Breast sarcoma: Epidemiology, risk factors, clinical presentation, diagnosis, and staging
- Rashmi Chugh, MD
Rashmi Chugh, MD
- Associate Professor of Medical Oncology
- University of Michigan Medical School
- Michael S Sabel, MD
Michael S Sabel, MD
- Associate Professor of Surgery
- University of Michigan Medical School
- Mary Feng, MD
Mary Feng, MD
- Associate Professor
- University of California at San Francisco
- Section Editors
- Robert Maki, MD, PhD
Robert Maki, MD, PhD
- Section Editor — Bone and Soft Tissue Tumors
- Professor of Medicine
- Monter Cancer Center
- Hofstra-Northwell School of Medicine
- Daniel F Hayes, MD
Daniel F Hayes, MD
- Section Editor — Breast Cancer
- Professor of Medicine
- University of Michigan School of Medicine
- Anees B Chagpar, MD, MSc, MA, MPH, MBA, FACS, FRCS(C)
Anees B Chagpar, MD, MSc, MA, MPH, MBA, FACS, FRCS(C)
- Section Editor — Breast Surgery
- Associate Professor, Department of Surgery
- Yale University School of Medicine
- Thomas F DeLaney, MD
Thomas F DeLaney, MD
- Section Editor — Bone and Soft Tissue Tumors
- Professor of Radiation Oncology
- Harvard Medical School
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 lymphedema of the arm or breast after treatment of another malignancy (therapy related, secondary) [2-6]. Although the clinical features of breast sarcoma mimic those of breast carcinoma in some ways, therapy and prognosis differ dramatically.
This topic review will cover the epidemiology, risk factors, clinical features, diagnosis and staging of breast sarcoma. Treatment and prognosis are discussed elsewhere as are other nonepithelial breast tumors including breast lymphomas, phyllodes tumors (including cystosarcoma phyllodes), and desmoid tumors of the breast. (See "Breast sarcoma: Treatment" and "Breast lymphoma" and "Desmoid tumors: Epidemiology, risk factors, molecular pathogenesis, clinical presentation, diagnosis, and local therapy", section on 'Breast desmoids'.)
Breast sarcomas are rare; they account for less than 1 percent of all breast malignancies  and <5 percent of all soft tissue sarcomas . In data compiled from the Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute, the annual incidence of breast sarcomas was 4.6 cases per million women .
The specific incidence of secondary, therapy-related breast sarcomas is difficult to discern. Secondary or treatment-related breast sarcomas most frequently arise following breast cancer treatment with RT. However, the absolute magnitude of the risk of a secondary breast sarcoma in women who undergo RT for breast cancer appears to be small (table 1).
The specific sarcoma subtype that is associated most strongly with treatment for a previous breast cancer is angiosarcoma. In a population-based study in Los Angeles County, the adjusted relative risk of developing an angiosarcoma for women with a prior diagnosis of breast cancer compared with women without breast cancer was 59 (95% CI 22-153) . Furthermore, women who receive RT as a component of breast cancer treatment have a 9- to 16-fold increase in the relative risk of developing an angiosarcoma relative to those treated with other modalities [6,11]. However, despite these high relative risks, the absolute magnitude of risk for a treatment-related angiosarcoma after RT remains small (table 1). The association between ionizing RT and breast sarcomas is discussed in more detail below. (See 'Ionizing radiation' below.)
- Berg JW, Hutter RV. Breast cancer. Cancer 1995; 75:257.
- Karlsson P, Holmberg E, Johansson KA, et al. Soft tissue sarcoma after treatment for breast cancer. Radiother Oncol 1996; 38:25.
- Brady MS, Garfein CF, Petrek JA, Brennan MF. Post-treatment sarcoma in breast cancer patients. Ann Surg Oncol 1994; 1:66.
- Lagrange JL, Ramaioli A, Chateau MC, et al. Sarcoma after radiation therapy: retrospective multiinstitutional study of 80 histologically confirmed cases. Radiation Therapist and Pathologist Groups of the Fédération Nationale des Centres de Lutte Contre le Cancer. Radiology 2000; 216:197.
- Blanchard DK, Reynolds C, Grant CS, et al. Radiation-induced breast sarcoma. Am J Surg 2002; 184:356.
- Huang J, Mackillop WJ. Increased risk of soft tissue sarcoma after radiotherapy in women with breast carcinoma. Cancer 2001; 92:172.
- McGowan TS, Cummings BJ, O'Sullivan B, et al. An analysis of 78 breast sarcoma patients without distant metastases at presentation. Int J Radiat Oncol Biol Phys 2000; 46:383.
- Russell WO, Cohen J, Enzinger F, et al. A clinical and pathological staging system for soft tissue sarcomas. Cancer 1977; 40:1562.
- Zelek L, Llombart-Cussac A, Terrier P, et al. Prognostic factors in primary breast sarcomas: a series of patients with long-term follow-up. J Clin Oncol 2003; 21:2583.
- Cozen W, Bernstein L, Wang F, et al. The risk of angiosarcoma following primary breast cancer. Br J Cancer 1999; 81:532.
- Yap J, Chuba PJ, Thomas R, et al. Sarcoma as a second malignancy after treatment for breast cancer. Int J Radiat Oncol Biol Phys 2002; 52:1231.
- Terrier P, Terrier-Lacombe MJ, Mouriesse H, et al. Primary breast sarcoma: a review of 33 cases with immunohistochemistry and prognostic factors. Breast Cancer Res Treat 1989; 13:39.
- Adem C, Reynolds C, Ingle JN, Nascimento AG. Primary breast sarcoma: clinicopathologic series from the Mayo Clinic and review of the literature. Br J Cancer 2004; 91:237.
- Blanchard DK, Reynolds CA, Grant CS, Donohue JH. Primary nonphylloides breast sarcomas. Am J Surg 2003; 186:359.
- Pandey M, Mathew A, Abraham EK, Rajan B. Primary sarcoma of the breast. J Surg Oncol 2004; 87:121.
- Granier G, Lemoine MC, Mares P, et al. [Primary angiosarcoma of the male breast]. Ann Pathol 2005; 25:235.
- Al-Benna S, Poggemann K, Steinau HU, Steinstraesser L. Diagnosis and management of primary breast sarcoma. Breast Cancer Res Treat 2010; 122:619.
- May DS, Stroup NE. The incidence of sarcomas of the breast among women in the United States, 1973-1986. Plast Reconstr Surg 1991; 87:193.
- Marchal C, Weber B, de Lafontan B, et al. Nine breast angiosarcomas after conservative treatment for breast carcinoma: a survey from French comprehensive Cancer Centers. Int J Radiat Oncol Biol Phys 1999; 44:113.
- Vorburger SA, Xing Y, Hunt KK, et al. Angiosarcoma of the breast. Cancer 2005; 104:2682.
- Shet T, Malaviya A, Nadkarni M, et al. Primary angiosarcoma of the breast: observations in Asian Indian women. J Surg Oncol 2006; 94:368.
- Sher T, Hennessy BT, Valero V, et al. Primary angiosarcomas of the breast. Cancer 2007; 110:173.
- Moore MP, Kinne DW. Breast sarcoma. Surg Clin North Am 1996; 76:383.
- STEWART FW, TREVES N. Lymphangiosarcoma in postmastectomy lymphedema; a report of six cases in elephantiasis chirurgica. Cancer 1948; 1:64.
- Sheth GR, Cranmer LD, Smith BD, et al. Radiation-induced sarcoma of the breast: a systematic review. Oncologist 2012; 17:405.
- Penel N, Grosjean J, Robin YM, et al. Frequency of certain established risk factors in soft tissue sarcomas in adults: a prospective descriptive study of 658 cases. Sarcoma 2008; 2008:459386.
- Kuttesch JF Jr, Wexler LH, Marcus RB, et al. Second malignancies after Ewing's sarcoma: radiation dose-dependency of secondary sarcomas. J Clin Oncol 1996; 14:2818.
- Overgaard M, Hansen PS, Overgaard J, et al. Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. Danish Breast Cancer Cooperative Group 82b Trial. N Engl J Med 1997; 337:949.
- Ragaz J, Jackson SM, Le N, et al. Adjuvant radiotherapy and chemotherapy in node-positive premenopausal women with breast cancer. N Engl J Med 1997; 337:956.
- Overgaard M, Jensen MB, Overgaard J, et al. Postoperative radiotherapy in high-risk postmenopausal breast-cancer patients given adjuvant tamoxifen: Danish Breast Cancer Cooperative Group DBCG 82c randomised trial. Lancet 1999; 353:1641.
- Rubino C, Shamsaldin A, Lê MG, et al. Radiation dose and risk of soft tissue and bone sarcoma after breast cancer treatment. Breast Cancer Res Treat 2005; 89:277.
- O'Brien MM, Donaldson SS, Balise RR, et al. Second malignant neoplasms in survivors of pediatric Hodgkin's lymphoma treated with low-dose radiation and chemotherapy. J Clin Oncol 2010; 28:1232.
- Kirova YM, Vilcoq JR, Asselain B, et al. Radiation-induced sarcomas after radiotherapy for breast carcinoma: a large-scale single-institution review. Cancer 2005; 104:856.
- Taghian A, de Vathaire F, Terrier P, et al. Long-term risk of sarcoma following radiation treatment for breast cancer. Int J Radiat Oncol Biol Phys 1991; 21:361.
- Zucali R, Merson M, Placucci M, et al. Soft tissue sarcoma of the breast after conservative surgery and irradiation for early mammary cancer. Radiother Oncol 1994; 30:271.
- Pierce SM, Recht A, Lingos TI, et al. Long-term radiation complications following conservative surgery (CS) and radiation therapy (RT) in patients with early stage breast cancer. Int J Radiat Oncol Biol Phys 1992; 23:915.
- Mery CM, George S, Bertagnolli MM, Raut CP. Secondary sarcomas after radiotherapy for breast cancer: sustained risk and poor survival. Cancer 2009; 115:4055.
- Laskin WB, Silverman TA, Enzinger FM. Postradiation soft tissue sarcomas. An analysis of 53 cases. Cancer 1988; 62:2330.
- Davidson T, Westbury G, Harmer CL. Radiation-induced soft-tissue sarcoma. Br J Surg 1986; 73:308.
- Chahin F, Paramesh A, Dwivedi A, et al. Angiosarcoma of the breast following breast preservation therapy and local radiation therapy for breast cancer. Breast J 2001; 7:120.
- Strobbe LJ, Peterse HL, van Tinteren H, et al. Angiosarcoma of the breast after conservation therapy for invasive cancer, the incidence and outcome. An unforseen sequela. Breast Cancer Res Treat 1998; 47:101.
- Billings SD, McKenney JK, Folpe AL, et al. Cutaneous angiosarcoma following breast-conserving surgery and radiation: an analysis of 27 cases. Am J Surg Pathol 2004; 28:781.
- Sessions SC, Smink RD Jr. Cutaneous angiosarcoma of the breast after segmental mastectomy and radiation therapy. Arch Surg 1992; 127:1362.
- Fineberg S, Rosen PP. Cutaneous angiosarcoma and atypical vascular lesions of the skin and breast after radiation therapy for breast carcinoma. Am J Clin Pathol 1994; 102:757.
- Krueger EA, Fraass BA, McShan DL, et al. Potential gains for irradiation of chest wall and regional nodes with intensity modulated radiotherapy. Int J Radiat Oncol Biol Phys 2003; 56:1023.
- Woodward AH, Ivins JC, Soule EH. Lymphangiosarcoma arising in chronic lymphedematous extremities. Cancer 1972; 30:562.
- Zahm SH, Fraumeni JF Jr. The epidemiology of soft tissue sarcoma. Semin Oncol 1997; 24:504.
- McGregor GI, Knowling MA, Este FA. Sarcoma and Cystosarcoma phyllodes tumors of the breast--a retrospective review of 58 cases. Am J Surg 1994; 167:477.
- Confavreux C, Lurkin A, Mitton N, et al. Sarcomas and malignant phyllodes tumours of the breast--a retrospective study. Eur J Cancer 2006; 42:2715.
- Bousquet G, Confavreux C, Magné N, et al. Outcome and prognostic factors in breast sarcoma: a multicenter study from the rare cancer network. Radiother Oncol 2007; 85:355.
- Rosen PP, Kimmel M, Ernsberger D. Mammary angiosarcoma. The prognostic significance of tumor differentiation. Cancer 1988; 62:2145.
- Donnell RM, Rosen PP, Lieberman PH, et al. Angiosarcoma and other vascular tumors of the breast. Am J Surg Pathol 1981; 5:629.
- Luini A, Gatti G, Diaz J, et al. Angiosarcoma of the breast: the experience of the European Institute of Oncology and a review of the literature. Breast Cancer Res Treat 2007; 105:81.
- Nascimento AF, Raut CP, Fletcher CD. Primary angiosarcoma of the breast: clinicopathologic analysis of 49 cases, suggesting that grade is not prognostic. Am J Surg Pathol 2008; 32:1896.
- Fletcher CDM, Bridge JA, Hogendoorn PCW, Mertens F. World Health Organization Classification of tumours of soft tissue and bone, 4th, IARC Press, Lyon 2013.
- Deyrup AT, Weiss SW. Grading of soft tissue sarcomas: the challenge of providing precise information in an imprecise world. Histopathology 2006; 48:42.
- Gutman H, Pollock RE, Ross MI, et al. Sarcoma of the breast: implications for extent of therapy. The M. D. Anderson experience. Surgery 1994; 116:505.
- Pollard SG, Marks PV, Temple LN, Thompson HH. Breast sarcoma. A clinicopathologic review of 25 cases. Cancer 1990; 66:941.
- North JH Jr, McPhee M, Arredondo M, Edge SB. Sarcoma of the breast: implications of the extent of local therapy. Am Surg 1998; 64:1059.
- Shabahang M, Franceschi D, Sundaram M, et al. Surgical management of primary breast sarcoma. Am Surg 2002; 68:673.
- Morgan EA, Kozono DE, Wang Q, et al. Cutaneous radiation-associated angiosarcoma of the breast: poor prognosis in a rare secondary malignancy. Ann Surg Oncol 2012; 19:3801.
- Smith TB, Gilcrease MZ, Santiago L, et al. Imaging features of primary breast sarcoma. AJR Am J Roentgenol 2012; 198:W386.
- Yang WT, Muttarak M, Ho LW. Nonmammary malignancies of the breast: ultrasound, CT, and MRI. Semin Ultrasound CT MR 2000; 21:375.
- Schnarkowski P, Kessler M, Arnholdt H, Helmberger T. Angiosarcoma of the breast: mammographic, sonographic, and pathological findings. Eur J Radiol 1997; 24:54.
- Liberman L, Dershaw DD, Kaufman RJ, Rosen PP. Angiosarcoma of the breast. Radiology 1992; 183:649.
- Williams EV, Banerjee D, Dallimore N, Monypenny IJ. Angiosarcoma of the breast following radiation therapy. Eur J Surg Oncol 1999; 25:221.
- Fant J, Grant M, May S, et al. Angiosarcoma of the breast: mammographic, clinical, and pathologic correlation. Breast J 2003; 9:252.
- Hodgson NC, Bowen-Wells C, Moffat F, et al. Angiosarcomas of the breast: a review of 70 cases. Am J Clin Oncol 2007; 30:570.
- Mills TD, Vinnicombe SJ, Wells CA, Carpenter R. Angiosarcoma of the breast after wide local excision and radiotherapy for breast carcinoma. Clin Radiol 2002; 57:63.
- Sanders LM, Groves AC, Schaefer S. Cutaneous angiosarcoma of the breast on MRI. AJR Am J Roentgenol 2006; 187:W143.
- Yang WT, Hennessy BT, Dryden MJ, et al. Mammary angiosarcomas: imaging findings in 24 patients. Radiology 2007; 242:725.
- Glazebrook KN, Morton MJ, Reynolds C. Vascular tumors of the breast: mammographic, sonographic, and MRI appearances. AJR Am J Roentgenol 2005; 184:331.
- Marchant LK, Orel SG, Perez-Jaffe LA, et al. Bilateral angiosarcoma of the breast on MR imaging. AJR Am J Roentgenol 1997; 169:1009.
- AJCC (American Joint Committee on Cancer). Cancer Staging Manual, 7th edition, Edge SB, Byrd DR, Compton CC, et al (Eds), Springer, New York 2010. p.291.
- Pollack R, Brennan M, Lawrence W Jr. Society of Surgical Oncology practice guidelines. Soft-tissue sarcoma surgical practice guidelines. Oncology (Williston Park) 1997; 11:1327.
- Bakheet SM, Powe J, Ezzat A, et al. F-18 FDG whole-body positron emission tomography scan in primary breast sarcoma. Clin Nucl Med 1998; 23:604.
- RISK FACTORS
- Ionizing radiation
- - Breast cancer survivors
- Inherited conditions
- Environmental factors
- HISTOLOGIC CLASSIFICATION
- CLINICAL FEATURES AND DIAGNOSIS
- - Imaging
- - Biopsy
- - Laboratory studies
- DIFFERENTIAL DIAGNOSIS
- Disease spread and the staging workup
- SUMMARY AND RECOMMENDATIONS