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R E V I E W O N C O L O G Y The role of surgery in the management of metastatic breast cancer? Authors A. Steyaert, A. Smeets, I. Cadron, H. Wildiers, M.R. Christiaens Key words Surgery, stage IV breast cancer, primary tumor, metastasis Summary Although metastatic breast cancer has a bad prognosis, the median survival of these patients has improved over the last 25 years. This review considers the role of surgical excision of the primary tumor and resection of metastases in patients with limited metastatic disease. There is emerging evidence that for women with stage IV breast cancer, resection of the primary tumor with negative margins significantly improves survival, especially in patients with solitary bone metasta- Introduction Nowadays, surgical treatment in patients with metastatic breast cancer is limited to palliative indications as these patients will ultimately die of their disease (overall survival of 2% at 20 years of followup) and aggressive approaches lead to useless patient distress and morbidity. However, it is important to realize that over the past 25 years, the median survival of these patients has improved significantly from 15 months in patients diagnosed between 1974-1979 to 51 months in patients diagnosed between 1995 and 2000.1 This improved survival is a consequence of patients presenting with minimal metastatic disease on the one hand and more effective therapies on the other hand.2 These findings force us to re-evaluate the role of surgical excision of the primary tumor in metastatic patients and to consider a resection of metastases for patients with limited metastatic disease. The role of surgery of the primary tumor in stage IV breast cancer patients Three theories concerning the development of distant metastasis in breast cancer have emerged in the B E L G I A N J O U R N A L O F M E D I C A L sis. For lung, liver, brain and sternum metastases, surgical resection of the metastasis seems to be associated with a greater median survival time and 5-year survival rate. The best candidates for surgery might be patients with a good response to systemic treatment, a long disease free interval after treatment of the primary tumor and a single site of metastases or metastases confined to one organ, provided that a complete excision of all metastases can be obtained. (BJMO 2009;Vol 3;5:184-190) first half of the 20th century, each of them having different implications for the treatment of patients. The first theory, also known as the Halsted theory, states that breast cancer starts as a local disease and that tumor cells spread from the primary tumor to axillary lymph nodes and then to metastatic sites.3 This view justifies an aggressive local therapy for local control of disease in the breast and the regional lymph nodes. Secondly, the Fisher theory, states that breast cancer is a systemic disease and that tumors which have the capacity to metastasize, will do so even before diagnosis.4 This view justifies an aggressive systemic therapy because the only hope for definitive cure is treatment of the (micro)metastasis. Local control according to this theory would have no effect on overall survival. Neither theory is correct as demonstrated in different clinical trials. The National Surgical Adjuvant Breast and Bowel Project breast carcinoma B-04 study (NSABP-B-04) showed no benefit of radical mastectomy over less radical surgery which brings in doubt the Halsted theory.5 On the other hand the significant reduction of the relative risk of death from breast cancer due to mammographic screening O N C O L O G Y vol. 3 issue 5 - 2009 184 R eview oncology compromises the systemic theory. Early detection of breast cancer does have an influence on the reduction of mortality and randomized controlled trials show a link between local control and overall survival in breast cancer, again bringing in doubt the validity of the systemic theory.6,7 The third theory, depicted as the Spectrum theory, is basically a blend of both the Halsted and the Fisher theory and states that the exact moment of metastasis to distant sites is unknown at the time of diagnosis.8,9 This theory emphasizes the importance of locoregional and systemic treatment through a multimodal approach. Recently however, new molecular-based hypotheses of development of metastasis in breast cancer, tumor immunology and tumor growth influence our view on the metastatic development and progression in breast cancer which is crucial in deciding whether surgery is indicated in these patients. Today, there is still limited understanding of the molecular mechanisms of metastasis but, according to Lang and colleagues, three new hypotheses can be distinguished.10 The first, known as the parallel evolution model, states that circulating or disseminated tumor cells are found early in tumorigenesis and are independent of the primary tumor. This theory justifies a surgical treatment of stage IV patients with an intact primary and a minimal metastatic burden. A second model based on the gene expression profile of the primary tumor, states that the metastatic potential is an inherent, genetic predetermined property that is expressed very early and that tumor cells are programmed to metastasize to a certain site in the presence of a favorable microenvironment. This model justifies an optimal local and systemic treatment to target the circulating tumor cells. The third hypothesis, depicted as the breast cancer stem cell model, states that specialized tumor-initiating cancer cells have the exclusive potential to metastasize. This theory justifies effective treatment directed at the stem cell population and surgical treatment of the primary tumor. New insights into the interaction between metastases and the host are also crucial in making a decision whether surgical intervention is appropriate in stage IV patients. A study of Danna et al indicated that, although patients with bulky primary tumors are immunosuppressed, primary tumor removal reverses immune suppression even in the presence of extensive metastatic disease.11 They concluded that reducing tumor burden either by surgery or by other conventional techniques could augment the efficacy 185 vol. 3 issue 5 - 2009 of immunotherapy which justifies surgical treatment in a metastatic breast cancer patient. Removal of the primary tumor seems to restore immune competence by removing a potentially dependent relationship between the primary tumor and its metastases. This has already been shown in other carcinoma’s. The South Western Oncology group (SWOG) trial examined the benefit of nephrectomy in patients with stage IV renal cell carcinoma, who were randomized to interleukin therapy, with or without nephrectomy.12 In this study, the overall median survival increased from 8 months without nephrectomy, to 11 months for patients who underwent nephrectomy, suggesting that aggressive locoregional treatment may contribute to a prolonged survival. The same benefit of surgical treatment was described in patients with colorectal and gastric cancer, for which a reduction in tumor burden has been reported to be effective in terms of increased survival.13,14 A potential argument against resection of the intact primary is the tumor dormancy theory. This theory states that removal of the primary tumor results in a proliferation of metastases by induction of angiogenesis, reduction of apoptosis and release of growth factors in response to surgical wounding. This theory however has never been proven by clinical studies (only level 4 evidence to support this theory) and is not seen in clinical practice.10 The main limitations in evaluating whether surgical treatment of the primary tumor in stage IV breast cancer patients is indicated, are selection biases in favor of operated patients and limited information on tumor characteristics and adjuvant therapy. A first study was conducted by Khan and colleagues.15 It is a retrospective review of data from the National Cancer Data Base (NCDB) between 1990 and 1993. A total of 16,023 patients were included of whom 6,861 (42.8%) received no operation and 9,162 (57.2%) underwent either partial (N= 3,513) or total (N= 5,649) mastectomy. The authors concluded that there is a statistically significant survival advantage in women undergoing surgery at the primary site, especially when negative margins were obtained. The 3 year survival rate was 17.3% in patients who had no surgical procedure and 35% in patients operated with negative margins. Independent prognostic co-variates were the number of metastatic sites, the type of metastatic burden and the extent of resection of the primary tumor. This large data set adds strength to the hypothesis that local therapy is valuable, even in the presence of distant disease. B E L G I A N J O U R N A L O F M E D I C A L O N C O L O G Y Furthermore, Babiera and colleagues reviewed the records of 224 primary metastatic breast cancer patients, treated between 1997 and 2002. Eighty-two patients (37%) underwent surgical treatment (52% total mastectomy, 48% partial mastectomy) and 142 patients (63%) were treated without surgery.16 The median follow-up in this study was 32.1 months. On multivariate analysis, surgery was associated with a trend towards improved overall survival (p= 0.12) and a significant improvement in metastatic progression-free survival (p= 0.0007). Rapiti and colleagues reported a retrospective study of 300 metastatic breast cancer patients recorded at the Geneva Cancer Registry between 1977 and 1996.17 Overall, 173 patients (58%) did not receive any kind of surgery of the primary tumor, whereas 127 (42%) underwent either mastectomy (N= 87) or partial mastectomy (N= 40). They concluded that women who had a complete excision of the primary tumor with negative surgical margins had a 40% reduced risk of death as a result of breast cancer compared with women who did not have surgery (multiadjusted HR= 0.6). This effect was even greater in the subgroup of women who had bone metastases only at the time diagnosis (HR= 0.2). However, the survival rate did not differ between women who underwent surgery with positive surgical margins and women who did not have surgery. The results of this study also provided some evidence of an additional beneficial effect of axillary lymph node dissection when performed together with removal of the primary tumor. Gnerlich and colleagues conducted a retrospective population based cohort study of 9,734 patients in the SEER database (Surveillance, Epidemiology and End Results program data).18 Data were collected between 1988 and 2003. Overall, 5,156 patients (53%) did not receive a surgical treatment whereas 4,578 (47%) underwent breast cancer surgery. In this study, the median survival was longer for women who had surgery than for women who did not. After controlling for demographic and clinical factors associated with survival, patients who underwent surgery were 37% less likely to die during the study period than women who did not undergo surgery. Furthermore, Ruiterkamp and colleagues performed a retrospective study on 728 stage IV breast cancer patients diagnosed between 1993 and 2004.19 A total of 40% of these patients underwent breast surgery. The median survival was 31 months in women who had surgery compared with 14 months in women who did not. Removal of the tumor was B E L G I A N J O U R N A L O F M E D I C A L associated with a reduction of the mortality risk of around 40%. In a retrospective single institution study reported by Shien et al including 344 patients who had stage IV breast cancer at diagnosis of which 47% had surgery of the primary tumor, the overall survival improved with surgery but also with young age and bone or soft tissue metastasis.20 Bafford et al conducted a retrospective review of 147 patients who presented with stage IV breast cancer. A total of 41% of the patients underwent surgery in this study.21 The mean overall survival, adjusted for age, number of sites of metastasis, systemic therapy, ER and HER2 status was 4.13 years in the surgery group versus 2.36 years in the non-surgery group (HR= 0.47, p= 0.003). In summary, all these clinical studies provide additional evidence that women with stage IV breast cancer have a significantly improved survival when the primary tumor is removed with negative margins, especially in patients with solitary bone metastasis. Selection of patients with stage IV breast cancer for resection of the primary tumor Mastectomy in stage IV breast cancer patients is conventionally the treatment of choice in case of ulceration, infection or bleeding. The treatment is palliative with the intention to have an optimal symptom control and to enhance the quality of life. In view of the recent clinical studies, there is emerging evidence that removal of the primary tumor and axillary lymph nodes in patients with stage IV breast cancer is also associated with improved metastatic progressionfree survival. Determining which patients will definitely benefit from surgery is now the key question. Based on the available data, the major benefit is noticed in young patients with only one site of metastasis, a good response to systemic therapy and in whom negative margins at the primary site can be obtained. Optimal timing of surgery in these patients appears to be 3-9 months after diagnosis.22 These findings may serve as the basis for designing a prospective randomized controlled trial. The role of surgery in the treatment of single or multiple metastatic lesions restricted to one site in stage IV breast cancer patients Rationale for resection of metastatic lesions A similar debate could be held on the treatment of the metastasis in patients with metastatic disease O N C O L O G Y vol. 3 issue 5 - 2009 186 R eview oncology limited to a solitary lesion or multiple lesions at a single organ. Only a few reports of breast cancer patients treated with aggressive local therapy to the metastatic site combined with systemic therapy have been reported. At the MD Anderson Cancer Center, 80 patients with solitary metastases were treated with surgery with or without radiation therapy followed by systemic therapy. Nearly 25% of patients were alive without disease 15 years after treatment.23 A recent study by Nieto and colleagues included 60 patients who were treated with surgical resection and radiation therapy when possible, followed by systemic chemotherapy.24 After a median followup of 62 months, more than half (51.6%) of these patients were disease-free. Other reports concerning gastric carcinoma or colorectal cancer confirm this trend, obliging us to reconsider the importance of surgery in patients with stage IV breast cancer.13,14 It has been suggested that the total tumor burden plays a central role in survival and that the primary tumor could be viewed as another metastatic site. Indications for resection of the metastatic lesions Urgencies which require regional radiotherapy (RT), surgery or interventional procedures prior to, or along with systemic therapy are: brain metastasis, cord compression, choroid disease, pleural effusion, pericardial effusion, pending/pathologic fracture and obstruction of the biliary tree, the ureters, the trachea, the bowel or the esophagus. Singletary and colleagues determined which patients with metastatic disease limited to a solitary lesion or to multiple lesions at a single organ site are the best candidates for surgery by reviewing the literature from 1992 until 2002 on each organ site.25 Several kinds of bias might influence these results, however the data are suggestive. Again the need for prospective randomized controlled trials in search for guidelines is emphasized. An overview of the available literature is summarized below. Across the four sites (lung, liver, brain, bone) better patient outcome after surgery was associated with good performance status, long disease free interval after treatment of the primary tumor, complete resection of the tumor and restriction of metastasis to single tumors or to multiple tumors at single site.25 Liver Isolated liver metastases are found in 5-25% of patients with metastatic breast cancer. The presence 187 vol. 3 issue 5 - 2009 of liver metastases implies poor prognosis with a reported median survival of 19 to 22 months. Singletary et al reviewed 6 small retrospective studies which indicated that there is evidence that surgery can significantly increase survival.25 The median survival times ranged from 22 to 44 months and the 5 years survival rates ranged from 22 to 38% with one study showing a 4-years survival rate of 46%. These results were confirmed in 5 more recent studies.26-30 Elias et al suggest to propose resection of the liver metastases when the three following conditions are absolutely confirmed: (1) a low operative risk, (2) liver metastases completely resectable and (3) no extra hepatic disease (except for rare bone metastases).30 Parameters that negatively influence survival are a short interval between breast surgery and the appearance of liver metastasis and a negative hormone receptor status. The role of radiofrequency ablation remains unclear. Several studies are currently ongoing and the first results seem promising.31,32 At this time, radiofrequency ablation should be reserved for patients unfit for surgery or used as an adjuvant to resection. Lung Of all women with breast cancer 3% will develop a solitary pulmonary lesion, of which 33% will be a breast metastasis.33,34 The remaining two thirds will consist of other tumortypes. In order to determine the optimal treatment strategies for these patients, early identification of the type of lesion is an additional reason for recommending surgical resection. In a study performed in 467 patients with lung metastases from breast cancer, a complete metastatic resection was obtained in 84% of patients, with a 5-year survival rate of 38%.35 A positive survival outcome after surgery was associated with a longer disease free interval after excision of the primary tumor and a positive hormone receptor status. These findings are in line with most of the published studies. Brain Off all women with breast cancer, 10% will develop brain metastases and in only one third of these patients the brain is the only site of metastasis.25 Conventionally, palliation of neurological symptoms is obtained by steroids and whole brain radiation therapy. Only 5 small studies considered the possible increase of survival by surgical excision added to whole brain radiation therapy. The median survival ranged from 15 to 37 months, with 5 years survival rates ranging from 7 to 38%. Good can- B E L G I A N J O U R N A L O F M E D I C A L O N C O L O G Y Key messages for clinical practice 1. Concepts of cancer biology and treatment are evolving. 2.There is emerging evidence of a potential survival benefit of loco-regional surgery in young patients with only one site of metastasis, a good response to systemic therapy and in whom negative margins at the primary site can be obtained. Optimal timing of surgery in these patients appears to be 3-9 months after diagnosis. 3.Candidates for surgery of metastases might be patients with a good response to systemic treatment, a long disease free interval and a single site of metastasis or multiple metastases confined to one organ, provided that a complete excision of all metastases can be obtained. didates for surgical therapy are patients who have a single operable brain lesion and well-controlled systemic disease. Leptomeningeal disease has a very poor prognosis and is a contra-indication for surgical excision Stereotactic radiation therapy is an alternative for surgical excision in those cases were the metastasis is located in an inaccessible site or is inoperable, though larger lesions may not respond. Bone Bone is the most common site of breast cancer metastasis, mainly in patients with receptor positive tumors, and is usually treated with systemic therapy. Surgery has been reserved for the treatment of lesions that are not responsive to systemic therapy in order to enhance the quality of life (pain relief), reduce fracture risk and treat spinal or nerve compression. Surgery as a curative treatment option for bone metastasis has only been considered in case of isolated sternal metastases. Data concerning patient selection are scarce, in the 1980s Noguchi et al suggested that surgical resection of solitary sternal metastases may have led to significantly better survival.36 The largest study is from Incarbone and colleagues.37 They reviewed 19 patients with local recurrences or metastases of breast tumors, the 5-year survival rate was 49% in patients with direct extension to the chest wall and 60% in patients with distant bone metastasis. However, an isolated sternal metastasis should be regarded with caution as Kwai et al demonstrated that 54% of patients with breast cancer and a solitary sternal metastasis developed other foci of distant disease within 20 months.38 Conclusion B E L G I A N J O U R N A L O F M E D I C A L As the concepts of cancer biology and treatment continue to evolve, so does the definition of “cure”. By changing the focus from complete eradication of all tumor cells as the goal of therapy to that of rendering the disease stable, selected patients with metastatic breast cancer might be candidates for surgery. There is emerging evidence of a potential survival benefit of loco-regional surgery in young patients with single site metastasis and a good response to systemic treatment, provided a complete loco-regional treatment is obtained (negative margins + axilla + RT). Candidates for surgery of metastasis might be patients with a good response to systemic treatment, a long disease free interval and a single site of metastasis or multiple metastases confined to one organ, provided that a complete excision of all metastases can be obtained. However, prospective studies are needed to validate these results. References 1. Giordano SH, Buzdar AU, Smith TL, Kau SW, Yang Y, Hortobagyi GN. Is breast cancer survival improving? Cancer 2004;100(1):44-52. 2. Rivera E, Holmes FA, Buzdar AU, Asmar L, Kau SW, Fraschini G, et al. Fluorouracil, doxorubicin, and cyclophosphamide followed by tamoxifen as adjuvant treatment for patients with stage IV breast cancer with no evidence of disease. Breast J 2002;8(1):2-9. 3. Halsted WS. The Results of Radical Operations for the Cure of Carcinoma of the Breast. Ann Surg 1907;46(1):1-19. 4. Fisher B. Biological and clinical considerations regarding the use of surgery and chemotherapy in the treatment of primary breast cancer. Cancer 1977;40(1 Suppl):574‑87. 5. Fisher B, Jeong JH, Anderson S, Bryant J, Fisher ER, Wolmark N. O N C O L O G Y vol. 3 issue 5 - 2009 188 R eview oncology Twenty-five-year follow-up of a randomized trial comparing radical mastectomy, total mastectomy, and total mastectomy followed by irradiation. N Engl J Med 2002;347(8):567-75. 6. Clarke M, Collins R, Darby S, Davies C, Elphinstone P, Evans E et al. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005;366(9503):2087-106. 7. Tabár L, Fagerberg CJ, Gad A, Baldetorp L, Holmberg LH, Gröntoft O et al. Reduction in mortality from breast cancer after mass screening with mammography. Randomised trial from the Breast Cancer Screening Working Group of the Swedish National Board of Health and Welfare. Lancet 1985;1(8433):829-32. 8. Hellman S, Harris JR. The appropriate breast cancer paradigm. Cancer Res 1987;47(2):339-42. 9. Hellman S. Karnofsky Memorial Lecture. Natural history of small breast cancers. J Clin Oncol 1994;12(10):2229-34. 10. Lang JE, Babiera GV. Locoregional Resection in Stage IV breast cancer: tumor biology, molecular and clinical perspectives. Surg Clin North Am 2007;87(2):527-38. 11. Danna EA, Sinha P, Gilbert M, Clements VK, Pulaski BA, Ostrand-Rosenberg S. Surgical removal of primary tumor reverses tumor-induced immunosuppression despite the presence of metastatic disease. Cancer Res 2004;64(6):2205-11. 12. Flanigan RC, Salmon SE, Blumenstein BA, Bearman SI, Roy V, McGrath PC,et al. Nephrectomy followed by interferon alfa-2b compared with interferon alfa-2b alone for metastatic renal-cell cancer. N Engl J Med 2001;345(23):1655-9. 13. Rosen SA, Buell JF, Yoshida A, Kazsuba S, Hurst R, Michelassi F,et al. Initial presentation with stage IV colorectal cancer: how aggressive should we be? Arch Surg 2000;135(5):530-4; discussion 534-5. 14. Hallissey MT, Allum WH, Roginski C, Fielding JW. Palliative surgery for gastric cancer. Cancer 1988;62(2):440-4. 15. Khan SA, Stewart AK, Morrow M. Does aggressive local therapy improve survival in metastatic breast cancer? Surgery 2002;132(4):620-6; discussion 626-7. 16. Babiera GV, Rao R, Feng L, Meric-Bernstam F, Kuerer HM, Singletary SE, et al. Effect of primary tumor extirpation in breast cancer patients who present with stage IV disease and an intact primary tumor. Ann Surg Oncol 2006;13(6):776-82. 17. Rapiti E, Verkooijen HM, Vlastos G, Fioretta G, Neyroud-Caspar I, Sappino AP, et al. Complete excision of primary breast tumor improves survival of patients with metastatic breast cancer at diagnosis. J Clin Oncol 2006;24(18):2743-9. 18. Gnerlich J, Jeffe DB, Deshpande AD, Beers C, Zander C, Margenthaler JA. Surgical removal of the primary tumor increases overall survival in patients with metastatic breast cancer: analysis of the 1988-2003 SEER data. Ann Surg Oncol 189 vol. 3 issue 5 - 2009 2007;14(8):2187-94. 19. Ruiterkamp J, Ernst MF, van de Poll-Franse LV, Bosscha K, Tjan-Heijnen VC, Voogd AC. Surgical resection of the primary tumour is associated with improved survival in patients with distant metastatic breast cancer at diagnosis. Eur J Surg Oncol 2009; Epub ahead of print. 20. Shien T, Kinoshita T, Shimizu C, Hojo T, Taira N, Doihara H, et al. Primary tumor resection improves the survival of younger patients with metastatic breast cancer. Oncol Rep 2009;21(3):827-32. 21. Bafford AC, Burstein HJ, Barkley CR, Smith BL, Lipsitz S, Iglehart JD, et al. Breast surgery in stage IV breast cancer: impact of staging and patient selection on overall survival. Breast Cancer Res Treat 2009;115(1):7-12. 22. Rao R, Feng L, Kuerer HM, Singletary SE, Bedrosian I, Hunt KK, et al. Timing of surgical intervention for the intact primary in stage IV breast cancer patients. Ann Surg Oncol 2008;15(6):1696-702. 23. Holmes FA, Buzdar AU, Kau S-W, et al. Combined modality approach for patients with isolated recurrences of breast cancer (IV-NED): the M. D. Anderson Cancer Center experience. Breast Dis 1994;7:7–20. 24. Nieto Y, Nawaz S, Jones RB, Shpall EJ, Cagnoni PJ, McSweeney PA, et al. Prognostic model for relapse after highdose chemotherapy with autologous stem-cell transplantation for stage IV oligometastatic breast cancer. J Clin Oncol 2002;20(3):707-18. 25. Singletary SE, Walsh G, Vauthey JN, Curley S, Sawaya R, Weber KL, et al. A role for curative surgery in the treatment of selected patients with metastatic breast cancer. Oncologist 2003;8(3):241-51. 26. Adam R, Aloia T, Krissat J, Bralet MP, Paule B, Giacchetti S, et al. Is liver resection justified for patients with hepatic metastases from breast cancer? Ann Surg 2006;244(6):897‑907; discussion 907-8. 27. Sakamoto Y, Yamamoto J, Yoshimoto M, Kasumi F, Kosuge T, Kokudo N, et al. Hepatic resection for metastatic breast cancer: prognostic analysis of 34 patients. World J Surg 2005;29(4):524-7. 28. Vlastos G, Smith DL, Singletary SE, Mirza NQ, Tuttle TM, Popat RJ, et al. Long-term survival after an aggressive surgical approach in patients with breast cancer hepatic metastases. Ann Surg Oncol 2004;11(9):869-74. 29. Caralt M, Bilbao I, Cortés J, Escartín A, Lázaro JL, Dopazo C, et al. Hepatic resection for liver metastases as part of the "oncosurgical" treatment of metastatic breast cancer. Ann Surg Oncol 2008;15(10):2804-10. 30. Elias D, Maisonnette F, Druet-Cabanac M, Ouellet JF, Guinebretiere JM, et al An attempt to clarify indications for hepatectomy for liver metastases from breast cancer. Am J Surg 2003;185(2):158-64. 31. Rath GK, Julka PK, Thulkar S, Sharma DN, Bahl A, B E L G I A N J O U R N A L O F M E D I C A L O N C O L O G Y Bhatnagar S. Radiofrequency ablation of hepatic metastasis: results of treatment in forty patients. J Cancer Res Ther 2008;4(1):14-7. 32. Jakobs TF, Hoffmann RT, Schrader A, Stemmler HJ, Trumm C, Lubienski A, et al. CT-guided radiofrequency ablation in patients with hepatic metastases from breast cancer. Cardiovasc Intervent Radiol 2009;32(1):38-46. 33. Casey JJ, Stempel BG, Scanlon EF, Fry WA. The solitary pulmonary nodule in the patient with breast cancer. Surgery 1984;96(4):801-5. 34. McDonald ML, Deschamps C, Ilstrup DM, Allen MS, Trastek VF, Pairolero PC. Pulmonary resection for metastatic breast cancer. Ann Thorac Surg 1994;58(6):1599-602. 35. Friedel G, Pastorino U, Ginsberg RJ, Goldstraw P, Johnston M, Pass H, et al. International Registry of Lung Metastases, London, England. Results of lung metastasectomy from breast cancer: prognostic criteria on the basis of 467 cases of the International Registry of Lung Metastases. Eur J Cardiothorac Surg 2002;22(3):335-44. 36. Noguchi S, Miyauchi K, Nishizawa Y, Imaoka S, Koyama H, Iwanaga T Results of surgical treatment for sternal metastasis of breast cancer. Cancer 1988;62(7):1397-401. 37. Incarbone M, Nava M, Lequaglie C, Ravasi G, Pastorino U. Sternal resection for primary or secondary tumors. J Thorac Cardiovasc Surg 1997;114(1):93-9. 38. Kwai AH, Stomper PC, Kaplan WD. Clinical significance of isolated scintigraphic sternal lesions in patients with breast cancer. J Nucl Med 1988;29(3):324-8. Correspondence address Authors: A. Steyaert, A. Smeets, I. Cadron, H. Wildiers, M.R. Christiaens. Multidisciplinary Breast Centre, University Hospitals Leuven. Please send all correspondence to: Dr. A. Smeets Multidisciplinary Breast Centre University Hospitals Leuven Herestraat 49 B-3000 Leuven Belgium Tel 0032 (0)16 34 68 32 Fax 0032 (0)16 34 68 34 [email protected] Conflicts of interest: The authors have nothing to disclose and indicate no potential conflicts of interest. Call for contributions from readers Dear reader, Inspired by this issue of the Belgian Journal of Medical Oncology (BJMO)? You yourself can also play a part in this educational platform in Belgium! Consider submitting a contribution, such as a Letter-to-the-Editor, a case report, a review article, or other interesting manuscripts. The goal of the BJMO is to provide you with practical clearcut updates within the field of Oncology, Radiotherapy and adherent fields. B E L G I A N J O U R N A L O F M E D I C A L The BJMO especially covers developments, which have a clear impact on your activities in daily clinical practice such as diagnostic workups and disease management. The BJMO welcomes spontaneously submitted manuscripts as long as these comply with our editorial format and sections. We await any contribution with interest and also are looking forward to receiving any comments you might have to develop this journal in future. The Editorial Board and Ariez Medical Publishing Ltd. O N C O L O G Y vol. 3 issue 5 - 2009 190