Surgical Bedside Electrochemotherapy for Local Control of a Recurrent Phylloid Malignant Breast Tumor: A Case Report.

BACKGROUND: We present the case of a recurrent malignant phyllodes tumor of the breast, after mastectomy and radiotherapy, in which electrochemotherapy (ECT) was applied to the tumor bed, to achieve better local control. CASE REPORT: A 66-year-old woman with a large malignant phyllodes tumor of the right breast with a size of 40 cm underwent right radical mastectomy and right axillary lymph node sampling. One month after surgery, with histologically clear margins, the woman presented with multiple small oval masses in the upper portion of the chest wall, indicating rapid disease progression. A second radical excision with clear margins was performed, followed by adjuvant radiotherapy. Two months after the end of treatment, a new 3-cm mass was present in the right axillary extension. The patient underwent a third extensive debulking surgery. At the end of the resection, ECT was applied on the tumor bed along the extensive skin flaps and resection margins. After eight months of follow-up, breast magnetic resonance imaging and total body computed tomography showed disease recurrence in the anterior portion of the right serratus muscle and in the lungs bilaterally. The area undergoing previous ECT showed no disease recurrence. The patient received two lines of palliative chemotherapy. She died 28 months after diagnosis. At the time of death, the large area treated with ECT was geometrically spared from local disease progression. CONCLUSION: This case report suggests the potential efficacy of ECT at the operating bedside to increase local control in aggressive malignancies.

Organoid models derived from patients with malignant phyllodes tumor of the breast.

PURPOSE: Phyllodes tumor of the breast is a kind of rare neoplasm, which accounts for less than 1% of all breast tumors. Malignant phyllodes tumor (MPT) is the highest risk subtype of phyllodes tumor, and is characterized by the tendency of local recurrence and distant metastasis. The prediction of prognosis and the individual therapy for MPT is still challenging. It's urgent to develop a new reliable in vitro preclinical model in order to understand this disease better and to explore appropriate anticancer drugs for individual patients. METHODS: Two surgically resected MPT specimens were processed for organoid establishment. MPT organoids were subsequently subjected to H&E staining, immunohistochemical analysis and drug screening, respectively. RESULTS: We successfully established two organoid lines from different patients with MPT. The MPT organoids can well retain the histological features and capture the marker expression in original tumor tissues, including p63, vimentin, Bcl-2, CD34, c-Kit, and Ki-67, even after a long-term culture. The dose titration tests of eight typical chemotherapeutic drugs (paclitaxel, docetaxel, vincristine, doxorubicin, cisplatin, gemcitabine, cyclophosphamide, ifosfamide) on the two MPT organoid lines showed patient-specific drug responses and varying IC50 values. Of all the drugs, doxorubicin and gemcitabine showed the best anti-tumor effect on the two organoid lines. CONCLUSION: Organoids derived from MPT may be a novel preclinical model for testing personalized therapies for patients with MPT.

[Which chemotherapy regimen in patients with metastatic phyllodes tumors of the breast? case report]. / Quelle chimiothérapie dans les tumeurs phyllodes métastatiques du sein? rapport de cas.

Phyllodes tumors (PT) of the breast are rare. They can be benign, borderline or malignant. Malignant forms account for 20-30% of PTs, with distant metastases in 10-26% of cases. Chemotherapy is one of the main therapeutic weapons for metastatic phyllodes tumors (MPTs). We here report four cases of MPTs of the breast managed at The Mohammed VI Center For Cancers Treatment in Casablanca from January 2015 to December 2017. The average age of patients ranged from 25 to 45 years. The mode of revelation was represented, in the majority of cases, by the occurrence of a huge breast mass and in all patients the histological diagnosis was based on the examination of mastectomy specimen. Three patients had lung metastases, two had axillary lymph-node metastases, two had bone metastases and only one had liver metastases. All patients received chemotherapy. Doxorubicin monotherapy and doxorubicin-ifosfamide (AI) were used. Only one patient had a very favorable outcome, with radiologic complete response after 3 AI regimens. MPTs of the breast have a poor prognosis. The role of systemic chemotherapy is to be defined, especially since there are no data available on optimal chemotherapy regimen.

Successful Treatment of a Locally Recurrent and Metastatic Malignant Phyllodes Tumor with Accelerated Radiotherapy and Nab-Paclitaxel, Cisplatin, and Liposomal Doxorubicin Chemotherapy.

Phyllodes tumors are rare breast lesions of fibroepithelial origin. Malignant transformation with metastases is linked with poor prognosis. We present a case of a 62-year-old woman with a recurrent malignant phyllodes tumor of the breast and lung metastases. The patient was originally presented with a borderline phyllodes tumor (7.4 cm) of the left breast, treated with wide local excision. A year later, the patient returned with palpable left breast masses. On PET-CT, increased uptake of 18F-FDG by large breast tumors was evident. A right lung lesion of metastatic origin was also present. A simple left breast mastectomy was performed. Histopathological report described 2 malignant phyllodes tumors (7 cm and 6.5 cm). One month later, during the CT simulation for radiotherapy planning, encysted fluid in the chest wall and 2 additional pulmonary lesions of the right lung were identified, confirming progressive lung metastatic disease. Both the chest wall and the regional lymph node area were irradiated with hypofractionated and accelerated radiotherapy. Biweekly chemotherapy with albumin-bound paclitaxel, cisplatin, and liposomal doxorubicin was also prescribed at the start of radiotherapy for 12 cycles. At the end of chemotherapy, complete regression of lung metastases was achieved, and there was no evidence of local recurrence. Within 2 years of follow-up, the patient is free of disease and treatment-related toxicities. Accelerated hypofractionated radiotherapy is effective in the locoregional control of malignant phyllodes tumors. The combination of cisplatin with nab-paclitaxel and liposomal doxorubicin chemotherapy has acceptable toxicity and is highly effective in eradicating metastatic lesions.

Apatinib treatment is effective for metastatic malignant phyllodes tumors of the breast: a case report.

BACKGROUND: We report a rare case of malignant phyllodes tumors (MPT) with partial response to apatinib. CASE PRESENTATION: A 26-year-old woman had a palpable mass in her right breast for over a year. After resection, pathology indicated malignant phyllodes tumor. Eleven months after surgery, she underwent reoperation for a lung nodule, which demonstrated lung metastasis. She refused chemotherapy and was rehospitalized six months later due to leg pain. Pelvic mass biopsy revealed metastatic malignant phyllodes tumor. After concurrent chemoradiotherapy of the pelvic mass, multiple lung metastases emerged. Subsequent treatment with apatinib 500 mg/day resulted in a reduction in mass size and partial response. She survived for more than 8 months. CONCLUSION: The present case showed the potential therapeutic effects of apatinib in patients with MPT.

A Giant Borderline Phyllodes Tumor of Breast With Skin Ulceration Leading to Non-Insular Tumorigenic Hypoglycemia: A Case Report and Literature Review.

Phyllodes tumor (PT) is a special type of breast tumors, including three types: malignant, borderline, and benign. Most of these tumors form unilateral disease and can rapidly increase in size. The occurrence of axillary lymph node metastasis is rare. Tumor-associated hypoglycemia can be divided into non-islet cell tumor and insulinoma. In non-islet cell tumor hypoglycemia (NICTH), a considerable high molecular weight form of insulin like growth factor 2 (IGF-2) is formed, which abnormally binds to insulin receptors in the tissues and causes hypoglycemia. Breast phyllodes tumors with NICTH are rare and first reported in 1983. Surgical resection is the main treatment and hypoglycemia symptoms usually resolve after surgery. Nevertheless, prior to surgery, intravenous glucose infusion is used to maintain blood glucose levels. A female patient presented with a rapidly growing breast mass and was diagnosed with a phyllodes tumor with NICTH at our hospital in August 2020; she was successfully treated through surgical resection. We reviewed the relevant literature to investigate and analyze the relationship between NICTH and phyllodes tumors, as well as optimize its diagnosis and treatment.

Breast Phyllodes Tumors Recruit and Repolarize Tumor-Associated Macrophages via Secreting CCL5 to Promote Malignant Progression, Which Can Be Inhibited by CCR5 Inhibition Therapy.

PURPOSE: Malignant phyllodes tumor (PT) is a fast-progression neoplasm derived from periductal stromal cells of the breast, which currently still lack effective treatment strategies. Our previous studies showed that the high density of tumor-associated macrophages (TAM) plays an important role in the malignant progression of PTs. TAMs secreted large amount of CCL18 to promote myofibroblast differentiation and invasion via binding to its receptor PIPTNM3 on myofibroblasts. Herein, we investigate the mechanism of how TAMs are recruited and repolarized by PTs to drive the malignant progression. EXPERIMENTAL DESIGN: The cytokines secreted by PTs were identified by the cytokine array. The clinical and pathologic correlations of the cytokine with PTs were estimated with IHC. The mechanisms of the cytokine that recruited and polarized the macrophage were explored with a coculture model of primary PT cells and macrophages in vitro and in vivo. The patient-derived xenografts (PDX) of malignant PTs were used to evaluate the therapeutic effect of CCR5 inhibitor. RESULTS: A high level of malignant PT-secreted CCL5 correlated with poor outcome of PTs and could be an independent prognostic factor of PTs. CCL5 bound to its receptor, CCR5, on macrophages thus activated AKT signaling to recruit and repolarize TAMs. Subsequently, the TAMs released CCL18 to further promote the aggressive phenotype of malignant PTs by enhancing and maintaining the myofibroblast differentiation and invasion in vitro and in vivo. In a murine PDX model of human malignant PTs, the CCL5-CCR5 axis blocked by maraviroc, an FDA-proved CCR5 inhibitor, prevented recruitment of monocytes to the tumor and dramatically suppressed tumor growth. CONCLUSIONS: Our findings indicate that malignant PTs recruit and repolarize TAMs through a CCL5-CCR5-driven signaling cascade. Thus, a positive feedback loop of CCL5-CCR5 and CCL18-PIPTNM3 between myofibroblast and TAMs is constituted to drive the malignant progression of PTs. Furthermore, targeting CCR5 with maraviroc represents a potential clinically available strategy to treat malignant PTs.

Case Report: Metastatic Phyllodes Tumor.

This report describes the clinical presentation, imaging findings, and treatment options of a case of metastatic malignant phyllodes.

[A case of malignant phyllodes tumor after surgery for breast cancer].

A 63-year-old woman underwent breast-conserving resection and axillary lymph node dissection for bilateral breast cancer in December 2008. Histopathological diagnosis for the right breast cancer was t=1.3 cm, n=1/29, estrogen receptor (ER) (+), progesterone receptor (PgR) (+), human epidermal growth factor receptor 2(HER2) (-), and that for the left breast cancer was t=1.8 cm, n=9/28, ER (+), PgR (+), and HER2 (-). She was administered adjuvant chemotherapy (4 courses of fluorouracil, epirubicin, and cyclophosphamide [FEC 100] and 4 courses of docetaxel[DTX], 75 mg/m²), letrozole, and bilateral radiation therapy for the remaining breast tissue. She noticed a mass in the left breast in December 2013. Fine-needle aspiration cytology and core-needle biopsy indicated a malignant phyllodes tumor or stromal sarcoma. Positron emission tomography-computed tomography (PET-CT) revealed the accumulation of fluorodeoxyglucose (FDG) only in the mass. The tumor enlarged rapidly to more than 5 cm during the pre-operative period. In January 2014, the patient underwent left mastectomy. The histopathological diagnosis was malignant phyllodes tumor in the left breast, with a tumor diameter of 7 cm, and negative margins. Presently, 6 months after the operation, the patient is alive without recurrence.

Challenges in management of phyllodes tumors of the breast: a retrospective analysis of 150 patients.

INTRODUCTION: Phyllodes tumors (PT) of the breast seem to get pre-operatively misdiagnosed as fibroadenomas resulting in inadequate resections and high local recurrence rates. MATERIALS AND METHODS: Data of 150 patients with PT of the breast managed from January, 2003 to February, 2013 were retrospectively analyzed. Statistical analysis performed using SPSS version 17 (Pearson Chi-square test and analysis of variance test for analysis). AIM: The aim of this study is to compare clinico-pathological profile and recurrence rates in patients with benign (B), borderline malignant (BL) and malignant (M) PT. RESULTS: In a total of 150 patients with PT (n = 77 B, n = 24 BL, n = 49 M), mean age was 36.92, 44.04 and 40.46 years respectively (P 0.015) and mean tumor size being 8.15 cm, 14.7 cm and 12.9 cm respectively (P 0.000). Pre-operatively cytology suggestive of PT in 24% patients with B PT and 63% in M PT; core tissue biopsy suggestive of PT in 85.4% patients with B PT and 100% in M PT. Recurrence seen in 34.7% out of which 32.7% were post-lumpectomy performed elsewhere. Majority of B PT had lumpectomy (49.3%)/wide local excision (WLE, 31.2%) compared with M PT where 55.1% had simple mastectomy (SM) due to large tumor size. Local recurrence was more in M PT (53%) compared with B PT (20%). We found recurrence rates in L (39.3%) compared with WLE (27.3%) and SM (33.9%) (P 0.049). CONCLUSIONS: Larger tumor size, incomplete resection and M/BL histology predicted higher recurrence in PT. Core biopsy is much more accurate than fine needle cytology in the diagnosis.

Unusual aggressive breast cancer: metastatic malignant phyllodes tumor.

For the year of 2012, it has been estimated that breast cancer will account for the greatest number of newly diagnosed cancers and the second highest proportion of cancer related deaths among women. Breast cancer, while often lumped together as one disease, represents a diverse group of malignancies with different imaging findings, histological appearances and behavior. While most invasive primary breast cancers are epithelial derived adenocarcinomas, rare neoplasms such as the phyllodes tumor may arise from mesenchymal tissue. Compared to the breast adenocarcinoma, the phyllodes tumor tends to affect a younger population, follows a different clinical course, is associated with different imaging and histological findings and is managed distinctively. There may be difficulty in differentiating the phyllodes tumor from a large fibroadenoma, but the mammographer plays a key role in reviewing the clinical and imaging data in order to arrive at the correct diagnosis. Early diagnosis with proper surgical management can often cure non-metastatic phyllodes tumors. However, in rare cases where metastasis occurs, prognosis tends to be poor. This report describes the presentation, imaging findings and management of a metastatic malignant phyllodes tumor.

Immunomarker studies of fine-needle cytopuncture cell blocks for tumor response prediction after preoperative chemotherapy and prognosis in operable nonmetastatic primary breast carcinoma.

Neo-adjuvant chemotherapy of breast cancer provides an opportunity to evaluate predictive factors at initial tumor biopsy. We evaluated these factors on cell blocks obtained by diagnostic fine-needle cytopuncture (FNC), with respect to tumor regression and outcome. A prospective study (1996-2003, median follow-up 82 months) involved 163 patients with breast carcinoma (T2 ≥ 3 cm, T3, T4 noninflammatory) diagnosed by means of FNC. Malignancy, cytologic grade, and the presence of lymphocytes were determined on cytologic smears. Ki67, estrogen receptor (ER), progesterone receptor (PgR), HER2, and p53 expression was assessed on cell blocks by means of immunohistochemistry. All the patients received anthracycline-based chemotherapy. A combined clinical and pathologic tumor regression score was calculated. Twelve cases (7.5%) showed a complete regression, 72 cases (44%) a partial regression and 79 cases (48.5%) no regression. Factors predictive of regression were high grade, presence of lymphocytes, pN0, high Ki67 expression, hormone receptor negativity, and the "triple negative" phenotype. In univariate analysis 5-year metastasis-free survival rate (MFS) correlated with cytologic grade, pN, ER, and p53 status, while overall survival (OS) correlated with cytologic grade, type of surgery, pN, and ER status. In multivariate analysis, MFS was significantly influenced by the regression score, Ki67, age, ER status, pN, HER2, and initial tumor size. Except for age, the same parameters correlated with OS. FNC with the cell block technique is a rapid, minimally invasive, reliable, and inexpensive method for analyzing predictive biomarkers, and may thus be useful in the management of breast cancer patients requiring neo-adjuvant chemotherapy.

Phyllodes tumor of the breast.

We present a case of 49-year-old woman who presented with a three month history of progressive right-sided breast pain and swelling and was found with bulky tumor at her initial presentation. She was diagnosed with phyllodes tumor of her breast and treated initially with neoadjuvant chemotherapy and mastectomy. We discuss recent advances in diagnosis and management of breast phyllodes tumors.

Focus on haematogenous dissemination of the malignant cystosarcoma phylloides: institutional experience.

INTRODUCTION: Cystosarcoma phylloides (CSP) is a fibro-epithelial neoplasm of the breast. Not all CSP cases present as malignant tumors; they are therefore classified as benign, malignant, and borderline subtypes according to the WHO classification. The classification is based on several histopathological features of the neoplasm, such as mitosis rate or invasive growth of the tumor. The progression of this disease is mainly influenced by the classification of their degree. In western countries, this tumor entity usually occurs between 50 and 60 years of age. The major problem in the handling of these patients is the high local recurrence rate, whereas haematogenous metastasis is seldom seen. We therefore report three cases of haematogenous spread in a group of eight patients (two borderline and six malignant cases of CSP). MATERIALS AND METHODS: In this study, we investigated all patients suffering from malignant or borderline CSP, between May 1995 and January 2009, who were under the care of the Department of Gynecology and Obstetrics, University Hospital, Ulm. A written and informed consent was obtained from all patients included in this retrospective study. During this period, eight patients, fulfilling the criteria discussed before, were under the care of the Department of Gynecology and Obstetrics. All therapeutic decisions were taken by the interdisciplinary tumor board of the department (after 1999). RESULTS: In the retrospective analysis of our study group, we found a high percentage of haematogenous metastasis that was always accompanied with a very poor prognosis in malignant CSP patients. Those patients always died within a short period of time. Two of these patients showed, while they underwent initial surgery, no metastatic suspect lesions and underwent R0 resection; both received a radical mastectomy. One patient already showed lung metastasis while undergoing first line surgery, because she initially declined surgery. We therefore speculate that postoperative adjuvant chemotherapy could lead to a favorable outcome in high risk patients, concerning the development of haematogenous metastasis.

Extreme delay in care for enlarging breast mass.

Phyllodes tumor (PT) of the breast is an uncommon fibroepithelial tumor accounting for 0.37% of primary breast cancers. Most PT are <5.0 cm, averaging 4-7 cm. We present a case of PT measuring 28 cm in diameter with an extreme computed tomography image with tumor size larger than the adjacent thoracic circumference. A 59-year-old uninsured woman without significant medical history presented with a massive ulcerated chest wall tumor. The mass was resected, and microscopic examination demonstrated spindled cells within a myxoid stroma, consistent with PT.

Adjuvant chemotherapy with doxorubicin and dacarbazine has no effect in recurrence-free survival of malignant phyllodes tumors of the breast.

The purpose of this study was to evaluate the role of adjuvant chemotherapy in malignant phyllodes tumors of the breast treated at the Instituto Nacional de Cancerología of Mexico. Twenty-eight patients with malignant phyllodes tumors of the breast enrolled in a observational study from January 1993 to December 2003 to receive four cycles of adjuvant chemotherapy with doxorubicin 65 mg/m(2) over 48 hours intravenous infusion and dacarbazine 960 mg/m(2) over 48 hours intravenous infusion (n = 17) versus observation (n = 11). All patients had surgical resection, and 38% had an axillary dissection. Seven patients (25%) received adjuvant radiotherapy. Log-rank test was used to test for differences in recurrence-free survival (RFS). The median patient age was 42 years (range, 23-76 years). The median tumor size was 13 cm (range, 3-30 cm), and 46% of the tumors were in the left breast. At a median follow-up of 15 months (range, 2-81 months), there were seven recurrences and five deaths. The 5 year RFS rate was 58% (95% CI = 36% and 92%) for the patients who received adjuvant therapy and 86% (95% CI = 63% and 100%) for the patients who did not (p = 0.17). The median survival after recurrence was 6.5 months. Adjuvant chemotherapy with doxorubicin and dacarbazine did not affect patient survival. Future studies to identify relevant molecular targets should be implemented in order to define effective therapies for phyllodes tumors of the breast.