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A Durable Complete Remission Between Two Isolated Presentations of Metastatic Breast Cancer, the Second with Intracardiac Disease
case
report A Durable Complete Remission Between Two Isolated Presentations of Metastatic Breast Cancer, the Second with Intracardiac Disease Reuben J. Broom,1 Vernon J. Harvey,1 Kenneth M. L. Lee2 Abstract We report a case of a postmenopausal patient with hormone receptor–positive breast cancer who, while receiving tamoxifen, experienced relapse with isolated ovarian metastases 4.5 years after her primary treatment. After resection of her pelvic disease, she commenced anastrozole, and while receiving this, remained disease free for an additional 7.5 years before experiencing relapse again with isolated metastatic disease in an unusual location: intracardiac disease causing superior vena cava obstruction. Clinical Breast Cancer, Vol. 7, No. 2, 162-163, 2006 Key words: Aromatase inhibitors, Endocrine therapy, Hormone receptor–positive disease
Introduction Complete durable remissions after documented metastatic breast cancer are rare but can occur. We report a case of a woman who underwent such a remission while receiving anastrozole after resection of her isolated ovarian disease. Ovarian metastases from breast cancer are not uncommon1 but are usually accompanied by disease elsewhere. Cardiac metastases from breast cancer are well documented in the postmortem setting2 but have only been described once when antemortem,3 and this appears to be the first case confirmed by histology.
Case History In 1991, a 51-year-old woman underwent a right total mastectomy for a 2-cm, grade II, infiltrating ductal carcinoma of the breast, which was strongly positive for estrogen receptor and progesterone receptor. All of the 13 nodes retrieved were involved with tumor, and there was evidence of extranodal spread. She elected not to have chemotherapy but commenced adjuvant tamoxifen. Four and a half years later, she underwent gynecologic surgery for a large pelvic mass (17.5 cm in greatest diam1Department
of Medical Oncology, Regional Cancer and Blood Service of Anatomical Pathology Auckland City Hospitial, New Zealand
2Department
Submitted: Nov 28, 2005; Revised: Mar 6, 2006; Accepted: Apr 11, 2006 Address for correspondence: Reuben J. Broom, MD, Auckland City Hospital, Park Road, Building 8, Grafton, Auckland, New Zealand Fax: 649-307-4926; e-mail: [email protected]
eter), and the histology from this revealed metastatic breast cancer invading both ovaries. Her hormonal therapy was changed to megestrol acetate but, because of weight gain, was switched again after a few months to anastrozole. She remained well and disease free for an additional 8 years from pelvic surgery until July 2004 when she presented with a 2-week history of swelling in the face and right arm, increased lacrimation, and breathlessness. A computed tomography scan revealed a 4-cm filling defect in the right atrium extending into the superior vena cava and the left brachiocephalic vein. There was no evidence of disease elsewhere, and her carcinoma antigen 15-3 level was normal. Subsequent transesophageal echocardiogram and cardiac magnetic resonance imaging studies confirmed a mass with extensive atrial wall involvement and also invasion of the aorta, right pulmonary veins, and brachiocephalic trunks (Figure 1). There was significant superior vena cava obstruction and associated thrombus. She consequently underwent anticoagulation with enoxaparin. The most probable radiologic diagnosis was an angiosarcoma. Surprisingly, the histology from an angiographically guided biopsy revealed metastatic lobular breast cancer. Doxorubicin chemotherapy was commenced, but her first cycle of treatment was complicated by an enormous left-trunk hematoma that caused her hemoglobin level to decrease to 5.1 g/dL. Her anticoagulation therapy was therefore stopped. After complaining of breathlessness, she died suddenly, presumably from tumor/thrombus migration or embolism. Because of the discrepancy between the histologic classification of the breast and cardiac biopsy specimens, a sub-
Electronic forwarding or copying is a violation of US and International Copyright Laws. Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by CIG Media Group, LP, ISSN #1526-8209, provided the appropriate fee is paid directly to Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923 USA 978-750-8400.
162 • Clinical Breast Cancer June 2006
Figure 1 Coronal Cardiac Magnetic Resonance (HASTE) Imaging of Cardiac Mass
Image shows the right atrial mass invading the aortic wall (curved arrow) and extending into the superior vena cava (straight arrow) and atrial appendage (star).
It is less common to develop breast cancer metastases in an isolated site (as occurred in this patient twice), and resection is often not performed because of the assumption that there is concurrent, occult, micrometastatic disease. There are, however, many series describing resection of isolated hepatic or pulmonary metastases from breast cancer with variable survival figures. Ovarian metastases are known to arise from breast cancer1 but are usually accompanied by disease elsewhere. Only 1 other case report describes isolated ovarian metastases that occurred 11 years after the patient’s primary treatment for early-stage breast cancer.9 Although durable (ie, > 5-year), complete remissions resulting from systemic or surgical therapy can occur after the diagnosis of metastatic breast cancer, they are rare. While receiving anastrozole, our patient had a > 7.5-year diseasefree interval after resection of a solitary site of disease. We cannot ascertain what contribution the aromatase inhibition made to this remission, however, and acknowledge that this long interval might have been the result of surgery alone. When she eventually experienced relapse with intracardiac disease, this again was an isolated relapse. Although cardiac metastases from breast cancer have been documented postmortem in autopsy series,2 to the present authors’ knowledge, the same diagnosis has only been reported once previously in the antemortem setting, and it was not proven by biopsy.3 This case, therefore, demonstrates an unusual pattern of spread in an indolently behaving, hormone receptor–positive, advanced-stage breast cancer and illuminates the heterogeneity of the condition.
References sequent pathology review was performed on all 3 histology samples retrieved over the course of the patient’s disease. This showed concordance between all the specimens; each was consistent with a hormone receptor–positive, E-cadherin–negative, classical lobular carcinoma. This review, which used more modern immunohistochemical techniques not available at the time of her original mastectomy, confirmed that, in hindsight, this patient had a classical lobular carcinoma all along.
Discussion Anastrozole is a selective, third-generation, nonsteroidal aromatase inhibitor that can induce tumor responses and has been shown to prolong time to progression when compared with tamoxifen as first-line therapy in postmenopausal patients with hormone receptor–positive metastatic breast cancer.4,5 More recently, it has been shown to confer a disease-free survival advantage in the adjuvant setting when compared with tamoxifen alone.6-8
1. Gagnon Y, Tetu B. Ovarian metastases of breast carcinoma. A clinicopathologic study of 59 cases. Cancer 1989; 64:892-898. 2. Karwinski B, Svendsen E. Trends in cardiac metastasis. APMIS 1989; 97:1018-1024. 3. Pavithran K, Doval DC, Ravi S, et al. Cardiac metastasis from carcinoma breast-a case report. Ind J Med Sci 1997; 51:15-17. 4. Nabholtz JM, Buzdar A, Pollak M, et al. Anastrozole is superior to tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: results of a North American multicenter randomized trial. J Clin Oncol 2000; 18:3758-3767. 5. Bonneterre J, Buzdar A, Nabholtz JM, et al. Anastrozole is superior to tamoxifen as first-line therapy in hormone receptor positive advanced breast carcinoma. Cancer 2001; 92:2247-2258. 6. ATAC Trialists’ Group. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years’ adjuvant treatment for breast cancer. Lancet 2005; 365:60-62. 7. Boccardo F, Rubagotti A, Puntoni M, et al. Switching to anastrozole versus continued tamoxifen treatment of early breast cancer: preliminary results of the Italian Tamoxifen Anastrozole Trial. J Clin Oncol 2005; 23:5138-147. 8. Jakesz R, Jonat W, Gnant M, et al. Switching of postmenopausal women with endocrine-responsive early breast cancer to anastrazole after 2 years’ adjuvant tamoxifen: combined results of ABCSG trial 8 and ARNO 95 trial. Lancet 2005; 366:455-462. 9. Debois JM, Charles K, Verbeke G, et al. A patient with unique bilateral ovarian metastases 11 years after the treatment of breast cancer. Acta Chirurgica Belgica 1997; 97:302-305.
Clinical Breast Cancer June 2006 • 163
report A Durable Complete Remission Between Two Isolated Presentations of Metastatic Breast Cancer, the Second with Intracardiac Disease Reuben J. Broom,1 Vernon J. Harvey,1 Kenneth M. L. Lee2 Abstract We report a case of a postmenopausal patient with hormone receptor–positive breast cancer who, while receiving tamoxifen, experienced relapse with isolated ovarian metastases 4.5 years after her primary treatment. After resection of her pelvic disease, she commenced anastrozole, and while receiving this, remained disease free for an additional 7.5 years before experiencing relapse again with isolated metastatic disease in an unusual location: intracardiac disease causing superior vena cava obstruction. Clinical Breast Cancer, Vol. 7, No. 2, 162-163, 2006 Key words: Aromatase inhibitors, Endocrine therapy, Hormone receptor–positive disease
Introduction Complete durable remissions after documented metastatic breast cancer are rare but can occur. We report a case of a woman who underwent such a remission while receiving anastrozole after resection of her isolated ovarian disease. Ovarian metastases from breast cancer are not uncommon1 but are usually accompanied by disease elsewhere. Cardiac metastases from breast cancer are well documented in the postmortem setting2 but have only been described once when antemortem,3 and this appears to be the first case confirmed by histology.
Case History In 1991, a 51-year-old woman underwent a right total mastectomy for a 2-cm, grade II, infiltrating ductal carcinoma of the breast, which was strongly positive for estrogen receptor and progesterone receptor. All of the 13 nodes retrieved were involved with tumor, and there was evidence of extranodal spread. She elected not to have chemotherapy but commenced adjuvant tamoxifen. Four and a half years later, she underwent gynecologic surgery for a large pelvic mass (17.5 cm in greatest diam1Department
of Medical Oncology, Regional Cancer and Blood Service of Anatomical Pathology Auckland City Hospitial, New Zealand
2Department
Submitted: Nov 28, 2005; Revised: Mar 6, 2006; Accepted: Apr 11, 2006 Address for correspondence: Reuben J. Broom, MD, Auckland City Hospital, Park Road, Building 8, Grafton, Auckland, New Zealand Fax: 649-307-4926; e-mail: [email protected]
eter), and the histology from this revealed metastatic breast cancer invading both ovaries. Her hormonal therapy was changed to megestrol acetate but, because of weight gain, was switched again after a few months to anastrozole. She remained well and disease free for an additional 8 years from pelvic surgery until July 2004 when she presented with a 2-week history of swelling in the face and right arm, increased lacrimation, and breathlessness. A computed tomography scan revealed a 4-cm filling defect in the right atrium extending into the superior vena cava and the left brachiocephalic vein. There was no evidence of disease elsewhere, and her carcinoma antigen 15-3 level was normal. Subsequent transesophageal echocardiogram and cardiac magnetic resonance imaging studies confirmed a mass with extensive atrial wall involvement and also invasion of the aorta, right pulmonary veins, and brachiocephalic trunks (Figure 1). There was significant superior vena cava obstruction and associated thrombus. She consequently underwent anticoagulation with enoxaparin. The most probable radiologic diagnosis was an angiosarcoma. Surprisingly, the histology from an angiographically guided biopsy revealed metastatic lobular breast cancer. Doxorubicin chemotherapy was commenced, but her first cycle of treatment was complicated by an enormous left-trunk hematoma that caused her hemoglobin level to decrease to 5.1 g/dL. Her anticoagulation therapy was therefore stopped. After complaining of breathlessness, she died suddenly, presumably from tumor/thrombus migration or embolism. Because of the discrepancy between the histologic classification of the breast and cardiac biopsy specimens, a sub-
Electronic forwarding or copying is a violation of US and International Copyright Laws. Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by CIG Media Group, LP, ISSN #1526-8209, provided the appropriate fee is paid directly to Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923 USA 978-750-8400.
162 • Clinical Breast Cancer June 2006
Figure 1 Coronal Cardiac Magnetic Resonance (HASTE) Imaging of Cardiac Mass
Image shows the right atrial mass invading the aortic wall (curved arrow) and extending into the superior vena cava (straight arrow) and atrial appendage (star).
It is less common to develop breast cancer metastases in an isolated site (as occurred in this patient twice), and resection is often not performed because of the assumption that there is concurrent, occult, micrometastatic disease. There are, however, many series describing resection of isolated hepatic or pulmonary metastases from breast cancer with variable survival figures. Ovarian metastases are known to arise from breast cancer1 but are usually accompanied by disease elsewhere. Only 1 other case report describes isolated ovarian metastases that occurred 11 years after the patient’s primary treatment for early-stage breast cancer.9 Although durable (ie, > 5-year), complete remissions resulting from systemic or surgical therapy can occur after the diagnosis of metastatic breast cancer, they are rare. While receiving anastrozole, our patient had a > 7.5-year diseasefree interval after resection of a solitary site of disease. We cannot ascertain what contribution the aromatase inhibition made to this remission, however, and acknowledge that this long interval might have been the result of surgery alone. When she eventually experienced relapse with intracardiac disease, this again was an isolated relapse. Although cardiac metastases from breast cancer have been documented postmortem in autopsy series,2 to the present authors’ knowledge, the same diagnosis has only been reported once previously in the antemortem setting, and it was not proven by biopsy.3 This case, therefore, demonstrates an unusual pattern of spread in an indolently behaving, hormone receptor–positive, advanced-stage breast cancer and illuminates the heterogeneity of the condition.
References sequent pathology review was performed on all 3 histology samples retrieved over the course of the patient’s disease. This showed concordance between all the specimens; each was consistent with a hormone receptor–positive, E-cadherin–negative, classical lobular carcinoma. This review, which used more modern immunohistochemical techniques not available at the time of her original mastectomy, confirmed that, in hindsight, this patient had a classical lobular carcinoma all along.
Discussion Anastrozole is a selective, third-generation, nonsteroidal aromatase inhibitor that can induce tumor responses and has been shown to prolong time to progression when compared with tamoxifen as first-line therapy in postmenopausal patients with hormone receptor–positive metastatic breast cancer.4,5 More recently, it has been shown to confer a disease-free survival advantage in the adjuvant setting when compared with tamoxifen alone.6-8
1. Gagnon Y, Tetu B. Ovarian metastases of breast carcinoma. A clinicopathologic study of 59 cases. Cancer 1989; 64:892-898. 2. Karwinski B, Svendsen E. Trends in cardiac metastasis. APMIS 1989; 97:1018-1024. 3. Pavithran K, Doval DC, Ravi S, et al. Cardiac metastasis from carcinoma breast-a case report. Ind J Med Sci 1997; 51:15-17. 4. Nabholtz JM, Buzdar A, Pollak M, et al. Anastrozole is superior to tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: results of a North American multicenter randomized trial. J Clin Oncol 2000; 18:3758-3767. 5. Bonneterre J, Buzdar A, Nabholtz JM, et al. Anastrozole is superior to tamoxifen as first-line therapy in hormone receptor positive advanced breast carcinoma. Cancer 2001; 92:2247-2258. 6. ATAC Trialists’ Group. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years’ adjuvant treatment for breast cancer. Lancet 2005; 365:60-62. 7. Boccardo F, Rubagotti A, Puntoni M, et al. Switching to anastrozole versus continued tamoxifen treatment of early breast cancer: preliminary results of the Italian Tamoxifen Anastrozole Trial. J Clin Oncol 2005; 23:5138-147. 8. Jakesz R, Jonat W, Gnant M, et al. Switching of postmenopausal women with endocrine-responsive early breast cancer to anastrazole after 2 years’ adjuvant tamoxifen: combined results of ABCSG trial 8 and ARNO 95 trial. Lancet 2005; 366:455-462. 9. Debois JM, Charles K, Verbeke G, et al. A patient with unique bilateral ovarian metastases 11 years after the treatment of breast cancer. Acta Chirurgica Belgica 1997; 97:302-305.
Clinical Breast Cancer June 2006 • 163