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Angiosarcoma of the breast and pregnancy: a new therapeutic approach
European Journal of Obstetrics Br Gynecology and Reproductive Biology 60 (1995) 87-89
ELSEVIER
Case report
An~osar~o~a of the breast and pre~ancy: a new therapeutic approach G. Barrenetxea*a, J. Schneidera, J-G. Tknagob, C. Pkrez”, MM. Centenoa, F.J. Rodriguez-Escuderoa ‘~e~r~~~~ ofObstetricsand Gyne&o~~y, HosFitaI de
Cruces (~~ecaI~~). Un~versi~ del Pais Vasco. Baracaiado ( Vizcaya). Bilbao, Spain ‘Department of Phthology, Hospital de Cruces (Ginecologia), Universidad del Pais Vasco, Baracalado (Vizcaya), Bilbao, Spain
Accepted 5 December 1994
Abstract
A case of angiosarcoma of the breast managed primarily by a chemotherapeutic approach is referred. A 29-year-old patient presented complaining of a painful mass in her right breast. An incisional biopsy carried out under general anesthesia showed a m~era~lydifferentiat~ angiosarcoma surrounded by fibrofatty tissue. Ruled out distant metastases, a decision was made to initiate neoadjuvant chemotherapy consisting of ifosfamide, vincristine and dactinimycin. After 2 courses of chemotherapy the tumor volume was reduced by 50% and the histologic examination of the mastectomy specimen revealed a well-differentiated angiosarcoma with widespread areas of necrosis probably produced by previous chemo~erapic treatment. The patient is clinically free of disease after 24 months of follow-up. Although this is a single case report, and by no means can be considered a guideline for future treatments, we nevertheless feel that the result obtained with the chemotherapeutic approach with this patient is encouraging. Keywords:
Mammary angiosarcoma;
Pregnancy
1. Introductlnn Angiosarcoma of the breast is a rare but highly malignant tumor of vascular origin. Sarcomas account for about O.l-0.5% of malignant tumors of the breast and the relative incidence of angiosarcoma among breast sarcomas ranges between 2.7% and 9.1%. In latter times, the incidence of cutaneous angiosarcoma after radiotherapy involved in breast conserving therapy for rn~a~ carcinoma has increased, and begins to be a matter of concern [ 1,2]. A variety of names have been applied to this lesion: angiosarcoma, hemangioendothelioma, heman~oblastoma and hemangiosarcoma [ 31. Angiosarcoma has the poorest prognosis of all breast malignancies. Death is usually the result of widespread metastatic disease [4,5]. The mean survival after diagnosis is 1.9-2.1 years [S]. Tumor type or grade is the single * Corresponding author.
most important prognostic factor described for mammary angiosarcoma so far [6,7]. The mean length of disease-free was 15 years, 12 years and 15 months for type I, II and III angiosarcomas in the series of Rosen et al. IS]. Tumor size and degree. of tumor differentiation are the important prognostic determinants, and the majority of long-term disease-free survivors had lesions less than 4 cm in size [S]. Surgery has been the standard treatment for this condition according to most reports, ranging from wide excision of the lesion to radical mastectomy [S]. Dactinomycin has been found to prolong survival in one study. Experience with chemothe~py for the treatment of breast angiosarcoma is, however, limited. 2. case report A 29-year-old patient presented on October 1992 in the 34th week of her second pregnancy, which had been uneventful until then complaining of a painful mass in
~28-~43#5~~.50 0 1995 Elsevier Science Ireland Ltd. All rights reserved SSDI 0028-2243(94)02029-
88
G. ~rr~~~lxea
et al. i European Journal
ofObstetrirs
& Gynecology md R~prod~~~~v~ Ri~iogy 60 (1995)
Fig. I. The biopsy showed a moderately-differentiated
her right breast. There was no family history of breast cancer. The patient had never received irradiation to the breast or chest wall. She had first noticed the mass 4 months before. A mammogram and an ultrasound examination at that time had been unconclusive. A breast aspiration consisting of bloody fluid had been also performed, and no malignant cells had been found in the cytological study. On physical examination, the right breast was notably larger than the left. A 10 x 10 cm tender, hard mass
87-89
angiosarcoma surrounded by iibrofatty tissue.
was palpable, ~upying the whole right breast. The mass did not appear to be fixed to the chest wall. There was increase in temperature of the breast. No angiomata were present on the skin. No axillary, supraclavicular or cervical nodes could be palpated. A &u-cut biopsy performed at the time of presentation at our hospital did not reveal malignancy. A larger incisional biopsy was then carried out under general anesthesia and showed a moderately-differentiated angiosarcoma surrounded by fibrofatty tissue (Fig. 1).
Fig. 2. The histologic examination revealed a well-differentiated angiosarcoma of the breast with widespread areas of necrosis probably produced by the chemotherapeutic treatment.
G. 3arrg~gtxea
et al. / Europem
journal
of obstetrics & Gyneeoiogy and reprobative
Screening for metastases, including chest X-ray, liver enzymes and abdominal ultrasound examination was negative. A decision was made together with the patient to initiate neoadjuvant chemotherapy immediately after delivery. The patient delivered vaginally a healthy male weighing 3450 g at 36 weeks’ gestation. The systemic work-up was completed at this point with a bone scan and distant metastases were ruled out. Induction polychemotherapy was then initiated consisting of ifosfamide 3000 mg/m* (on days 1, 2, and 3), vincristine 1.5 mg/m* (on days 1, 8, and 15), dactinomycin 1.5 mg/m* (on day 1) and mesna 3.6 mg/m* (on days 1, 2, and 3) every 3 weeks, which was well tolerated. After two courses of chemotherapy the tumor volume was reduced by 50%, and a simple mastectomy was performed. The mast~tomy specimen showed areas of haemorrhage and hemosiderin deposits. Histologic examination revealed a well-differentiated angiosarcoma of the breast with widespread areas of necrosis probably produced by the chemotherapeutic treatment (Fig. 2). The therapeutic approach was completed with two additional courses of the same chemotherapy regimen. During the follow-up clinical examinations, contralateral ma~o~ams, liver ultrasound examinations, X-ray chest exams, bone scans and liver enzymes determinations were performed. The patient is clinically free of disease after 24 months of follow-up. A reconstruction of the breast is being considered. 3. Discussion Patients with mammary angiosarcoma tend to be younger than patients with mammal aden~rcino~ [S,S]. Due to the relative youth of patients with angiosarcoma, it is not surprising that this tumor has developed in a number of patients while they were pregnant. Coexisting pregnancy and mammary angiosarcoma were found in 6% of patients of the series of Rosen et al. [SJ. There is no evidence that these tumors are hormone dependent, although the presence of estrogen and glucocorticoid receptors in breast angiosarcomas has been reported [9]. Until recently, early and complete surgical excision has been considered the only successful curative treatment for angiosarcoma of the breast. Because axillary node metastases are rare and fixation to skin and chest wall is unusual, simple mast~tomy is considered the procedure of choice 151.Care must be taken to obtain tumor-free surgical margins, because the neoplasm often extends microscopically beyond its gross limits. Although initial studies proved that both radiotherapy and chemotherapy were ineffective, with no significant improvement in survival [lo], most reports referred to large lesions or to cases with dis-
Biology 60 (199s)
87-89
89
seminated disease. More recent reports suggest that adjuvant chemotherapy may improve survival in patients with mammary angiosarcoma [l I]. Rosen et al. reported a series of 63 patients with different therapeutic approaches. The recurrence rate of their patients was 24%, 33% and 85% for type I, II and III angiosarcoma, respectively. The recurrence rate was lower for patients treated with adjuvant chemotherapy 181. Neoadjuvant therapy for reducing large or inoperable lesions has been first reported by Bonadonna et al. [12] in a large series with successful preliminary results. These tumors were all in~l~ating ductal carcinomas. The treatment modality, besides reducing the tumor volume preoperatively, also allows one to monitor the response to chemotherapy ‘in vivo’. We chose this approach with our patient, which has not been reported previously for this kind of tumor, for both these reasons. Although this is only a single case report, and by no means can be considered a guideline for future treatment, we nevertheless feel that the result obtained with this single patient is encouraging. References 111Zucali R, Merson M, Placucci M, Di Pahna S, Veronesi U. Soft tissue sarcoma of the breast after conservative surgery and irradiation for early mammary cancer. Radiother Oncol, 1994; 30: 271-273. 121Del Mastro L, Garrone 0, Guenzi M, Nicolo G, Rosso R, Venturini M. Angiosarcoma of the residual breast after conservative surgery and radiotherapy for primary carcinoma. Ann Oncol, 1994; 5: 163-165. 131 Ryan JF, Kealy WF. Concomitant angiosarcoma and carcinoma of the breast: a cese report. Histopathology, 1985; 9: 893-899. [41 Stewart FW. Tumors of the breast. In: Armed Forces Institute of Pathology. Section IX Fascicle 34. Atlas of tumor pathology; 1950: 75, Washin~on, DC. PI Hunter ThB, Martin PC, Dietzen CD, Tyler LT. Angiosarcoma of the breast. Two case reports and a review of the literature. Cancer, 1985; 56: 2099-2106. H Rosner D. Angiosarcoma of the breast: long-term survival following adjuvant chemotherapy. J Surg Oncol, 1988; 39: 90-95. VI Sellke FW, Loughry CW, Kashkari S. Angiosarcoma of the breast: report of two long-term survivals. Int Surg, 1988; 73: 193-19s. an~o~rcoma. Bl Rosen PP, Kirnmel M, Ernsberger D. Mamas The prognostic significance of tumor differentiation. Cancer, 1988; 62: 2145-2151. [91 Brentani MM, Pacheco MM, Oshima CT, Nagai MA, Lemos LR Goes JC. Steroid receptors in breast angiosarcoma. Cancer, 1983; 51: 2105-2111. wx Savage R. The treatment of angiosarcoma of the breast. J Surg Oncol, 1981; 18; 129-134. IllI Donnell RM, Rosen PP, Lieberman PH. Angiosarcoma and other vascular tumors of the breast. Am J Surg Pathol, 1981; 5: 629-642. WI Bonadonna G, Veronesi U, Brambilla C, Ferrari L, Luinia A, Greco M et al. Primary chemotherapy to avoid mastectomy in tumors with diameters of three centimetres or more. J Nat1 Cancer Inst, 1990; 82: 1539.
ELSEVIER
Case report
An~osar~o~a of the breast and pre~ancy: a new therapeutic approach G. Barrenetxea*a, J. Schneidera, J-G. Tknagob, C. Pkrez”, MM. Centenoa, F.J. Rodriguez-Escuderoa ‘~e~r~~~~ ofObstetricsand Gyne&o~~y, HosFitaI de
Cruces (~~ecaI~~). Un~versi~ del Pais Vasco. Baracaiado ( Vizcaya). Bilbao, Spain ‘Department of Phthology, Hospital de Cruces (Ginecologia), Universidad del Pais Vasco, Baracalado (Vizcaya), Bilbao, Spain
Accepted 5 December 1994
Abstract
A case of angiosarcoma of the breast managed primarily by a chemotherapeutic approach is referred. A 29-year-old patient presented complaining of a painful mass in her right breast. An incisional biopsy carried out under general anesthesia showed a m~era~lydifferentiat~ angiosarcoma surrounded by fibrofatty tissue. Ruled out distant metastases, a decision was made to initiate neoadjuvant chemotherapy consisting of ifosfamide, vincristine and dactinimycin. After 2 courses of chemotherapy the tumor volume was reduced by 50% and the histologic examination of the mastectomy specimen revealed a well-differentiated angiosarcoma with widespread areas of necrosis probably produced by previous chemo~erapic treatment. The patient is clinically free of disease after 24 months of follow-up. Although this is a single case report, and by no means can be considered a guideline for future treatments, we nevertheless feel that the result obtained with the chemotherapeutic approach with this patient is encouraging. Keywords:
Mammary angiosarcoma;
Pregnancy
1. Introductlnn Angiosarcoma of the breast is a rare but highly malignant tumor of vascular origin. Sarcomas account for about O.l-0.5% of malignant tumors of the breast and the relative incidence of angiosarcoma among breast sarcomas ranges between 2.7% and 9.1%. In latter times, the incidence of cutaneous angiosarcoma after radiotherapy involved in breast conserving therapy for rn~a~ carcinoma has increased, and begins to be a matter of concern [ 1,2]. A variety of names have been applied to this lesion: angiosarcoma, hemangioendothelioma, heman~oblastoma and hemangiosarcoma [ 31. Angiosarcoma has the poorest prognosis of all breast malignancies. Death is usually the result of widespread metastatic disease [4,5]. The mean survival after diagnosis is 1.9-2.1 years [S]. Tumor type or grade is the single * Corresponding author.
most important prognostic factor described for mammary angiosarcoma so far [6,7]. The mean length of disease-free was 15 years, 12 years and 15 months for type I, II and III angiosarcomas in the series of Rosen et al. IS]. Tumor size and degree. of tumor differentiation are the important prognostic determinants, and the majority of long-term disease-free survivors had lesions less than 4 cm in size [S]. Surgery has been the standard treatment for this condition according to most reports, ranging from wide excision of the lesion to radical mastectomy [S]. Dactinomycin has been found to prolong survival in one study. Experience with chemothe~py for the treatment of breast angiosarcoma is, however, limited. 2. case report A 29-year-old patient presented on October 1992 in the 34th week of her second pregnancy, which had been uneventful until then complaining of a painful mass in
~28-~43#5~~.50 0 1995 Elsevier Science Ireland Ltd. All rights reserved SSDI 0028-2243(94)02029-
88
G. ~rr~~~lxea
et al. i European Journal
ofObstetrirs
& Gynecology md R~prod~~~~v~ Ri~iogy 60 (1995)
Fig. I. The biopsy showed a moderately-differentiated
her right breast. There was no family history of breast cancer. The patient had never received irradiation to the breast or chest wall. She had first noticed the mass 4 months before. A mammogram and an ultrasound examination at that time had been unconclusive. A breast aspiration consisting of bloody fluid had been also performed, and no malignant cells had been found in the cytological study. On physical examination, the right breast was notably larger than the left. A 10 x 10 cm tender, hard mass
87-89
angiosarcoma surrounded by iibrofatty tissue.
was palpable, ~upying the whole right breast. The mass did not appear to be fixed to the chest wall. There was increase in temperature of the breast. No angiomata were present on the skin. No axillary, supraclavicular or cervical nodes could be palpated. A &u-cut biopsy performed at the time of presentation at our hospital did not reveal malignancy. A larger incisional biopsy was then carried out under general anesthesia and showed a moderately-differentiated angiosarcoma surrounded by fibrofatty tissue (Fig. 1).
Fig. 2. The histologic examination revealed a well-differentiated angiosarcoma of the breast with widespread areas of necrosis probably produced by the chemotherapeutic treatment.
G. 3arrg~gtxea
et al. / Europem
journal
of obstetrics & Gyneeoiogy and reprobative
Screening for metastases, including chest X-ray, liver enzymes and abdominal ultrasound examination was negative. A decision was made together with the patient to initiate neoadjuvant chemotherapy immediately after delivery. The patient delivered vaginally a healthy male weighing 3450 g at 36 weeks’ gestation. The systemic work-up was completed at this point with a bone scan and distant metastases were ruled out. Induction polychemotherapy was then initiated consisting of ifosfamide 3000 mg/m* (on days 1, 2, and 3), vincristine 1.5 mg/m* (on days 1, 8, and 15), dactinomycin 1.5 mg/m* (on day 1) and mesna 3.6 mg/m* (on days 1, 2, and 3) every 3 weeks, which was well tolerated. After two courses of chemotherapy the tumor volume was reduced by 50%, and a simple mastectomy was performed. The mast~tomy specimen showed areas of haemorrhage and hemosiderin deposits. Histologic examination revealed a well-differentiated angiosarcoma of the breast with widespread areas of necrosis probably produced by the chemotherapeutic treatment (Fig. 2). The therapeutic approach was completed with two additional courses of the same chemotherapy regimen. During the follow-up clinical examinations, contralateral ma~o~ams, liver ultrasound examinations, X-ray chest exams, bone scans and liver enzymes determinations were performed. The patient is clinically free of disease after 24 months of follow-up. A reconstruction of the breast is being considered. 3. Discussion Patients with mammary angiosarcoma tend to be younger than patients with mammal aden~rcino~ [S,S]. Due to the relative youth of patients with angiosarcoma, it is not surprising that this tumor has developed in a number of patients while they were pregnant. Coexisting pregnancy and mammary angiosarcoma were found in 6% of patients of the series of Rosen et al. [SJ. There is no evidence that these tumors are hormone dependent, although the presence of estrogen and glucocorticoid receptors in breast angiosarcomas has been reported [9]. Until recently, early and complete surgical excision has been considered the only successful curative treatment for angiosarcoma of the breast. Because axillary node metastases are rare and fixation to skin and chest wall is unusual, simple mast~tomy is considered the procedure of choice 151.Care must be taken to obtain tumor-free surgical margins, because the neoplasm often extends microscopically beyond its gross limits. Although initial studies proved that both radiotherapy and chemotherapy were ineffective, with no significant improvement in survival [lo], most reports referred to large lesions or to cases with dis-
Biology 60 (199s)
87-89
89
seminated disease. More recent reports suggest that adjuvant chemotherapy may improve survival in patients with mammary angiosarcoma [l I]. Rosen et al. reported a series of 63 patients with different therapeutic approaches. The recurrence rate of their patients was 24%, 33% and 85% for type I, II and III angiosarcoma, respectively. The recurrence rate was lower for patients treated with adjuvant chemotherapy 181. Neoadjuvant therapy for reducing large or inoperable lesions has been first reported by Bonadonna et al. [12] in a large series with successful preliminary results. These tumors were all in~l~ating ductal carcinomas. The treatment modality, besides reducing the tumor volume preoperatively, also allows one to monitor the response to chemotherapy ‘in vivo’. We chose this approach with our patient, which has not been reported previously for this kind of tumor, for both these reasons. Although this is only a single case report, and by no means can be considered a guideline for future treatment, we nevertheless feel that the result obtained with this single patient is encouraging. References 111Zucali R, Merson M, Placucci M, Di Pahna S, Veronesi U. Soft tissue sarcoma of the breast after conservative surgery and irradiation for early mammary cancer. Radiother Oncol, 1994; 30: 271-273. 121Del Mastro L, Garrone 0, Guenzi M, Nicolo G, Rosso R, Venturini M. Angiosarcoma of the residual breast after conservative surgery and radiotherapy for primary carcinoma. Ann Oncol, 1994; 5: 163-165. 131 Ryan JF, Kealy WF. Concomitant angiosarcoma and carcinoma of the breast: a cese report. Histopathology, 1985; 9: 893-899. [41 Stewart FW. Tumors of the breast. In: Armed Forces Institute of Pathology. Section IX Fascicle 34. Atlas of tumor pathology; 1950: 75, Washin~on, DC. PI Hunter ThB, Martin PC, Dietzen CD, Tyler LT. Angiosarcoma of the breast. Two case reports and a review of the literature. Cancer, 1985; 56: 2099-2106. H Rosner D. Angiosarcoma of the breast: long-term survival following adjuvant chemotherapy. J Surg Oncol, 1988; 39: 90-95. VI Sellke FW, Loughry CW, Kashkari S. Angiosarcoma of the breast: report of two long-term survivals. Int Surg, 1988; 73: 193-19s. an~o~rcoma. Bl Rosen PP, Kirnmel M, Ernsberger D. Mamas The prognostic significance of tumor differentiation. Cancer, 1988; 62: 2145-2151. [91 Brentani MM, Pacheco MM, Oshima CT, Nagai MA, Lemos LR Goes JC. Steroid receptors in breast angiosarcoma. Cancer, 1983; 51: 2105-2111. wx Savage R. The treatment of angiosarcoma of the breast. J Surg Oncol, 1981; 18; 129-134. IllI Donnell RM, Rosen PP, Lieberman PH. Angiosarcoma and other vascular tumors of the breast. Am J Surg Pathol, 1981; 5: 629-642. WI Bonadonna G, Veronesi U, Brambilla C, Ferrari L, Luinia A, Greco M et al. Primary chemotherapy to avoid mastectomy in tumors with diameters of three centimetres or more. J Nat1 Cancer Inst, 1990; 82: 1539.