Primary nonphylloides breast sarcomas

The American Journal of Surgery 186 (2003) 359 –361

Scientific paper

Primary nonphylloides breast sarcomas D. Kay Blanchard, M.D., Ph.D.a, Carol A. Reynolds, M.D.b, Clive S. Grant, M.D.a, John H. Donohue, M.D.a,* a

Department of Surgery, Mayo W-6, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA b Department of Pathology, Mayo Clinic, Rochester, MN, USA Manuscript received June 3, 2003; revised manuscript June 21, 2003

Presented at the Fourth Annual Meeting of the American Society of Breast Surgeons, Atlanta, Georgia, April 30 –May 4, 2003

Abstract Background: The prevalence of primary breast sarcoma is low, occurring in fewer than 1% of women with breast malignancies. The purpose of this study was to examine the presentation, treatment, and prognosis of patients presenting with these neoplasms. Methods: This was a retrospective review of patients with a primary breast sarcoma treated at Mayo Clinic, Rochester, Minnesota, between 1975 and 2001. Follow-up information was obtained. Results: Of the 55 patients, 17 had breast-conserving therapy and 38 women had mastectomy. The mean patient age at presentation was 52 years (range 22 to 82). The types of sarcoma included angiosarcoma (18), malignant fibrous histiocytoma (11), stromal sarcoma (8), liposarcoma (4), leiomyosarcoma (4), dermatofibrosarcoma protuberans (4), osteosarcoma (3), fibrosarcoma (2), and rhabdomyosarcoma (1). Follow-up information was available for 53 patients, with a mean follow-up of 81 months. Twenty-nine of 53 patients (55%) developed recurrent sarcoma, and 23 patients (43%) died of their disease. Twenty-seven patients had no evidence of recurrence, and 3 patients were alive with disease at last follow-up. Overall median survival of patients with breast sarcoma was 58 months. Patients with angiosarcoma had a poorer outcome than other sarcoma patients. Twelve of 18 patients (67%) died of angiosarcoma, compared with 11 of 32 patients (34%) of all other sarcoma patients combined. Of 34 patients who did not receive adjuvant chemotherapy or radiation, 13 died of their disease (38%), as compared with 10 of 16 patients (63%) who did receive adjuvant therapy. Conclusions: While primary nonphylloides breast sarcomas are rare tumors, their treatment and prognosis are poor. Adjuvant chemotherapy and radiation did not improve survival in this report. Surgical extirpation remains the only effective treatment. © 2003 Excerpta Medica, Inc. All rights reserved. Keywords: Breast neoplasms; Primary breast sarcoma; Angiosarcoma; Malignant fibrous histiocytoma

Primary breast sarcoma is a rare entity, comprising less than 1% of all breast malignancies [1,2]. Surgical resection is the primary treatment for these lesions, with an unclear role for adjuvant chemotherapy or radiation [3,4]. While other soft tissue sarcomas, particularly those found on the extremity, are responsive to radiotherapy, the optimal treatment of breast sarcomas is unclear owing to the rarity of these tumors.

with a primary breast sarcoma were performed. Patients with phylloides tumors were excluded from this review. The study was approved by the Institutional Review Board. Follow-up data on 53 patients were obtained. Two patients were lost to follow-up. Statistical analyses were performed by JMP software, version 4.0.4, utilizing one-way analysis of variance, univariate survival analysis, and Fisher exact t tests.

Methods Results For the present study, retrospective chart reviews of patients diagnosed from 1975 to 2001 at the Mayo Clinic * Corresponding author. Tel.: ⫹1-507-284-0362; fax: ⫹1-507-2845196.

The mean age of patients at the time of the breast sarcoma was 52 years (range 22 to 82). The histopathology of the sarcomas included: angiosarcoma (n ⫽ 18), malignant fibrous histiocytoma ([MFH] n ⫽ 11), stromal sarcoma (8),

0002-9610/03/$ – see front matter © 2003 Excerpta Medica, Inc. All rights reserved. doi:10.1016/S0002-9610(03)00269-1

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K. Blanchard et al. / The American Journal of Surgery 186 (2003) 359 –361 Table 2 Median survival and disease-free survival according to histologic type

Table 1 Size of tumors according to histological type Histologic type

Number (%)

Size ⫾ SD (cm)*

Angiosarcoma MFH Stromal sarcoma Liposarcoma Leiomyosarcoma DFSP Osteosarcoma Fibrosarcoma Rhabdomyosarcoma All

18 (34) 11 (21) 8 (15) 4 (8) 4 (8) 4 (8) 2 (4) 1 (2) 1 (2) 53 (100)

4.5 ⫾ 3.2 3.5 ⫾ 2.3 7.7 ⫾ 3.9 3.7 ⫾ 2.0 7.3 ⫾ 10.5 4.1 ⫾ 2.5 7.0 ⫾ 4.2 5.2 4.7 5.8 ⫾ 5.8

* No significant differences (P ⬎ 0.05). MFH ⫽ malignant fibrous histocytoma; DFSP ⫽ dermatofibrosarcoma protuberans.

liposarcoma (n ⫽ 4), leiomyosarcoma (n ⫽ 4), dermatofibrosarcoma protuberans (n ⫽ 4), osteogenic sarcoma (n ⫽ 3), fibroblastic sarcoma (n ⫽ 2), and rhabdomyosarcoma (n ⫽ 1). As shown in Table 1, size of the original tumors did not differ significantly according to histologic type. All patients underwent surgical therapy as primary treatment. Sixteen women had wide local excision of their lesion, 17 had a simple mastectomy, and 22 had a modified radical mastectomy. Thirty-eight patients had negative margins, 4 patients had microscopically involved margins, and the margin status of 13 patients was not specified. Of the 22 patients with axillary dissections, positive nodes were found in 2 patients; 1 patient with MFH had 1 of 4 nodes positive, and the patient with rhabdomyosarcoma had 5 of 9 nodes positive for metastases. Both patients also had distant metastatic disease at presentation. During a mean follow-up period of 81 months, 29 of 53 patients (55%) developed recurrent disease. Mean time to recurrence was 25 months (median 13). Patterns of failure included 10 patients with local recurrence only, 14 patients with distant metastases, 3 patients with both local and distant failure, and 2 patients with recurrence at unknown locations. Overall, 23 of 53 patients (43%) died of their disease, and 3 patients were alive with recurrent sarcoma at last follow-up. Median survival of patients with breast sarcoma was 58 months (range 5 to 310), and median diseasefree survival was 13 months (range 3 to 117). Analyses were performed to determine factors that influenced recurrence and overall survival. All 4 patients with microscopically involved margins of their original tumor died of their disease, with recurrences diagnosed at 4, 13, 21, and 78 months. Of the 36 patients with negative margins for whom follow-up information was available, 21 patients (58%) had no evidence of recurrent disease (P ⫽ 0.034). Of the 13 patients with unknown margin status, 5 patients (38%) had no evidence of recurrent disease at last followup. The extent of the surgical resection did not affect overall survival or recurrence rates. Of the 16 patients having wide

Histology

N

Overall survival (months)

Disease-free survival (months)

Angiosarcoma MFH Stromal sarcoma Liposarcoma Leiomyosarcoma DFSP Osteosarcoma Fibrosarcoma Rhabdomyosarcoma All

18 11 8 4 4 4 2 1 1 53

60 58 122 58 155 83 41 48 7 58

25 9 7 54 117 18 41 54 7 13

MFH ⫽ malignant fibrous histiocytoma; DFSP ⫽ dermatofibrosarcoma protuberans.

local excision of their tumor, 6 patients (38%) developed recurrent disease and 4 patients died of their disease (25%). Thirty-seven patients had either simple mastectomy or modified radical mastectomy; 23 of those recurred (62%) and 19 died of metastatic disease (51%; P ⬎ 0.05). In this study, there was no correlation between the size of the primary tumor and risk of recurrence or death from disease. Of the 22 patients that had recurrent disease, mean tumor size was 5.7 ⫾ 3.3 cm, compared with 5.0 ⫾ 4.8 cm for the 24 patients without recurrence (P ⫽ 0.44). The tumor size of the 25 patients without evidence of disease at follow-up was 4.9 ⫾ 4.8 cm, compared with 5.8 ⫾ 3.5 cm of 18 patients who died of disease (P ⫽ 0.34). There was also no statistical difference between recurrence or overall survival and the histologic grade of sarcoma (data not shown). The histopathology did not significantly influence patient survival in this study. The median overall survival and disease-free survival by histology type are shown in Table 2. When angiosarcoma results were compared with the other sarcomas, the patient mortality was higher with 12 of 18 patients (67%) dying of this tumor, compared with 11 of 32 patients (34%) of all other breast sarcomas combined (P ⫽ 0.06). Compared with the other subtypes MFH revealed no significant differences. Five of 11 patients (36%) died with MFH versus 19 of 42 patients (45%) with other sarcomas (P ⫽ 0.72). Thirty-four patients (68%) received no adjuvant therapy after surgical extirpation of their primary tumor. Five patients (10%) had adjuvant chemotherapy, 8 patients (16%) received radiation to the affected breast or chest wall, and 3 patients (6%) had both chemotherapy and radiation. The effect of adjuvant therapy on disease-free survival is shown in Table 3. In this experience, administration of adjuvant therapy was inversely related to disease-free survival, (P ⫽ 0.026). Of the patients who did not receive adjuvant therapy, 20 (59%) had no evidence of disease at follow-up and 14 patients (41%) developed recurrent sarcoma. In contrast, of 16 patients who received adjuvant therapy; only 4 (25%)

K. Blanchard et al. / The American Journal of Surgery 186 (2003) 359 –361 Table 3 Effect of adjuvant therapy on survival Adjuvant treatment

Disease-free survival (%)

Overall survival (%)

None Chemotherapy or radiation therapy or both Total

20/34 (59%) 4/16 (25%)

21/34 (62%) 5/16 (31%)

24/50 (48%)

26/50 (52%)

had no tumor recurrence. Similar adverse results were noted for overall survival after adjuvant therapy. Of 34 patients who did not receive chemotherapy or radiation, 13 died of their disease (38%), compared with 10 of 16 patients (63%) who received adjuvant therapy (P ⫽ 0.050). Comments As suggested in other reports on primary breast sarcomas, complete microscopic resection of the primary tumor is an important factor for local disease control [3,4], and was an important factor in overall survival and disease-free survival in the present report. Mastectomy was not found to be necessary to improve disease-free survival in this report, and wide local excision yielded as good local control. Axillary dissection is generally thought of as unnecessary for most soft tissue sarcomas, since these tumors rarely metastasize through lymphatics [3– 6]. Surprisingly, of the 22 axillary dissections performed in the present study, 2 showed metastatically involved lymph nodes. However, both patients presented with widespread disease. In this retrospective study of breast sarcomas, there was no significant correlation found between size of primary tumor and overall survival or disease-free survival. This differs from other reports that noted an increased mortality with larger tumor size [3,5,7]. The present data represent a 26-year period and 9 different histologic types of sarcoma. The lack of statistically significant differences may have been due to sample size or the wide range of tumor sizes and malignant potential. Another useful prognostic indicator for soft-tissue sarcomas is the tumor grade, with higher mitotic indices correlating with higher mortality [4,7,8]. In the present study, 70% of tumors were reported as grade 3 or 4. No significant correlations were noted between grade and patient survival or disease recurrence, again likely due to the sample size and tumor diversity. Some authors [6,9] have suggested that angiosarcoma has a different clinical course than other sarcomas. In this report, patients with angiosarcoma had a higher mortality compared with patients with other histologic types, although this value did not reach statistical significance.

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The role of radiation and chemotherapy in breast sarcoma is unclear. While some authors [4,9] suggest radiation is efficacious after surgical resection, particularly with microscopically involved margins, this was not demonstrable in our experience. Only 16 of 50 patients (32%) with follow-up information received adjuvant therapy, with 11 who had radiation therapy. There was no improvement in overall survival or disease-free survival with adjuvant therapy, probably because it was reserved for patients with unfavorable tumor features. Three patients had received radiation therapy because of microscopically involved chest wall margins. Despite this treatment, all developed local failure and died of metastatic disease. The optimal treatment of primary breast sarcoma is still to be clarified. For the nonmetastatic breast sarcoma, the most important treatment element in maximizing diseasefree survival and overall survival is complete surgical removal of the sarcoma. If this can be accomplished with breast conservation therapy, this provides outcomes comparable with mastectomy. An axillary dissection is not warranted unless clinically involved lymph nodes are apparent. Although patients with completely resected, high-grade sarcomas are at significant risk for distant recurrent disease, no routine systemic adjuvant therapy can be currently recommended. For patients in whom surgical margins are limited or microscopically involved, adjuvant or therapeutic radiation therapy should be considered.

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