrices and radiotherapy in breast reconstruction: a systematic review and meta-analysis of the literature. Plast Surg Int 2014;2014:472604.
15. Moyer HR, Pinell-White X, Losken A. The effect of radiation on acellular dermal matrix and capsule formation in breast reconstruction: clinical outcomes and histologic analysis. Plast Reconstr Surg 2014;133:214–21.
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Article information Continued

Figure 1.

Acellular dermal matrix (Megaderm®).

Figure 2.

Acellular dermal matrix (ADM) replacement. In the procedure of applying breast-conserving surgery using ADM. (A) We removed the tumor from the lesion located at the 3 o’clock of left breast using a circumareolar incision and removed it from the bottom to the top using an energy device. (B) We then applied Megaderm® over the tumor defect site.

Figure 3.

Follow-up at 6 months after acellular dermal matrix (ADM) insertion. (A) Mammogram demonstrating postoperative distortion and mild parenchymal edema. (B) Ultrasound demonstrating the postoperative state of the ADM insertion with mild parenchymal edema without a focal lesion. (C) Magnetic resonance imaging demonstrating the postoperative state of ADM insertion with mild parenchymal edema and skin thickening.

Figure 4.

Images for follow-up 12 months after acellular dermal matrix (ADM) insertion. (A) Mammogram demonstrating postoperative distortion and fat necrosis with no focal lesion. (B) Ultrasound demonstrating postoperative state of ADM insertion without edema.

Table 1.

Clinicopathologic characteristics

Variables No. (%)
Surgeons
 1 17 (65.4)
 2 4 (15.4)
 3 5 (19.2)
Age (yr) 49.9 ± 9.0
Body mass index (kg/m2) 23.8 ± 3.3
Menopausal status
 Premenopause 18 (69.2)
 Postmenopause 8 (30.8)
Hypertension
 No 21 (80.8)
 Yes 5 (19.2)
Diabetesmellitus
 No 23 (88.5)
 Yes 3 (11.5)
Histology
 IDC 25 (96.2)
 Mixed IDC and ILC 1 (3.8)
Location
 Left 14 (53.8)
 Right 8 (30.8)
 Bilateral 4 (15.4)
Axillary surgery
 SLNB 22 (84.6)
 ALND 4 (15.4)
Clavien-Dindo complication grades
 None 21 (80.8)
 Ι 5 (19.2)
Patient score 7.6 ± 2.1
Surgeon score 8.8 ± 0.9
Subtype
 HR+/HER2- 17 (65.4)
 HR+/HER2+ 4 (15.4)
 HR-/HER2+ 0 (0.0)
 HR-/HER2- 5 (19.2)
Ki-67
 20% or less 10 (38.5)
 More than 20% 16 (61.5)
Bloom-richardson's histologic grade
 1 8 (30.8)
 2 12 (46.2)
 3 6 (23.1)
Pathologic T stage*
 Ι 13 (50.0)
 ΙΙ 13 (50.0)
Pathologic N stage*
 0 17 (65.4)
 Mircometa 3 (11.5)
 Ι 3 (11.5)
 ΙΙ 2 (7.7)
 ΙΙΙ 1 (3.8)
Pathologic stage*
 Ι 13 (50.0)
 ΙΙ 10 (38.5)
 ΙΙΙ 3 (11.5)
Adjuvant chemotherapy
 No 6 (23.1)
 Yes 17 (65.4)
 Unknown 3 (11.5)
Adjuvant radiotherapy
 No
 Yes 23 (88.5)
 Unknown 3 (11.5)
Adjuvant hormone therapy
 No 5 (19.2)
 Yes 18 (69.2)
 Unknown 3 (11.5)
Adjuvant target therapy
 No 19 (73.1)
 Yes 2 (7.7)
 Unknown 5 (19.2)
Recurrence
 No 19 (73.1)
 Yes 3 (11.5)
 Unknown 4 (15.4)
Mean follow-up (mo) 35.2±17.4

Values are presented as the mean±standard deviation or n (%).

IDC=invasive ductal carcinoma; ILC=invasive lobular carcinoma; SLNB=sentinel lymph node biopsy; ALND=axillary lymph node dissection; HR=hormone receptor; HER2=human epidermal growth factor receptor 2.

*

Based on the pathologic TNM stages described in the American Joint Committee on Cancer 7th edition.

Table 2.

Postoperative complication compared among different surgeons

Type of complication Professor
p-value
1 2 3 Total
None 13 (76.5) 3 (75.0) 4 (80.0) 20 (76.9) 0.248
Seroma 4 (23.5) 1 (25.0) 0 5 (19.2)
Red breast syndrome 0 0 1 (20.0) 1 (3.9)
Total 17 (100.0) 4 (100.0) 5 (100.0) 26 (100.0)

Table 3.

Cosmetic satisfaction in patients and surgeons

Variables Professor
p-value
1 2 3
Total 17 (65.4) 4 (15.4) 5 (19.2)
Patient’s score Score 0.444
3 0 1 (25.0) 0
4 1 (5.9) 0 0
5 1 (5.9) 0 1 (20.0)
6 3 (17.6) 0 2 (40.0)
7 3 (17.6) 0 0
8 3 (17.6) 0 0
9 3 (17.6) 1 (25.0) 1 (20.0)
10 3 (17.6) 2 (50.0) 1 (20.0)
7.6 ± 1.8 8.0 ± 3.4 7.2 ± 2.2
Surgeon’s score Score
6 0 0 1 (20.0) 0.267
7 0 0 0
8 3 (17.6) 2 (50.0) 1 (20.0)
9 10 (58.8) 1 (25.0) 3 (60.0)
10 4 (23.5) 1 (25.0) 0
9.1 ± 0.7 8.8 ± 1.0 8.2 ± 1.3

Values are presented as the mean±standard deviation or n (%).

Table 4.

Types of recurrence in patients

Outcomes No. of patients (%)
Recurrence Local 0
Regional* 2 (7.7)
Distant 1 (3.8)
No recurrence 19 (73.1)
Follow up loss 4 (15.4)
*

One patient had a TP53 mutation, leading to sequential regional and distant metastasis.