Clinico-pathological Factors Determining Recurrence in Phyllodes Tumor of the Breast: The 25-Year Experience at a Tertiary Cancer Center in Eastern India

Baijaeek Sain; Arnab Gupta; Sudip Halder; Vishal Mukherjee; Samir Bhattacharya; Radha Raman Mondal; Bijan Saha; Aditya Narayan Sen; Shravasti Roy

doi:10.4103/bjoc.bjoc_10_22

ORIGINAL ARTICLES

Year : 2022 | Volume : 2 | Issue : 1 | Page : 11-16

Clinico-pathological Factors Determining Recurrence in Phyllodes Tumor of the Breast: The 25-Year Experience at a Tertiary Cancer Center in Eastern India

Baijaeek Sain¹, Arnab Gupta², Sudip Halder², Vishal Mukherjee², Samir Bhattacharya², Radha Raman Mondal², Bijan Saha², Aditya Narayan Sen², Shravasti Roy³
¹ Imperial College London Healthcare NHS Trust UK, London, UK; Department of Surgical Oncology, SGCCRI, Kolkata, India
² Department of Surgical Oncology, SGCCRI, Kolkata, India
³ Department of Pathology, SGCCRI, Kolkata, India

Date of Submission	17-Sep-2022
Date of Decision	23-Oct-2022
Date of Acceptance	23-Nov-2022
Date of Web Publication	31-Mar-2023

Correspondence Address:
Baijaeek Sain
Specialty Trainee ST-2 and Clinical Fellow, Dept. of Trauma & Orthopaedics Surgery, St. Mary’s Hospital, Imperial College Healthcare NHS Trust, London
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/bjoc.bjoc_10_22

Abstract

Background: Phyllodes tumour(PT) of the breast are rare fibroepithelial tumours that are generally more prone to recurrence. Aims and objective: The study aimed to assess the clinico-pathological features, diagnostic modalities and therapeutic interventions with their outcomes leading to recurrence in Phyllodes tumour of the breast. Materials and Methods: A retrospective cohort and observational study which entailed clinico-pathological data of patients who were previously diagnosed or presented with Phyllodes tumour of the breast between 1996 and 2021 were analysed. Data included- total number of patients diagnosed with Phyllodes tumour of the breast, age, type of tumour on initial presentation or biopsy, side, size, therapeutic interventions carried out- surgery(mastectomy or lumpectomy) and adjuvant radiotherapy, final biopsy type, recurrence, type of recurrence and time to recurrence. Results: We analysed a total of 87 patients who were pathologically proven to have PT and 46 patients(52.87%) were found to have recurrence. All patients were recorded to be in the female gender only with a mean age at diagnosis of 39 years (range 15–70). Age <40 years had the highest incidence of recurrence of 56.82%(n = 25) followed by age>40 years with 48.84%(n = 21). 55.4% patients presented with primary phylloides and 44.6% had recurrent phylloides at presentation. Average time of local recurrence from the time of completion of treatment were 13.8 months whereas for systemic recurrence it were 15.29 months. Surgery(mastectomy/lumpectomy) with regard to local recurrence was the major determinant for recurrence followed by adjuvant radiation. (P <0.05)Conclusion: Patients who received adjuvant radiation had minimal recurrence. Patients who were found to have malignant type of biopsy on initial diagnosis(triple assessment) had more incidence and were prone to systemic recurrence over local recurrence. Surgery again played a determining factor leading to increased rate of local recurrence following lumpectomy over mastectomy.

Keywords: Breast, local, metastasis, phyllodes, recurrence, surgery, systemic

How to cite this article:
Sain B, Gupta A, Halder S, Mukherjee V, Bhattacharya S, Mondal RR, Saha B, Sen AN, Roy S. Clinico-pathological Factors Determining Recurrence in Phyllodes Tumor of the Breast: The 25-Year Experience at a Tertiary Cancer Center in Eastern India. Bengal J Cancer 2022;2:11-6

How to cite this URL:
Sain B, Gupta A, Halder S, Mukherjee V, Bhattacharya S, Mondal RR, Saha B, Sen AN, Roy S. Clinico-pathological Factors Determining Recurrence in Phyllodes Tumor of the Breast: The 25-Year Experience at a Tertiary Cancer Center in Eastern India. Bengal J Cancer [serial online] 2022 [cited 2023 Jun 6];2:11-6. Available from: http://www.bengaljcancer.org/text.asp?2022/2/1/11/373311

Introduction

Phyllodes tumour(PT) of the breast are rare fibroepithelial tumours that constitute 0.3–0.5% and 2–3% of primary breast tumours and fibroepithelial tumours, respectively. Although the prognosis of phyllodes tumor(PT) is good, with an 87% 10-year survival but these tumours are generally more prone to recur.^[1] The recurrence risk varies with tumor size and surgical approach. Most phyllodes tumors behave benignly, with local recurrences occurring in a small proportion of cases. In certain cases the tumor may metastasize, mostly in a background of malignant tumour therefore carrying a poor prognosis.^[2] Local recurrences can occur in all phyllodes tumors, at an overall rate of 21%, with ranges of 10% to 17%, 14% to 25%, and 23% to 30% for benign, borderline and malignant phyllodes tumors respectively. Local recurrences generally develop within 2 to 3 years. Distant metastases are almost exclusively a feature of malignant PT. The lungs (66%), the bones (28%), and the brain (9%) are the most common sites of spread. Rarely, metastases can involve the liver and heart.^[3] We herein carried out this study to analyse the clinico-pathological factors determining recurrence of PT of the breast.

Aims and Objectives

The study aimed to assess the clinico-pathological features, diagnostic modalities and therapeutic interventions with their outcomes leading to recurrence in Phyllodes tumour of the breast.

Materials and Methods

Study design and participants

We carried out a retrospective cohort and observational study which entailed clinico-pathological data of patients who were previously diagnosed or presented with Phyllodes tumour of the breast between 1996 and 2021 were analysed at Saroj Gupta Cancer Centre and Research Institute(SGCCRI), Kolkata. The centre annually caters to approximately 50,000 cancer patients across the South-Asian subcontinent primarily covering Eastern India and adjacent southern states alongside Bangladesh and few other neighbouring countries.

Data collection and analysis

After obtaining clearance from the Institutional Ethics Committee(IEC) of SGCCRI Kolkata, the following data were retrieved from medical records and analysed- total number of patients diagnosed with Phyllodes tumour of the breast, age, type of tumour on initial presentation or biopsy, side, size, therapeutic interventions carried out- surgery(mastectomy or lumpectomy) and adjuvant radiotherapy, final biopsy type, recurrence, type of recurrence and time to recurrence.

Statistical methods

Data management and statistical analysis were performed using Python 3.0. Numerical data were summarised using means and standard deviations or median ranges. Categorical data was summarised as percentages. The association between categorical data were tested using Chi-square test. All tests were conducted with the two-sided 0.05-level with no adjustments for multiple comparisons. We assessed all study variables to analyse correlations with recurrence using univariate logistic regression with all clinico-pathological factors at first followed by multiple logistic regression analysis. The correlation of local and systemic recurrence with all clinico-pathological variables were further analysed with multi-nominal logistic regression.

Results

We analysed a total of 87 patients who were pathologically proven to have Phyllodes tumour of the breast and were treated during the period from 1996 to 2021. Out of the 87, 46 were found to have recurrence.

Demographic and clinical characteristics

All patients were recorded to be in the female gender only with a mean age at diagnosis of 39 years (range 15–70). Age <40 years had the highest incidence of recurrence of 56.82%(n = 25) followed by age>40 years with 48.84%(n = 21). All patients presented with a breast mass, in 46 cases, the tumour was huge involving almost the whole breast. 51.61%(n = 16) patients with tumour size>10 cm and 53.57%(n = 30) showed recurrence. The average diameter of tumour at the time of presentation was found to be 8.65 cm. The longest diameter of tumour at presentation was 27 cm while the smallest was found to be 3 cm. 58.18%(n = 32) right sided tumours and 43.75%(n = 14) left sided tumours were recurrent. None of the patients had family history of breast cancer or phyllodes tumour.

Local and systemic recurrence

48 patients(55.4%) presented with primary phyllodes and 39 patients(44.6%) had recurrent phyllodes at presentation. Among patients who presented as recurrent phyllodes at presentation, 18 were diagnosed at local stage and 21 had systemic metastasis. Most common type of phyllodes tumuor on final biopsy was found to be malignant with 52.78%(n = 38), followed by borderline and benign was the least. A total of 46 patients (52.87%) had recurrence. The distribution of local and systemic recurrence with patients having surgery and receiving adjuvant radiation is shown in [Figure 1]. The longest time duration to present as local recurrence from the time of completion of treatment was found to be 84 months whereas the shortest was 2 months. The longest and shortest time duration to present as systemic recurrence from the time of completion of treatment were 96 months and 1 month respectively. Average time of local recurrence from the time of completion of treatment were 13.8 months whereas for systemic recurrence it were 15.29 months [Figure 2].

Figure 1: The distribution of local and systemic recurrence with patients having surgery and receiving adjuvant radiation

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Figure 2: Time of recurrence following completion of treatment

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Several factors were studied in correlation with local recurrence as shown in [Table 1][Table 2][Table 3], the most important was surgery(mastectomy/lumpectomy) with P = 0.0067 on univariate analysis, P = 0.008 on logistic regression and P = 0.007 on multinomial logistic regression with regard to local recurrence. Adjuvant radiation was found to be a significant factor and initial histological subtype of the tumor was also a significant factor for systemic recurrence as benign cases showed lower recurrence rates (43.75%) compared with borderline malignant phyllodes cases (54.92%). Distant metastasis occurred in 21 patients (24.13%), 8 with borderline phyllodes, and 13 with malignant phyllodes. The most common site for metastasis was in the lungs. Other areas for metastasis included bones, iliac nodes, chest wall and mediastinal nodes.

Table 1: Relation of different clinicopathological factors with regard to recurrent phyllodes tumour of the breast

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Table 2: Relation of different clinicopathological factors with regard to local recurrence with multinomial logistic regression analysis

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Table 3: Relation of different clinicopathological factors with regard to systemic recurrence with multinomial logistic regression analysis

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Discussion

Phyllodes tumor (PT) is an uncommon breast lesion usually occurring in women aged 35–50 years. However, malignant PTs may present later.^[1] This correlates with our cohort, where the mean age at diagnosis was 39 years, as compared to 46 years for the malignant PTs.

Although these tumors have an average size of 5 cm, lesions of up to 40 cm have been reported.^[1] The association between tumor size and malignancy is controversial; however, rapid growth may be detected in malignant tumors.^[2] In our study, the mean pathological tumor size was 8.65 cm, which is consistent with existing literature and the largest PT was 27 cm in diameter, which was diagnosed as malignant PT. In addition, the smallest tumour was found to be 3 cm in diameter. Affected sides are almost always equal in number. Multifocality and bilaterality in cases of phyllodes tumour are infrequent.^[3] In our cohort, right breasts were more affected as compared to left breasts(55 and 32 cases, respectively).

Fine needle aspiration cytology(FNAC), core needle biopsy(CNB), incisional, and excisional biopsies can be used in preoperative histopathologic diagnosis of PT. Distinction of benign PT from cellular fibroadenoma (FA) and malignant PT from spindle cell metaplastic carcinoma and primary breast sarcoma are the chief histopathologic dilemmas.^[4] CNB is considered more reliable than FNAC in obtaining a correct diagnosis because it can provide specific histopathologic findings. However, its sensitivity was reported as approximately 65% in the definitive diagnosis of PT.^[5] 11 patients were initially misdiagnosed as benign on FNAC and later diagnosed as malignant on final biopsy whereas only 1 patient was correctly diagnosed as malignant on FNAC. 75 patients were correctly diagnosed as malignant on CNB. In this study, histologic diagnosis was confirmed correctly by CNB in the majority of cases, with an approximately 85.76% diagnostic accuracy for PT. This was in accordance with other studies that found CNB to be a valuable tool in the differential diagnosis of PT, with high specificity and sensitivity rates.^[6] The association of recurrence has shown concordant findings with the same where final biopsy of malignant and borderline tumours with CNB have been found to have recurrence of 52.78% and 72.72% respectively. In our experience, CNB played an important role in the preoperative histopathologic diagnosis of PT whereas FNAC was used in 16 patients and suspicion of PT was reported in only 1 of these. Excisional biopsy was preferred in cases that were strongly considered as FA or another benign lesion in the preoperative clinical and radiologic evaluations.

Wide local excision (WLE), with removal of tumor keeping at least 1-cm clear microscopic margins, is the mainstay for PT while mastectomy may be needed in patients with large malignant tumors or those with high tumor-breast tissue ratio.^[7],[8] In our study, WLE was the most commonly performed initial surgery (44.1%), while mastectomy was mostly done in recurrent cases (61.4%). Axillary dissection is not recommended as part of routine surgical treatment because PT usually spreads via a hematogenous route and nodal involvement is extremely rare. However, axillary dissection may be considered in patients with malignant PT and axillary metastasis.^[9]

In the 16 cases of benign PTs treated by WLE, 3 recurrences occurred, 2 of which progressed, one to borderline and the other to malignant PT. Among the 4 benign cases that were treated with mastectomy, only 1 recurred. In another study by the same investigators that included a series of 33 cases, they found no relationship was found between width of surgical margin and disease recurrence.^[10]

A retrospective review of 44 Asian cases found no cases of local recurrence in benign tumors treated with simple excision (enucleation), regardless of margin status, after a mean follow-up of 47.6 months. Hence, a benign PT diagnosed after representative sampling of an excision specimen may be conservatively handled even when positive margins are encountered.^[11] Conversely, malignant PTs are associated with a recurrence rate of 29.6%, with metastases and death being observed in 22%, underscoring the need to recognize this subset of aggressive PTs for complete surgical eradication.^[12] In our study, in cases of malignant PTs, those treated with mastectomy showed better results and less recurrence in this study. The number was further lower in those who received adjuvant radiation. This was somewhat similar to those reported in the literature.^[13]

Distant metastasis (DM) can be seen in 10% of cases, which most often affects the lungs and bones.^[14] In our cohort, Distant metastasis occurred in 21 patients (24.13%), 8 with borderline phyllodes, and 13 with malignant phyllodes. The most common site for metastasis was in the lungs. Other areas for metastasis included bones, iliac nodes, chest wall and mediastinal nodes.

In our study, 33 patients who received adjuvant radiation following mastectomy showed no recurrence [Figure 1]. There is no global consensus on the role of adjuvant radiotherapy and chemotherapy in the management of PT.^[15] However, application of radiotherapy to the breast after surgery for borderline and malignant PTs was shown to reduce the risk of local recurrence.^[16] In our study, the median dose of radiotherapy dose used was 50Gy/25# for adjuvant radiation with subsequent tumour bed boosting in cases of lumpectomy. Adjuvant radiotherapy should be considered in patients with borderline and malignant PT on an individualized basis however it still lacks clear guidelines precipitating the need of further trial studies.^[4] In a study by Ibreaheem et al., adjuvant radiotherapy was employed in 9 patients, 2 in borderline phyllodes, and 7 in malignant phyllodes; however, post-radiotherapy recurrence occurred in 5 patients, all of them were of the malignant subtype.^[17]

Conclusion

Surgery and Adjuvant radiation contributed significantly in determining recurrence where patients who underwent only lumpectomy had more recurrence than patients undergoing mastectomy. Patients who received adjuvant radiation had minimal recurrence. Patients who were found to have malignant type of biopsy on initial diagnosis(triple assessment) had more incidence and were prone to systemic recurrence over local recurrence. Surgery again played a determining factor leading to increased rate of local recurrence following lumpectomy over mastectomy.

Limitations

Retrospective study with old datas lost to follow up therefore no availability of survival rate in old medical records. Hence difficult to predict disease free survival rates in recurrent tumours following treatment.

IEC approval

Obtained before starting this retrospective observational study. IEC SGCCRI REF NO- 23/04/2021/NON-REG/BS/08.

Acknowledgements

We sincerely acknowledge the help from our Medical Records Department and entire research division of SGCCRI, Kolkata alongside the entire surgical and radiation oncology team for their support. We would like to specially thank Dr Saradindu Ghosh and Dr Rahul Roychowdhury and our beloved and respected Dr Saroj Gupta.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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