Ern Y Tan, Puay Hoon Tan, Tan Puay Hoon, Wei S Yong, Hwee B Wong, Gay Hui Ho, Ho G Hui, Allen W Y Yeo, Chow Y Wong
Recurrent phyllodes tumours of the breast: pathological features and clinical implications.
ANZ J Surg. 2006 Jun;76(6):476-80. doi: 10.1111/j.1445-2197.2006.03754.x.
Abstract/Text
BACKGROUND: Phyllodes tumours (PT) of the breast are fibro-epithelial neoplasms that are known to recur locally in up to 19% of patients. The failure to achieve adequate surgical margins is an important risk factor for local recurrence. This, however, is a common problem as PT are clinically similar to the more common fibro-adenoma and are therefore often locally excised without any gross surgical margins. It is still debatable as to whether it is necessary to subject the patient to repeat surgery to obtain pathologically negative margins after a diagnosis of a benign or borderline PT is made. Although the majority of recurrences are histologically similar to the initial tumour, a malignant recurrence is possible. Malignant tumours can metastasize through the haematogenous route and metastases are associated with a poor prognosis as they are poorly responsive to conventional chemotherapy.
METHODS: We retrospectively reviewed 37 women who presented with local recurrence over a 10-year period to the Singapore General Hospital. Data, including age at the time of diagnosis, clinical presentation, histological features, type of surgery carried out, clinical progression and characteristics of locally recurrent disease, were analysed. Comparisons were made between those with benign, borderline and malignant tumours, as well as between those who developed a malignant recurrence and those who did not.
RESULTS: The mean age at the time of diagnosis was 39.6 +/- 7.4 years and the mean tumour size was 6.0 +/- 5.1 cm. A total of 22 patients were classified as having benign tumour, 9 as having borderline tumour and 6 as having malignant tumour. Tumour grade did not influence the tumour size, the adequacy of surgical margins or the time interval to local recurrence or the number of recurrences. Local recurrence occurred after a median interval of 20 months. Although malignant tumours tended to recur earlier, this was not found to be statistically significant. The majority of recurrent tumours were histologically similar to the initial tumour; however, seven patients (19%) developed a malignant recurrence from an initially benign or borderline tumour. Although these tumours were larger, recurred more frequently and within a shorter interval, no significant predictive factor was found on multivariate analysis. Distant metastasis developed only in patients with malignant tumours and accounted for all three mortalities in the study.
CONCLUSIONS: It may be acceptable to use an expectant management towards benign and borderline tumours that are excised without adequate surgical margins. However, surgery for locally recurrent tumours, as well as malignant tumours, should aim to achieve adequate surgical margins to reduce the risk of local recurrence, particularly that of a malignant recurrence.
Sammy Al-Benna, Kerstin Poggemann, Hans-Ulrich Steinau, Lars Steinstraesser
Diagnosis and management of primary breast sarcoma.
Breast Cancer Res Treat. 2010 Aug;122(3):619-26. doi: 10.1007/s10549-010-0915-y. Epub 2010 May 18.
Abstract/Text
Primary sarcoma of the breast is an extremely rare and heterogeneous disease. The rarity of this tumour limits most studies to small retrospective case reviews and case reports and has made clinicopathological study difficult. This article reviews the current literature on the diagnosis and management of breast sarcoma. The optimal treatment of breast sarcoma involves a multidisciplinary team prior to the initiation of treatment. Patients with tumours less than 5 cm that are easily resectable should undergo complete resection to the extent required to provide negative surgical margins. Negative surgical margins are more important for local recurrence and overall survival than the extent of surgical resection. Thus, neoadjuvant chemotherapy should be considered in order to shrink the tumour and help obtain negative surgical margins. Whether chemotherapy is indicated is primarily determined by tumour size. There is evidence that tumours larger than 5 cm are associated with an elevated risk of systemic failure and a poor prognosis. After surgical resection, patients with chemosensitive tumours should undergo additional adjuvant chemotherapy to treat micrometastatic disease. Radiation therapy should be used to improve local control in cases in which the tumour is larger than 5 cm and in cases with positive surgical margins. We propose to treat the patients according to the clinical practice guidelines in use for soft tissue sarcomas and address them to a reference centre for sarcoma. The appropriate treatment of breast sarcoma requires a multidisciplinary team approach necessitating experienced sarcoma surgeons, pathologists, radiotherapists and medical oncologists. Treating rare tumours in the same place should permit us to standardise pathological data and to include patients into multicentric radiotherapy or chemotherapy protocols to improve overall survival.
Grishma R Sheth, Lee D Cranmer, Benjamin D Smith, Lauren Grasso-Lebeau, Julie E Lang
Radiation-induced sarcoma of the breast: a systematic review.
Oncologist. 2012;17(3):405-18. doi: 10.1634/theoncologist.2011-0282. Epub 2012 Feb 14.
Abstract/Text
INTRODUCTION: Radiation-induced sarcoma (RIS) is a rare, aggressive malignancy. Breast cancer survivors treated with radiotherapy constitute a large fraction of RIS patients. To evaluate evidenced-based practices for RIS treatment, we performed a systematic review of the published English-language literature.
METHODS: We performed a systematic keyword search of PubMed for original research articles pertaining to RIS of the breast. We classified and evaluated the articles based on hierarchical levels of scientific evidence.
RESULTS: We identified 124 original articles available for analysis, which included 1,831 patients. No randomized controlled trials involving RIS patients were found. We present the best available evidence for the etiology, comparative biology to primary sarcoma, prognostic factors, and treatment options for RIS of the breast.
CONCLUSION: Although the evidence to guide clinical practice is limited to single institutional cohort studies, registry studies, case-control studies, and case reports, we applied the available evidence to address clinically relevant questions related to best practice in patient management. Surgery with widely negative margins remains the primary treatment of RIS. Unfortunately, the role of adjuvant and neoadjuvant chemotherapy remains uncertain. This systematic review highlights the need for additional well-designed studies to inform the management of RIS.
Taletha B Smith, Michael Z Gilcrease, Lumarie Santiago, Kelly K Hunt, Wei T Yang
Imaging features of primary breast sarcoma.
AJR Am J Roentgenol. 2012 Apr;198(4):W386-93. doi: 10.2214/AJR.11.7341.
Abstract/Text
OBJECTIVE: This purpose of this study is to describe the imaging findings in patients who presented with a diagnosis of primary breast sarcoma.
MATERIALS AND METHODS: A search was performed of the pathology database at a single institution for patients with a histopathologic diagnosis of primary breast sarcoma or pure sarcomatoid carcinoma and who underwent preoperative mammography, sonography, or MRI. Patients with malignant phyllodes tumors were excluded. The imaging studies were retrospectively reviewed using the American College of Radiology BI-RADS lexicon. We documented clinical presentation, histopathologic characteristics, axillary nodal status, and the presence of distant metastases.
RESULTS: Twenty-four women were included in the study; their mean age was 56 years (range, 21-86 years), and the mean tumor size was 6.1 cm (range, 0.9-15 cm). Only one tumor was identified in each patient. The predominant mammographic finding was a noncalcified oval mass with indistinct (9/14 [64%]) margins. Sonography most commonly revealed an oval (19/22 [86%]) solid mass with indistinct margins (17/22 [77%]). The masses were frequently hypoechoic (18/21 [86%]) and hypervascular (17/20 [85%]) and had posterior acoustic enhancement (13/21 [62%]). MRI showed a round or oval T2-hyperintense mass with irregular margins in four of five (80%) patients, and inhomogeneous enhancement was most common (3/4 [75%]).
CONCLUSION: Primary breast sarcoma has imaging features that are not typically seen in infiltrating ductal carcinoma. A large oval hypervascular mass with indistinct margins should raise the suspicion for a primary breast sarcoma and prompt biopsy.
Marlon A Guerrero, Billy R Ballard, Ana M Grau
Malignant phyllodes tumor of the breast: review of the literature and case report of stromal overgrowth.
Surg Oncol. 2003 Jul;12(1):27-37.
Abstract/Text
Cystosarcoma phyllodes constitutes only 0.3-0.9% of all breast tumors. The term "sarcoma" was initially used because of its fleshy appearance, a more modern term is Phyllodes tumor (PT). The behavior of PT constitutes a spectrum from benign and locally recurrent to malignant and metastatic. In a general surgical series, 6.2% of the tumors were malignant. The microscopic appearance of PT is that of epithelial elements and connective tissue stroma. Malignancy is determined by characteristics of the stroma. The metastatic spread of malignant PT is mainly hematogenous to lung, with infrequent lymphatic involvement. Wide local excision with 2 cm margins is the treatment of choice. In 20% of both benign and malignant cases, PT will locally recur. There is no proven benefit of radiation or chemotherapy, although radiotherapy may be useful in selected cases. We present a case of a sarcomatous overgrowth in a malignant phyllodes tumor involving multiple histologic types.
Naruto Taira, Daisuke Takabatake, Kenjiro Aogi, Shozo Ohsumi, Shigemitsu Takashima, Rieko Nishimura, Norihiro Teramoto
Phyllodes tumor of the breast: stromal overgrowth and histological classification are useful prognosis-predictive factors for local recurrence in patients with a positive surgical margin.
Jpn J Clin Oncol. 2007 Oct;37(10):730-6. doi: 10.1093/jjco/hym099. Epub 2007 Oct 11.
Abstract/Text
BACKGROUND: The local recurrence rate of phyllodes tumors is high and ensuring a sufficient surgical margin is considered important for local control. However, the preoperative diagnosis rate of phyllodes tumors is low and we often encounter cases in which a sufficient surgical margin is not achieved, since in routine medical practice the lesion may not be diagnosed as phyllodes tumor until postoperative biopsy of a mammary mass. Furthermore, there are no established therapeutic guidelines for surgical stump-positive phyllodes tumors. We reviewed the outcomes of excision of phyllodes tumors to investigate factors involved in local recurrence and to determine the indication for re-excision in stump-positive cases.
METHODS: The subjects were 45 patients treated for phyllodes tumors at our institution from January 1980 to July 2005. Age, tumor size, surgical method, stromal cellular atypia, mitotic activity, stromal overgrowth, histological classification and surgical stump status were analyzed.
RESULTS: Median age was 45 years old (range 28-75) and tumor size was 1-17 cm (median 3.5 cm). Pathologic diagnoses were benign, borderline and malignant in 31, five and nine cases, respectively, and the surgical stump was negative in 27 lesions and positive in 15. Median follow-up was 101 months (range 1-273), with local recurrence in six cases and distant metastasis in one. The local recurrence-free rate was 88, 88 and 84% and the disease-free rate was 85, 85 and 81% after 5, 10 and 15 years, respectively. Overall 10-year survival was 97%. In univariate analysis, a positive surgical margin, stromal overgrowth and histological classification were predictive factors for local recurrence after breast-conservation surgery (P = 0.0034, 0.0003, 0.026). A positive surgical stump was the only independent predictor of local recurrence in multivariate analysis (RR 0.086; 95% CI 0.01-0.743, P = 0.012). Stromal overgrowth was a predictive factor for local recurrence in cases with a positive surgical margin (P = 0.0139).
CONCLUSION: Wide excision is the preferred therapy for phyllodes tumor and preoperative diagnosis is important for good local control. Re-excision is recommended in cases with a positive surgical margin and stromal overgrowth and malignancy.
Gianluca Spitaleri, Antonio Toesca, Edoardo Botteri, Luca Bottiglieri, Nicole Rotmensz, Sabrina Boselli, Claudia Sangalli, Chiara Catania, Francesca Toffalorio, Cristina Noberasco, Angelo Delmonte, Alberto Luini, Paolo Veronesi, Marco Colleoni, Giuseppe Viale, Stefano Zurrida, Aron Goldhirsch, Umberto Veronesi, Tommaso De Pas
Breast phyllodes tumor: a review of literature and a single center retrospective series analysis.
Crit Rev Oncol Hematol. 2013 Nov;88(2):427-36. doi: 10.1016/j.critrevonc.2013.06.005. Epub 2013 Jul 17.
Abstract/Text
PURPOSE: Complete surgical resection is the standard treatment for localized breast phyllodes tumors. Post-surgical treatments are still a matter of debate. We carried out an overview of the literature to investigate the clinical outcome of patients with phyllodes tumor. A retrospective analysis of mono-institutional series has been included as well.
METHODS: We reviewed all the retrospective series reported from 1951 until April 2012. We analyzed cases treated at our institution from 1999 to 2010.
RESULTS: Eighty-three articles (5530 patients; 1956 malignant tumors) were reviewed. Local recurrences were independent of histology. Distant recurrences were more frequent in the malignant tumors (22%). A total of 172 phyllodes tumors were included in the retrospective analysis.
DISCUSSION: Prognosis of phyllodes tumors is excellent. There are no convincing data to recommend any adjuvant treatment after surgery. Molecular characterization may well provide new clues to permit identification of active treatments for the rare poor prognosis cases.
Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Cha Kyong Yom, Wonshik Han, Sung-Won Kim, So Yeon Park, In Ae Park, Dong-Young Noh
Reappraisal of conventional risk stratification for local recurrence based on clinical outcomes in 285 resected phyllodes tumors of the breast.
Ann Surg Oncol. 2015 Sep;22(9):2912-8. doi: 10.1245/s10434-015-4395-5. Epub 2015 Feb 5.
Abstract/Text
PURPOSE: To ensure a surgical margin of ≥1 cm for the effective treatment of phyllodes tumors of the breast (PTB) a second resection has been recommended, but the outcomes of an extensive series of cases employing the aforementioned criterion cast doubt on this clinical approach. The aim of this study was to identify the local recurrence (LR) risk factors of PTB and determine future optimal surgical treatment according to verified risks.
METHODS: All cases given a diagnosis of PTB, and resected between 1989 and 2008, were retrospectively evaluated. Clinicopathologic data and clinical outcomes were analyzed and stratified according to the risks for LR.
RESULTS: All 285 cases were categorized as benign (191, 67.0 %), borderline (61, 21.4 %), or malignant (33, 11.6 %). Median follow-up was 6.7 years and there were 20 LRs during follow-up. All benign PTB recurred as benign PTB lesions. Mitoses (p < 0.001) and tumor size (p = 0.021) were independent prognostic factors for LR in multivariate analysis. Neither margin status (p = 0.758) nor type of surgery (p = 0.922) had any significance for LR. In the risk stratification for LR, PTB ≤5 cm in size with ≥10 mitoses/10 high-power fields (HPFs) had the highest LR rate (55.6 %) compared with all other subgroups (p < 0.001).
CONCLUSIONS: It is recommended a wide excision and clear margin of 1 cm be ascertained in only small PTB with frequent mitoses, if necessary by means of a second surgery, which could be considered in order to avoid the risk of LR in this distinct and limited group.
Yiwen Lu, Yanbo Chen, Liling Zhu, Paul Cartwright, Erwei Song, Lisa Jacobs, Kai Chen
Local Recurrence of Benign, Borderline, and Malignant Phyllodes Tumors of the Breast: A Systematic Review and Meta-analysis.
Ann Surg Oncol. 2019 May;26(5):1263-1275. doi: 10.1245/s10434-018-07134-5. Epub 2019 Jan 7.
Abstract/Text
BACKGROUND: This systematic review and meta-analysis aimed to investigate local recurrence (LR) rates among the three grades (benign, borderline, and malignant) of phyllodes tumors (PTs). The study also assessed various risk factors for LR.
METHODS: Electronic articles published between 1 January 1995 and 31 May 2018, were searched and critically appraised. The authors independently reviewed the abstracts and extracted data for LR rates and LR risk factors.
RESULTS: The review incorporated 54 studies with 9234 individual cases. The pooled LR rates were 8% for benign, 13% for borderline, and 18% for malignant PTs. The risk of LR was significantly increased by borderline versus benign PTs (odds ratio [OR] 2.00; 95% confidence interval [CI] 1.68-2.38) and malignant versus borderline PTs (OR 1.28; 95% CI 1.05-1.55). The significant risk factors for LR were mitoses, tumor border (infiltrating vs. pushing), stromal cellularity (moderate/severe vs. mild), stromal atypia (severe vs. mild/absent), stromal overgrowth (severe vs. mild/absent), and tumor necrosis (positive vs. negative). Age and tumor size were not associated with LR risk. The subgroup analysis showed that breast-conserving surgery versus mastectomy and positive versus negative surgical margins were significantly associated with an increased LR risk only in malignant PTs.
CONCLUSIONS: The risk of LR was significantly increased from benign to borderline to malignant PTs. Mitoses, tumor border, stromal cellularity, stromal atypia, stromal overgrowth, tumor necrosis, type of surgery, and surgical margin status may be risk factors for LR. Different management strategies could be considered for different PT grades.
土井原博義: 乳癌以外の悪性腫瘍. 乳腺腫瘍学, 日本乳癌学会編, 金原出版, 2012; 264-267.
Jeffrey K Mito, Devarati Mitra, Constance M Barysauskas, Adrián Mariño-Enriquez, Elizabeth A Morgan, Christopher D M Fletcher, Chandrajit P Raut, Elizabeth H Baldini, Leona A Doyle
A Comparison of Outcomes and Prognostic Features for Radiation-Associated Angiosarcoma of the Breast and Other Radiation-Associated Sarcomas.
Int J Radiat Oncol Biol Phys. 2019 Jun 1;104(2):425-435. doi: 10.1016/j.ijrobp.2019.01.082. Epub 2019 Jan 29.
Abstract/Text
PURPOSE: Radiation-associated sarcomas (RAS) are considered to have a poor prognosis. Although the incidence is anticipated to rise, contemporary data regarding predictors of outcomes are few. We performed a retrospective analysis to identify RAS prognostic factors and subset analyses for radiation-associated angiosarcoma arising after treatment for breast cancer (RAAB) and other RAS subtypes (other-RAS).
METHODS AND MATERIALS: Patients with localized RAS evaluated at an institutional multidisciplinary sarcoma clinic were identified. Clinical and histologic review was performed, and outcomes were assessed to identify prognostic features. A subset of cases underwent molecular analysis by next-generation sequencing.
RESULTS: Among 176 patients, histologic subtypes of RAS included angiosarcoma (41%), undifferentiated/unclassified sarcoma (40%), leiomyosarcoma (8%), malignant peripheral nerve sheath tumor (6%), and osteosarcoma (2%). Sixty-seven patients (38%) had RAAB, and 109 (62%) had other-RAS. RAAB had significantly shorter latency from time of initial radiation compared with other-RAS (8 vs. 15 years; P < .001). Treatment approaches included surgery (91%), chemotherapy (44%), and radiation therapy (27%). Median follow-up was 3.2 years; 3-year overall survival (OS) was 74%. On multivariate analysis, positive margins (P < .0001), deep tumor location (intrathoracic/intra-abdominal, P = .002), and high grade (P < .0001) were associated with worse OS. In particular, 3-year OS with negative versus positive margins was 90% versus 66%. Patients with RAAB versus other-RAS showed a trend for higher 3-year OS (84% vs 68%; P = .09), significantly higher 3-year metastasis-free survival (82% vs 67%; P = .001), but similar 3-year local recurrence-free survival (54% vs 61%; P = .28). Next-generation sequencing identified overall low tumor mutational burden, recurrent MYC amplification in RAAB, and few clinically actionable mutations.
CONCLUSIONS: Margin negative excision, superficial tumor location, and low tumor grade are determinants of improved OS for RAS, suggesting that complete surgical excision, when possible, is an optimal component of treatment. RAAB is a clinicopathologically distinct type of RAS with shorter latency from initial RT, different recurrence patterns, and when aggressively managed has potentially better outcomes compared with other-RAS.
Copyright © 2019 Elsevier Inc. All rights reserved.
日本乳癌学会編:乳癌診療ガイドライン1.治療編 2018年版、p299-301、BQ14、葉状腫瘍と診断された場合に外科的切除が勧められるか、金原出版、2018.
Richard J Barth, Wendy A Wells, Sandra E Mitchell, Bernard F Cole
A prospective, multi-institutional study of adjuvant radiotherapy after resection of malignant phyllodes tumors.
Ann Surg Oncol. 2009 Aug;16(8):2288-94. doi: 10.1245/s10434-009-0489-2. Epub 2009 May 8.
Abstract/Text
BACKGROUND: Malignant phyllodes tumors of the breast are unusual neoplasms, with an incidence of approximately 500 cases annually in the United States. Published local recurrence rates after margin-negative breast-conserving resections of borderline malignant and malignant phyllodes tumors are unacceptably high, at 24 and 20%, respectively. It is uncertain whether radiotherapy after resection of phyllodes tumors is beneficial.
METHODS: We prospectively enrolled patients who were treated with a margin-negative breast-conserving resection of borderline malignant or malignant phyllodes tumors to adjuvant radiotherapy. The primary endpoint was local recurrence.
RESULTS: Forty-six women were treated at 30 different institutions. The mean patient age was 49 years (range, 18-76 years). Thirty patients (65%) had malignant phyllodes tumors; the rest were borderline malignant. The mean tumor diameter was 3.7 cm (range, .8-11 cm). Eighteen patients had a negative margin on the first excision. The median size of the negative margin was .35 cm (range, <.1-2 cm). Twenty-eight patients underwent a re-excision because of positive margins in the initial resection. Two patients died of metastatic phyllodes tumor. During a median follow-up of 56 months (range, 12-129 months), none of the 46 patients developed a local recurrence (local recurrence rate, 0%; 95% confidence interval, 0-8).
CONCLUSIONS: Margin-negative resection combined with adjuvant radiotherapy is very effective therapy for local control of borderline and malignant phyllodes tumors. The local recurrence rate with adjuvant radiotherapy was significantly less than that observed in reported patients treated with margin-negative resection alone.
Shiyan Zeng, Xindan Zhang, Dejuan Yang, Xiaoyi Wang, Guosheng Ren
Effects of adjuvant radiotherapy on borderline and malignant phyllodes tumors: A systematic review and meta-analysis.
Mol Clin Oncol. 2015 May;3(3):663-671. doi: 10.3892/mco.2015.503. Epub 2015 Feb 6.
Abstract/Text
The standard treatment for borderline and malignant phyllodes tumors is wide local excision (margins ≥1 cm), in the context of either breast-conserving surgery (BCS) or total mastectomy (TM). Due to the high risk of local recurrence (LR) following surgical intervention alone, the addition of adjuvant radiotherapy (RT) has been previously investigated; however, the conclusions have been inconsistent. This systematic review and meta-analysis was designed to assess the efficacy of adjuvant RT for borderline and malignant phyllodes tumors. Pubmed and Web of Science were systematically searched to identify relevant studies assessing the effect of adjuvant RT on borderline and malignant phyllodes tumors from the inception of this technique through May, 2014. A total of 8 studies were identified among 332 citations. In this meta-analysis, patients who received adjuvant RT had a lower relative risk of LR [hazard ratio (HR) = 0.43, 95% confidence interval (CI): 0.23-0.64]. The absolute risk difference was 10.1% (95% CI: 4.9-17.6), corresponding to a number needed to treat of 10. Our pooled meta-analysis clearly demonstrated a decreased risk of LR in patients with borderline and malignant phyllodes tumors who received RT following BCS (HR=0.31, 95% CI: -0.10-0.72). However, the combined HR for LR in the TM group did not demonstrate that adjuvant RT was superior to no RT (HR=0.68, 95% CI: -0.28-1.64). No significant differences were observed in overall survival (OS) or disease-free survival (DFS) between the two groups. Our analysis suggested that adjuvant RT for borderline and malignant phyllodes tumors decreased the LR rate in patients undergoing BCS. However, adjuvant RT was not found to exert an effect on OS or DFS.
[www.nccn.org NCCN Clinical Practice Guidelines in Oncology. Breast Cancer. ver. 1. 2018.].
Flavia Morales-Vásquez, Ana Maria Gonzalez-Angulo, Kristine Broglio, Horacio N Lopez-Basave, Dolores Gallardo, Gabriel N Hortobagyi, Jaime G De La Garza
Adjuvant chemotherapy with doxorubicin and dacarbazine has no effect in recurrence-free survival of malignant phyllodes tumors of the breast.
Breast J. 2007 Nov-Dec;13(6):551-6. doi: 10.1111/j.1524-4741.2007.00510.x.
Abstract/Text
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.
Yao Tian, Xiaofeng Liu, Yingxi Li, Qingxiang Meng, Yumian Jia, Baichuan Wang, Xianghui He
Analysis of Clinicopathological Characteristics and Prognosis of Carcinosarcoma of the Breast.
Breast J. 2022;2022:3614979. doi: 10.1155/2022/3614979. Epub 2022 Jul 1.
Abstract/Text
Background: Few cases of carcinosarcoma of the breast have been reported because of its low incidence rate and rapid progression. Seeking effective therapeutic methods becomes urgent in clinical practice. This study was aimed to investigate the clinical characteristics of carcinosarcoma of the breast and to explore proper therapeutic methods for patients with this rare tumor.
Methods: We conducted a retrospective analysis on 47 patients with carcinosarcoma of the breast receiving treatment in our hospital from 2003 to 2020. Most of these patients received primary surgery followed by adjuvant chemotherapy, while four patients had lumpectomy only. Statistics showed no preference in age and menopausal status of patients.
Results: The overall survival rate and progression-free survival rate of all patients at a median follow-up time of 33 months were 63.8% and 57.4%, respectively. Tumor size at diagnosis and chemotherapy strategies were both significant prognostic factors in reference to disease-free survival (DFS) and overall survival (OS) of the patients (tumor size: p=0.023 for DFS and p=0.021 for OS; therapeutic method: p=0.041 for DFS and p=0.024 for OS). N stage at diagnosis was significant only with reference to overall survival of the patients (p=0.009). EGFR expression was positive in some patients.
Conclusions: Our results elucidated that the patients received comprehensive therapy, especially adjuvant chemotherapy was indispensable for better outcomes. Early detection and treatment were necessary for a higher survival rate when the tumor size was less than 5 cm without lymph node metastasis. Prospective outcomes with novel strategies targeting EGFR need to be further investigated.
Copyright © 2022 Yao Tian et al.
日本乳癌学会編:乳癌診療ガイドライン1.治療編 2015年版、p119-121、乳腺悪性葉状腫瘍の遠隔転移に対して化学療法は勧められるか、金原出版、2015.
In Hae Park, Youngmee Kwon, Eun-A Kim, Keun Seok Lee, Jungsil Ro
Major response to sunitinib (Sutene) in metastatic malignant phyllodes tumor of breast.
Invest New Drugs. 2009 Aug;27(4):387-8. doi: 10.1007/s10637-008-9195-3. Epub 2008 Nov 11.
Abstract/Text
Winette T A van der Graaf, Jean-Yves Blay, Sant P Chawla, Dong-Wan Kim, Binh Bui-Nguyen, Paolo G Casali, Patrick Schöffski, Massimo Aglietta, Arthur P Staddon, Yasuo Beppu, Axel Le Cesne, Hans Gelderblom, Ian R Judson, Nobuhito Araki, Monia Ouali, Sandrine Marreaud, Rachel Hodge, Mohammed R Dewji, Corneel Coens, George D Demetri, Christopher D Fletcher, Angelo Paolo Dei Tos, Peter Hohenberger, EORTC Soft Tissue and Bone Sarcoma Group, PALETTE study group
Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial.
Lancet. 2012 May 19;379(9829):1879-86. doi: 10.1016/S0140-6736(12)60651-5. Epub 2012 May 16.
Abstract/Text
BACKGROUND: Pazopanib, a multitargeted tyrosine kinase inhibitor, has single-agent activity in patients with advanced non-adipocytic soft-tissue sarcoma. We investigated the effect of pazopanib on progression-free survival in patients with metastatic non-adipocytic soft-tissue sarcoma after failure of standard chemotherapy.
METHODS: This phase 3 study was done in 72 institutions, across 13 countries. Patients with angiogenesis inhibitor-naive, metastatic soft-tissue sarcoma, progressing despite previous standard chemotherapy, were randomly assigned by an interactive voice randomisation system in a 2:1 ratio in permuted blocks (with block sizes of six) to receive either pazopanib 800 mg once daily or placebo, with no subsequent cross-over. Patients, investigators who gave the treatment, those assessing outcomes, and those who did the analysis were masked to the allocation. The primary endpoint was progression-free survival. Efficacy analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00753688.
FINDINGS: 372 patients were registered and 369 were randomly assigned to receive pazopanib (n=246) or placebo (n=123). Median progression-free survival was 4·6 months (95% CI 3·7-4·8) for pazopanib compared with 1·6 months (0·9-1·8) for placebo (hazard ratio [HR] 0·31, 95% CI 0·24-0·40; p<0·0001). Overall survival was 12·5 months (10·6-14·8) with pazopanib versus 10·7 months (8·7-12·8) with placebo (HR 0·86, 0·67-1·11; p=0·25). The most common adverse events were fatigue (60 in the placebo group [49%] vs 155 in the pazopanib group [65%]), diarrhoea (20 [16%] vs 138 [58%]), nausea (34 [28%] vs 129 [54%]), weight loss (25 [20%] vs 115 [48%]), and hypertension (8 [7%] vs 99 [41%]). The median relative dose intensity was 100% for placebo and 96% for pazopanib.
INTERPRETATION: Pazopanib is a new treatment option for patients with metastatic non-adipocytic soft-tissue sarcoma after previous chemotherapy.
FUNDING: GlaxoSmithKline.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Stefan Sleijfer, Isabelle Ray-Coquard, Zsuzsa Papai, Axel Le Cesne, Michelle Scurr, Patrick Schöffski, Françoise Collin, Lini Pandite, Sandrine Marreaud, Annick De Brauwer, Martine van Glabbeke, Jaap Verweij, Jean-Yves Blay
Pazopanib, a multikinase angiogenesis inhibitor, in patients with relapsed or refractory advanced soft tissue sarcoma: a phase II study from the European organisation for research and treatment of cancer-soft tissue and bone sarcoma group (EORTC study 62043).
J Clin Oncol. 2009 Jul 1;27(19):3126-32. doi: 10.1200/JCO.2008.21.3223. Epub 2009 May 18.
Abstract/Text
PURPOSE Given the importance of angiogenesis in soft tissue sarcoma (STS), pazopanib, an oral angiogenesis inhibitor that targets vascular endothelial growth factor receptor and platelet-derived growth factor receptor, was explored in patients with advanced STS. PATIENTS AND METHODS Patients with intermediate- or high-grade advanced STS who were ineligible for chemotherapy or who had received no more than two prior cytotoxic agents for advanced disease, who had documented progression, who had adequate performance status, and who had good organ function were eligible. Pazopanib 800 mg was given daily. The primary end point was progression-free rate at 12 weeks (PFR(12 weeks)). Secondary end points were response, safety, and overall survival. Four different strata were studied: adipocytic STS, leiomyosarcomas, synovial sarcomas, and other STS types. A Simon two-stage design was applied (P1 = 40%; P0 = 20%; alpha = beta = .1) for each stratum. Results One hundred forty-two patients were enrolled. The adipocytic STS stratum was closed after the first stage, given insufficient activity (PFR(12 weeks), five [26%] of19). PFR(12 weeks) was 18 (44%) of 41 patients in the leiomyosarcoma cohort, 18 (49%) of 37 in the synovial sarcomas, and 16 (39%) of 41 in the other STS types. Compared with historical controls who were treated with second-line chemotherapy, progression-free and overall survivals were prolonged in the three cohorts in which the primary end point was reached. The most frequent drug-related toxicities were hypertension, fatigue, hypopigmentation, and nausea. Other toxicities included liver enzyme elevations, myelosuppression, and proteinuria, all of which were mostly grades 1 to 2. The most frequent grades 3 to 4 toxicities were hyperbilirubinemia (6.3%), hypertension (7.7%), and fatigue (7.7%). CONCLUSION Pazopanib is well tolerated in patients with relapsed, advanced STS and demonstrates interesting activity that warrants additional study in patients with leiomyosarcomas, synovial sarcomas, and other STS types.
Dung T Le, Jennifer N Uram, Hao Wang, Bjarne R Bartlett, Holly Kemberling, Aleksandra D Eyring, Andrew D Skora, Brandon S Luber, Nilofer S Azad, Dan Laheru, Barbara Biedrzycki, Ross C Donehower, Atif Zaheer, George A Fisher, Todd S Crocenzi, James J Lee, Steven M Duffy, Richard M Goldberg, Albert de la Chapelle, Minori Koshiji, Feriyl Bhaijee, Thomas Huebner, Ralph H Hruban, Laura D Wood, Nathan Cuka, Drew M Pardoll, Nickolas Papadopoulos, Kenneth W Kinzler, Shibin Zhou, Toby C Cornish, Janis M Taube, Robert A Anders, James R Eshleman, Bert Vogelstein, Luis A Diaz
PD-1 Blockade in Tumors with Mismatch-Repair Deficiency.
N Engl J Med. 2015 Jun 25;372(26):2509-20. doi: 10.1056/NEJMoa1500596. Epub 2015 May 30.
Abstract/Text
BACKGROUND: Somatic mutations have the potential to encode "non-self" immunogenic antigens. We hypothesized that tumors with a large number of somatic mutations due to mismatch-repair defects may be susceptible to immune checkpoint blockade.
METHODS: We conducted a phase 2 study to evaluate the clinical activity of pembrolizumab, an anti-programmed death 1 immune checkpoint inhibitor, in 41 patients with progressive metastatic carcinoma with or without mismatch-repair deficiency. Pembrolizumab was administered intravenously at a dose of 10 mg per kilogram of body weight every 14 days in patients with mismatch repair-deficient colorectal cancers, patients with mismatch repair-proficient colorectal cancers, and patients with mismatch repair-deficient cancers that were not colorectal. The coprimary end points were the immune-related objective response rate and the 20-week immune-related progression-free survival rate.
RESULTS: The immune-related objective response rate and immune-related progression-free survival rate were 40% (4 of 10 patients) and 78% (7 of 9 patients), respectively, for mismatch repair-deficient colorectal cancers and 0% (0 of 18 patients) and 11% (2 of 18 patients) for mismatch repair-proficient colorectal cancers. The median progression-free survival and overall survival were not reached in the cohort with mismatch repair-deficient colorectal cancer but were 2.2 and 5.0 months, respectively, in the cohort with mismatch repair-proficient colorectal cancer (hazard ratio for disease progression or death, 0.10 [P<0.001], and hazard ratio for death, 0.22 [P=0.05]). Patients with mismatch repair-deficient noncolorectal cancer had responses similar to those of patients with mismatch repair-deficient colorectal cancer (immune-related objective response rate, 71% [5 of 7 patients]; immune-related progression-free survival rate, 67% [4 of 6 patients]). Whole-exome sequencing revealed a mean of 1782 somatic mutations per tumor in mismatch repair-deficient tumors, as compared with 73 in mismatch repair-proficient tumors (P=0.007), and high somatic mutation loads were associated with prolonged progression-free survival (P=0.02).
CONCLUSIONS: This study showed that mismatch-repair status predicted clinical benefit of immune checkpoint blockade with pembrolizumab. (Funded by Johns Hopkins University and others; ClinicalTrials.gov number, NCT01876511.).