INTRODUCTION — Breast sarcomas are rare, histologically heterogeneous nonepithelial malignancies that arise from the connective tissue within the breast. They can develop de novo (primary), after radiation therapy (RT), or in the setting of chronic lymphedema of the arm or breast (therapy-related, secondary). Although the clinical features of breast sarcoma can mimic those of breast carcinoma in some ways, therapy and prognosis differ dramatically.
GENERAL PRINCIPLES — Given the rarity of breast sarcomas, there are no prospective randomized trials to guide therapy. Treatment principles have been derived from small retrospective case reviews of breast sarcomas and extrapolated from studies of nonbreast soft tissue sarcomas of the extremity and chest wall since clinical behavior, histology, and prognosis are similar.
As with soft tissue sarcomas arising in other areas of the body, a multidisciplinary approach at an experienced center involving surgical, radiation, and medical oncologists is preferred [1,2]. In general, the choice of treatment is influenced by stage, histologic grade, and tumor size.
SURGERY — Surgery represents the only potentially curative modality for breast sarcomas. The type and extent of the operation is based upon both the size of the tumor and the size of the breast, as well as histology:
●An adequate resection margin is the single most important determinant of long-term survival with breast sarcomas [3-5]. For larger tumors (ie, those >5 cm), the overall cosmetic result is often better with a mastectomy and reconstruction than with lumpectomy. Deep-seated tumors, which are close to or involve the chest wall, may require en bloc resection of the chest wall [4,6,7]. With the exception of angiosarcomas, the majority of primary breast sarcomas are not multicentric [3], and negative surgical margins are more important than the extent of surgical resection [3,8-10]. Breast angiosarcomas (primary or therapy-related) often affect a much larger field of the breast or chest wall than anticipated, and mastectomy is the standard treatment [11,12].
●A study of 100 cases of angiosarcoma treated with breast-conserving therapy demonstrated that the majority of patients recurred locally within one year (73 percent) [13]. Angiosarcomas often have infiltrative cutaneous disease that extends well beyond the visible tumor, and recurrences are often seen at the margins of the prior operation in a shotgun pellet pattern. Accordingly, special attention should be given to ensuring the skin margin is clear and margins of 3 cm have been proposed [14]. Hence, the authors prefer a mastectomy rather than breast conservation surgery for this histology. Furthermore, given the high risk of recurrence with this histology, reconstruction should generally be delayed.
In many cases, the wide excision of skin that is necessary to achieve negative margins precludes closure and requires a skin graft or myocutaneous flap. It is often wise to employ temporary coverage until the margin status on final pathology is known and perform definitive coverage in a delayed fashion. Frozen section analysis of the margins can be inaccurate as angiosarcomas tend to have low-grade changes at the margins that can be difficult to differentiate from radiation changes [15]. Resection by a surgeon with experience in this disease is advised.
●Patients with radiation-associated angiosarcoma of the breast should seek multidisciplinary evaluation (including a surgeon with expertise in treating sarcomas) at a sarcoma center of excellence, as observational studies suggest improved clinical outcomes with this approach. In a study of 49 patients with radiation-associated angiosarcoma of the breast, patients managed by a sarcoma multidisciplinary team were more likely to undergo radical resection with reconstruction than those who were not (96 versus 17 percent), as well as receive adjuvant therapy [2]. This multidisciplinary treatment approach also resulted in lower local recurrence rates (38 versus 83 percent). Another tertiary referral center reported their outcomes in 76 females with radiation therapy (RT)-associated breast angiosarcoma who underwent "radical" resection (mastectomy/resection of all previously irradiated skin) or "conservative" resection (mastectomy/wide excision with partial skin resection). In this study, five-year disease-specific survival for radical versus conservative resections was 86 and 46 percent, respectively [16].
Management of regional nodes — Breast sarcomas tend to spread by direct local invasion or hematogenously; regional lymph node involvement is rare except in the setting of widespread metastatic disease [3,17,18]. The incidence of lymphatic spread is 5 percent or less overall, and lymphadenectomy does not appear to improve outcomes [6,19,20]. While angiosarcomas in general have a higher rate of lymph node metastases as compared with other sarcoma subtypes, up to 13 percent in one series [21], the incidence is still relatively low, and prophylactic lymph node dissection is not indicated for a clinically negative axilla. Even when axillary lymphadenopathy is palpable, pathologic examination often reveals only reactive nodes without disease spread [22]. Despite this, the national surgical patterns of care study in the United States and the rare cancer network study in Europe found that approximately 40 percent of patients with primary breast sarcoma have some degree of regional lymphadenectomy [19,23]. Changing this practice could reduce unnecessary morbidity of treatment.
●For the patient with a clinically negative axilla, sentinel lymph node biopsy or axillary lymph node dissection is not routinely indicated [8,14,24].
●For the patient with clinically suspicious nodes, ultrasound-guided fine needle aspiration of enlarged nodes can accurately document regional metastases. When lymph node metastases are detected in a patient with a breast sarcoma, the pathology should be reevaluated, as metaplastic carcinoma or carcinosarcoma should be in the differential diagnosis. (See "Pathology of breast cancer", section on 'Metaplastic carcinoma'.)
●If the diagnosis of lymph node involvement in a patient with breast sarcoma is confirmed and there is no evidence of distant disease, lymph node dissection is appropriate. Uncontrolled disease in the axilla can be associated with significant morbidity. Furthermore, nodal metastases do not carry the same poor prognostic implication as distant metastases in soft tissue sarcoma. As a result, regional nodal metastases were reclassified from stage IV to stage III disease in the 2010 modification of the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) staging system (table 1).
ADJUVANT RADIATION THERAPY
Primary breast sarcomas — The benefit of adjuvant radiation therapy (RT) for primary (de novo) breast sarcomas is controversial. Adjuvant RT has not been proven in prospective phase II or randomized trials, and available observational data are conflicting regarding the benefit of this approach. These studies are comprised of varied histologies, extents of resection, and use of RT with likely selection biases which renders the data very difficult to interpret. Our approach to adjuvant RT in patients with breast sarcoma parallel those for extremity sarcomas:
●We do not use adjuvant RT for most breast sarcomas if wide margins are achieved (>1 cm) either by wide resection or mastectomy. If resection margins are close, we obtain reresection to obtain wider margins, if feasible.
●We suggest adjuvant RT for select patients with high-grade breast sarcomas and positive margins in whom reresection is not feasible. Adjuvant RT is also an option for patients with large (>5 cm) high-grade tumors and close, deep margins. However, RT cannot compensate for inadequate surgery, and re-excision to ensure negative margins is strongly encouraged in these cases.
●For patients with large low-grade sarcomas, RT is typically not indicated unless the margins are very close or positive and salvage surgery would not be feasible. In these situations, the risk-to-benefit ratio should be weighed carefully given the association of breast RT with long-term complications. (See "Overview of long-term complications of therapy in breast cancer survivors and patterns of relapse", section on 'Second cancers'.)
●For large, deep tumors where the surgeon expects close or positive margins, preoperative (neoadjuvant) RT may be indicated in an attempt to increase resectability. However, if the surgeon feels that adequate margins are likely to be obtained, we prefer surgery initially, reserving the decision regarding RT until after review of the final pathology from the resection specimen.
Available data from retrospective observational studies provide conflicting data for the benefit of adjuvant RT in primary breast sarcomas [6,8,9,18,23,25-28]. While some studies have found no benefit for adjuvant RT [6,18,23,25,28,29], others suggest improved outcomes, particularly for large, high-grade breast sarcomas [3,8,17,26,30,31]. Most of the benefit seems to be in reducing rates of locoregional recurrence; the impact on overall survival remains uncertain [3,8,9,25,30,32].
Other data that potentially support RT in conjunction with surgery for primary breast sarcoma are extrapolated from randomized trials conducted in patients with nonbreast soft tissue sarcomas, which uniformly demonstrate improvement in local control but without an impact on survival. (See "Overview of multimodality treatment for primary soft tissue sarcoma of the extremities and superficial trunk", section on 'Radiation therapy'.)
A preference for preoperative as compared with postoperative external beam RT in patients with extremity sarcoma is based upon results from a randomized Canadian trial that demonstrated similar efficacy but a lower rate of generally irreversible late complications with preoperative therapy, including grade 3 to 4 fibrosis. None of the patients in this trial had primary breast sarcoma, and whether these benefits can be extrapolated to patients with breast sarcomas is unclear. These data are discussed in detail separately. (See "Overview of multimodality treatment for primary soft tissue sarcoma of the extremities and superficial trunk", section on 'Choosing between preoperative and postoperative RT'.)
Radiotherapy-associated breast sarcomas — The benefit of adjuvant RT for radiation-associated breast sarcomas is undefined, and in the setting of prior RT to the same area, the potential late effects of a high cumulative RT dose (rib fracture, pneumonitis, soft tissue necrosis) must be carefully taken into account [33]. However, particularly for therapy-related angiosarcomas, the concern for late side effects must be counterbalanced by the high rate of disease recurrence with surgery alone (50 to 73 percent) [13,34].
Reirradiation, often with a hyperfractionated schedule of treatment administration, has been used in the neoadjuvant or adjuvant setting in some patients with favorable results [35,36]. On the other hand, very good local control for radiation-associated breast angiosarcoma has been achieved with surgery alone without reirradiation when mastectomy with radical resection of all previously irradiated skin is performed [16].
These are challenging patients given the difficulties of radical resection and reconstruction as well as the difficulties of reirradiation. Therefore, treatment must be individualized and is best performed at high-volume expert sarcoma centers.
ADJUVANT CHEMOTHERAPY
Treatment approach — Adjuvant chemotherapy cannot be recommended routinely after resection of a breast sarcoma. The appropriateness of adjuvant chemotherapy must be addressed on a case-by-case basis, taking into account the patient's performance status, comorbid factors (including age), disease location, tumor size, and histologic subtype.
Adjuvant chemotherapy is a reasonable option for patients with high-risk primary (stage III, as defined by tumor, node, metastasis [TNM] staging system (table 1)) or recurrent sarcomas, and because of their worse outcome, for angiosarcomas between 3 and 5 cm in size.
In all of these settings, the potential for benefit must be discussed in the context and potential of expected treatment-related toxicities including sterility in younger individuals, cardiomyopathy (particularly in patients with therapy-related breast sarcomas, who may have received prior doxorubicin-based adjuvant chemotherapy), renal damage, second cancers, and overall impairment of quality of life. (See "Adjuvant and neoadjuvant chemotherapy for soft tissue sarcoma of the extremities", section on 'Sarcomas more commonly seen in adults' and "Clinical manifestations, diagnosis, and treatment of anthracycline-induced cardiotoxicity" and "Risk and prevention of anthracycline cardiotoxicity".)
In general, when chemotherapy is indicated based upon evaluation of all patient-specific factors, a neoadjuvant rather than adjuvant approach is often preferred to allow for an in vivo response assessment and the potential for improved surgical outcomes. (See 'Neoadjuvant therapy for large, locally advanced, initially unresectable lesions' below.)
When adjuvant or neoadjuvant chemotherapy is chosen, we use the combination of doxorubicin plus ifosfamide. However, in a patient with a treatment-related angiosarcoma who has received prior anthracycline-based chemotherapy, a taxane-containing regimen is an appropriate option. (See "Adjuvant and neoadjuvant chemotherapy for soft tissue sarcoma of the extremities", section on 'Summary and recommendations'.)
Efficacy — As with adjuvant radiation therapy (RT), the role of adjuvant chemotherapy for breast sarcoma is undefined. Systemic chemotherapy is a routine component of treatment for several apparently localized soft tissue sarcomas that occur predominantly in children (ie, rhabdomyosarcoma). (See "Adjuvant and neoadjuvant chemotherapy for soft tissue sarcoma of the extremities", section on 'Pediatric-type sarcomas'.)
However, despite many randomized trials, the role of adjuvant chemotherapy for the more common adult subtypes of soft tissue sarcoma (such as liposarcoma, synovial sarcoma, leiomyosarcoma, and angiosarcoma), including those that arise within the breast, is uncertain. Pooled analyses from multiple studies provide the largest amount of patient data; however, they remain difficult to interpret based on inclusion of soft tissue sarcoma of differing grades, sites, and histologies as well as disparities in treatment used. (See "Adjuvant and neoadjuvant chemotherapy for soft tissue sarcoma of the extremities".)
●An analysis from the Sarcoma Meta-Analysis Collaboration (SMAC) suggests a significant 11 percent improvement in survival for doxorubicin and ifosfamide-based adjuvant chemotherapy compared with resection alone in patients with extremity sarcomas [37].
●However, a pooled analysis of individual patient data from the two largest adjuvant trials of doxorubicin and ifosfamide-based chemotherapy (both performed by the European Organisation for Research and Treatment of Cancer [EORTC], only one of which was included in the SMAC meta-analysis) was negative for any survival advantage. (See "Adjuvant and neoadjuvant chemotherapy for soft tissue sarcoma of the extremities", section on 'Pooled analysis of the EORTC trials'.)
There are no trials specifically addressing the benefit of adjuvant chemotherapy for breast sarcomas. While one retrospective analysis suggests improved disease-free survival and a trend toward improved survival for patients who received adjuvant chemotherapy [20], and another suggests improved local control [38], others report no benefit [32,39]. Furthermore, in most studies, chemotherapy responsiveness, as judged by response rates to neoadjuvant chemotherapy, was limited [3,23,24,40,41]. As a result, it is difficult to conclude from any of these series that adjuvant chemotherapy is definitely beneficial.
We generally discuss adjuvant chemotherapy as an option with patients who have a good functional status and a high-risk localized sarcoma, specifically stage III disease as defined by the TNM staging system (table 1). This includes patients with a high-grade breast sarcoma that is >5 cm in size or has nodal involvement. Given the relatively poor prognosis of angiosarcomas in the subset of patients with tumor size from 3 to 5 cm, adjuvant chemotherapy is reasonable but only after extensive discussion of the potential risks and benefits. As in other soft tissue sarcoma settings, if adjuvant chemotherapy is administered, we prefer doxorubicin and ifosfamide in combination, although a taxane-based regimen is an option for patients with angiosarcoma. (See "Treatment protocols for soft tissue and bone sarcoma" and "Adjuvant and neoadjuvant chemotherapy for soft tissue sarcoma of the extremities".)
For patients with treatment-related sarcomas, the treatment issues are more complicated and this necessitates individualized decision-making. Patients who have received prior anthracycline-based chemotherapy may not be candidates for additional doxorubicin-based chemotherapy, even if they have a stage III tumor, because of the excessive risk of cardiotoxicity with higher cumulative doses of anthracycline. (See "Risk and prevention of anthracycline cardiotoxicity".)
If these patients have high-risk angiosarcomas (>5 cm), a histology for which taxanes are effective in the setting of advanced disease, an adjuvant taxane-based chemotherapy regimen is reasonable but only after a frank discussion of the risks, benefits, and lack of available data proving efficacy in the adjuvant setting. (See "Overview of the initial treatment of metastatic soft tissue sarcoma", section on 'Angiosarcoma'.)
Another group of patients with treatment-related sarcomas presenting a particular challenge are those who have radiation-associated sarcomas who are not candidates for additional radiation. Depending on the tumor location, sometimes very close or positive margins are achieved and additional resection for wide margins is not possible without significant morbidity. If these patients have high-grade tumors, regardless of size (although typically over at least 3 cm), adjuvant chemotherapy is sometimes offered to improve local control when usual measures are not possible.
These general treatment principles are in keeping with consensus-based guidelines from the National Comprehensive Cancer Network (NCCN) and the European Society for Medical Oncology (ESMO) [42], which suggest that the appropriateness of adjuvant chemotherapy be addressed on a case-by-case basis, taking into account the patient's performance status, comorbid factors (including age), disease location, tumor size, and histologic subtype. (See "Adjuvant and neoadjuvant chemotherapy for soft tissue sarcoma of the extremities", section on 'Summary and recommendations'.)
NEOADJUVANT THERAPY FOR LARGE, LOCALLY ADVANCED, INITIALLY UNRESECTABLE LESIONS — Neoadjuvant rather than adjuvant therapy may be an appropriate approach in the setting of a large or recurrent initially unresectable or borderline resectable high-grade tumor. Decisions about neoadjuvant therapy for patients with large, locally advanced or recurrent breast sarcomas should be made on a case-by-case basis, and these decisions are best made within a multidisciplinary group of sarcoma experts.
In some cases (eg, locally unresectable or borderline resectable tumors), preoperative (neoadjuvant) radiation therapy (RT) may be preferred over chemotherapy given the risk of progression on chemotherapy. Alternatively, in the case of a radiation-associated sarcoma, additional RT may not be an option and thus chemotherapy (with regional hyperthermia, where available) or an initial surgical approach may be favored. When neoadjuvant chemotherapy is chosen, we often offer the option of taxanes for angiosarcoma and the combination of doxorubicin and ifosfamide for other histologies.
Given the importance of negative surgical margins for local control and survival, neoadjuvant therapy may increase the likelihood of successful surgical resection for large high-grade breast sarcomas. There are no data from randomized trials or large retrospective reviews on preoperative RT or chemoradiotherapy for breast sarcomas; in the setting of extremity and chest wall sarcomas, the specific neoadjuvant approach (RT alone, concurrent chemoradiotherapy, or sequential chemotherapy followed by RT) depends upon institutional expertise and experience.
For large, deep-seated tumors where the surgeon expects close or positive margins, preoperative treatment may be preferred over initial surgery in an attempt to improve resectability and the likelihood of achieving negative margins. (See "Treatment of locally recurrent and unresectable, locally advanced soft tissue sarcoma of the extremities", section on 'Radiation therapy and chemoradiation'.)
Chemotherapy alone has been proposed as an effective strategy for neoadjuvant therapy of breast sarcomas, but there is a lack of prospective data to support this approach [10]. Furthermore, as noted above, concerns have been raised given that chemotherapy response rates in breast sarcomas are limited and not durable [3].
Chemotherapy with local hyperthermia has also been proposed for the management of locally advanced, high-risk, and recurrent breast sarcoma [43]. A European randomized trial reported benefit from the addition of regional hyperthermia to neoadjuvant chemotherapy compared with neoadjuvant chemotherapy alone among patients with large high-grade tumors or initially unresectable disease involving the extremities or nonextremity sites (of which only 18 percent arose on the trunk). Whether benefit can be extrapolated to large, locally advanced breast sarcomas is uncertain. This approach, which is not widely used outside of Europe, is discussed in detail elsewhere. (See "Treatment of locally recurrent and unresectable, locally advanced soft tissue sarcoma of the extremities", section on 'Chemotherapy with regional hyperthermia'.)
OUTCOMES — Five-year disease-free survival rates for breast sarcomas range from 44 to 66 percent, and five-year overall survival rates are between 49 and 67 percent [3,8,22,24,40,41,44,45]. As with soft tissue sarcomas arising elsewhere in the body, the prognosis for breast sarcomas is highly dependent upon histologic grade and tumor size; these factors determine disease stage (table 1) [3,8,17,20,22,23,44,46].
The association of grade and tumor size with outcome in primary (nontherapy-related) breast sarcomas can be illustrated by a series of 90 patients, in which the 10-year survival rates for grade 1, 2, and 3 tumors were 82, 62, and 36 percent, respectively [3]. The corresponding 10-year survival rates for tumors <5 cm, 5 to 10 cm, and >10 cm were 76, 68, and 28 percent, respectively.
The influence of histologic grade on outcomes for angiosarcomas of the breast is less clear. Although some series indicate a better prognosis for low-grade tumors [23,29,47,48], others do not [49,50]; histologic grading is generally not recommended for angiosarcomas. Given their poor clinical outcomes, they all represent high-grade (grade 3/3) tumors. (See "Breast sarcoma: Epidemiology, risk factors, clinical presentation, diagnosis, and staging", section on 'Histologic classification'.)
Positive surgical margins increase the risk for local recurrence and death [4,8,18,23,31,44]. Adjuvant radiation therapy (RT) does not compensate for inadequate surgery, and reexcision to ensure clean margins is strongly encouraged in these cases. (See 'Adjuvant radiation therapy' above.)
Histologic subtype does not influence prognosis with the exception of angiosarcoma [3,8,22]. (See 'Angiosarcoma' below.)
Radiation-associated sarcomas often present at an advanced clinical stage and are reported to have a worse clinical outcome than sporadic breast sarcomas. This is at least in part because the diagnosis is difficult to make in an irradiated breast and because angiosarcomas, which are the predominant subtype, have a particularly poor prognosis (see 'Angiosarcoma' below). However, in one study, the significantly lower disease-free survival rates in radiation-associated as compared with sporadic sarcomas were independent of histologic subtype [51].
Angiosarcoma — Angiosarcomas metastasize early, most often to the lung and liver. They also metastasize to bones, brain, skin, and the contralateral breast, which are unusual locations for other soft tissue sarcomas [29,52]. In most (but not all [18,20]) series, angiosarcomas have a worse prognosis than do other histologies [3,17,24,25,40,46,52-57].
As an example, in the SArcoma and PHYllode Retrospective (SAPHYR) study, the three-year disease-free and overall survival rates for the 17 patients with primary angiosarcomas were 7 and 23 percent, respectively [40]. In contrast, the three-year disease-free and overall survival rates for the 27 nonangiosarcoma primary breast sarcomas were 45 and 60 percent, respectively. These data are consistent with the relative risk of metastases for these two sarcoma subtypes.
With more aggressive resection and increased use of multimodality therapy, outcomes may be slightly better, although the available data are limited [46,58]. As an example, in a retrospective series of 55 females with breast angiosarcoma (23 radiation-associated, 32 primary), the two- and five-year overall survival rates were 64 and 38 percent, respectively [46].
These better outcomes may be attributable to case mix. In many series, patients who develop angiosarcomas in radiation or lymphedema fields are more prone to local and distant recurrence and death from disease than are those who have primary angiosarcoma, even if they undergo a microscopically complete (R0) resection [56,59]. As an example, in one series of 31 patients with a radiation-associated breast angiosarcoma who underwent surgery, R0 resection was possible in 23 [59]. However, local recurrence occurred after a median of six months in 19 (83 percent), and regional or distant recurrences developed in 13 (57 percent). Only three patients remained alive after 2, 2.5, and 9 years, respectively, with no evidence of disease.
However, this is not a uniform finding. In the retrospective series of 55 angiosarcomas described above, patients with radiation-naïve angiosarcomas appeared to have a more favorable disease-free and overall survival in the first three years, but the overall Kaplan-Meier survival curves were not significantly different for the two groups [46].
POSTTREATMENT CANCER SURVEILLANCE — Since isolated limited metastatic tumor to the lung can be potentially resected for cure and is frequently asymptomatic, we recommend frequent follow-up, particularly in the first two years after treatment, since more than 80 percent of recurrences will be detected during this period. (See "Surgical resection of pulmonary metastases: Benefits, indications, preoperative evaluation, and techniques" and "Surgical treatment and other localized therapy for metastatic soft tissue sarcoma", section on 'Pulmonary metastases'.)
Although posttreatment cancer surveillance guidelines have not been established through rigorous clinical investigation [60], we follow patients according to the National Comprehensive Cancer Network (NCCN) consensus guidelines for soft tissue sarcoma of the extremity and trunk listed below [61].
●Stage I disease:
•History and physical examination every three to six months for two to three years, then annually.
•"Consider" chest imaging every 6 to 12 months.
•Periodic imaging of the primary site, based on estimated risk of local-regional recurrence.
●Stage II and III disease:
•History and physical examination and chest imaging every three to six months for two to three years, then every six months for the next two years, then annually.
•Periodic imaging of the primary site, based on estimated risk of local-regional recurrence.
In general, we follow these guidelines:
●Imaging of the primary site can be accomplished using magnetic resonance imaging (MRI) or computed tomography (CT) of the chest if a mastectomy has been performed. Breast MRI or ultrasound can be performed in patients who have had a lumpectomy. For those patients at higher risk of local recurrence, such as those with positive margins or those whose primary tumor site is not easily examined, we prefer MRI over CT scans. We scan the primary site at six-month intervals for the first two years and then resume routine breast surveillance.
●When planning the posttreatment surveillance strategy, care should be taken to limit the number of CT scans, particularly in younger individuals, given concerns about radiation exposure and the risk for second malignancies. However, the benefit of judicious periodic imaging likely outweighs the risks. (See "Radiation-related risks of imaging".)
●For angiosarcomas, given their propensity to recur, earlier detection may allow for systemic therapeutic intervention, but such therapy is palliative in nature and there are no data (nor are there likely to be) that earlier diagnosis favorably affects outcome.
TREATMENT OF RECURRENT OR METASTATIC DISEASE — Because most recurrences are local, surgery may be potentially curative [3,4]. Even locally recurrent angiosarcomas may be amenable to complete resection, especially if the tumor is <5 cm. In a series of 44 patients treated for locally recurrent angiosarcoma, the breast was the primary site of disease in 14 patients [62]. Most of the patients were treated with surgery, and some also received adjuvant treatment. At a median follow-up of 36 months, nine developed a second local recurrence and 14 had distant metastatic disease. Systemic spread was more common in patients who did not have surgery or were incompletely resected (71 versus 13 percent in those who underwent a complete macroscopic resection). The estimated one-, two-, and five-year disease-specific survival rates were 80, 64, and 42 percent, respectively. Tumor size >5 cm was the only independent predictor of adverse outcome on multivariate analysis.
For patients who initially had breast-conserving surgery, mastectomy may be indicated [3]. In all other cases of locoregionally advanced locally recurrent disease, treatment is similar to that for soft tissue sarcomas at other sites. (See "Treatment of locally recurrent and unresectable, locally advanced soft tissue sarcoma of the extremities".)
In rare cases, potentially curative metastasectomy may be feasible; this is most likely in patients with isolated limited pulmonary metastases and nonangiosarcoma histologies [62]. (See "Surgical treatment and other localized therapy for metastatic soft tissue sarcoma", section on 'Pulmonary metastases'.)
However, most patients with metastatic breast sarcoma are not surgical candidates and instead are offered chemotherapy with palliative intent. Active chemotherapy regimens and expected outcomes to treatment are similar to other metastatic soft tissue sarcomas regardless of the breast origin. Unfortunately, benefit from conventional chemotherapy is often short-lived, particularly in patients with angiosarcoma [17,27,54,62-72]. However, in contrast to other common adult-type soft tissues sarcomas, patients with advanced angiosarcoma may benefit from taxanes. There are also emerging data suggesting benefit of immune checkpoint inhibitors in a subset of patients with angiosarcoma [73]. (See "Overview of the initial treatment of metastatic soft tissue sarcoma", section on 'Angiosarcoma' and "Second and later lines of therapy for metastatic soft tissue sarcoma", section on 'Angiosarcoma'.)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Soft tissue sarcoma".)
SUMMARY AND RECOMMENDATIONS
●Risk factors for breast sarcoma – Breast sarcomas are primary nonepithelial malignancies arising from the connective tissue within the breast. Sarcomas of the breast can arise de novo (primary) or as a result of radiation therapy (RT) or lymphedema of the arm or breast following treatment of another malignancy (therapy-related). (See "Breast sarcoma: Epidemiology, risk factors, clinical presentation, diagnosis, and staging", section on 'Introduction'.)
●Multidisciplinary treatment approach – As with soft tissue sarcomas arising in other areas of the body, a multidisciplinary approach at an experienced center involving surgical, radiation, and medical oncologists is preferred. (See 'General principles' above.)
●Surgery – Surgery represents the only potentially curative modality for breast sarcomas. Mastectomy is often required for tumors that arise in previously irradiated tissue and for angiosarcomas. An adequate resection margin is the single most important determinant of long-term survival. (See 'Surgery' above.)
•We recommend not performing axillary lymph node dissection in the setting of a clinically negative axilla (Grade 1B). The incidence of lymphatic spread is low for most soft tissue sarcomas, and lymphadenectomy does not improve outcomes. (See 'Management of regional nodes' above.)
•Preoperative RT may be indicated for large, deep tumors in a previously unirradiated field where the surgeon expects close or positive margins. However, if the surgeon feels that adequate margins are likely to be obtained, we prefer surgery initially, reserving the decision regarding RT until after review of the final pathology from the resection specimen. (See 'Adjuvant radiation therapy' above.)
●Indications for adjuvant radiation therapy – The role of adjuvant RT for breast sarcomas is controversial. Our approach is as follows (see 'Adjuvant radiation therapy' above):
•We do not use adjuvant RT for most breast sarcomas if wide margins are achieved (>1 cm) either by wide resection or mastectomy. If resection margins are close, we obtain reresection to obtain wider margins, if feasible. (See 'Primary breast sarcomas' above.)
•We suggest the addition of adjuvant RT to surgical resection for select patients with positive margins in whom reresection is not feasible, or those with large high-grade lesions (>5 cm) and close, deep margins (Grade 2C). However, RT cannot compensate for inadequate surgery, and re-excision to ensure negative margins is strongly encouraged in these cases. (See 'Primary breast sarcomas' above.)
•For patients with radiation-associated secondary breast sarcomas, the role of adjuvant RT is unclear, and the decision to pursue reirradiation must be individualized. The amount of additional RT that may be given in a previously irradiated field is limited, and toxicities are greater. (See 'Radiotherapy-associated breast sarcomas' above.)
●Adjuvant chemotherapy – Adjuvant chemotherapy cannot be recommended routinely after resection of a breast sarcoma. Our approach is as follows:
•Indications – We suggest chemotherapy for patients with high-risk primary (stage III disease with tumor size >5 cm and high-grade, or node-positive (table 1)) or recurrent breast sarcoma, and for patients with an angiosarcoma between 3 and 5 cm (Grade 2C). However, given the limitations in the data and toxicities of chemotherapy, some patients and providers may reasonably opt against chemotherapy in this setting. (See 'Adjuvant chemotherapy' above.)
The use of adjuvant chemotherapy must be addressed on a case-by-case basis, taking into account the patient's performance status, age, comorbid factors, disease location, tumor size, histologic subtype, and treatment-related toxicities. The potential for benefit must be discussed in the context of expected treatment-related toxicities including sterility in younger individuals, cardiomyopathy, renal damage, second cancers, and overall impairment of quality of life.
•Choice of chemotherapy – For patients who decide to undergo adjuvant chemotherapy, as in other settings, we suggest using a regimen that contains both ifosfamide and doxorubicin (Grade 2B). (See 'Treatment approach' above and "Adjuvant and neoadjuvant chemotherapy for soft tissue sarcoma of the extremities", section on 'Summary' and "Treatment protocols for soft tissue and bone sarcoma".)
For patients with angiosarcoma, including treatment-related angiosarcomas who have previously received prior anthracycline-based chemotherapy, an adjuvant taxane-containing regimen is an appropriate alternative. (See "Overview of the initial treatment of metastatic soft tissue sarcoma", section on 'Angiosarcoma'.)
●Indications for neoadjuvant therapy – Neoadjuvant rather than adjuvant therapy may be an appropriate approach in the setting of a large or recurrent initially unresectable or borderline resectable high-grade tumor. The optimal form of neoadjuvant therapy in such situations is not established. Decisions about neoadjuvant therapy should be individualized and are best made within a multidisciplinary group of sarcoma experts. (See 'Neoadjuvant therapy for large, locally advanced, initially unresectable lesions' above.)
●Posttreatment surveillance – Following treatment, our approach to posttreatment surveillance is as follows (see 'Posttreatment cancer surveillance' above):
•For patients with stage I disease, we perform a history and physical examination at three- to six-month intervals for the first two years, and yearly thereafter. Periodic imaging of the primary site is also indicated.
•For patients with stage II or III (table 1) disease, we perform history and physical examination and chest imaging every three to six months for two to three years, then every six months for the next two years, then annually.
•For patients at higher risk of local recurrence such as those with positive margins or whose primary tumor site is not easily examined, MRI is preferred over CT scanning. (See 'Posttreatment cancer surveillance' above.)
●Recurrent or metastatic breast sarcoma
•Locally recurrent disease – Most breast sarcoma recurrences are local and surgery may be potentially curative. (See 'Treatment of recurrent or metastatic disease' above.)
•Metastatic disease – Palliative chemotherapy can offer some benefits in patients with metastatic breast sarcoma. In rare cases, potentially curative metastasectomy may be feasible; this is most likely in patients with isolated limited pulmonary metastases. (See "Overview of the initial treatment of metastatic soft tissue sarcoma" and "Surgical treatment and other localized therapy for metastatic soft tissue sarcoma", section on 'Pulmonary metastases'.)
ACKNOWLEDGEMENT — The UpToDate editorial staff acknowledges Thomas F DeLaney, MD, who contributed to an earlier version of this topic review.
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