Fungating and Ulcerating Breast Cancer: Wound Closure Algorithm, Complications, and Survival Trends

Abstract

Fungating breast cancer severely affects patients’ daily lives, and patient management poses major oncology challenges. To present 10-year outcomes of unique tumor presentation, suggesting a focused algorithm for surgical management and providing deep analysis for factors affecting survival and surgical outcomes. Eighty-two patients with fungating breast cancer were enrolled in the period from January 2010 to February 2020 in the Mansoura University Oncology Center database. Epidemiological and pathological characteristics, risk factors, different surgical treatment techniques, and surgical and oncological outcomes were reviewed. Preoperative systemic therapy was used in 41 patients, with the majority (77.8%) showing progressive response. Mastectomy was performed in 81 (98.8%) patients, with primary wound closure in 71 (86.6%), and wide local excision in a single patient (1.2%). Different reconstructive techniques in non-primary closure operations were used. Complications were reported in 33 (40.7%) patients, of which 16 (48.5%) were of Clavien-Dindo grade II category. Loco-regional recurrence occurred in 20.7% of patients. The mortality rate during follow-up was 31.7% (n = 26). Estimated mean overall survival (with 95% CI) was 55.96 (41.98–69.9) months; estimated mean loco-regional recurrence-free survival (with 95% CI) was 38.01 (24.6–51.4) months. Surgery is a cornerstone fungating breast cancer treatment option, but at the expense of high morbidity. Sophisticated reconstructive procedures may be indicated for wound closure. A suggested algorithm based on the center’s experience of wound management in difficult mastectomy cases is displayed.

Introduction

The most frequently diagnosed malignancy in women and the most common cause of cancer-related death among women worldwide is breast cancer [1]. Since the 1990s, locally advanced breast cancer (LABC) incidence has decreased from 30–60% [2] to 20–25% of all new cases [3], with decreasing mortality [4, 5]. However, a subpopulation of these cases still present with advanced fungating/ulcerating disease, classified as T4b [6], with much higher incidence in developing countries, possibly due to a lack of adequate screening, awareness, and healthcare resource accessibility [7–12], although there is very limited data available to support such intuitive claims [6].

Despite great improvements in the screening and management of breast cancer, locally advanced fungating disease is still presented as a primary complaint and poses a major challenge for both patients and oncologists.

This study aims at elaborating the presentation, epidemiologic, and pathologic pattern of fungating breast cancer in a low-mid income country, as well as evaluate surgical and oncologic outcomes of those patients. In addition, the authors suggest a surgical treatment algorithm in light of their experience.

Patients and Methods

Patient Cohort and Study Design

This was a retrospective single tertiary hospital-based study. The hospital software was searched with breast cancer and malignant disease of the breast diagnoses in 10 years period from January 2010 to February 2020.

Inclusion criteria include any patient with (1.) pathologically proved breast carcinoma and (2.) evidence of clinically and pathologically ulcerating excavating lesion or fungating tumor extending above the skin surface with a fungus or cauliflower-like appearance. Exclusion criteria include (1.) patients with other pathologies, such as sarcomas and phyllodes tumors, (2.) fungating recurrences, and (3.) patients with fungating breast cancer who were not managed surgically.

Research gap: fungating and ulcerating breast cancer are rarely studied in isolation of other locally advanced breast cancers; as such, outcomes of resection are unknown.

Outcomes: primary outcome was surgical complications, and secondary outcomes include recurrence and survival after surgical resection.

Data collected: epidemiological and pathological characteristics, surgical techniques, complications, recurrence, mortality, local recurrence-free survival, and overall survival.

The patients were followed up until August 2020.

This study was approved by the IRB of the Faculty of Medicine, Mansoura University (number R.20.10.1040).

Statistical Analysis

Patient data were analyzed and statistical values were obtained using SPSS version 22 (SPSS Inc., Chicago, IL). Continuous variables were presented as mean values when symmetrical, or median and range when asymmetrical. Categorical variables were presented as proportions. Bivariate analysis was done using chi-square and Kruskal–Wallis tests. Survival analysis was done using the Kaplan–Meier curve, and significance was determined by log-rank test. Significant factors affecting overall survival were processed in multivariate analysis using Cox’s regression test. A p-value < 0.05 was considered significant.

Results

Demographic and Clinical Characteristics

Eighty-two patients fulfilled the inclusion criteria, of whom 80 (97.6%) were females and 2 (2.4%) were males. The mean age at diagnosis was 60.8 years (+ / − 14.2). The interval between symptom and first visit was a median of 6.5 months, ranging from 1 to 180 months (one male patient was complaining of a breast lump for nearly 15 years, and was diagnosed with breast cancer only when he presented with fungation). Urban/rural residency did not affect the period between the complaint and the start of treatment (p = 0.45) (Table 1). Clinical presentation of some of these patients is shown in Fig. 1.

Table 1.

Demographic and clinical characteristics

Variable	Value
Age mean + / − SD years	60.8 + / − 14.2 (31–86)
Sex
Female	80 (97.6%)
Male	2 (2.4%)
BMI mean + / − SD kg/m2	32.3 + / − 7.7 (19.8–50.8)
Urban/rural (N = 80)	37 & 43 (45.1 & 52.4%)
Family history of breast cancer	8/67 (11.9%)
The interval between symptom and 1st visit median (range) month	6.5 (1–180)
Rural	6 (1–180)
Urban	8 (2–84)
Clinical size median (range) cm	5.5 (2–20)
Radiologic size median (range) cm	6 (2–10)
Radiologic suspicious nodes (N = 66)	56 (84.8%)
The stage at diagnosis (N = 81)
III	27 (33.3%)
IV	54 (66.7%)

Fig. 1.

Examples of fungating breast tumors: upper inner quadrant fungating lesion with nipple/areola destruction, upper inner quadrant fungating lesion with diffuse peau d’ orange, fungating axillary tail lesion showing necrotic surface, huge fungating lesion with necrotic surface involving the entire chest wall extending to anterior abdominal wall and back

Surgical Treatments

Thirty patients underwent modified radical mastectomy (MRM), while 44 underwent simple mastectomy, 7 patients underwent mastectomy with axillary lymph nodes sampling, and 1 patient underwent wide local excision only. Of 81 patients who underwent mastectomy, 71 had their wounds closed primarily (Table 2). Different techniques were used for non-primary closure, but the most common was regional flaps (Fig. 2), and one patient was left raw for healing by secondary intention.

Table 2.

Operative details and complications

Variable	Value
Surgery
MRM	30 (36.6%)
Simple mastectomy	44 (53.7%)
Mastectomy with axillary sampling	7 (8.5%)
Wide local excision	1 (1.2%)
Wound closure
Primary	71 (86.6%)
Other	11 (13.4%)
Methods of non-primary closure
Raw	1 (9.1%)
Rotational	4 (36.4%)
TRAM	3 (27.3%)
Thoracoepigastric	1 (9.1%)
Thoracoabdominal	1 (9.1%)
Thoracoabdominal + contralateral internal mammary artery perforator flap	1 (9.1%)
Axillary staging (N = 82)
No	45 (54.9%)
Axillary lymph node sampling	7 (8.5%)
ALND	30 (36.6%)
Operative time median (range) minute	90 (20–300)
Complications (N = 81)
No	48 (59.3%)
Yes	33 (40.7%)
Type of complications
Infection	7 (21.2%)
Dehiscence	10 (30.3%)
Seroma	5 (15.2%)
Hematoma	3 (9.1%)
Partial flap necrosis	2 (6%)
Partial flap necrosis & hematoma	2 (6%)
Medical (cardiac-DKA-septic shock-MOF)	4 (12.2%)
Clavien-Dindo
II	16 (48.5%)
IIa	5 (15.2%)
IIIb	8 (24.2%)
IVa	1 (3%)
V	3 (9.1%)

Fig. 2.

Techniques for closure: primary simple closure (A), posteriorly based thoracoabdominal flap (B), medially based thoracoepigastric flap (C), combined posteriorly based thoracoabdominal and contralateral internal mammary artery perforator flap (D)

Neoadjuvant Therapy and Pathological Data

As shown in Table 3, 41 patients were known to receive NAT (10 patients with stage III and 31 patients with stage IV at the time of diagnosis), and 20 received only chemotherapy in different regimens (Anthracycline in 12, Anthracycline + Taxane + Navelbine in 2, Anthracycline + Gemcitabine in 1, Anthracycline + Taxane in 2, Anthracycline + Taxane + Gemcitabine in 2, and regimen missing in 1). Nine patients received combined chemotherapy and hormonal therapy (Anthracycline/Taxane/Anthracycline + Taxane with Tamoxifen in 3 or Anthracycline + AIs in 6). Seven patients received only hormonal therapy (6 with AIs, 1 missing regimen). Three patients received combined chemotherapy (Anthracycline and Taxane) and targeted therapy (1 with Trastuzumab, 2 with Lapitinib). One patient received combined chemotherapy, hormonal, and targeted therapy (Anthracycline + Taxane + Navelbine + Gemcitabine + Vinblastine + Tamoxifen + Trastuzumab), and another 1 patient the NAT regimen is missing. Twenty-eight of them progressed on therapy, 8 patients of stage III and 20 patients of stage IV disease.

Table 3.

Neoadjuvant therapy and pathologic data

Variable	Value
NAT (N = 77)
No	36 (46.8%)
Yes	41 (53.2%)
Response to NAT (N = 36)
Regressed	4 (11.1%)
Stationary	4 (11.1%)
Progressed	28 (77.8%)
Pathologic type (N = 81)
DCIS	1 (1.2%)
IDC	70 (86.4%)
ILC	3 (3.7%)
Mixed	1 (1.2%)
Mucinous	2 (2.5%)
Medullary	1 (1.2%)
Undifferentiated	1 (1.2%)
Metaplastic	1 (1.2%)
Intracystic papillary with invasion	1 (1.2%)
Grade (N = 71)
II	40 (56.3%)
III	31 (43.7%)
Pathologic size median (range) cm	9 (3–27)
Retrieved nodes median (range)	Median 8 (1–32)
Infiltrated lymph nodes median (range)	Median 4 (0–29)
pT (N = 80)
is	1 (1.3%)
4b	76 (95%)
4c	2 (2.5%)
4d	1 (1.3%)
pN (N = 30)
0	4 (13.3%)
1	9 (30%)
2	10 (33.3%)
3	7 (23.3%)
Pathologic node status (N = 37)*
Negative	4 (10.8%)
Positive	33 (89.2%)
Pathologic stage (N = 78)
IIb	1 (1.3%)
IIIa	1 (1.3%)
IIIb	15 (19.2%)
IIIc	7 (9%)
IV	54 (69.2%)
ER (N = 69)
Negative	25 (36.2%)
Positive	44 (63.8%)
PR (N = 68)
Negative	27 (39.7%)
Positive	41 (60.3%)
HER2 (N = 63)
Negative	20 (31.7%)
Positive	43 (68.3%)
Molecular type (N = 65)
Luminal A	2 (3.1%)
Luminal B	44 (67.7%)
HER2-enriched	16 (24.6%)
Triple-negative	3 (4.6%)

The most common pathology was IDC (n = 70, 86.4%), followed by ILC (n = 3, 3.7%). One patient with postoperative diagnosis of DCIS was a 72-year-old woman with an ulcerated left breast mass lesion for 1-year duration underwent incisional biopsy, with a resultant nipple adenoma that was positive for SMA and P63, so the patient did not receive any NAT regimen. A simple mastectomy was performed, and the postoperative pathology was nipple adenoma (florid papillomatosis at the nipple) with low-grade DCIS and ulceration of the overlying nipple and skin, with the mass sized 10 cm. IHC for P63 and CK 5/6 delineated the myoepithelial cells throughout the lesion and at the periphery of the dilated duct, with focal reduction of stained cells at the suspicious foci. IHC for ER showed diffuse strong nuclear staining of the epithelial cells throughout the lesion, with negative nuclear staining of the suspicious foci.

Postoperative Outcomes

Postoperative Complications

Complications occurred in 40.7% of patients, the most common of which was wound dehiscence (n = 10), followed by wound sepsis (n = 7) (Table 2). Almost half of these patients were treated by non-operative measures (dressing + / − antibiotics), thus they were classified as Clavien-Dindo scale II.

Postoperative Mortality

Three patients died in the postoperative period. The first patient was 49 years old, with 35.6 BMI, with fungating metastatic luminal B disease to the lung. The patient underwent simple mastectomy and primary closure then showed rapidly deteriorated lung and heart functions in the form of ventricular tachycardia, requiring frequent direct current (DC) cardioversion and medications. Severe pulmonary edema was followed by multi-organ failure. The second patient was 69 years old, with 50.8 BMI, hypertension, and atrophic right kidney with renal impairment. The patient received different lines of preoperative systemic therapy for HER2/neu enriched disease, then underwent wide local excision for the fungating lesion, and succumbed to renal failure. The third patient was 86 years old with HER2/neu enriched metastatic (bone and liver) fungating disease, with intra-thoracic extension progressive on preoperative systemic therapy. The patient underwent palliative simple mastectomy with reconstruction via random local rotational flap, and then progressed to multi-organ failure and eventual death.

Adjuvant Therapies

Chemotherapy and hormonal therapy were the main lines of adjuvant therapies. Chemotherapy only was given in 16 patients (Anthracycline in 9/Taxane in 2/Gemcitabine in 1/Anthracycline + Taxane in 1/Taxane + Gemcitabine in 1/Taxane + Carboplatine in 1/one patient with missing regimen). Hormonal therapy only was given in 20 patients (AIs in 18, Tamoxifen in 1, and Tamoxifen + LHRH agonist in 1). Combined chemotherapy and hormonal therapy was given in 15 patients (Anthracycline: with Tamoxifen in 3, AIs in 7, combined in 1, and missing agent in another 1, Anthracycline + Taxane with AIs in 2, missing chemotherapy agent with Tamoxifen in 1 patient). Combined chemotherapy and targeted therapy was given in 3 patients (Anthracycline + Taxane + Trastuzumab in 1, and Capecitabine + Lapitinib in 2). Finally, combined three elements were given in 1 patient (Anthracycline + Taxane + AIs + Trastuzumab) (Table 4).

Table 4.

Adjuvant therapies

Variable	Value
Adjuvant chemo (N = 71)
No	36 (50.7%)
Yes	35 (49.3%)
Adjuvant hormonal (N = 59)
No	23 (39%)
Yes	36 (61%)
Adjuvant radio (N = 42)
No	35 (83.3%)
Yes	7 (16.7%)

Recurrence, Mortality, and Survival

Loco-regional recurrence after surgery occurred in 20.7% of patients. However, overall recurrence in the subgroup of patients who were not initially metastatic (i.e., stage III at presentation) was 44.4%, and the vast majority of them (66.7%) had both loco-regional and distant metastasis. Lungs were the most common site of distant spread (54.5%). Thus, only 15 out of 82 patients (18.3%) achieved a potential cure, with no evidence of recurrence/persistent disease during follow-up. The median follow-up was 18 (0–101) months. Recurrence pattern and mortality are displayed in Table 5.

Table 5.

Recurrence, mortality, and survival data

Loco-regional recurrence after surgery (N = 82)	17 (20.7%)
Recurrence in non-metastatic patients (N = 27)  • Loco-regional  • Distant  • Both	12 (44.4%) 1 (8.3%) 3 (25%) 8 (66.7%)
Mortality during follow-up	26 (31.7%)
Estimated mean overall survival (OS) (95% CI) month	55.96 (41.98–69.9)
Estimated mean loco-regional recurrence-free survival (LRFS) (95% CI) month	38.01 (24.6–51.4)

In terms of univariate analysis, the following variables were found to significantly affect OS from time of diagnosis: stage at diagnosis (p = 0.044), preoperative systemic therapy (p = 0.039), primary closure (p < 0.001), HER2/neu status (p = 0.005), and adjuvant hormonal therapy (p < 0.001). In multivariate analysis, stage IV showed a nearly fourfold increase in the risk of shorter survival (HR 3.9, p = 0.49), and four times shorter OS for those with HER2/neu positive status (HR 4.3, p = 0.03), and primary wound closure was related to 50 times longer survival (HR 0.02, p = 0.001) (Table 6) (Fig. 3).

Table 6.

Significant factors affecting overall and loco-regional recurrence-free survival in univariate analysis and the result of their Cox regression analysis

Variable	Univariate analysis		Multivariate analysis
	Mean survival	p-value	HR (95%CI)	Significance
Overall survival (OS) from diagnosis
Stage at diagnosis
III	76.6 (56.4–96.9)	.044	3.9	.049
IV	37.4 (28.7–46.1)		(1.01–14.8)
Preoperative systemic therapy
No	85.3 (71–99.5)	.039	5.7	.052
Yes	46.8 (33.1–60.5)		(0.98–32.8)
Primary closure
No	14.2 (6.7–21.7)	< .001	0.02	.001
Yes	65.5 (52–79)		(0.002–0.21)
HER2/neu status
No	77.9 (58.5–	.005	4.3	.03
Yes	97.3) 33.7 (15.8–51.6)		(1.2–16.1)
Adjuvant hormonal
No	27.3 (10.8–43.8)	< .001	0.42	.14
Yes	66.1 (49.9–82.3)		(0.13–1.3)
Overall survival (OS) from surgery
Preoperative systemic therapy
No	81.39 (65.2–97.5)	.003	4.66	.018
Yes	24.1 (15.5–32.7)		(1.3–16.7)
Stage at diagnosis
III	76.06 (54.5–97.6)	.015	2.24	.198
IV	22.51 (16.4–28.6)		(0.66–7.6)
Primary closure
No	6.16 (2.6–9.7)	.001	0.34	.075
Yes	61.01 (46.2–75.8)		(0.1–1.12)
Adjuvant hormonal
No	20.3 (9.02–31.5)	< .001	0.17	.004
Yes	64.9 (48–81.8)		(0.05–0.57)
Loco-regional recurrence-free survival (LRFS)
Preoperative systemic therapy
No	57.8 (37.9–77.6)	.015	4.2	.007
Yes	15.1 (9.3–21)		(1.5–11.9)
Primary closure
No	4.4 (2.2–6.7)	.001	0.23	.014
Yes	43.5 (28.5–58.5)		(0.07–0.74)
Her2/neu status
Negative	56.9 (32.3–81.5)	.033	2.12	.159
Positive	14.03 (9.1–18.9)		(0.74–6.1)
Adjuvant hormonal
No	5.9 (3.2–8.5)	< .001	0.36	.052
Yes	26.5 (20–33.1)		(0.13–1)

The significant P values are bolded

Fig. 3.

Kaplan–Meier curve showing significant factors affecting overall survival (OS) from diagnosis, A stage at diagnosis, B HER2/neu status

In univariate analysis, the following were found to significantly affect OS from surgery: stage at diagnosis (p = 0.015), preoperative systemic therapy (p = 0.003), primary closure (p = 0.001), and adjuvant hormonal therapy (p < 0.001). Loco-regional recurrence post-surgery did not affect overall survival (p = 0.37). In multivariate analysis, preoperative systemic therapy was associated with four times shorter OS (HR 4.66, p = 0.018), and adjuvant hormonal therapy was linked with six times longer survival (HR = 0.17, p = 0.004) (Table 6) (Fig. 4).

Fig. 4.

Kaplan–Meier curve showing significant factors affecting overall survival (OS) from surgery, A NAT, B adjuvant hormonal therapy

In univariate analysis, the following were found to significantly affect LRFS: preoperative systemic therapy (p = 0.015), primary closure (p = 0.001), HER2 status (p = 0.033), and adjuvant hormonal (p < 0.001). Also, axillary node dissection did not affect loco-regional recurrence-free survival (p = 0.34), even in the subgroup of patients without synchronous distant metastasis (p = 0.53). Besides, the presence of wound complications did not worsen LRFS (p = 0.08). In multivariate analysis, the use of preoperative systemic therapy was associated with shorter LRFS (HR = 4.2, p = 0.007) and primary closure with better LRFS (HR = 0.23, p = 0.014) (Fig. 5).

Fig. 5.

Kaplan–Meier curve showing significant factors affecting local recurrence-free survival (LRFS), A NAT, B primary wound closure

Discussion

There is a dearth of research regarding fungating breast cancer, although it is known to represent a major clinical problem. Approximately 5–10% of patients with any type of cancer will have fungating wounds, and up to 70% of those present in women with breast cancer [13]. A survey of 114 radiotherapy and oncology units reported that the breast is the most common site (62%) for fungating wounds [14], although lower prevalence of 49% has been reported [15]. In Nigeria, fungating tumor was found in 83 (39%) of 212 breast cancer patients, with clinical evidence of metastatic disease reported among 28 patients (13%) [16]. Another study from India included 30 patients with fungating breast cancer [17].

To our knowledge, this may be the first report about fungating breast cancer cases from Egypt and the Arab World.

From a pathological point of view, malignant fungating lesions arise from local tumor growth and direct invasion of the overlying skin and/or local blood and lymph vessels [18], causing tissue de-oxygenation, impaired blood supply, and lymphatic drainage, thereby resulting in impaired wound healing, with added secondary bacterial infection and further tissue necrosis [6].

A major risk factor in fungation development is delayed diagnosis [19], and this coincides with our findings that the median time from lump sensation to clinical assessment was 6.5 months. But it should be emphasized that there are numerous other factors to be considered, including tumor biology [20] and location/breast volume (superficial and near the skin surface, or within breast quadrants and less volume of breast tissue), lack of availability of screening services, and limited use of the multidisciplinary approaches in clinical management [21, 22].

Different clinical scenarios of fungating breast cancer were detected in our cohort, including 77.8% of our patients had a progressed/newly appeared fungation/ulceration while on neoadjuvant therapy and as much as 2/3 were already metastatic on presentation. Also, fungation/ulceration was present with tumors, as small as 2 cm.

Fungating breast cancer affects patients’ daily lives dramatically in the physical, psychological, and social dimensions. Additional malodorous exudate, bleeding, ulceration, infection, and pain usually result in altered body image, low self-esteem, loss of feelings of femininity and sexuality, a deep sense of vulnerability, social isolation, and impaired quality of life (QOL) [23–27].

Different lines of treatment have been used over the years. Palliative wound care involves debridement, frequent dressing, topical antibacterial, and topical and systemic analgesics [9, 28]. Local and systemic therapies include neoadjuvant chemotherapy (NACT) [20, 29, 30], hormone therapy, radiation therapy [20, 31], surgical resection with or without reconstruction [30, 32], and endovascular embolization [33–36]. The major problem facing oncoplastic surgeons in managing fungating breast cancer is that many patients at the time of presentation are not candidates for upfront surgery due to the inability to perform safe and sound wound closure, or obtain R0 or R1 resection margins [20, 28].

Surgery for locally advanced/fungating breast cancer is still contentious in relation to timing and surgical approach [37], with preoperative therapy continuing to be commonly used [38]. The rationale for preoperative systemic therapy include allowing later curative surgery in cases with non-metastatic disease, trialing the control of fungation growth for better resection and possible curation among non-metastatic-disease patients, and palliative therapy for patients with metastatic disease. In our cohort, surgery was performed as a last resort to control either newly developed/progressive fungation with complications such as uncontrollable bleeding, infection, and toxemia, denoting the failure of systemic therapies. This is why there were different regimens of preoperative systemic therapy given, pending the availability of a valid indication for surgery. Other cases with initially fungating disease were operated on without starting preoperative systemic therapy, due to relatively broad scope of professional autonomy, or the absence of well-documented guidelines.

Certain aspects that pose a technical challenge should be considered while locally managing fungating breast cancer.

• Tumor location: certain locations are more demanding than others in terms of closure and/or relation to important structures, for example, the medial edge near the sternum, the upper edge near the clavicle, the inframammary sulcus, and the axillary region.

• Male patients typically have insufficient skin and tissue depth to allow simple closure for chest surgery, and they have commensurately increased possibility of underlying chest wall invasion.

• Tumor to breast ratio: the combination of a large tumor and small breast is the worst scenario to handle, due to the need to cover a vast exposed area.

• Skin elasticity and tissue redundancy: ample skin allows simple closure or easier loco-regional flap harvest, with or without skin undermining.

• Donor site morbidity: this should be as minimal as possible, and tolerated by the patient.

• Inflammatory breast cancer: this is the worst-case scenario due to its extensive spread, possibly even beyond the breast, involving the entire chest wall, leaving less volume of healthy skin for wound closure.

• Surgeon and operation team experience/center facilities with different reconstructive techniques and good insight into the philosophy of treatment are conducive to more favorable surgical and oncological outcomes.

• Patient combined physical and psychological health status: some patients can tolerate a one-stage advanced surgical approach, while others benefit from a staged strategy.

Primary wound closure is feasible in the majority of patients; this was the case in 86.6% of patients in this cohort.

A primary goal of any reconstructive technique of fungating breast cancer patients is to facilitate convenient wound closure, thus covering any exposed vital structures, and preventing the delay of adjuvant therapies leading to optimal oncological benefit; also pain, odor, and discharge reduction improve wound healing and hygiene, as well as patient QOL [39, 40]. Different techniques could be used when simple wound closure is not possible including extensive skin undermining, loco-regional fasciocutaneous flaps as thoracoepigastric or thoracoabdominal, LDF, TRAM, free flaps, synthetic meshes, leaving the wound open for secondary healing by granulation tissue, or the use of combined flaps or techniques to cover wide exposed areas. A suggested algorithm based on our experience for wound management in difficult mastectomy is displayed in Fig. 6.

Fig. 6.

Suggested algorithm for management of wound defect following resection

Reconstructive surgeries can result in local complications, such as infection, bleeding, hematoma formation, wound disruption, and flap necrosis; or systemic outcomes, such as chest infection, septic shock, and multi-organ failure. Most patients respond efficiently to prophylactic and conservative measures, such as appropriate wound dressings and antibiotics, or even minor surgical interventions such as aspiration, evacuation, debridement, and re-closure. In our cohort, 40.7% of the operated patients have had complications, and about quarter of the patients (24.2%) required a second surgical intervention under general anesthesia.

Concerning loco-regional recurrence-free survival (LRFS) analysis, the patients who received preoperative systemic therapy showed worse results, which could be attributed to being diagnosed with either aggressive locally advanced primary tumor, requiring neoadjuvant chemotherapy as a primary line of treatment for local control, or systemic therapy for metastatic disease at the time of diagnosis, coupled with a progressive response to the systemic therapy accounted for the majority of patients (77.8%), denoting more aggressive tumor biology with more difficult local control. Also, the center’s main practice was not to use radiotherapy for primary site in patients diagnosed with fungating distant metastatic disease, either pre- or post-surgery, as there is no additional overall survival benefit and treatment for such patients was palliative. Other patients may have been missed due to long recovery period, wound complications, or lost to follow-up.

Prospective studies evaluating local treatment of primary tumor (adequate standard surgery and adjuvant radiotherapy) in the setting of metastatic breast cancer showed no OS benefits; however, there was an improvement in both LRR and loco-regional progression-free survival [41, 42].

Despite the surgical success of reconstructive techniques in this series, LRFS was significantly poorer compared to primary closure, which is simply explained by the fact that advanced reconstructive techniques were used for highly aggressive extensive fungating lesions, which usually progressed on preoperative systemic therapy.

The average life expectancy for patients with a fungating malignant wound is around 6–12 months [43], but decreasing breast cancer mortality in general has been reported since the 1990s [4, 5], mostly due to the combined effect of early detection in the form of greater awareness and wider implementation of screening programs, and the invention of newer more effective systemic therapies [28, 44]. Consequently, patients with an advanced presentation may have a prolonged survival window compared to what was previously expected [28]. This is supported by our results, which showed an estimated mean OS (95% CI) of 55.96 (41.98–69.9) months, and an estimated mean LRFS (95% CI) of 38.01 (24.6–51.4) months.

Due to the paucity of reported cases on fungating breast cancer and inclusion of related data as part of the broader series of studies on malignant fungating wounds, RCTs are needed to adequately address patients in all aspects of management, to allow for better understanding, treatment, survival, and quality of life.

Limitations of the Study

This study is retrospective, with classic limitations such as missing and heterogeneous data. The study also has a single descriptive arm, with no possibility for survival comparison with other disease categories, and a relatively small patient cohort was included, which may limit the generalizability of the results.

Conclusions

Fungating breast cancer is relatively frequent in Egypt. Surgery still plays a pivotal role in management, both with curative and palliative intent. Primary wound closure is still feasible in most cases; however, reconstructive procedures could be used in selected cases with accepted outcomes. Surgery for fungation is associated with high morbidity. Metastasis, HER2 mutation, and failure of primary wound closure worsen overall survival, while upfront surgery and primary wound closure improve local control-free survival.

Author Contribution

All authors have read and approved the manuscript. Data collection and revision: AA, AE, KA, KAW, SA, MZ, OH. Conceptualization, writing: AA. Supervision and revision: MA, KAW, IH, MZ, OH. Statistical analysis: IH. Editing: OH.

Data Availability

All the clinical, radiological, and pathological data used in this manuscript is available on Mansoura University medical system (Ibn Sina Hospital Management System). http://srv137.mans.edu.eg/mus/newSystem/

Declarations

Ethics Approval and Consent to Participate

All procedures performed in the study involving human participants followed the ethical standards of the institutional research committee and the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. All the patients signed written consent for the surgical maneuvers for resection and reconstruction. This is a retrospective study. Consent for participation in the study itself is not applicable. Approval was obtained from the Institutional Review Board of the Faculty of Medicine, Mansoura University (MFM-IRB), under code number R.20.10.1040.

Consent for Publication

N/A.

Conflict of Interest

The authors declare no competing interests.