[Borderlines and malignant phyllodes tumors of the breast: From the anatomopathological challenge to the standard of care]. / Tumeurs phyllodes borderlines et malignes du sein : du défi anatomopathologique à l'élaboration d'un standard de prise en charge.

Phyllodes tumors, borderline (BPT) and malignant (MPT), represent a rare group of fibroepithelial breast tumors. Due to their rarity, their treatment remains poorly codified. The precise incidence of these tumors remains unknown. TPMs represent half of breast sarcomas and 1 % of breast tumors. Their treatment at the localized stage is based on surgery, that can be conservative surgery or a mastectomy. The impact of oncoplastic techniques and immediate breast reconstruction is not documented. The excision margins of the BPT and MPT must be free, a wider margin can provide a benefit in local recurrence but in also overall survival in the case of TPM. The optimal width of the excision margin is not known. In the event of positive margins, a second surgery could make up the result of an insufficient first surgery. Chemotherapy does not seem to provide any benefit on recurrence-free survival, but the available data are particularly weak. The data on adjuvant radiotherapy are more important. This allows better local control in the event of breast-conserving surgery. The benefit of post-mastectomy radiotherapy is less documented but can be considered in cases of poor prognostic factors. The management of TPM at the metastatic stage is based on the use of chemotherapy (anthracyclines, Ifosfamide) and local treatment of metastases in cases of oligometastatic disease. Due to the rarity of these tumors, it is essential that their management be discussed within a network of qualified professionals (NETSARC+).

Malignant phyllodes: 10 year review of management through a sarcoma service.

BACKGROUND: Phyllodes tumours of the breast are rare, and their treatment is still subject to discussion. They are classified as benign, borderline, or malignant based on histopathological characteristics of the stroma. This study demonstrates 10 years' experience in diagnosis and management of malignant phyllodes. METHODS: All patients referred for discussion at our sarcoma multidisciplinary team meeting from 2003 to 2013 with a diagnosis of malignant phyllodes were identified. Patient demographics, biopsy details, excision extent, final pathology, reconstruction, adjuvant treatment, recurrence and overall survival were assessed. RESULTS: Thirty patients were identified over the 10 year period. Eight (26.7 %) had their diagnosis upgraded to malignant phyllodes on completion excision, compared to initial biopsy. Nine (30 %) had breast surgery elsewhere as definitive treatment before referral to our service. Four of these (44.4 %) required more extensive excision and three developed metastases (33.3 %) and died. Twenty-one patients had primary surgery through our service and three (14.3 %) died from disease. Overall, 13 patients had radical mastectomy, 92.3 % with adequate margins (>1 cm histologically) and no local recurrence, 9 simple mastectomy 22.2 % with adequate margins and 1 local recurrence and 8 wide local excision with 37.5 % adequate margins and 1 local recurrence. CONCLUSION: For malignant phyllodes patients, the best chance to reduce recurrence and improve survival is adequate excision and radical mastectomy should be considered. For borderline lesions, consideration should be given for referral to a specialist centre and we recommend delayed reconstruction, because of the chance of histological upgrade to malignancy.

The Impact of Adjuvant Chemotherapy on the Long-Term Prognosis of Breast Malignant Phyllodes Tumors: A Propensity Score-Matched Study.

BACKGROUND: Malignant phyllodes tumors (MPTs) are rare breast tumors with high risks of local recurrence and distant metastasis. Surgical intervention is the primary treatment, but the effectiveness of adjuvant therapies is uncertain. This study was designed to analyze the prognostic risk factors associated with MPTs and evaluate the efficacy of postoperative adjuvant chemotherapy. PATIENTS AND METHODS: Patients who were first diagnosed with MPT without distant metastasis and received R0 resection surgery between 1999 and 2023 were included in the present study and stratified into 2 groups: chemotherapy and nonchemotherapy groups. Propensity score matching (PSM) was used to balance baseline characteristics between groups. Kaplan-Meier curves were used to estimate local recurrence-free survival (LRFS) and overall survival (OS). Cox proportional hazards analyses (univariate and multivariate) were conducted to identify prognostic risk factors. RESULTS: We conducted a study involving 145 patients, 31 of whom underwent a total of 12 different chemotherapy regimens following initial surgical resection. Most patients received chemotherapy regimens primarily consisting of anthracyclines, including anthracycline + ifosfamide (AI) or anthracycline + cyclophosphamide/docetaxel (AC-T) regimens. After a median follow-up of 54.5 months, 37 (25.5%) patients experienced local recurrence and 24 (16.6%) experienced distant metastasis. No significant difference was detected in the rates of local recurrence or distant metastasis between the 2 groups. Axillary lymph node positivity was the only risk factor for LRFS, whereas older age, larger tumors, axillary lymph node positivity, local recurrence, and distant metastasis were significantly associated with worse OS. Chemotherapy did not emerge as a protective factor for LRFS (P=.501) or OS (P=.854). After PSM, patients in the chemotherapy group did not exhibit better 5-year LRFS (P=.934) or 5-year OS (P=.328). CONCLUSIONS: According to our retrospective evaluation, postoperative adjuvant chemotherapy was not associated with improved survival in patients with MPTs without distant metastasis.

Phyllodes Tumors of the Breast: Canadian National Consensus Document Using Modified Delphi Methodology.

PURPOSE: Phyllodes tumors are rare breast neoplasms with limited prospective data to guide treatment, leading to heterogeneous management of this disease. We developed National consensus statements using modified Delphi methodology including patients and practitioners across Canada. METHODS: Statements were developed based on a literature review. Two iterations of surveys were distributed with a planned virtual consensus meeting. Panelists were invited from surgery, radiation oncology, medical oncology, pathology, radiology, and plastic surgery. RESULTS: Twenty-three participants attended the virtual conference. One hundred statements regarding diagnostics, pathology, surgical planning, adjuvant therapies, recurrence, surveillance, and patient support were approved with an a priori defined consensus of ≥ 80%. Two tables on locoregional management were developed and approved. The management of borderline phyllodes tumors was a source of uncertainty, and recommendations reflect the lack of evidence in this rare presentation. CONCLUSION: A consensus document containing all approved statements for the care and management of phyllodes tumors was developed to help guide practice and future research.

Breast Sarcomas, Phyllodes Tumors, and Desmoid Tumors: Epidemiology, Diagnosis, Staging, and Histology-Specific Management Considerations.

Breast sarcomas arise from connective tissues of the breast and account for fewer than 1% of all breast malignancies. They can be subclassified as primary breast sarcomas, which arise de novo and are histologically diverse, and secondary breast sarcomas, which arise as a result of radiation or lymphedema and are most commonly angiosarcomas. Two other connective tissue neoplasms that occur within the breast include phyllodes tumors and desmoid tumors, which exhibit a spectrum of behaviors. Malignant phyllodes tumors are biologically similar to primary breast sarcomas, whereas desmoid tumors are technically benign but often locally aggressive. Patients with breast sarcomas often present with a rapidly growing mass or, in cases of radiation-associated angiosarcoma, violaceous cutaneous lesions. Core needle biopsy is generally required to confirm the diagnosis of sarcomas. Staging workup includes MRI and chest imaging, although these are not required in the case of benign phyllodes or desmoid tumors. In general, localized breast sarcomas should be resected, with the extent of resection tailored to histologic subtype. Radiation and chemotherapy can be used in the neoadjuvant or adjuvant setting, but data are limited, so treatment decisions should be made on an individualized basis. Systemic therapy options for metastatic disease and refractory breast desmoids mimic those used for the same histologies when present in other sites. Given the rarity and heterogeneity of breast sarcoma, as well as limited literature describing these entities, expert multidisciplinary evaluation is crucial for optimal decision making.

Management of Pediatric Breast Masses: A Multi-institutional Retrospective Cohort Study.

BACKGROUND: The objective of our study was to describe the workup, management, and outcomes of pediatric patients with breast masses undergoing operative intervention. MATERIALS AND METHODS: A retrospective cohort study was conducted of girls 10-21 y of age who underwent surgery for a breast mass across 11 children's hospitals from 2011 to 2016. Demographic and clinical characteristics were summarized. RESULTS: Four hundred and fifty-three female patients with a median age of 16 y (IQR: 3) underwent surgery for a breast mass during the study period. The most common preoperative imaging was breast ultrasound (95%); 28% reported the Breast Imaging Reporting and Data System (BI-RADS) classification. Preoperative core biopsy was performed in 12%. All patients underwent lumpectomy, most commonly due to mass size (45%) or growth (29%). The median maximum dimension of a mass on preoperative ultrasound was 2.8 cm (IQR: 1.9). Most operations were performed by pediatric surgeons (65%) and breast surgeons (25%). The most frequent pathology was fibroadenoma (75%); 3% were phyllodes. BI-RADS scoring ≥4 on breast ultrasound had a sensitivity of 0% and a negative predictive value of 93% for identifying phyllodes tumors. CONCLUSIONS: Most pediatric breast masses are self-identified and benign. BI-RADS classification based on ultrasound was not consistently assigned and had little clinical utility for identifying phyllodes.

The role of adjuvant radiotherapy in patients with malignant phyllodes tumor of the breast: a propensity-score matching analysis.

BACKGROUND AND OBJECTIVES: Malignant phyllodes tumor of the breast (MPTB) is a kind of rare tumor. Our objective was to investigate the role of adjuvant radiotherapy (RT) in MPTB patients. METHODS: MPTB patients were identified in the Surveillance, Epidemiology and End Results (SEER) database. Kaplan-Meier curves and multivariable Cox proportional hazards analyses were conducted to determine the effect of adjuvant RT on MPTB patients. Propensity-score matching (PSM) method was used to balance the clinicopathological characteristics. RESULTS: A total of 1353 MPTB patients were included in our study and the median follow-up time was 99 months (range: 0-331 months). 16.7% (226) MPTB patients received adjuvant RT, of which 49.1% (111) received mastectomy and 50.9% (115) underwent breast conservation surgery (BCS). Patients receiving adjuvant RT were more likely to be white, with better differentiation and larger tumors (p < 0.05). Multivariate analysis showed that poorer tumor differentiation grade, larger tumor size, and lymph node metastasis were associated with reduced survival while BCS was a protective factor of disease-specific survival (DSS) (HR 0.297; 95% CI 0.184-0.480) and overall survival (OS) (HR 0.445; 95% CI 0.321-0.616). After PSM, survival curves showed patients did not achieve an improved OS or DSS from adjuvant RT (p > 0.05). In subgroup analysis, no subgroup benefited from adjuvant RT. Exploratory analysis showed a survival benefit trend from adjuvant RT in patients with tumor larger than 50 mm and undergoing BCS. CONCLUSIONS: Among MPTB patients, adjuvant RT did not improve OS or DSS. In patients with tumor larger than 50 mm and receiving BCS, a survival benefit trend from adjuvant RT existed.

The Impact of Radiotherapy and Histological Risk Factors on Outcomes in Malignant Phyllodes Tumors.

PURPOSE: Breast phyllodes tumors (PT) are classified into benign, borderline, and malignant grades based on histopathologic characteristics. Specific to malignant PT (MPT), surgery is the mainstay yet relapse rates are high and knowledge gaps in the literature exist regarding adjuvant radiotherapy (RT). We aimed to investigate the outcomes of patients with MPT treated in a tertiary Asian institution. METHODS AND MATERIALS: Patients with nonmetastatic MPT treated from February 1992 to June 2019 were analyzed retrospectively. RT details and relapse fields were studied. Outcomes of patients with and without RT were compared and hazard ratios were calculated using Cox proportional hazard test. Multivariable analysis was performed. RESULTS: Twenty-two of 89 patients received adjuvant RT and the median dose was 60 Gy. In the no-RT group, 4 patients received RT on relapse and had no further recurrences; a further 2 received RT for fungating relapses with good symptomatic relief. RT was only increasingly prescribed after 2004. Median follow-up in the RT group was 3.31 years, compared with 6.17 years in the no-RT group. In the RT group, 15 patients (68.2%) underwent mastectomy, versus 39 (58.2%) in the no-RT group. One patient in the RT group developed an infield local relapse, compared with 21 of 67 patients in the no-RT group. Multivariate model showed that RT decreased risk of locoregional failure (hazard ratio 0.12, 95% confidence interval [CI] 0.02-0.92, P = .04). Three-year locoregional recurrence-free survival was higher in the RT group, 92.3% (95% CI, 78.9-100) versus 73.3% (95% CI, 63.1-85.1) in the no-RT group (P = .03). There were no differences in 3-year survival. CONCLUSIONS: We recommend that adjuvant radiotherapy be discussed for malignant PT for local control, even after mastectomy.

Radiotherapy with apatinib for recurrence of malignant phyllodes tumor of the breast: A case report.

RATIONALE: Malignant phyllodes tumors of the breast are rare, and there are currently no guidelines and a large number of clinical trials to guide the treatment of recurrence tumor. Here we reported a case of radiotherapy with apatinib for the treatment of recurrent malignant phyllodes tumor of the breast. PATIENT CONCERNS: A 58-year-old patient with massive breast mass was admitted to our hospital. Two months after surgical treatment, the tumor recurred in the chest wall scar. DIAGNOSES: The histopathologic diagnoses was right breast malignant phyllodes tumor with chondrosarcomas and osteosarcomas in some areas. INTERVENTIONS: The patient was first treated with surgery. Malignant phyllodes tumor recurred in the chest wall two months after surgery and was treated with radiotherapy and apatinib. OUTCOMES: With surgery, radiotherapy and apatinib treatment, the patient still died within several months. LESSONS: Apatinib and radiotherapy failed to obtain good therapeutic effect in the recurrence of breast malignant phyllodes tumor in this case.

Fibroepithelial Lesions (FELs) of the Breast: Is Routine Excision Always Necessary?

BACKGROUND: When needle core biopsies (NCBs) of the breast reveal fibroepithelial lesions (FELs), excision is often performed to rule out a phyllodes tumor (PT), despite low malignancy rates. Consequently, the natural history of observed FELs is not well described. We analyzed the malignancy risk in excised FELs and the natural history of FELs undergoing active surveillance (AS). METHODS: We retrospectively studied the pathology and imaging records of 215 patients with FELs (n = 252) diagnosed on NCB. Incidence of growth was determined by Kaplan-Meier method. RESULTS: Of 252 FELs, 80% were immediately excised and 20% underwent AS. Of the excised FELs, 198 (98%) were benign: fibroadenoma (FA) or benign breast tissue in 137 (68%), benign PT in 59 (29%), or LCIS in 2 (1%). Borderline PT or malignant lesions were found in 4 (2%). On ultrasound, malignant and borderline PTs were larger than benign lesions [median 3.9 vs 1.3 cm, p = 0.006]. Fifty FELs underwent AS, with a median follow-up of 17 (range 2-79) months. The majority remained stable or decreased in size: at 2 years, only 35% increased in volume by ≥ 50%. Of those tumors undergoing AS that were later excised (n = 4), all were benign. CONCLUSIONS: Almost all FELs (98%) were benign on surgical excision, and the majority undergoing AS remained stable, with benign pathology if later excised. Most FELs on NCB can be safely followed with US, with surgery reserved for patients with FELs that are large, symptomatic, or growing. This could spare most women with FELs unnecessary surgery.

Surgical Margins and Adjuvant Therapies in Malignant Phyllodes Tumors of the Breast: A Multicenter Retrospective Study.

BACKGROUND: The optimal threshold of surgical margins for breast malignant phyllodes tumors (MPTs) and the impact of adjuvant chemotherapy and radiotherapy were investigated. PATIENTS AND METHODS: We conducted a multicenter nationwide retrospective study of all MPT cases with central pathological review within the French Sarcoma Group. Endpoints were local recurrence-free survival (LRFS), metastasis-free survival (MFS), and overall survival (OS) rates. RESULTS: Overall, 212 patients were included in the study. All non-metastatic patients underwent primary surgical treatment, including 58.6% of conservative surgeries. An R0 resection was achieved in 117 patients (59.4%: 26.9% of patients with 1-2 mm margins, 12.2% of patients with 3-7 mm margins, 20.3% of patients with ≥ 8 mm margins). Ninety-four patients (45%) underwent a second surgery (SS) to obtain R0 margins, with a final mastectomy rate of 72.6%. Radiotherapy and chemotherapy were performed in 91 (43.1%) and 23 patients (10.9%), respectively, but were not associated with better outcomes. Mastectomy was significantly associated with better LRFS (p < 0.001). Margins of 0, 1, or 2 mm with SS were associated with better MFS (hazard ratio [HR] 0.3, p = 0.005) and OS (HR 0.32, p = 0.005) compared with margins of 0-1-2 mm without SS. Wider margins (> 8 mm) were not superior to margins of 3-7 mm (3-7 mm vs. > 8 mm; HR 0.81, p = 0.69). Age (HR 2.14, p = 0.038) and tumor necrosis (HR 1.96, p = 0.047) were found to be poor prognostic factors and were associated with MFS. CONCLUSIONS: This study suggests that 3 mm margins are necessary and sufficient for surgical management of MPTs, and emphasizes the importance of SS to obtain clear margins in case of 0-1-2 mm margins. No impact of adjuvant chemotherapy or radiotherapy was detected in this study.

Malignant phyllodes tumors of the breast: A comprehensive literature review.

Malignant phyllodes tumors (MPT) have always been a great deal of controversy among fibroepithelial tumors of the breast. Genetics, histopathology, and tumor behavior on the cellular scale shape their extent of aggressiveness. Diagnosis is based on radiological and pathological findings. Cure is surgical excision. This article reveals the most common clinical indices, which should raise the surgeon's concerns on a benign-looking tumor to further investigate its nature, and the importance of an adequate surgical intervention, preferably done by an oncoplastic breast surgeon, in order to accomplish the ideal outcome for the patient.

Impact of Metastasis Surgery and Alkylating-Agent-Based Chemotherapy on Outcomes of Metastatic Malignant Phyllodes Tumors: A Multicenter Retrospective Study.

BACKGROUND: Metastatic phyllodes tumors have poor prognosis with median overall survival of 11.5 months. The objective of this study is to identify prognostic factors and the best options for management of metastatic malignant phyllode tumors (MMPTs). PATIENTS AND METHODS: A multicentric retrospective study, including cases of MMPT from 10 sarcoma centers, was conducted. The primary end-point was overall survival (OS), and the secondary end-point was the clinical benefit of chemotherapy (CBCT) rate. RESULTS: 51 MMPT patients were included. Median time from diagnosis to metastatic recurrence was 13 months. Management of MMPT consisted in surgery of the metastatic disease for 16 patients (31.3%), radiation therapy of the metastatic disease for 15 patients (31.9%), and chemotherapy for 37 patients (72.5%). Median follow-up was 62.1 months [95% confidence interval (CI) 31-80 months]. Median OS was 11.5 months (95% CI 7.5-18.7 months). On multivariate analysis, two or more metastatic sites [hazard ratio (HR) 2.81, 95% CI 1.27-6.19; p = 0.01] and surgery of metastasis (HR 0.33, 95% CI 0.14-0.78; p = 0.01) were independently associated with OS. The CBCT rate was 31.4% and 16.7% for the first and second lines. Polychemotherapy was not superior to single-agent therapy. Alkylating-agent-based chemotherapy, possibly associated with anthracyclines, was associated with a better CBCT rate than anthracyclines alone (p = 0.049). CONCLUSIONS: The results of this study emphasize the impact of the number of metastatic sites on survival of MMPT patients and the leading role of metastasis surgery in MMPT management. If systemic therapy is used, it should include alkylating agents, which are associated with a better clinical benefit.

Recurrent giant fibroadenomas with transformation to cystosarcoma phyllodes in a 17-year-old girl: a rare case report from Syria.

BACKGROUND: Fibroadenoma is the most prevalent benign breast lesion that generally affects middle-aged women; it is rare in adolescents and younger children. The transformation into malignancy is not common. However, multiple recurrences of rapidly enlarging fibroadenomas suggest a high possibility of transforming into phyllodes tumors, which are uncommon fibroepithelial lesions that account for 0.3-0.5% of female breast tumors and typically present in premenopausal women. CASE PRESENTATION: We report a case of a 17-year-old Syrian girl who previously had three episodes of recurrence of multiple rapidly enlarging fibroadenomas in her left breast and underwent three operations for complete resection of the lesions. However, a few months later, she was readmitted with multiple large masses in the same breast, and pathological findings confirmed a surprising combination of multiple fibroadenomas for the fourth time with a malignant phyllodes tumor (cystosarcoma phyllodes). The patient underwent lumpectomies followed by adjuvant radiotherapy. Long-term follow-up was recommended. CONCLUSION: Our patient had an extraordinary number of episodes of recurrence at a young age and a rare combination of malignant and benign lesions in the same breast with multiple recurrences. We present her unique, very challenging case with the aim of highlighting the importance of clinical correlation, detailed diagnosis, and careful follow-up.

Malignant phyllodes tumor in Lynch syndrome: a case report.

BACKGROUND: Lynch syndrome, or hereditary nonpolyposis colorectal cancer, is an autosomal dominant genetic syndrome that predisposes individuals to multiple cancer types. The known cancers associated with Lynch syndrome include colorectal and endometrial cancers as well as cancers of the stomach, ovary, urinary tract, hepatobiliary tract, pancreas, small bowel, and brain. There are no searchable cases of malignant phyllodes of the breast associated with Lynch syndrome. CASE PRESENTATION: Our patient was a 43-year-old Caucasian woman who felt a lump in her left breast and was found to have a spindle cell neoplasm. Definitive surgery revealed a malignant phyllodes tumor. On the basis of her cancer diagnosis and family history of multiple cancers, a Myriad myRisk Hereditary Cancer® test panel of 25 genes was performed. This testing revealed that she had a heterozygous MSH6 mutation as part of the Lynch syndrome panel. Due to positive margins, the patient received adjuvant chemotherapy with doxorubicin and ifosfamide. She also had a subsequent total abdominal hysterectomy and a bilateral salpingo-oophorectomy for risk reduction. She remains in a high-risk surveillance program. Her family members have been tested, which revealed that her two brothers and daughter also carry the genetic mutation. CONCLUSIONS: This case highlights the importance of genetic testing with rare malignancies because the full scope of phenotypic sequelae for known hereditary syndromes has not been mapped.