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Breast cancer and second primary ovarian cancer in dermatomyositis
GYNECOLOGIC
ONCOLOGY
43, 286-290 (1991)
CASE REPORT Breast Cancer and Second Primary Ovarian Cancer in Dermatomyositis NARIN VORAVUD,
MELETIOS
DIMOPOULOS,
GABRIEL
HORTOBAGYI,
MERRICK Ross, AND RICHARD THERIAULT’
Department of Medical Oncology, The University of Texas M. D. Anderson Cancer Center, I515 Holcombe Boulevard, Houszon, Texa 77030 Received February 19, 1991
We report six femalepatientswith breastcancerwho developed dermatomyositisand compareour data with those from other reports. The developmentof dermatomyositisin two patientsled to the discovery of a secondprimary ovarian carcinoma,whereas the developmentof dermatomyositisin another two patients led to the discovery of recurrent breastcancer. In three patients the diagnosisof dermatomyositisprecededthe diagnosisof breast cancer, while the rest developeddermatomyositisafter the diagnosisof breast cancer. A parallel clinical courseof dermatomyositisand breast cancer was seenin only one patient. Coexisting dermatomyositisand breastcancer is a rare phenomenon, and dermatomyositisthat developsduring the courseof breast cancer may indicate the occurrenceof a secondprimary malignancy or recurrent breastcancer. The onsetof dermatomyositis may precede, coincide with, or follow the diagnosisof breast cancer. The clinical courseof dermatomyositissometimes,but not always, parallels the courseof breastcancer. There are no specificclinical or laboratory markersto distinguishpatientswith dermatomyositiswho have malignancyfrom thosewithout cancer. 0 1991 Academic
Press, Inc.
INTRODUCTION
An estimated 150,900 new cases of breast cancer, the most common neoplasm in American women, will be reported in this country in 1990 [l] and, in rare cases, the breast cancer will be associated with dermatomyositis. Dermatomyositis, a paraneoplastic syndrome, is associated with internal malignancy in 1530% of adult patients [2]. It is reported to be more common in cancers of the ovary, which account for 9% of all cancer associated with dermatomyositis and 14% of malignancy in females with dermatomyositis [3-41. Because of the rarity of dermatomyositis in breast cancer patients, the possibility of a ’ To whom reprint requests should be addressed at Department of Medical Oncology, Box 95, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030. 286 al90-82586x
$1.50 Copyright 0 1991 by Academic Press, All rights of reproduction in any form
Inc. reserved.
cause-effect relationship between the two diseases and the natural history and the prognosis of this particular patient population are unclear. To examine these questions, we reviewed the charts of breast cancer patients with dermatomyositis who were treated in our institute from 1944 to 1989. We found only six well-documented cases of breast cancer and dermatomyositis registered at the University of Texas M. D. Anderson Cancer Center, Department of Patient Studies, during that period. The clinical presentation and subsequent course of these patients are reported. PATIENTS
Case 1 A 54-year-old Black female noticed a mass in her right breast after minor trauma to her chest. Five months later, she developed a rash on her extremities and back, associated with proximal muscle weakness, and malaise. She had typical signs of dermatomyositis consisting of a heliotrope rash, Gottron’s papules, and periungual telangiectasia. An extensive scaling, erythematous rash involved most of her body (Fig. 1). Her clinical features, muscle enzymes, and electromyography results were consistent with dermatomyositis. Fine-needle aspiration of her breast mass and axillary node revealed nuclear grade I, anaplastic, ductal carcinoma of the breast that was estrogen- and progesterone-receptor negative, with palpable matted axillary lymph node metastasis. Clinically; she had, stage IIIb (T4N2MO) breast cancer. She was subsequently treated with four courses of 5-FU, doxorubicin (Adriamycin), and cyclophosphamide (FAC) chemotherapy with partial regression of her breast cancer and improvement of her dermatomyositis (both skin lesions and the myopathy). There was also a significant decrease in her muscle enzymes. However, she had a
CASE REPORT
287
with no improvement. Her dermatomyositis did not respond to high doses of steroids and methotrexate combination. Case3
FIG. 1. Case 1 developed a exensive scaling and erythematous rash in association with proximal muscle weakness 5 months after the detection of her breast cancer.
recurrence of her dermatomyositis upon completion of chemotherapy. This was well controlled with the addition of prednisolone. She underwent a right modified radical mastectomy after four cycles of FAC chemotherapy. Light microscopy of the surgical specimen demonstrated residual tumor involving the breast and axillary lymph nodes. In view of the patient’s initial good response to chemotherapy and aggressive pathology, another four courses of FAC chemotherapy were administered postoperatively. The clinical course of dermatomyositis in this patient improved parallel to the clinical response of her primary breast cancer. Case2
A 57-year-old White female developed proximal weakness of her upper extremities 5 months prior to the detection of a left breast mass. An erythematous scaly skin rash was seen on her left breast after skin preparation for an excisional biopsy of the breast; the rash rapidly spread to her extremities, trunk, and face, sparing the abdomen and back. Muscle enzyme analysis, electromyography, and muscle biopsy were consistent with dermatomyositis. Lumpectomy revealed stage I (TlNXMO) infiltrating ductal carcinoma. She received postoperative radiation to the left breast that resulted in severe dermatitis of the radiated area (Fig. 2). There was some improvement of the patient’s dermatomyositis with highdose steroids. Four months after radiation, she experienced progressive proximal muscle weakness, dysphagia, and severe skin rash, especially in the previously radiated breast area. Restaging procedures revealed left supraclavicular and right axillary lymphadenopathy. The patient was treated with FAC chemotherapy for 4 months
A 46-year-old White female underwent a right modified radical mastectomy for breast cancer. There was no evidence of recurrent tumor during 11 years of follow-up. Subsequently, she developed progressive proximal muscle weakness, dysphagia, and skin rash. The diagnosis of dermatomyositis was confirmed by muscle enzyme analysis, electromyography, and muscle biopsy. She did not respond to high-dose steroid therapy and developed aspiration pneumonia as a consequence of cricopharyngeal muscle involvement by dermatomyositis. The search for underlying malignancy revealed a stage III papillary adenocarcinoma of the ovary. After total abdominal hysterectomy and bilateral salpingo-oophorectomy, she was treated with four courses of melphalan, while the steroid therapy was continued. Although she developed malignant pleural effusions, her dermatomyositis improved clinically and enzymatically after the addition of an alkylating agent to steroid treatment, and despite the clinical progression of her ovarian cancer. She was then treated with six courses of hexamethylmelamine, doxorubicin, and cyclophosphamide, with her disease achieving a minor response to this therapy and her dermatomyositis remaining quiescent. Unfortunately the tumor progressed after completion of the chemotherapy and the patient died of intestinal obstruction and generalized peritoneal carcinomatosis 1 year after the diagnosis of the ovarian cancer. There was no deterioration of her dermatomyositis, despite the progression of her cancer.
FIG. 2. Case 2 developed postoperative radiation to the left breast that was involved by dermatomyositis, resulting in severe dermatitis of the radiated area.
288
VORAVUD
Case 4 A 71-year-old White female underwent total abdominal hysterectomy for carcinoma of the uterus in 1946 and right modified radical mastectomy for breast cancer in 1949. Twenty-five years later she developed biopsy proven dermatomyositis with esophageal muscle involvement. Her disease did not respond to high-dose steroids and methotrexate combination. This lead to the search for underlying malignancy, which revealed a stage IV serous adenocarcinoma of the right ovary with liver metastasis. After surgical removal of the ovarian cancer, the dermatomyositis improved during melphalan chemotherapy and high-dose steroid treatment. However, after three courses of chemotherapy, the patient had progression in her liver metastases concomitant with the progression of dermatomyositis. The patient developed aspiration pneumonia, her condition gradually deteriorated, and she died 3 months after the diagnosis of ovarian cancer. Case 5 A 42-year-old White female underwent lumpectomy of her left breast for a stage I (TlNOMO) infiltrating ductal carcinoma in 1979. She had a left modified radical mastectomy followed by postoperative radiotherapy for local recurrence of her breast cancer in 1983. Two years later, she developed dermatomyositis, documented by typical clinical presentation, muscle enzyme analysis, and electromyography. Metastatic workup for underlying cancer detected a right kidney mass. Tissue obtained during right radical nephrectomy showed metastatic adenocarcinoma consistent with breast cancer. One month after surgery, computed tomography of the abdomen revealed liver metastases. At that time, FAC chemotherapy was initiated, and she had complete response of her liver lesions after four courses of treatment. The patient’s dermatomyositis was well controlled by steroid therapy. There was no evidence of recurrent breast cancer at the last follow-up. Case 6 A 40-year-old Hispanic female was found to have a left breast mass; however, she deferred further evaluation. Ten months later, she developed a scaling, erythematous rash on her face and scalp, followed by diffuse facial edema, heliotrope rash, and progression of the erythematous rash to her trunk, breast, and extremities. Subsequently, she underwent a left modified radical mastectomy, which revealed a 3.5cm, poorly differentiated adenocarcinoma with 2 of 14 axillary lymph nodes involved by the tumor. The results of the estrogen- and progesterone-receptor analyses were negative. She did not receive postoperative radiotherapy for fear of exacerbation of her skin disease. Following discharge from
ET AL.
the hospital after her mastectomy, she experienced a sudden onset of proximal muscle weakness. The diagnosis of dermatomyositis was made on the basis of her clinical presentation, muscle enzyme analysis, electromyography results, and muscle biopsy. Treatment with 80 mg prednisolone per day was started. Her muscle weakness and skin lesions persisted despite treatment. She also received six courses of adjuvant chemotherapy with FAC. Since her symptoms persisted, 15 mg of methotrexate weekly intramuscularly was added to her steroid therapy. This resulted in fairly good control of her disease. Although the severity of her dermatomyositis fluctuated clinically during the next 3 years of follow-up, there was no detectable evidence of residual, or recurrent, breast cancer. DISCUSSION Dermatomyositis is a condition of unknown etiology in which the skeletal muscle is damaged by a nonsuppurative inflammatory process dominated by lymphocytic infiltration, associated with a characteristic skin rash. About onethird of the cases are associated with various connective tissue diseases and only one-tenth with malignancy [5]. The two leading hypotheses about the etiology of this condition are that the disease could be due to a viral infection of the skeletal muscle or it may represent an autoimmune disorder [6]. A clinical classification of polymyositis-dermatomyositis was proposed by Bohan et al., based partly on known differences in the associated conditions [7]. The two diseases were classified into primary idiopathic polymyositis, primary idiopathic dermatomyositis, dermatomyositis associated with neoplasia, childhood dermatomyositis associated with vasculitis, and polymyositis with associated collagen vascular disease. In childhood polymyositis-dermatomyositis, the frequency of malignancy is no greater than that observed in the general population. Dermatomyositis may precede, occur concomitantly with, or follow the detection of the associated malignancy, with each sequence occurring with approximately equal frequency [8]. The malignancy may antedate or postdate the onset of the myositis by up to 2 years. The likelihood of this syndrome being paraneoplastic is higher in patients over 60 years old with myositis. The common malignancies associated with dermatomyositis are lung, ovarian, breast, and gastrointestinal tract cancers as well as myeloproliferative disorders [9]. Recent studies, however, have questioned the association between dermatomyositis and malignancy [lo]. One case-control study involving 71 patients with polymyositis-dermatomyositis supports the association between dermatomyositis and malignant neoplasms when the malignant neoplasms are diagnosed at or before the time of diagnosis of polymyositis-dermatomyositis [ 111. In a pop-
289
CASE REPORT
ulation-based study, polymyositis-dermatomyositis was not found to be associated with an increased incidence of malignancy [12]. These conflicting data may be due to the small number of patients involved and the effect of referral bias. Patients with both conditions are more likely to be referred to academic medical centers than patients who have either disease alone. Because of these conflicting views on the relationship between dermatomyositis and malignancy, the value of extensive investigation of patients with dermatomyositis in the absence of overt clinical evidence suggestive of an underlying malignancy is uncertain. One author suggests that a limited investigation, including full blood count, urinalysis, liver function tests, fecal occult blood testing, chest roentgenogram, and sigmoidoscopy is adequate in a patient with dermatomyositis who does not have clinical symptoms or signs suggestive of malignancy [ 131. Among our series of patients, Cases 1 and 6 developed dermatomyositis shortly after self-detecting a breast mass. In Cases 3 and 4 the development of dermatomyositis led to the discovery of a second primary ovarian carcinoma, whereas the development of dermatomyositis in Case 5 led to the discovery of metastatic breast cancer. Case 2 developed dermatomyositis before the detection of her breast cancer; interestingly, radiation to the breast that was involved by dermatomyositis resulted in severe dermatitis. To avoid this complication, radiation treatment to the breast was not given in Case 6, in which the patient also had dermatomyositis involving a breast. The clinical course of dermatomyositis was not parallel to that of breast cancer in most of our patients. The treatment of underlying breast cancer did not significantly alter the natural course of dermatomyositis except in Case 1. The severity of dermatomyositis correlated with the extent of the tumor observed in Cases 3 and 4, both of whom had severe myopathy and bulky ovarian cancer. Both patients had poor prognosis with respiratory and pharyngeal muscle involvement by dermatomyositis. Death in both cases was related to advanced cancer but not to dermatomyositis. Patients with breast cancer have a high likelihood of developing recurrent cancer or second primary tumors. On the basis of our reported cases, dermatomyositis that occurs during the course of breast cancer may be an important sign of recurrent or second primary malignancy. Unfortunately, there are no well-established clinical or laboratory tests that can distinguish dermatomyositis from dermatomyositis associated with neoplasia. Cutaneous necrosis and elevation of erythrocyte sedimentation rate (ESR) (more than 40 mm/hr) are two predictive signs of malignancy in adult dermatomyositis inferred from 32 dermatomyositis patients; 13 had dermatomyositis associated with cancer [14]. Cutaneous necrosis was not seen in any of our patients. Patients with polymyositis-dermato-
myositis associated with malignancy are reported to have clinical courses different from those of patients without cancer, in that they more frequently have dysphagia due to pharyngeal and respiratory muscle involvement [15,16]. Three of our patients had this clinical feature. Among the reported poor prognosis factors in dermatomyositis are the presence of cancer, old age, the type and severity of the myositis, the presence of dysphagia, extensive lesions on the trunk, and ESR [14]. To our knowledge, prognostic factors of breast cancer patients who developed dermatomyositis have not been reported. Postoperative radiotherapy to the breast was not given to Case 6 because it was involved by dermatomyositis. Although the effect of radiation on dermatomyositis is not well studied, our second patient developed a severe skin reaction to radiation. Perhaps radiation to the breast that is involved by dermatomyositis should be avoided, provided that alternative therapeutic options are available. While refractory myositis may indicate underlying malignancy [17,18], there is no clear established association between the clinical course of dermatomyositis and malignancy in patients who have both diseases. Dermatomyositis may or may not improve with tumor removal or treatment and may relapse with recurrence of the malignancy. Only in Case 1 was dermatomyositis well controlled in parallel with the response of her breast cancer. Death is usually related to metastatic disease and not to progressive, uncontrollable myopathy [7]. We conclude that the coexistence of dermatomyositis and breast cancer is a rare phenomenon. When dermatomyositis occurs in patients with breast cancer, the search for recurrent breast cancer or second primary tumor, especially ovarian cancer, should be considered. Radiation to the breast area that is involved by dermatomyositis may induce severe radiation dermatitis. Apart from this, the management of patients with breast cancer who also have dermatomyositis should not vary from the usual treatment for each disease. REFERENCES 1. Silverberg, E., Boring, C. C., and Squires, T. S. Cancer statistics, CA 40, 9-26 1990. 2. Callen, J. P. Dermatomyositis and female malignancy, J. Surg. Oncol. 32, 121-124 (1986). 3. Barnes, B. E. Dermatomyositis and female malignancy, Ann. Intern.
Med.
84, 68-76
(1976).
4. Verducci, M. A., Malkasian, G. D., Freedman, S. J., et al. Gynecologic carcinoma associated with dermatomyositis-polymyositis, Obstet.
Gynecol.
614, 695-698
(1984).
5. Richardson, J. B., and Callen, J. P. Dermatomyositis and malignancy, Med. Clin. North Am. 73, 1211 (1989).
290
VORAVUD
6. Caldwell, D. S., and McCallum, R. M. Rheumatic manifestation of cancer, Med. Clin. North Am. 70, 385-417 (1986). 7. Bohan, A., Peter, J. B., Bowman, R. L., et al. A computer-assisted analysis of 153 patients with polymyositis and dermatomyositis, Medicine 56, 255-286 (1977). 8. Callen, J. P. Dermatomyositis and malignancy, Clin. Rheum. Dis. 8, 369-381 (1982). 9. Strauss, K. W., Gonzalez-Buritica, H., Khamashta, M., et al. Polymyositis-dermatomyositis: A clinical review, Postgrad. Med. J. 65, 437-443 (1989). 10. Lakhanpal, S., Bunch, T. W., Ilstrup, D. M., et al. Polymyositis/dermatomyositis and malignant lesion: Does an association exist? Mayo Clin. Proc. 61, 645-653 (1986). Il. Manchul, L. A., Jin, A., Pritchard, K. I., et al. The frequency of malignant neoplasm in patients with polymyositis-dermatomyositis: A controlled study. Arch. Intern. Med. 145, 1835-1839 (1985).
ET AL. 12. Medsger, T. A., Jr., Dawson, W. N., Jr., and Masi, A. T. The epidemiology of polymyositis, Am. J. Med. 48, 715-723 (1970). 13. Cox, N. H., Lawrence, C. M., Langtry, J. A., et al. Dermatomyositis: Disease associations and an evaluation of screening investigations for malignancy, Arch. Dermatol. 126, 61-65 (1990). 14. Basset-Seguin, N., Roujeau, J. C., Gherardi, R., et al. Prognosis factors and predictive signs of malignancy in adult dermato-myositis, Arch. Dermatol. 126, 633-637 (1990). 15. Pearson, C. M. Polymyositis, Annu. Rev. Med. 17, 63-82 (1966). 16. Talbott, J. H. Acute dermatomyositis-polymyositis and malignancy, Semin. Arthritis Rheum. 6, 305-360 (1977). 17. Callen, J. P. Dermatomyositis and malignancy-A continuing controversy, Cancer Bull. 35, 277-280 (1983). 18. Callen, J. P. Myositis and malignancy, Clin. Rheum. Dis. 10, 117130 (1984).
ONCOLOGY
43, 286-290 (1991)
CASE REPORT Breast Cancer and Second Primary Ovarian Cancer in Dermatomyositis NARIN VORAVUD,
MELETIOS
DIMOPOULOS,
GABRIEL
HORTOBAGYI,
MERRICK Ross, AND RICHARD THERIAULT’
Department of Medical Oncology, The University of Texas M. D. Anderson Cancer Center, I515 Holcombe Boulevard, Houszon, Texa 77030 Received February 19, 1991
We report six femalepatientswith breastcancerwho developed dermatomyositisand compareour data with those from other reports. The developmentof dermatomyositisin two patientsled to the discovery of a secondprimary ovarian carcinoma,whereas the developmentof dermatomyositisin another two patients led to the discovery of recurrent breastcancer. In three patients the diagnosisof dermatomyositisprecededthe diagnosisof breast cancer, while the rest developeddermatomyositisafter the diagnosisof breast cancer. A parallel clinical courseof dermatomyositisand breast cancer was seenin only one patient. Coexisting dermatomyositisand breastcancer is a rare phenomenon, and dermatomyositisthat developsduring the courseof breast cancer may indicate the occurrenceof a secondprimary malignancy or recurrent breastcancer. The onsetof dermatomyositis may precede, coincide with, or follow the diagnosisof breast cancer. The clinical courseof dermatomyositissometimes,but not always, parallels the courseof breastcancer. There are no specificclinical or laboratory markersto distinguishpatientswith dermatomyositiswho have malignancyfrom thosewithout cancer. 0 1991 Academic
Press, Inc.
INTRODUCTION
An estimated 150,900 new cases of breast cancer, the most common neoplasm in American women, will be reported in this country in 1990 [l] and, in rare cases, the breast cancer will be associated with dermatomyositis. Dermatomyositis, a paraneoplastic syndrome, is associated with internal malignancy in 1530% of adult patients [2]. It is reported to be more common in cancers of the ovary, which account for 9% of all cancer associated with dermatomyositis and 14% of malignancy in females with dermatomyositis [3-41. Because of the rarity of dermatomyositis in breast cancer patients, the possibility of a ’ To whom reprint requests should be addressed at Department of Medical Oncology, Box 95, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030. 286 al90-82586x
$1.50 Copyright 0 1991 by Academic Press, All rights of reproduction in any form
Inc. reserved.
cause-effect relationship between the two diseases and the natural history and the prognosis of this particular patient population are unclear. To examine these questions, we reviewed the charts of breast cancer patients with dermatomyositis who were treated in our institute from 1944 to 1989. We found only six well-documented cases of breast cancer and dermatomyositis registered at the University of Texas M. D. Anderson Cancer Center, Department of Patient Studies, during that period. The clinical presentation and subsequent course of these patients are reported. PATIENTS
Case 1 A 54-year-old Black female noticed a mass in her right breast after minor trauma to her chest. Five months later, she developed a rash on her extremities and back, associated with proximal muscle weakness, and malaise. She had typical signs of dermatomyositis consisting of a heliotrope rash, Gottron’s papules, and periungual telangiectasia. An extensive scaling, erythematous rash involved most of her body (Fig. 1). Her clinical features, muscle enzymes, and electromyography results were consistent with dermatomyositis. Fine-needle aspiration of her breast mass and axillary node revealed nuclear grade I, anaplastic, ductal carcinoma of the breast that was estrogen- and progesterone-receptor negative, with palpable matted axillary lymph node metastasis. Clinically; she had, stage IIIb (T4N2MO) breast cancer. She was subsequently treated with four courses of 5-FU, doxorubicin (Adriamycin), and cyclophosphamide (FAC) chemotherapy with partial regression of her breast cancer and improvement of her dermatomyositis (both skin lesions and the myopathy). There was also a significant decrease in her muscle enzymes. However, she had a
CASE REPORT
287
with no improvement. Her dermatomyositis did not respond to high doses of steroids and methotrexate combination. Case3
FIG. 1. Case 1 developed a exensive scaling and erythematous rash in association with proximal muscle weakness 5 months after the detection of her breast cancer.
recurrence of her dermatomyositis upon completion of chemotherapy. This was well controlled with the addition of prednisolone. She underwent a right modified radical mastectomy after four cycles of FAC chemotherapy. Light microscopy of the surgical specimen demonstrated residual tumor involving the breast and axillary lymph nodes. In view of the patient’s initial good response to chemotherapy and aggressive pathology, another four courses of FAC chemotherapy were administered postoperatively. The clinical course of dermatomyositis in this patient improved parallel to the clinical response of her primary breast cancer. Case2
A 57-year-old White female developed proximal weakness of her upper extremities 5 months prior to the detection of a left breast mass. An erythematous scaly skin rash was seen on her left breast after skin preparation for an excisional biopsy of the breast; the rash rapidly spread to her extremities, trunk, and face, sparing the abdomen and back. Muscle enzyme analysis, electromyography, and muscle biopsy were consistent with dermatomyositis. Lumpectomy revealed stage I (TlNXMO) infiltrating ductal carcinoma. She received postoperative radiation to the left breast that resulted in severe dermatitis of the radiated area (Fig. 2). There was some improvement of the patient’s dermatomyositis with highdose steroids. Four months after radiation, she experienced progressive proximal muscle weakness, dysphagia, and severe skin rash, especially in the previously radiated breast area. Restaging procedures revealed left supraclavicular and right axillary lymphadenopathy. The patient was treated with FAC chemotherapy for 4 months
A 46-year-old White female underwent a right modified radical mastectomy for breast cancer. There was no evidence of recurrent tumor during 11 years of follow-up. Subsequently, she developed progressive proximal muscle weakness, dysphagia, and skin rash. The diagnosis of dermatomyositis was confirmed by muscle enzyme analysis, electromyography, and muscle biopsy. She did not respond to high-dose steroid therapy and developed aspiration pneumonia as a consequence of cricopharyngeal muscle involvement by dermatomyositis. The search for underlying malignancy revealed a stage III papillary adenocarcinoma of the ovary. After total abdominal hysterectomy and bilateral salpingo-oophorectomy, she was treated with four courses of melphalan, while the steroid therapy was continued. Although she developed malignant pleural effusions, her dermatomyositis improved clinically and enzymatically after the addition of an alkylating agent to steroid treatment, and despite the clinical progression of her ovarian cancer. She was then treated with six courses of hexamethylmelamine, doxorubicin, and cyclophosphamide, with her disease achieving a minor response to this therapy and her dermatomyositis remaining quiescent. Unfortunately the tumor progressed after completion of the chemotherapy and the patient died of intestinal obstruction and generalized peritoneal carcinomatosis 1 year after the diagnosis of the ovarian cancer. There was no deterioration of her dermatomyositis, despite the progression of her cancer.
FIG. 2. Case 2 developed postoperative radiation to the left breast that was involved by dermatomyositis, resulting in severe dermatitis of the radiated area.
288
VORAVUD
Case 4 A 71-year-old White female underwent total abdominal hysterectomy for carcinoma of the uterus in 1946 and right modified radical mastectomy for breast cancer in 1949. Twenty-five years later she developed biopsy proven dermatomyositis with esophageal muscle involvement. Her disease did not respond to high-dose steroids and methotrexate combination. This lead to the search for underlying malignancy, which revealed a stage IV serous adenocarcinoma of the right ovary with liver metastasis. After surgical removal of the ovarian cancer, the dermatomyositis improved during melphalan chemotherapy and high-dose steroid treatment. However, after three courses of chemotherapy, the patient had progression in her liver metastases concomitant with the progression of dermatomyositis. The patient developed aspiration pneumonia, her condition gradually deteriorated, and she died 3 months after the diagnosis of ovarian cancer. Case 5 A 42-year-old White female underwent lumpectomy of her left breast for a stage I (TlNOMO) infiltrating ductal carcinoma in 1979. She had a left modified radical mastectomy followed by postoperative radiotherapy for local recurrence of her breast cancer in 1983. Two years later, she developed dermatomyositis, documented by typical clinical presentation, muscle enzyme analysis, and electromyography. Metastatic workup for underlying cancer detected a right kidney mass. Tissue obtained during right radical nephrectomy showed metastatic adenocarcinoma consistent with breast cancer. One month after surgery, computed tomography of the abdomen revealed liver metastases. At that time, FAC chemotherapy was initiated, and she had complete response of her liver lesions after four courses of treatment. The patient’s dermatomyositis was well controlled by steroid therapy. There was no evidence of recurrent breast cancer at the last follow-up. Case 6 A 40-year-old Hispanic female was found to have a left breast mass; however, she deferred further evaluation. Ten months later, she developed a scaling, erythematous rash on her face and scalp, followed by diffuse facial edema, heliotrope rash, and progression of the erythematous rash to her trunk, breast, and extremities. Subsequently, she underwent a left modified radical mastectomy, which revealed a 3.5cm, poorly differentiated adenocarcinoma with 2 of 14 axillary lymph nodes involved by the tumor. The results of the estrogen- and progesterone-receptor analyses were negative. She did not receive postoperative radiotherapy for fear of exacerbation of her skin disease. Following discharge from
ET AL.
the hospital after her mastectomy, she experienced a sudden onset of proximal muscle weakness. The diagnosis of dermatomyositis was made on the basis of her clinical presentation, muscle enzyme analysis, electromyography results, and muscle biopsy. Treatment with 80 mg prednisolone per day was started. Her muscle weakness and skin lesions persisted despite treatment. She also received six courses of adjuvant chemotherapy with FAC. Since her symptoms persisted, 15 mg of methotrexate weekly intramuscularly was added to her steroid therapy. This resulted in fairly good control of her disease. Although the severity of her dermatomyositis fluctuated clinically during the next 3 years of follow-up, there was no detectable evidence of residual, or recurrent, breast cancer. DISCUSSION Dermatomyositis is a condition of unknown etiology in which the skeletal muscle is damaged by a nonsuppurative inflammatory process dominated by lymphocytic infiltration, associated with a characteristic skin rash. About onethird of the cases are associated with various connective tissue diseases and only one-tenth with malignancy [5]. The two leading hypotheses about the etiology of this condition are that the disease could be due to a viral infection of the skeletal muscle or it may represent an autoimmune disorder [6]. A clinical classification of polymyositis-dermatomyositis was proposed by Bohan et al., based partly on known differences in the associated conditions [7]. The two diseases were classified into primary idiopathic polymyositis, primary idiopathic dermatomyositis, dermatomyositis associated with neoplasia, childhood dermatomyositis associated with vasculitis, and polymyositis with associated collagen vascular disease. In childhood polymyositis-dermatomyositis, the frequency of malignancy is no greater than that observed in the general population. Dermatomyositis may precede, occur concomitantly with, or follow the detection of the associated malignancy, with each sequence occurring with approximately equal frequency [8]. The malignancy may antedate or postdate the onset of the myositis by up to 2 years. The likelihood of this syndrome being paraneoplastic is higher in patients over 60 years old with myositis. The common malignancies associated with dermatomyositis are lung, ovarian, breast, and gastrointestinal tract cancers as well as myeloproliferative disorders [9]. Recent studies, however, have questioned the association between dermatomyositis and malignancy [lo]. One case-control study involving 71 patients with polymyositis-dermatomyositis supports the association between dermatomyositis and malignant neoplasms when the malignant neoplasms are diagnosed at or before the time of diagnosis of polymyositis-dermatomyositis [ 111. In a pop-
289
CASE REPORT
ulation-based study, polymyositis-dermatomyositis was not found to be associated with an increased incidence of malignancy [12]. These conflicting data may be due to the small number of patients involved and the effect of referral bias. Patients with both conditions are more likely to be referred to academic medical centers than patients who have either disease alone. Because of these conflicting views on the relationship between dermatomyositis and malignancy, the value of extensive investigation of patients with dermatomyositis in the absence of overt clinical evidence suggestive of an underlying malignancy is uncertain. One author suggests that a limited investigation, including full blood count, urinalysis, liver function tests, fecal occult blood testing, chest roentgenogram, and sigmoidoscopy is adequate in a patient with dermatomyositis who does not have clinical symptoms or signs suggestive of malignancy [ 131. Among our series of patients, Cases 1 and 6 developed dermatomyositis shortly after self-detecting a breast mass. In Cases 3 and 4 the development of dermatomyositis led to the discovery of a second primary ovarian carcinoma, whereas the development of dermatomyositis in Case 5 led to the discovery of metastatic breast cancer. Case 2 developed dermatomyositis before the detection of her breast cancer; interestingly, radiation to the breast that was involved by dermatomyositis resulted in severe dermatitis. To avoid this complication, radiation treatment to the breast was not given in Case 6, in which the patient also had dermatomyositis involving a breast. The clinical course of dermatomyositis was not parallel to that of breast cancer in most of our patients. The treatment of underlying breast cancer did not significantly alter the natural course of dermatomyositis except in Case 1. The severity of dermatomyositis correlated with the extent of the tumor observed in Cases 3 and 4, both of whom had severe myopathy and bulky ovarian cancer. Both patients had poor prognosis with respiratory and pharyngeal muscle involvement by dermatomyositis. Death in both cases was related to advanced cancer but not to dermatomyositis. Patients with breast cancer have a high likelihood of developing recurrent cancer or second primary tumors. On the basis of our reported cases, dermatomyositis that occurs during the course of breast cancer may be an important sign of recurrent or second primary malignancy. Unfortunately, there are no well-established clinical or laboratory tests that can distinguish dermatomyositis from dermatomyositis associated with neoplasia. Cutaneous necrosis and elevation of erythrocyte sedimentation rate (ESR) (more than 40 mm/hr) are two predictive signs of malignancy in adult dermatomyositis inferred from 32 dermatomyositis patients; 13 had dermatomyositis associated with cancer [14]. Cutaneous necrosis was not seen in any of our patients. Patients with polymyositis-dermato-
myositis associated with malignancy are reported to have clinical courses different from those of patients without cancer, in that they more frequently have dysphagia due to pharyngeal and respiratory muscle involvement [15,16]. Three of our patients had this clinical feature. Among the reported poor prognosis factors in dermatomyositis are the presence of cancer, old age, the type and severity of the myositis, the presence of dysphagia, extensive lesions on the trunk, and ESR [14]. To our knowledge, prognostic factors of breast cancer patients who developed dermatomyositis have not been reported. Postoperative radiotherapy to the breast was not given to Case 6 because it was involved by dermatomyositis. Although the effect of radiation on dermatomyositis is not well studied, our second patient developed a severe skin reaction to radiation. Perhaps radiation to the breast that is involved by dermatomyositis should be avoided, provided that alternative therapeutic options are available. While refractory myositis may indicate underlying malignancy [17,18], there is no clear established association between the clinical course of dermatomyositis and malignancy in patients who have both diseases. Dermatomyositis may or may not improve with tumor removal or treatment and may relapse with recurrence of the malignancy. Only in Case 1 was dermatomyositis well controlled in parallel with the response of her breast cancer. Death is usually related to metastatic disease and not to progressive, uncontrollable myopathy [7]. We conclude that the coexistence of dermatomyositis and breast cancer is a rare phenomenon. When dermatomyositis occurs in patients with breast cancer, the search for recurrent breast cancer or second primary tumor, especially ovarian cancer, should be considered. Radiation to the breast area that is involved by dermatomyositis may induce severe radiation dermatitis. Apart from this, the management of patients with breast cancer who also have dermatomyositis should not vary from the usual treatment for each disease. REFERENCES 1. Silverberg, E., Boring, C. C., and Squires, T. S. Cancer statistics, CA 40, 9-26 1990. 2. Callen, J. P. Dermatomyositis and female malignancy, J. Surg. Oncol. 32, 121-124 (1986). 3. Barnes, B. E. Dermatomyositis and female malignancy, Ann. Intern.
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