Sarcoma of the Breast: Outcome and Reconstructive Options

IntroductionSurgery is the mainstay of treatment for all breast sarcomas. The role of adjuvant chemotherapy and radiation therapy has not been clearly defined. The aim of this single-center retrospective study was to analyze prognostic factors, outcome, and recent advances.Materials and MethodsData from 203 patients with all breast sarcomas treated in a single center were collected from 1996 to 2010. Phyllodes tumors and metastatic disease at presentation were excluded from the population. Thirty-six women and 1 man were included in the analysis. Local recurrence, metastatic disease, survival, and reconstructive outcome were evaluated.ResultsThirty-four patients out of 37 (91.9%) had an angiosarcoma and 3 had a stromal sarcoma (8.1%). Twenty-one patients (56.8%) had previously undergone breast radiation therapy for breast carcinoma or lymphoma. Twenty-six patients (70.3%) underwent mastectomy, 14 of whom (53.8%) with breast reconstruction. Thirty-six patients (97.3%) had free margins, 1 (2.7%) had a microscopically focally involved margin after surgery. Five patients received adjuvant chemotherapy and 6 received adjuvant radiation therapy. Median follow-up was 58 months (range, 4-146 months). Twelve sarcoma-related deaths were observed with a 5-year cumulative incidence of 43.4%. Twenty-four sarcoma-related events were observed with a 5-year cumulative incidence of 70.8%. The same figure was 49.7% in patients affected by primary sarcoma and 85.7% in patients with secondary sarcoma (P = .06).ConclusionSecondary sarcomas were associated with a higher risk of events. Patients undergoing breast conservative surgery or reconstruction after mastectomy did not show a worse prognosis compared with patients undergoing mastectomy.     

Breast Cancer and Secondary Cancer Recurrences After Autologous Tissue Reconstruction

BackgroundThe medical literature defining breast cancer recurrence and secondary cancers after autologous tissue reconstruction for breast cancer is sparse. We sought to identify and analyze occurrences at our institution.Patients and MethodsA 20-year retrospective review of cancer recurrences and atypical breast neoplasms after autologous tissue breast reconstruction at Roswell Park Comprehensive Cancer Center was conducted after being granted a waiver from the institutional review board.ResultsEighteen locoregional recurrences among 337 cases were identified and analyzed. Overall recurrence rate was 5.3%. Four secondary cancers (1.2%) were radiation-induced angiosarcoma, undifferentiated pleomorphic sarcoma, and metaplastic carcinoma. One case of flat epithelial atypia was identified.ConclusionOur retrospective review found incidence and survival after treatment of breast cancer concordant with reports in the literature. We also identified and analyzed secondary neoplasms, including a unique case of undifferentiated pleomorphic sarcoma and metachronous recurrence of breast carcinoma. A case of recurrence as metaplastic carcinoma was identified.     

The Role of Imaging in the Diagnosis of Primary and Secondary Breast Angiosarcoma: Twenty-Five-Year Experience of a Provincial Cancer Institution

BackgroundBreast angiosarcoma may arise spontaneously (primary breast angiosarcoma (PBA)) or may arise secondary to a biological insult, such as radiation therapy (secondary breast angiosarcoma (SBA)). We evaluated the imaging findings of patients diagnosed with PBA and SBA within the province of British Columbia, Canada.Materials and MethodsThis was a multi-center, retrospective study of patients diagnosed with PBA and SBA over a 25-year period. Patients were identified via a provincial database which registers all cases of sarcoma. Patients diagnosed with histologically proven PBA and SBA were eligible for inclusion. Multimodal breast imaging reviewed included mammography, ultrasound, magnetic resonance imaging, and computed tomography.ResultsThirteen patients were diagnosed with PBA and 22 patients were diagnosed with SBA. The median (interquartile range (IQR)) age of patients diagnosed with PBA (45.5 years (19.7 years)) was less than that of patients diagnosed with SBA (75.8 years (13.8 years), P < .001). Patients diagnosed with PBA (90.9%) were more likely to present with a parenchymal mass clinically and radiographically than those with SBA (28.6%, P < .002). Patients diagnosed with SBA (71.4%) were more likely to present with cutaneous findings than patients diagnosed with PBA (0.0%, P < .05). Without specific clinical context, the imaging findings of PBA and SBA were observed to be non-specific.ConclusionThis is the only study which evaluated the imaging findings of patients diagnosed with PBA and SBA within a large, defined geographical area. Given non-specific imaging findings, awareness of the disease and clear and timely communication between radiologists and clinicians is required to ensure appropriate diagnosis and management.     

Sarcoma as a second malignancy after treatment for breast cancer

: Second malignant neoplasms may be a consequence of radiotherapy for the treatment of breast cancer. Prior studies evaluating sarcomas as second malignant neoplasms in breast cancer patients have been limited by the numbers of patients and relatively low incidence of sarcoma. Using data from the Surveillance, Epidemiology and End Results registries, we evaluated the influence of radiation therapy on the development of subsequent sarcomas in cases with primary breast cancer.

: Cases with primary invasive breast cancer (n = 274,572) were identified in the Surveillance, Epidemiology and End Results Cancer Incidence Public-Use Database (1973–1997). The database was then queried to determine the cases developing subsequent sarcomas (n = 263). Eighty-seven of these cases received radiation therapy, and 176 had no radiation therapy. The cumulative incidence of developing secondary sarcoma and the survival post developing secondary sarcoma were determined by the Kaplan-Meier method.

: The occurrence of sarcoma was low, regardless of whether cases received or did not receive radiation therapy: 3.2 per 1,000 (SE [standard error] = 0.4) and 2.3 per 1,000 (SE = 0.2) cumulative incidence at 15 years post diagnosis, respectively (p = 0.001). Of the sarcomas occurring within the field of radiation, angiosarcoma accounted for 56.8%, compared to only 5.7% of angiosarcomas occurring in cases not receiving radiotherapy. The cumulative incidence of angiosarcoma at 15 years post diagnosis was 0.9 per 1,000 for cases receiving radiation (SE = 0.2) and 0.1 per 1,000 for cases not receiving radiation (SE < 0.1). Overall survival was poor for cases of sarcoma after breast cancer (27–35% at 5 years), but not significantly different between patients receiving or not receiving radiation therapy for their primary breast cancer.

: Radiotherapy in the treatment of breast cancer is associated with an increased risk of subsequent sarcoma, but the magnitude of this risk is small. Angiosarcoma is significantly more prevalent in cases treated with radiotherapy, occurring especially in or adjacent to the radiation field. The small difference in risk of subsequent sarcoma for breast cancer patients receiving radiotherapy does not supersede the benefit of radiotherapy.     

Radiation-associated angiosarcoma of the breast: An international multicenter analysis

IntroductionRadiation-associated angiosarcoma (RAAS) is a rare and serious complication of breast irradiation. Due to the rarity of the condition, clinical experience is limited and publications on this topic include only retrospective studies or case reports.Materials and methodsAll patients diagnosed with RAAS between January 2000 and December 2017 in twelve centers across the Czech Republic and Slovakia were evaluated.ResultsData of 53 patients were analyzed. The median age at diagnosis was 72 (range 44–89) years. The median latency period between irradiation and diagnosis of RAAS was 78 (range 36–172) months. The median radiation dose was 57.6 (range 34–66) Gy. The whole breast radiation therapy with radiation boost to the tumor bed was the most common radiotherapy regimen. Total mastectomy due to RAAS was performed in 43 patients (81%), radical excision in 8 (15%); 2 patients were not surgically treated due to unresectable disease. Adjuvant chemotherapy followed surgical therapy of RAAS in 18 patients, 3 patients underwent adjuvant radiotherapy. The local recurrence rate of RAAS was 43% and the median time from surgery to the onset of recurrence was 7.5 months (range 3–66 months). The 3-year survival rate was 56%, the 5-year survival rate was only 33%. 46% of patients died during the follow-up period.ConclusionThe present data demonstrate that RAAS is a rare condition with high local recurrence rate (43%) and mortality (the 5-year survival rate was 33%.). Early diagnosis of RAAS based on biopsy is crucial for treatment with radical intent. Surgery with negative margins constitutes the most important part of the therapy; the role of adjuvant chemotherapy and radiotherapy is still unclear.     

Clinical Outcomes and Prognostic Features of Angiosarcoma: Significance of Prior Radiation Therapy

Aims

Angiosarcoma is a rare and aggressive malignancy with a poor prognosis. There is limited literature describing prognostic factors and guidelines for treatment. We aim to describe outcomes in angiosarcoma, including the impact of patient-, tumour- and treatment-related factors on prognosis.

乳腺血管肉瘤的临床特征和预后分析

  目的  乳腺血管肉瘤是一种少见的、异质性的疾病,约占原发性乳腺癌的0.04%和乳腺肉瘤的8%。回顾性分析1975年10月至2009年6月天津医科大学肿瘤医院13例乳腺血管肉瘤患者的临床特征和预后。  方法  使用Kaplan-Meier方法统计分析不同肿物大小、肿物切缘状态及组织学分级对OS和DFS的影响。通过Log-rank单因素检测分析患者的预后。  结果  患者确诊时的中位和平均年龄分别为48岁和44岁。随访中位时间50（7~98）个月,所有患者均接受手术治疗,2例进行化疗,8例死于复发或转移。  结论  乳腺血管肉瘤预后极差,中位DFS和OS分别为28个月和45个月。肿瘤大小和手术切缘与预后密切相关（P < 0.05）,组织学级别高的乳腺血管肉瘤存在OS较短特征（P>0.05）,且具有较高的局部复发和转移的风险（P < 0.05）。      

Incidence,Clinical Features,and Outcomes of Langerhans Cell Sarcoma in the United States

BackgroundLimited knowledge exists on the incidence, treatment patterns, and long-term outcomes of Langerhans cell sarcoma (LCS) in the United States.Patients and MethodsWe performed a retrospective study of LCS patients diagnosed between 2001 and 2014 using the Surveillance, Epidemiology, and End Results (SEER) and National Cancer Data Base (NCDB) databases. Incidence was calculated from SEER, and treatment patterns and outcomes were calculated from NCDB.ResultsA total of 25 and 52 cases of LCS were reported to SEER and NCDB, respectively. The overall incidence of the disease was 0.2 per 10,000,000 and did not differ by race (P = .56) or sex (P = .33). The median age at diagnosis was 62 (range, 19-90) years. Of the 52 patients from NCDB, 20 (39%) received chemotherapy as first-line therapy, 24 (46%) received surgery, and 15 (29%) received radiotherapy. The 1-year overall survival (OS) rate was 62%, and the median OS was 19 months. After censoring the patients with bone marrow and reticuloendothelial system involvement, no significant difference in OS was noted between the patients who were managed with or without surgery (P = .75). Postsurgical radiation or chemotherapy were not associated with improvement in median OS (P = .25). Patients who were managed with radiotherapy had a better OS compared to those who received no radiotherapy (P = .03).ConclusionThis dual-national registry study shows that LCS is extremely rare and has a poor prognosis. Radiotherapy may offer a survival advantage to patients with locoregional disease without bone marrow and reticuloendothelial system involvement.     

Primary and secondary angiosarcomas of the breast: a single institution experience

Angiosarcomas of the breast (ASB) are rare, representing <1% of breast malignancies. They can develop as a primary or secondary malignancy, also called post-radiation angiosarcoma. The aim of the this study is to discuss diagnosis, treatment, and outcome of primary and secondary ASB patients, diagnosed and treated in a single institution, over a 10-year period and to further compare the two conditions. We retrieved 28 consecutive cases of ASB, diagnosed from 1999 to 2009 at the European Institute of Oncology. Clinical and pathologic findings and survival analyses were performed. Of the 28 cases (27 women and 1 man), eight were primary breast angiosarcomas (PBA) and 20 were secondary breast angiosarcomas (SBA). Median follow-up was 23 months (range 1–112 months). Type of treatment (conservative or radical surgery) did not affect survival in both types of angiosarcomas. The clinical course observed was characterized by a high rate of local recurrence rather than distant metastasis or death from disease. There was a correlation between histological grade and prognosis of angiosarcomas with high-grade tumors presenting worse prognosis. SBA had a poorer prognosis compared to PBA. Our data indicate that primary and secondary ASB are distinct clinical and pathological features. SBA showed worse prognosis and was more often diagnosed in the study period compared to PBA. Physicians who care for patients who have been treated with radiation must be aware of its potential to induce angiosarcoma and stay vigilant in its detection.     

Angiosarcoma of the breast

BACKGROUND: Angiosarcoma of the breast is a rare entity. The objectives of this study were to evaluate prognostic factors and determine outcomes in a large contemporary series of patients. METHODS: Clinical and pathologic factors were analyzed in all patients with angiosarcoma of the breast treated between 1990 and 2003. Overall survival (OS) and disease-free survival (DFS) were estimated using the methods of Kaplan and Meier. Multivariate analyses were performed to evaluate prognostic factors. RESULTS: Fifty-five women with angiosarcoma of the breast were identified. The median age was 49.1 years, and the median follow-up time was 3.7 years. The median OS and DFS were 2.96 years and 2.26 years, respectively. For the 32 patients with primary angiosarcoma of the breast 5-year OS was 59%. Twenty-three (42%) patients had received prior radiation therapy for the treatment of breast cancer. These patients with radiation therapy-associated angiosarcoma were on average 30 years older and less likely to present with distant metastatic disease than patients presenting with radiation-naive angiosarcoma of the breast. Although radiation-naive patients appeared to have had better early DFS and OS, the Kaplan-Meier curves were not statistically different between patients with radiation therapy-associated disease and radiation therapy-naive patients. On multivariate analysis, tumor recurrence (P = 0.006) was the only significant adverse prognostic factor noted for OS. CONCLUSIONS: In this series of 55 patients with angiosarcoma of the breast, radiation therapy-naive angiosarcomas occurred in younger patients, but they behaved similarly to radiation therapy-associated angiosarcomas.     

Sarcomas of the breast

Sarcomas of the breast are a rare group of heterogeneous mesenchymal tumors accounting for less than 1% of all breast malignancies. Owing to the rarity of the disease, current knowledge is mostly based on numerous case reports and relatively small retrospective series; unlike epithelial breast cancer, there is no high level evidence to support a standard of care for primary and/or adjuvant therapy. To overcome this relative shortage of data, most therapeutic strategies for breast sarcoma are extrapolated from current treatment for soft tissue sarcoma in other locations, mainly of the extremities and thoracic wall. In general, the therapeutic approach to sarcoma of the breast should be based on a multidisciplinary strategy including surgery, radiation to improve local control and systemic chemotherapy in selected patients. This review discusses the results of the key larger retrospective studies including data on incidence, etiology, presentation, diagnosis, management and prognosis of this challenging rare disease entity.     

Cardiac radiation-induced sarcomas: A SEER population-based study and a literature review

PurposeThe aim of this study was to better understand the incidence and the clinical characteristics of cardiac radiation-induced sarcomas (RIS).Material and methodsWe used the surveillance, epidemiology, and end results (SEER) program cancer registry data, the largest cancer database in the United States in order to identify all cardiac RIS between 1973 and 2015. We relied on the Memorial Sloan–Kettering Cancer Center (MSKCC)-modified 1948 Cahan criterions for RIS identification.ResultsOut of 8,136,951 cancer patients from the SEER database, we identified 448 patients diagnosed with cardiac sarcomas. Of these 448 cardiac sarcoma patients, two were considered to have developed a cardiac RIS: a metastatic rhabdomyosarcoma occurring after one to two years following lung carcinoma irradiation, and a soft tissue sarcoma (of unspecified type) developed six years after radiation therapy for an aggressive left-sided breast carcinoma. Based on this observation, we estimated that cardiac RIS represented about 0.4% (95% CI 0.1%–1.6%) of all cardiac sarcomas. A literature review has been conducted and yielded three additional cases of cardiac RIS.ConclusionCardiac RIS are extremely rare malignancies, associated with a very pejorative prognosis. The two reported histologies are angiosarcomas and rhabdomyosarcomas, which might be over-represented among cardiac RIS. A metastatic evolution is possible for cardiac radiation-induced rhabdomyosarcomas. Surgical excision, when feasible, is a therapeutic option and is the only specific treatment reported to this date.     

Primary and Secondary Breast Sarcoma: Clinical and Pathological Characteristics,Prognostic Factors,and Nomograms for Predicting Survival

BackgroundBreast sarcoma is one of the rare types of breast tumors with different features and outcomes compared to carcinoma. Our study aims to describe the clinical and pathological characteristics of primary breast sarcoma (PBS) and secondary breast sarcoma (SBS) along with determining prognostic factors and developing nomograms for predicting survival.MethodsUsing the Surveillance, Epidemiology, and End Results (SEER) Program, female patients diagnosed with breast sarcoma between 1975 and 2016 were identified. Cox regression was used to evaluate the association between survival and clinical features.ResultsOut of 1334 included patients, 816 had PBS and 518 had SBS. PBS had a significantly better overall survival than SBS with median survival months of 107 for PBS and 45 for SBS. The primary tumor site did not have a significant impact on the survival of SBS. Cox regression showed worse survival of PBS patients who were > 60 years (HR 3.04, 95% CI 2.46-3.74) and had tumor size > 50 mm (HR 2.01, 95% CI 1.61-2.51). Being not married was associated with worse survival of PBS (HR 1.29, 95% CI 1.06-1.56) and SBS (HR 1.50, 95% CI 1.19-1.90). Surgery was associated with better survival of PBS (HR 0.60, 95% CI 0.42-0.85) and SBS (HR 0.46, 95% CI 0.31-0.68). The C-indexes of created nomograms were 0.73 for PBS and 0.69 for SBS.ConclusionAge and size were the most important prognostic factors for the survival. Surgery was associated with better survival. However, radiation and chemotherapy did not show significant improvement in survival.     

Extraskeletal Ewing's Sarcoma Family of Tumours in Adults: Analysis of 57 Patients from a Single Institution

AimsExtraskeletal Ewing's sarcoma (EES) is a rare form of soft tissue sarcoma. The aim of the present study was to assess the outcome and the prognosis of adult patients presenting with EES treated with multi-modality therapy.Materials and methodsAll EES patients older than 15 years referred to our institution between January 1995 and December 2004 were reviewed. In total, 57 patients were identified. Their median age at diagnosis was 20 years (range 15–57).ResultsThe median size of the primary tumour was 11 cm (range 4–30 cm). Eighteen patients (31%) had metastatic disease at initial presentation. Wide surgical resection with negative margins was achieved in 23 cases (40%). Chemotherapy consisting of vincristine, adriamycin, ifosfamide, actinomycin D was given in 50 patients (88%). Radiotherapy was delivered in 37 patients (65%). Forty-one patients (72%) achieved complete remission and 16 (28%) progressed on therapy. Twenty-one patients (51%) relapsed. Local recurrence was encountered in 15 patients (36%). At a median follow-up of 46 months (range 6–143 months), the 5-year event-free survival and overall survival rates were 35 and 47%, respectively. Metastases at presentation, tumour size and surgical resection margin associated significantly with overall survival and event-free survival.ConclusionEES is an aggressive type of tumour with a high incidence of local recurrence and distant metastasis. This series showed that the outcome of adult EES is not unlike that of skeletal Ewing's sarcoma in terms of response to multi-modality treatment and the prognostic factors influencing treatment outcome. Adequate surgical resection, aggressive chemotherapy and adjuvant local radiation therapy, when indicated, constitute the optimal treatment to achieve the best results in this rare type of disease.     

Angiosarcoma arising in an unirradiated breast with subsequent pituitary metastasis

Angiosarcoma of the breast is a rare condition with known risk factors. The Stewart-Treves syndrome describes angiosarcoma of the arm or breast in the setting of adjuvant radiation therapy (RT) after breast conservation surgery. Angiosarcoma of the breast, in the absence of RT, is rarer still. We present a unique case of angiosarcoma of the breast, diagnosed 6 years after conservative surgery for carcinoma of the breast when no adjuvant RT was given. Chronic postoperative lymphoedema in the breast delayed the investigation of skin changes, with an eventual diagnosis of angiosarcoma. An isolated pituitary metastasis 9 months from the diagnosis, the first such reported case, adds to the complexity of the case. The diagnosis and management of angiosarcoma of the breast is discussed. Angiosarcoma is a rare occurrence after breast conservative surgery. Postoperative lymphoedema can impede early diagnosis. The disease can display unique metastatic potential.     

Angiosarcoma of the breast following surgery and radiotherapy for breast cancer

Breast angiosarcoma following surgery and radiotherapy for breast cancer is a rare but important clinical entity. This article reviews all published cases and includes data on incidence, etiology, presentation, diagnosis, management and prognosis. Breast angiosarcoma remains challenging clinically, radiologically and histologically, and thus a high index of suspicion is required in susceptible patients. Surgery is the primary treatment option and there are an increasing number of studies on the use of radiotherapy and chemotherapy, each with variable success. There have been recent reports of patients with metastatic disease responding to taxane chemotherapy, and there might be a future role for targeted agents given the expression of c-KIT in a subset of angiosarcomas. Overall survival, however, remains poor.     

Soft tissue sarcoma of the breast after conservative surgery and irradiation for early mammary cancer

At Istituto Tumori of Milano in a series of 3295 patients treated with conservative surgery and radiotherapy for breast cancer from 1973 to 1989 three cases of soft tissue sarcoma were observed in irradiated breasts. One patient developed a fibrosarcoma of the breast stroma, 16 months after irradiation. A grade II bulky angiosarcoma was diagnosed in the breast of a patient treated 59 months previously. The third was a grade II angiosarcoma detected 41 months after therapy. At present, the risk of a second primary in the irradiated breast seems too low to justify modification of our present policy of conservative therapy of breast cancer, but a careful and longer follow-up is needed.     

Treatment and prognostic factors of radiation-associated angiosarcoma (RAAS) after primary breast cancer: A systematic review

BackgroundRadiation-associated angiosarcoma (RAAS) of the breast is a rare, aggressive disease. The incidence is increasing with the prolonged survival of women irradiated for primary breast cancer. Surgery is the current treatment of choice. Prognosis is poor. This review aims to evaluate all publications on primary treatment of RAAS to identify prognostic factors and evaluate treatment modalities.MethodsDatabases were searched for articles with published individual patient data on prognostic factors, treatment and follow-up of patients with RAAS. A regression analysis was performed to test the prognostic values of age, interval between primary treatment and RAAS, tumour size and grade on the local recurrence-free interval (LRFI) and overall survival (OS). The effects of treatment modalities surgery, radiation (with or without hyperthermia) and chemotherapy or combinations were evaluated.Results74 articles were included, representing data on 222 patients. In these patients, the 5-year OS was 43% and 5-year LRFI was 32%. Tumour size and age were significant prognostic factors on LRFI and OS. Of all patients, 68% received surgery alone, 17% surgery and reirradiation and 6% surgery with chemotherapy. The remaining 9% received primary treatments without surgery. Surgery with radiotherapy had a better 5-year LRFI of 57% compared to 34% for surgery alone (p = 0.008). The value of other treatment modalities could not be assessed.ConclusionsThis systematic review confirms the poor prognosis of RAAS. Tumour size and age were of prognostic value. The addition of reirradiation to surgery in the treatment of RAAS appears to enhance local control.     

Clinicopathological features of breast angiosarcoma

Background

Breast angiosarcomas are rare neoplasm. Due to its rarity, our therapeutic strategy is extremely limited. Therefore, we investigated the clinicopathologic features and examined the treatment for angiosarcoma compared with some literatures.

Methods

We conducted a retrospective chart and slide review of all patients in our division seen from 1997 to 2012 with a diagnosis of primary or secondary breast angiosarcoma at the National Cancer Center Hospital (Tokyo, Japan).

Results

Nine patients were diagnosed with breast angiosarcoma (six primary and three secondary cases). The median age of patients with primary angiosarcoma was 39 years (range 27–65 years). The median tumor size was 6.78 cm (range 3.0–8.8 cm). In the primary tumor, 4 patients had total mastectomy and 2 had a breast conserving surgery. 3- and 5-year disease-free survival (DFS) of the patients with primary angiosarcoma was 20 and 0 %. 5-year surviving rate of primary angiosarcoma was 50 %. In all patients with secondary angiosarcoma, recurrence was observed in all cases. But one case obtained long-term survival in local control therapy.

Conclusions

Our study demonstrates breast angiosarcoma exhibits high recurrence rates. Tumor size and surgical margin may be important factor to obtain long-term survival. In this point of view, total mastectomy with adequate tumor margin with early detection is desired. In case of recurrence, if it is local, surgery may be potentially curative.