- Email: [email protected]
Long-term survival of a patient with primarily chemo-resistant metastatic breast cancer treated with medroxyprogesterone acetate
ARTICLE IN PRESS The Breast (2004) 13, 321–324
THE
BREAST www.elsevier.com/locate/breast
CASE REPORT
Long-term survival of a patient with primarily chemo-resistant metastatic breast cancer treated with medroxyprogesterone acetate ! R. Zaucha*, K. Sosinska-Mielcarek, J. Jassem ! Department of Oncology and Radiotherapy, Medical University of Gdansk, ul. Debinki 7, 80-211 Gdansk, Poland Received 19 January 2004; received in revised form 14 April 2004; accepted 18 May 2004
KEYWORDS Breast cancer; Liver metastases; Medroxyprogesterone acetate; Long-term survival
Summary The prognosis of breast cancer patients with liver metastases is extremely poor. Here we present the case of a 66-year-old female breast cancer patient with multiple liver metastases diagnosed 2 years after a radical modified mastectomy followed by adjuvant tamoxifen. At progression, anthracycline-based chemotherapy was administered, but a CT scan following two cycles of FEC (5-fluorouracil, epirubicin, cyclophosphamide) showed progression of the liver metastases. Chemotherapy was therefore switched to medroxyprogesterone acetate (MPA). After 3 months the patient’s general status improved, and disease stabilization was observed at the next CT scan. A further 4 months of MPA treatment resulted in complete response of all liver lesions. Treatment with oral MPA was continued for 4 years. At present, 11 years after the diagnosis of metastatic liver involvement, the patient is alive, free of cancer, and fully ambulatory. Despite bulky visceral disease and chemoresistance, hormonal treatment with MPA resulted in a spectacular and long-lasting response. & 2004 Elsevier Ltd. All rights reserved.
Introduction Conventional treatment methods in metastatic breast cancer generally do not result in a cure, long-term survival is being seen in only 1–3% of patients.1,2 Therefore, improvement of the quality of life and, in some cases, prolongation of life are the main treatment goals. Young age, good performance status, limited metastatic disease, and *Corresponding author. Tel./fax: þ 48-349-2270. E-mail address: [email protected] (R. Zaucha).
objective response to the first-line treatment are regarded as essential for prolonged survival.2–5 In most series the median survival of women with metastatic disease has varied from 18 to 24 months.2,3,6–8 The liver is the site of approximately half of all breast cancer metastases.9,10 Median survival in this group of patients is in the range of 6–11 months.4 Survival is longer (median 24–44 months) in a selected group of patients with surgically treated isolated liver metastases.10–13 Although initial response rates of visceral and of other metastases are similar, the duration of
0960-9776/$ - see front matter & 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.breast.2004.05.003
ARTICLE IN PRESS 322
response and survival is particularly poor in patients with the former.4,10,13 About 20% of these women will die with symptoms of hepatic failure.14 Medroxyprogesterone acetate (MPA)Fa 17-OHprogesteroneFis a progestagen. It has been used for years as a second- or third-line endocrine treatment of advanced breast cancer.15 Its exact mechanism of action is not fully understood, but suppression of adrenal steroid synthesis, suppression of estrogen, activation of androgen receptors, and direct killing of tumor cells have been suggested.16,17 Its efficacy is similar to that of tamoxifen. Thromboembolic events, edema, weight gain, vaginal bleeding, and adrenal suppression are the main side effects, but this compound is generally well tolerated. In this paper we present a breast cancer patient diagnosed with multiple liver metastases 2 years after radical mastectomy followed by adjuvant tamoxifen. Despite bulky visceral disease and resistance to the first-line chemotherapy, treatment with MPA resulted in long-lasting complete response.
R. Zaucha et al.
chemotherapy, the patient’s general condition deteriorated, and a subsequent CT scan showed disease progression in the liver. Chemotherapy was therefore switched to a second-line hormonal treatment including MPA given as weekly 500-mg intramuscular injections. A CT scan done 3 months after the onset of MPA treatment showed persistence of multiple metastatic foci up to 3 cm in diameter in the liver, but the general status of the patient had improved. A CT scan performed after a further 4 months of MPA treatment showed complete remission of all liver lesions (Fig. 2). There were virtually no side effects throughout the entire MPA treatment period. In September 1993, a single painful osteolytic metastasis in the sacral bone was found and a palliative radiotherapy (8 Gy in 1 fraction) was
Case presentation In February 1990, a 64-year-old retired dentist was diagnosed with a cT2N0M0 (pT2N1) cancer of the left breast. Following modified radical mastectomy she was prescribed adjuvant tamoxifen. At the time of primary treatment the steroid receptor status and HER-2 expression were unknown. Subsequent examination of the paraffin blocks confirmed the presence of Richardson–Bloom grade 3 ductal infiltrative breast cancer, which was Her-2 negative, strongly ER positive (90% of cancer cells), and moderately PgR positive (30% of cancer cells). In September 1992 this patient was admitted to hospital with intractable abdominal and back pain. Clinical and radiological examinations (computed tomography, ultrasonography) revealed multiple liver metastases (Fig. 1) although neither jaundice nor ascites was present, and her performance status was moderately impaired (WHO 2). In view of the apparent hepatic involvement, no liver biopsy was attempted. Biochemical work-up revealed a mild elevation of the CEA level (10 ng/ml; normal range o5.0 ng/ml). All other assays were normal. Chest X-ray and bone scintigraphy did not show any additional metastatic lesions. In October 1992 anthracycline-based chemotherapy was administered (FEC regimen: 5-fluorouracil 500 mg/m2, epirubicin 50 mg/m2, cyclophosphamide 500 mg/ m2, every 3 weeks). Following two cycles of
Figurer 1 Prechemotherapy CT scan of the patient (30 November 1992), showing multiple liver metastases.
Figure 2 CT scan of the same patient performed after 8 months of hormonal treatment (08 November 1993), showing complete remission of metastatic liver lesions.
ARTICLE IN PRESS Long-term survival of a patient with primarily chemo-resistant metastatic breast cancer
administered. In February 1995 the patient was admitted to the hospital with paraplegia. A second bone relapse was diagnosed in the lumbar spine. An immediate palliative radiotherapy (25 Gy in 5 fractions) was administered, and the patient made a complete recovery. In June 1993 MPA therapy was switched from intramuscular to the oral form, and the medication was continued at a dose of 300 mg tid for the next 4 years with excellent tolerance. At the time of writing (November 2003), 11 years after the diagnosis of liver metastases, the patient is alive and free of disease with no further breast cancer treatment.
Discussion Visceral metastases in breast cancer are associated with a particularly poor prognosis. Our patient presented with all known adverse prognostic factors: early relapse during adjuvant hormonal treatment, multiple liver lesions and chemoresistance. Nonetheless, a complete response to second-line hormonal therapy was achieved, with a slow but long-lasting remission. The standard management for patients with liver metastases who relapse while receiving endocrine treatment is anthracycline-based chemotherapy. This was also attempted in our patient, but was withdrawn after a short time due to obvious disease progression. Subsequent MPA treatment resulted in a spectacular tumor response achieved with virtually no side effects. In our patient, the intramuscular and oral doses of MPA were 500 and 300 mg, respectively. The recommended dose of MPA varies between 300 and 1500 mg, since higher doses do not provide any further survival benefit and are associated with considerable side effects.15,18,19 Toyama et al.20 reported a similar case, in which MPA added to FAC chemotherapy stopped disease progression and finally resulted in long-term partial response. An initial daily dose of 1200 mg MPA caused a pronounced gain in body weight, whereas subsequent daily doses of 400 mg were well tolerated and were safely administered for 6 years. MPA, 1200 mg daily, added to FAC chemotherapy was shown to be superior to FAC alone in the randomized study conducted by Tominaga et al.21 Importantly, in this study combined treatment was associated with improved performance status, and reduction of chemotherapy-related toxicity and weight loss, in addition to the higher response rates and longer duration of responses. Finally, in the study by Nishimura et al.22 high-dose MPA therapy (with MPA serum concentration above 55 ng/ml) improved performance status and survi-
323
val of metastatic breast cancer patients. More recently, salvage MPA therapy has been widely replaced by second- and third-generation aromatase inhibitors. Metastatic breast cancer remains a therapeutic challenge. In recent decades a lot of effort has been devoted to improving the outcome, but still only a small proportion of patients enjoy long-term survival. Different treatment methods, including taxane-based chemotherapy and novel aromatase inhibitors, have been proposed for liver metastases in breast cancer patients, but there are still only anecdotal reports of long-term survival.23–26 Tekin et al.14 achieved a long-term remission (7 years) in a patient with liver metastases who received regional intra-arterial chemotherapy (mitomycin C, doxorubicin, 5-fluorouracyl). Naomoto et al.27 achieved an 8-year remission following a combination of intrahepatic chemotherapy (cyclophosphamide, 5-fluorouracil) and tumor necrosis factor. Selzner et al.10 reported excellent survival after metastasectomy in 6 patients with isolated liver metastases. There has been one reported case of a 33-month survival after successful liver transplantation for hepatic metastases from breast cancer.28 To conclude, this long-lasting complete response achieved following a second-line hormonal treatment in our patient despite her initial resistance to chemotherapy should be considered an interesting, yet exceptional, event. Advanced breast cancers very probably represent a wide range of biologically different entities, each with a distinct prognosis and response to treatment. Hopefully, rapidly developing knowledge in molecular biology will lead to a better understanding of this issue.
References 1. Greenberg PA, Hortobagyi GN, Smith TL, Ziegler LD, Frye DK, Buzdar AU. Long-term follow-up of patients with complete remission following combination chemotherapy for metastatic breast cancer. J Clin Oncol 1996;14:2197–205. 2. Hortobagyi GN. Can we cure limited metastatic breast cancer? J Clin Oncol 2002;20:620–3. 3. Pierga JY, Robain M, Jouve M, et al. Response to chemotherapy is a major parameter influencing long-term survival of metastatic breast cancer patients. Ann Oncol 2001; 12:231–7. 4. Zinser JW, Hortobagyi GN, Buzdar AU, Smith TL, Fraschini G. Clinical course of breast cancer patients with liver metastases. J Clin Oncol 1987;5:773–82. 5. O’Shaughnessy J, Twelves C, Aapro M. Treatment for anthracycline-pretreated metastatic breast cancer. Oncologist 2002;7(Suppl 6):4–12. 6. Ryberg M, Nielsen D, Osterlind K, Skovsgaard T, Dombernowsky P. Prognostic factors and long-term survival in 585 patients with metastatic breast cancer treated with epirubicin-based chemotherapy. Ann Oncol 2001;12:81–7.
ARTICLE IN PRESS 324
7. Jassem J, Pienkowski T, Pluzanska A, et al. Doxorubicin and paclitaxel versus fluorouracil, doxorubicin, and cyclophosphamide as first-line therapy for women with metastatic breast cancer: final results of a randomized phase III multicenter trial. J Clin Oncol 2001;19:1707–15. 8. Fossati R, Confalonieri C, Torri V, et al. Cytotoxic and hormonal treatment for metastatic breast cancer: a systematic review of published randomized trials involving 31,510 women. J Clin Oncol 1998;16:3439–60. 9. Jardines L, Callans LS, Torosian MH. Recurrent breast cancer: presentation, diagnosis, and treatment. Semin Oncol 1993;20:538–47. 10. Selzner M, Morse MA, Vredenburgh JJ, Meyers WC, Clavien PA. Liver metastases from breast cancer: long-term survival after curative resection. Surgery 2000;127:383–9. 11. Schneebaum S, Walker MJ, Young D, Farrar WB, Minton JP. The regional treatment of liver metastases from breast cancer. J Surg Oncol 1994;55:26–31. 12. Carlini M, Lonardo MT, Carboni F, et al. Liver metastases from breast cancer. Results of surgical resection. Hepatogastroenterology 2002;49:1597–601. 13. Maksan SM, Lehnert T, Bastert G, Herfarth C. Curative liver resection for metastatic breast cancer. Eur J Surg Oncol 2000;26:209–12. 14. Tekin K, Kocaoglu H, Bayar S. Long-term survival after regional chemotherapy for liver metastases from breast cancer. A case report. Tumori 2002;88:167–9. 15. Parazzini F, Colli E, Scatigna M, Tozzi L. Treatment with tamoxifen and progestins for metastatic breast cancer in postmenopausal women: a quantitative review of published randomized clinical trials. Oncology 1993;50:483–9. 16. Bentel JM, Birrell SN, Pickering MA, Holds DJ, Horsfall DJ, Tilley WD. Androgen receptor agonist activity of the synthetic progestin, medroxyprogesterone acetate, in human breast cancer cells. Mol Cell Endocrinol 1999;154:11–20. 17. Hackenberg R, Hawighorst T, Filmer A, Nia AH, Schulz KD. Medroxyprogesterone acetate inhibits the proliferation of estrogen- and progesterone-receptor negative MFM-223 human mammary cancer cells via the androgen receptor. Breast Cancer Res Treat 1993;25:217–24. 18. Davila E, Vogel CL, East D, Cairns V, Hilsenbeck S. Clinical trial of high-dose oral medroxyprogesterone acetate in the
R. Zaucha et al.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
treatment of metastatic breast cancer and review of the literature. Cancer 1988;61:2161–7. Cavalli F, Goldhirsch A, Jungi F, Martz G, Mermillod B, Alberto P. Randomized trial of low- versus high-dose medroxyprogesterone acetate in the induction treatment of postmenopausal patients with advanced breast cancer. J Clin Oncol 1984;2:414–9. Toyama T, Yamashita H, Hara Y, Hikosaka Y, Kobayashi S, Iwase H. Successful management of breast cancer with liver metastases with medroxyprogesterone acetate treatment. Int J Clin Oncol 2001;6:306–9. Tominaga T, Abe O, Ohshima A, et al. Comparison of chemotherapy with or without medroxyprogesterone acetate for advanced or recurrent breast cancer. Eur J Cancer 1994;30A:959–64. Nishimura R, Nagao K, Matsuda M, et al. Benefits of medroxyprogesterone acetate (MPA) in advanced or recurrent breast cancer with higher serum concentration. Breast Cancer 1995;2:133–41. Mauriac L, Pippen JE, Quaresma Albano J, Gertler SZ, Osborne CK. Fulvestrant (Faslodex) versus anastrozole for the second-line treatment of advanced breast cancer in subgroups of postmenopausal women with visceral and nonvisceral metastases: combined results from two multicentre trials. Eur J Cancer 2003;39:1228–33. Nabholtz JM, Mackey JR, Smylie M, et al. Phase II study of docetaxel, doxorubicin, and cyclophosphamide as first-line chemotherapy for metastatic breast cancer. J Clin Oncol 2001;19:314–21. Nabholtz JM, Reese DM. Third-generation aromatase inhibitors in the treatment of advanced breast cancer. Breast Cancer 2001;8:305–9. Nabholtz JM, Riva A. Taxane/anthracycline combinations: setting a new standard in breast cancer? Oncologist 2001;6(Suppl 3):5–12. Naomoto Y, Sadamori H, Matsukawa H, et al. Multiple liver metastases of breast cancer: report of a case successfully treated with hormone-cytokine-chemotherapy. Jpn J Clin Oncol 1999;29:390–4. Wilson JM, Carder P, Downey S, Davies MH, Wyatt JI, Brennan TG. Treatment of metastatic breast cancer with liver transplantation. Breast J 2003;9:126–8.
THE
BREAST www.elsevier.com/locate/breast
CASE REPORT
Long-term survival of a patient with primarily chemo-resistant metastatic breast cancer treated with medroxyprogesterone acetate ! R. Zaucha*, K. Sosinska-Mielcarek, J. Jassem ! Department of Oncology and Radiotherapy, Medical University of Gdansk, ul. Debinki 7, 80-211 Gdansk, Poland Received 19 January 2004; received in revised form 14 April 2004; accepted 18 May 2004
KEYWORDS Breast cancer; Liver metastases; Medroxyprogesterone acetate; Long-term survival
Summary The prognosis of breast cancer patients with liver metastases is extremely poor. Here we present the case of a 66-year-old female breast cancer patient with multiple liver metastases diagnosed 2 years after a radical modified mastectomy followed by adjuvant tamoxifen. At progression, anthracycline-based chemotherapy was administered, but a CT scan following two cycles of FEC (5-fluorouracil, epirubicin, cyclophosphamide) showed progression of the liver metastases. Chemotherapy was therefore switched to medroxyprogesterone acetate (MPA). After 3 months the patient’s general status improved, and disease stabilization was observed at the next CT scan. A further 4 months of MPA treatment resulted in complete response of all liver lesions. Treatment with oral MPA was continued for 4 years. At present, 11 years after the diagnosis of metastatic liver involvement, the patient is alive, free of cancer, and fully ambulatory. Despite bulky visceral disease and chemoresistance, hormonal treatment with MPA resulted in a spectacular and long-lasting response. & 2004 Elsevier Ltd. All rights reserved.
Introduction Conventional treatment methods in metastatic breast cancer generally do not result in a cure, long-term survival is being seen in only 1–3% of patients.1,2 Therefore, improvement of the quality of life and, in some cases, prolongation of life are the main treatment goals. Young age, good performance status, limited metastatic disease, and *Corresponding author. Tel./fax: þ 48-349-2270. E-mail address: [email protected] (R. Zaucha).
objective response to the first-line treatment are regarded as essential for prolonged survival.2–5 In most series the median survival of women with metastatic disease has varied from 18 to 24 months.2,3,6–8 The liver is the site of approximately half of all breast cancer metastases.9,10 Median survival in this group of patients is in the range of 6–11 months.4 Survival is longer (median 24–44 months) in a selected group of patients with surgically treated isolated liver metastases.10–13 Although initial response rates of visceral and of other metastases are similar, the duration of
0960-9776/$ - see front matter & 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.breast.2004.05.003
ARTICLE IN PRESS 322
response and survival is particularly poor in patients with the former.4,10,13 About 20% of these women will die with symptoms of hepatic failure.14 Medroxyprogesterone acetate (MPA)Fa 17-OHprogesteroneFis a progestagen. It has been used for years as a second- or third-line endocrine treatment of advanced breast cancer.15 Its exact mechanism of action is not fully understood, but suppression of adrenal steroid synthesis, suppression of estrogen, activation of androgen receptors, and direct killing of tumor cells have been suggested.16,17 Its efficacy is similar to that of tamoxifen. Thromboembolic events, edema, weight gain, vaginal bleeding, and adrenal suppression are the main side effects, but this compound is generally well tolerated. In this paper we present a breast cancer patient diagnosed with multiple liver metastases 2 years after radical mastectomy followed by adjuvant tamoxifen. Despite bulky visceral disease and resistance to the first-line chemotherapy, treatment with MPA resulted in long-lasting complete response.
R. Zaucha et al.
chemotherapy, the patient’s general condition deteriorated, and a subsequent CT scan showed disease progression in the liver. Chemotherapy was therefore switched to a second-line hormonal treatment including MPA given as weekly 500-mg intramuscular injections. A CT scan done 3 months after the onset of MPA treatment showed persistence of multiple metastatic foci up to 3 cm in diameter in the liver, but the general status of the patient had improved. A CT scan performed after a further 4 months of MPA treatment showed complete remission of all liver lesions (Fig. 2). There were virtually no side effects throughout the entire MPA treatment period. In September 1993, a single painful osteolytic metastasis in the sacral bone was found and a palliative radiotherapy (8 Gy in 1 fraction) was
Case presentation In February 1990, a 64-year-old retired dentist was diagnosed with a cT2N0M0 (pT2N1) cancer of the left breast. Following modified radical mastectomy she was prescribed adjuvant tamoxifen. At the time of primary treatment the steroid receptor status and HER-2 expression were unknown. Subsequent examination of the paraffin blocks confirmed the presence of Richardson–Bloom grade 3 ductal infiltrative breast cancer, which was Her-2 negative, strongly ER positive (90% of cancer cells), and moderately PgR positive (30% of cancer cells). In September 1992 this patient was admitted to hospital with intractable abdominal and back pain. Clinical and radiological examinations (computed tomography, ultrasonography) revealed multiple liver metastases (Fig. 1) although neither jaundice nor ascites was present, and her performance status was moderately impaired (WHO 2). In view of the apparent hepatic involvement, no liver biopsy was attempted. Biochemical work-up revealed a mild elevation of the CEA level (10 ng/ml; normal range o5.0 ng/ml). All other assays were normal. Chest X-ray and bone scintigraphy did not show any additional metastatic lesions. In October 1992 anthracycline-based chemotherapy was administered (FEC regimen: 5-fluorouracil 500 mg/m2, epirubicin 50 mg/m2, cyclophosphamide 500 mg/ m2, every 3 weeks). Following two cycles of
Figurer 1 Prechemotherapy CT scan of the patient (30 November 1992), showing multiple liver metastases.
Figure 2 CT scan of the same patient performed after 8 months of hormonal treatment (08 November 1993), showing complete remission of metastatic liver lesions.
ARTICLE IN PRESS Long-term survival of a patient with primarily chemo-resistant metastatic breast cancer
administered. In February 1995 the patient was admitted to the hospital with paraplegia. A second bone relapse was diagnosed in the lumbar spine. An immediate palliative radiotherapy (25 Gy in 5 fractions) was administered, and the patient made a complete recovery. In June 1993 MPA therapy was switched from intramuscular to the oral form, and the medication was continued at a dose of 300 mg tid for the next 4 years with excellent tolerance. At the time of writing (November 2003), 11 years after the diagnosis of liver metastases, the patient is alive and free of disease with no further breast cancer treatment.
Discussion Visceral metastases in breast cancer are associated with a particularly poor prognosis. Our patient presented with all known adverse prognostic factors: early relapse during adjuvant hormonal treatment, multiple liver lesions and chemoresistance. Nonetheless, a complete response to second-line hormonal therapy was achieved, with a slow but long-lasting remission. The standard management for patients with liver metastases who relapse while receiving endocrine treatment is anthracycline-based chemotherapy. This was also attempted in our patient, but was withdrawn after a short time due to obvious disease progression. Subsequent MPA treatment resulted in a spectacular tumor response achieved with virtually no side effects. In our patient, the intramuscular and oral doses of MPA were 500 and 300 mg, respectively. The recommended dose of MPA varies between 300 and 1500 mg, since higher doses do not provide any further survival benefit and are associated with considerable side effects.15,18,19 Toyama et al.20 reported a similar case, in which MPA added to FAC chemotherapy stopped disease progression and finally resulted in long-term partial response. An initial daily dose of 1200 mg MPA caused a pronounced gain in body weight, whereas subsequent daily doses of 400 mg were well tolerated and were safely administered for 6 years. MPA, 1200 mg daily, added to FAC chemotherapy was shown to be superior to FAC alone in the randomized study conducted by Tominaga et al.21 Importantly, in this study combined treatment was associated with improved performance status, and reduction of chemotherapy-related toxicity and weight loss, in addition to the higher response rates and longer duration of responses. Finally, in the study by Nishimura et al.22 high-dose MPA therapy (with MPA serum concentration above 55 ng/ml) improved performance status and survi-
323
val of metastatic breast cancer patients. More recently, salvage MPA therapy has been widely replaced by second- and third-generation aromatase inhibitors. Metastatic breast cancer remains a therapeutic challenge. In recent decades a lot of effort has been devoted to improving the outcome, but still only a small proportion of patients enjoy long-term survival. Different treatment methods, including taxane-based chemotherapy and novel aromatase inhibitors, have been proposed for liver metastases in breast cancer patients, but there are still only anecdotal reports of long-term survival.23–26 Tekin et al.14 achieved a long-term remission (7 years) in a patient with liver metastases who received regional intra-arterial chemotherapy (mitomycin C, doxorubicin, 5-fluorouracyl). Naomoto et al.27 achieved an 8-year remission following a combination of intrahepatic chemotherapy (cyclophosphamide, 5-fluorouracil) and tumor necrosis factor. Selzner et al.10 reported excellent survival after metastasectomy in 6 patients with isolated liver metastases. There has been one reported case of a 33-month survival after successful liver transplantation for hepatic metastases from breast cancer.28 To conclude, this long-lasting complete response achieved following a second-line hormonal treatment in our patient despite her initial resistance to chemotherapy should be considered an interesting, yet exceptional, event. Advanced breast cancers very probably represent a wide range of biologically different entities, each with a distinct prognosis and response to treatment. Hopefully, rapidly developing knowledge in molecular biology will lead to a better understanding of this issue.
References 1. Greenberg PA, Hortobagyi GN, Smith TL, Ziegler LD, Frye DK, Buzdar AU. Long-term follow-up of patients with complete remission following combination chemotherapy for metastatic breast cancer. J Clin Oncol 1996;14:2197–205. 2. Hortobagyi GN. Can we cure limited metastatic breast cancer? J Clin Oncol 2002;20:620–3. 3. Pierga JY, Robain M, Jouve M, et al. Response to chemotherapy is a major parameter influencing long-term survival of metastatic breast cancer patients. Ann Oncol 2001; 12:231–7. 4. Zinser JW, Hortobagyi GN, Buzdar AU, Smith TL, Fraschini G. Clinical course of breast cancer patients with liver metastases. J Clin Oncol 1987;5:773–82. 5. O’Shaughnessy J, Twelves C, Aapro M. Treatment for anthracycline-pretreated metastatic breast cancer. Oncologist 2002;7(Suppl 6):4–12. 6. Ryberg M, Nielsen D, Osterlind K, Skovsgaard T, Dombernowsky P. Prognostic factors and long-term survival in 585 patients with metastatic breast cancer treated with epirubicin-based chemotherapy. Ann Oncol 2001;12:81–7.
ARTICLE IN PRESS 324
7. Jassem J, Pienkowski T, Pluzanska A, et al. Doxorubicin and paclitaxel versus fluorouracil, doxorubicin, and cyclophosphamide as first-line therapy for women with metastatic breast cancer: final results of a randomized phase III multicenter trial. J Clin Oncol 2001;19:1707–15. 8. Fossati R, Confalonieri C, Torri V, et al. Cytotoxic and hormonal treatment for metastatic breast cancer: a systematic review of published randomized trials involving 31,510 women. J Clin Oncol 1998;16:3439–60. 9. Jardines L, Callans LS, Torosian MH. Recurrent breast cancer: presentation, diagnosis, and treatment. Semin Oncol 1993;20:538–47. 10. Selzner M, Morse MA, Vredenburgh JJ, Meyers WC, Clavien PA. Liver metastases from breast cancer: long-term survival after curative resection. Surgery 2000;127:383–9. 11. Schneebaum S, Walker MJ, Young D, Farrar WB, Minton JP. The regional treatment of liver metastases from breast cancer. J Surg Oncol 1994;55:26–31. 12. Carlini M, Lonardo MT, Carboni F, et al. Liver metastases from breast cancer. Results of surgical resection. Hepatogastroenterology 2002;49:1597–601. 13. Maksan SM, Lehnert T, Bastert G, Herfarth C. Curative liver resection for metastatic breast cancer. Eur J Surg Oncol 2000;26:209–12. 14. Tekin K, Kocaoglu H, Bayar S. Long-term survival after regional chemotherapy for liver metastases from breast cancer. A case report. Tumori 2002;88:167–9. 15. Parazzini F, Colli E, Scatigna M, Tozzi L. Treatment with tamoxifen and progestins for metastatic breast cancer in postmenopausal women: a quantitative review of published randomized clinical trials. Oncology 1993;50:483–9. 16. Bentel JM, Birrell SN, Pickering MA, Holds DJ, Horsfall DJ, Tilley WD. Androgen receptor agonist activity of the synthetic progestin, medroxyprogesterone acetate, in human breast cancer cells. Mol Cell Endocrinol 1999;154:11–20. 17. Hackenberg R, Hawighorst T, Filmer A, Nia AH, Schulz KD. Medroxyprogesterone acetate inhibits the proliferation of estrogen- and progesterone-receptor negative MFM-223 human mammary cancer cells via the androgen receptor. Breast Cancer Res Treat 1993;25:217–24. 18. Davila E, Vogel CL, East D, Cairns V, Hilsenbeck S. Clinical trial of high-dose oral medroxyprogesterone acetate in the
R. Zaucha et al.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
treatment of metastatic breast cancer and review of the literature. Cancer 1988;61:2161–7. Cavalli F, Goldhirsch A, Jungi F, Martz G, Mermillod B, Alberto P. Randomized trial of low- versus high-dose medroxyprogesterone acetate in the induction treatment of postmenopausal patients with advanced breast cancer. J Clin Oncol 1984;2:414–9. Toyama T, Yamashita H, Hara Y, Hikosaka Y, Kobayashi S, Iwase H. Successful management of breast cancer with liver metastases with medroxyprogesterone acetate treatment. Int J Clin Oncol 2001;6:306–9. Tominaga T, Abe O, Ohshima A, et al. Comparison of chemotherapy with or without medroxyprogesterone acetate for advanced or recurrent breast cancer. Eur J Cancer 1994;30A:959–64. Nishimura R, Nagao K, Matsuda M, et al. Benefits of medroxyprogesterone acetate (MPA) in advanced or recurrent breast cancer with higher serum concentration. Breast Cancer 1995;2:133–41. Mauriac L, Pippen JE, Quaresma Albano J, Gertler SZ, Osborne CK. Fulvestrant (Faslodex) versus anastrozole for the second-line treatment of advanced breast cancer in subgroups of postmenopausal women with visceral and nonvisceral metastases: combined results from two multicentre trials. Eur J Cancer 2003;39:1228–33. Nabholtz JM, Mackey JR, Smylie M, et al. Phase II study of docetaxel, doxorubicin, and cyclophosphamide as first-line chemotherapy for metastatic breast cancer. J Clin Oncol 2001;19:314–21. Nabholtz JM, Reese DM. Third-generation aromatase inhibitors in the treatment of advanced breast cancer. Breast Cancer 2001;8:305–9. Nabholtz JM, Riva A. Taxane/anthracycline combinations: setting a new standard in breast cancer? Oncologist 2001;6(Suppl 3):5–12. Naomoto Y, Sadamori H, Matsukawa H, et al. Multiple liver metastases of breast cancer: report of a case successfully treated with hormone-cytokine-chemotherapy. Jpn J Clin Oncol 1999;29:390–4. Wilson JM, Carder P, Downey S, Davies MH, Wyatt JI, Brennan TG. Treatment of metastatic breast cancer with liver transplantation. Breast J 2003;9:126–8.