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The Management of Regional Lymph Nodes in Cancer
Posted 12/12/2003 Summary and Introduction Early clinical observation in cancer patients suggested that tumours spread in a methodical, stepwise fashion from the primary site to the regional lymphatics, and only then to distant locations. Based on these observations, the regional lymphatics were believed to be mechanical barriers preventing the widespread dissemination of tumour. Despite evidence now available disputing its validity, this barrier theory has guided the surgical management of the regional lymphatics for more than a century, influencing the use of such surgical modalities as therapeutic lymph node dissection, elective lymph node dissection and most recently sentinel lymph node biopsy. No published randomized controlled trial exists that demonstrates improved overall survival for patients with cancer of any type undergoing surgery of the regional lymphatics. We believe the presence of tumour in the regional lymphatics indicates the presence of systemic disease, and therapeutic interventions should be directed accordingly. Introduction Management of the regional lymph nodes (RLNs) in potentially metastatic cancer is fraught with controversies and misunderstandings. Early surgical oncologists observed many times that the RLNs were enlarged in advanced cancers before distant disease appeared, leading to the theory that the RLNs served as mechanical barriers temporarily preventing systemic dissemination of tumour. Based on this theory, surgeons removed these enlarged lymph nodes along with the primary tumour, an approach known as therapeutic lymph node dissection (TLND), in an attempt at surgical cure of locally advanced disease. Unacceptable cure rates, believed to be a result of unresected microscopic disease, led to the removal of clinically normal RLNs, a procedure known as elective lymph node dissection (ELND), in an effort to remove these nonpalpable tumour deposits. By the early twentieth century, routine dissections of the regional lymphatics in an effort to remove all microscopic disease had become the dogma of surgical oncology based exclusively on observation and theory rather than sound scientific evidence. This barrier theory of lymph node biology continues to influence the management of the RLNs in cancer surgery today. In light of current knowledge, does it make sense to perform surgical dissection of RLNs in patients with cancer? Through well-designed laboratory studies we know that the lymph nodes serve specific and important functions that aid in essential immunological responses. We also know that an intact immune system is critical for host tumour defence mechanisms. Laboratory and clinical studies have cast doubt on the theory that lymph nodes serve as mechanical barriers to widespread tumour dissemination. Furthermore, abundant randomized controlled clinical trials have critically evaluated the role of lymph node dissections in cancer management and have failed to demonstrate a significant survival advantage. This paper will review this evidence and will make recommendations regarding the management of the RLNs in cancer patients, with an emphasis on patients with melanoma. Historical Perspective The theoretical value of TLND, or removal of clinically palpable lymph nodes, was proposed by the earliest surgical oncologists. In the late eighteenth century, Heister first advocated axillary dissection for the treatment of breast cancer after observing the clinical course of patients with advanced disease.[1] Clinical observation in these patients suggested that the tumour spread in an orderly fashion from the primary site to the RLNs, and finally to distant locations. Based on these observations, the prevailing theory that developed and was perpetuated until late in the twentieth century was that the lymph nodes served as physical barriers to tumour dissemination. This was tested by Halsted's experiments in radical mastectomies for breast cancer that entailed en bloc removal of the breast, the pectoralis muscles and the entire axillary contents.[2] Although Halsted initially reported improved survival for patients undergoing his radical surgery in 1894, he later retracted this conclusion after re-analysing the data in 1907.[3] Halsted's contemporaries argued that the reason the radical mastectomy failed to improve survival was that trapped, nonpalpable (microscopic) disease was left behind in other nondissected lymph node basins. However, attempts to improve on the results of the Halsted mastectomy by dissecting all regional nodal basins (including the supraclavicular and internal mammary nodes) were met only with increased operative mortality.[4,5] If more aggressive surgery failed to improve survival in patients with advanced disease, perhaps earlier, prophylactic lymph node surgery in patients with more localized disease would. The emphasis of cancer treatment subsequently shifted to early diagnosis in order to facilitate surgery in advance of the development of palpable lymphadenopathy. The theoretical goal of surgical oncology remained removal of trapped tumour cells within the lymphatics, but at a time when tumour burden was small and the chance of systemic dissemination was thought to be insignificant. Thus dawned the age of the ELND. The theoretical benefit of ELND seemed unassailable when considered in the context of the belief that the RLNs served as physical barriers to tumour dissemination. During a time when little else could be offered to cancer patients, this seemingly rational theory and the chance of a surgical cure for this dreaded disease captured the attention of surgeons around the world. Numerous retrospective and single institutional studies were published that supported the widespread use of ELND in nearly all forms of cancer with the potential for nodal metastasis including cancer of the breast, uterus, cervix, vulva, prostate, head and neck, penis and, of course, melanoma.[6-14] Advocates of ELND used the results of these uncontrolled studies to validate the theory that the RLNs were in fact barriers to systemic tumour dissemination. Consequently, the role of ELND in cancer surgery remained unchallenged in surgical oncology until late in the twentieth century.
of the National Surgical Adjuvant Breast and Bowel Program, began an ambitious study that was to be the first randomized controlled trial (RCT) investigating the value of the ELND in breast cancer patients.[15] To the surprise of most, Fisher's study of 1700 patients failed to reveal any statistically significant survival advantage for patients undergoing ELND. Although the lymph node dissection group experienced fewer recurrences in the treated lymph node basin, this improvement in local control did not translate to a benefit in overall survival. In fact, when these patients did have recurrences, these were more likely to be distant disease. Since Fisher's landmark study, five RCTs evaluating ELND in breast cancer patients have failed to reveal a statistically significant survival advantage for patients treated with ELND.[16] The lack of evidence supporting the value of ELND for breast cancer patients in these five trials raised significant questions regarding the dogmatic but unproven traditional approach to surgical management in patients with cancer.
critical evaluation of the value of ELND in other cancers. There have been four RCTs evaluating ELND in 1718 patients with cutaneous melanoma.[17-20] Melanoma patients randomized to ELND experienced fewer recurrences in the dissected lymph node basin, but none of the studies showed a statistically significant survival advantage. The largest of these trials, the Intergroup Melanoma Surgical Trial,[17] included 740 patients with melanomas 1-4 mm thick. As with the other three trials, there was no survival advantage for those patients undergoing ELND compared with those patients treated with TLND at disease recurrence. Even though retrospective subgroup analysis found trends in favour of ELND in patients less than 60 years old with nonulcerated, intermediate thickness melanomas (1-2 mm thick), this type of post hoc analysis attempts to discern therapeutic benefits in subsets of patients for which the study was not initially designed, and is fraught with considerable bias. For this reason, many experts remain hesitant to advocate ELND for their patients based on this type of statistical analysis. Published RCTs evaluating ELND in the management of other cancers are few. Two small RCTs of only 35 and 75 patients failed to reveal any statistically significant survival advantage for patients with squamous cell carcinoma of the oral cavity undergoing ELND.[21,22] Although statistically meaningful conclusions cannot be made from such a small patient population, as in breast cancer and melanoma patients those patients randomized to ELND experienced fewer regional recurrences in the dissected lymph node basin. The improvement in local control offered by ELND in patients with head and neck cancer may provide a tangible benefit in this functionally important area. Control of disease influence on tracheal, oesophageal and cervical neurovascular function would certainly maintain a high priority in disease management. This may explain why neck dissections remain an important tool in the treatment of patients with head and neck cancer despite a lack of evidence of improved overall survival for those undergoing such interventions. As sound scientific evidence accumulated to show that ELND offered no survival advantage for cancer patients, surgeons in the late twentieth century began to look for other ways to assess the status of the regional lymphatics for staging purposes. In 1992, Morton et al. reported the technique of sentinel lymph node (SLN) biopsy (SLNB) in patients with early stage melanoma.[23] As initially described, isosulfan blue dye was injected around the primary melanoma and soon afterwards the RLN basin was dissected to locate the initial or sentinel draining lymph node. Because of the prevailing belief in the barrier theory of the regional lymphatics, it was theorized that the histological status of the sentinel node would accurately predict whether or not the tumour had metastasized from the primary site. In patients with melanoma, the status of the SLN using standard histology became the single most accurate prognostic indicator of metastatic disease.[24] Now performed with the use of radiolabelled sulphur colloid, SLNB has become a widely used staging tool in cancers of all types with the potential for spread to the regional lymphatics.[25-31] In these cancers, the status of the SLN often guides further therapeutic interventions including completion lymphadenectomy and adjuvant chemotherapy or radiation therapy. However, like TLND and ELND before it, the theoretical value of SLNB is based on the barrier theory of the RLNs and remains an experimental procedure with no proven therapeutic benefit. The Role of the Regional Lymph Nodes So why are surgeons continuing to submit cancer patients to surgery of the RLNs without any sound scientific evidence of significant survival benefit? Perhaps some continue to dissect RLN basins in cancer patients based more on surgical tradition rather than scientific evidence. Many surgeons probably remain convinced that the RLNs are mechanical barriers preventing tumour dissemination and that design flaws in the RCTs testing ELND prevent the detection of a small but real benefit for patients undergoing elective node dissection. Likewise, some melanoma experts argue that all studies evaluating ELND in melanoma patients prior to the advent of SLNB are confounded by the fact that in a small but significant percentage of patients the wrong lymph node basin would have been dissected. These arguments may have some validity, but with each large-scale RCT published that fails to demonstrate a survival advantage for ELND, regardless of cancer type, it becomes more difficult to dismiss all these studies as scientifically flawed. We believe that the reason ELND does not benefit patients with cancer is because the RLNs are not mechanical filters or dams preventing the spread of tumour to the systemic circulation but are instead indicators of the presence of systemic metastasis. Therefore, removal of lymph nodes, even in early disease, will only remove the metastases that are in the RLNs, not those that simultaneously metastasize elsewhere. Early research by Fisher that led to the initiation of his landmark breast cancer trial cast significant doubt on the belief that lymph nodes were passive filters for metastasizing cancer cells or that nodes were exposed to tumour before the systemic circulation. His studies in rodents demonstrated that tumour emboli, even when large, could pass through the draining lymphatics and at times bypassed the lymph node altogether.[32-35] Other studies demonstrated malignant cells in the venous runoff from various types of solid tumours thought at that time to spread only via lymphatics.[36,37] This lymph node permeability is due in part to abundant intranodal and lymphaticovenous shunts that can be demonstrated by functional studies as well as by electron microscopy.[32,35,38-42] If lymph nodes are not mechanical filters for tumour emboli, then what influences the location where a tumour metastasis develops? Recent research illustrates that various tumour types clearly have organ specificity for their metastases.[43-47] This organ specificity appears to be dictated by surface proteins called adhesion molecules on both the tumour cells and the tissue where the metastasis comes to rest. After the tumour cell breaks away from the primary lesion, it circulates through the lymphatic and arteriovenous system, bouncing and even rolling across the endothelium within various organs and tissues. As it does so, adhesion molecules on the tumour cell regularly come in contact with adhesion molecules on the endothelium of the organ or tissue in question. These adhesion molecules must be complementary in order for metastases to develop.[48,49] If complementary adhesion molecules exist, the tumour cell binds to the endothelium and may become a clinical metastasis if it is successful at avoiding tumour defence mechanisms. Consequently, if complementary adhesion molecules do not exist in the RLNs, tumour emboli circulating in the lymphatic system will bypass the RLNs while metastasizing to distant locations.[44,45,50-53] This means that the presence of tumour within RLNs, as in a positive SLNB, indicates only that the primary tumour has gained the ability to spread and that complementary adhesion molecules exist on both the tumour surface and the lymph node stroma. Removal of the RLNs at this point does nothing to counteract the systemic nature of the disease unless the RLNs are the only anatomical location that contains the necessary complementary adhesion molecules. Whether the tumour has disseminated to other distant locations depends on the presence of the corresponding adhesion molecule in the tissue in question rather than any intrinsic property of the RLNs. If lymph nodes are not passive filters for tumour emboli, then what role do they play in metastatic disease? We know that the lymph nodes, and other lymphoid organs, serve to orchestrate important immunological responses to foreign antigens.[54] This immunological process is important for host defence mechanisms in the early stages of primary tumour growth when appropriate antigen recognition and immunological response may prevent the widespread dissemination of tumour cells.[55-57] Surgical alteration of regional lymphatic structure and function at this early stage of tumour growth may provide the tumour with a growth advantage. Surgical alteration of RLN function may also affect future therapeutic interventions, as research in both animals and humans has demonstrated that removal of the tumour-draining RLNs prior to antitumour vaccination significantly diminishes antitumour activity.[58,59] With recent efforts to develop immunological therapies for many forms of cancer, the value of maintaining an intact RLN basin in this process will need critical evaluation. What then are the consequences of tumour metastases developing in the RLNs? When the volume of metastasis is small, the immunological effect generated against the primary tumour can be sufficient to control potentially lethal cells in a dormant state for a long period of time[60,61] and occasionally may result in cell death without further growth or dissemination.[38] Removal of these clinically irrelevant cells would be unnecessary and might even be harmful from an immunological standpoint. Yet, as the tumour grows, eventual immunosuppression is likely to develop through a variety of tumour-induced mechanisms.[62] Eventually, the normal lymph node architecture is destroyed rendering the lymph node immunologically ineffective and a possible source for further tumour dissemination. At this point, once the tumour has become biologically active and has obliterated the normal structure and function of the node, removal would serve to decrease tumour burden and potentially decrease further tumour-based immunosuppression.[38,63-65] Unfortunately, current technology does not permit us to determine what constitutes relevant nodal disease. In one breast cancer trial, 20% of the observation group eventually developed clinically palpable lymph node metastases as the site of first recurrence.[15] This is much less than the 38% of patients found to have microscopic tumour by standard histology after ELND, suggesting that an immunological response against the tumour cells may have prevented further growth of microscopic disease in 18% of patients. The use of more sensitive techniques such as serial sectioning and immunohistochemistry further increases the number of patients with 'positive' axillary metastases who never go on to develop clinically positive axillary disease: this was as high as 60% in one study.[66] When nodes are examined even more closely for submicroscopic disease via polymerase chain reaction (PCR) analysis, the results are even more surprising. In melanoma, 60% of patients with primary tumours < 0.75 mm thick had SLNs that were positive by PCR analysis.[67] This is a remarkably high number of patients labelled as having positive nodes by PCR in a subset of melanoma patients who historically have a very favourable prognosis and never go on to develop clinical lymph node disease. Clearly, the presence of microscopic and submicroscopic disease does not correlate with clinical course and overestimates the number of patients who will develop clinically positive nodal disease. Future research may allow for a determination of which patients among those with microscopic or submicroscopic disease contain actively proliferating nodal disease. Identification of these patients would create a classification of patients who could potentially benefit from lymph node dissection. Conclusions One can conclude from this discussion that the RLNs are biologically important organs that play a vital role in tumour defence mechanisms. The presence of metastases in the RLNs is an indication that the tumour has gained the ability to spread and that the stroma of the lymph node contains the necessary surface proteins to facilitate tumour attachment. The RLNs should no longer be considered mechanical filters or barriers preventing the systemic dissemination of metastatic tumour. In fact, tumour dissemination and ultimately tumour metastasis is a much more active process than once believed, and results from a dynamic interaction between the tumour cell and the surface of the endothelium of the organ where the metastasis eventually develops. Traditional surgical management of the RLNs for most of the twentieth century was based on the theory that the lymph nodes served to limit the systemic spread of tumour metastasis. We now know this theory to be false and we have demonstrated that no scientific evidence exists to support the routine elective removal of clinically uninvolved lymph nodes in any cancer in an attempt to prolong survival. Based on the arguments presented in this article, specific recommendations regarding the management of the regional lymphatics in cancer can be made. When no effective adjuvant therapy exists for metastatic disease, close clinical follow-up and TLND at disease recurrence is an acceptable approach in patient management. TLND in this case allows for improved local control and may on occasion even salvage a small number of patients. ELND in this patient population may also improve local control and assist with staging procedures but this potential benefit should be weighed against the risks of the procedure, and in patients who desire more prognostic information SLNB may be a more appropriate intervention. When proven effective adjuvant therapy exists for patients with cancer, SLNB can be used as a staging tool to determine those patients eligible for adjuvant treatment. Staging information obtained from lymph node dissection, whether used for prognostic purposes or for decisions about adjuvant therapy, should be interpreted with caution and an understanding that the presence or absence of metastatic disease in the RLNs is unrelated to the presence of metastatic disease in other organs. For patients with melanoma, the above guidelines also apply. The routine use of ELND offers patients no survival advantage vs. observation and TLND upon nodal recurrence, and should be abandoned. However, TLND is a useful tool in the clinical management of patients with recurrent nodal disease and will serve to improve local control.[68-74] The use of SLNB is a valuable prognostic tool, but attempts to justify this procedure as standard of care in patients with melanoma are premature. As no proven effective adjuvant therapy exists for patients with metastatic melanoma, the additional prognostic information gained by SLNB should be weighed against the small but real risks of the procedure. As SLNB remains an experimental procedure, we believe that the use of the procedure in patients with melanoma should only be performed within the confines of a controlled experimental protocol. 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Axillary dissection in melanoma: prognostic variables in node-positive patients. Ann Surg 1990; 212: 125-31. ---------------------------------------------------- More studies on lymph node surgery: Nippon Geka Gakkai Zasshi 2001 Jun;102(6):465-72 Related Articles, Books Management of axillary and internal mammary lymph nodes in primary breast cancer. Masuda N, Tamaki Y, Noguchi S. Department of Surgery and Clinical Oncology, Graduate School of Medicine, Osaka University, Suita, Japan. Axillary lymph node dissection (ALND) is an effective staging procedure and is essential for local control of breast cancer. The regimen of the adjuvant systemic therapy is largely based on the number of nodes involved. There is as yet no evidence of survival benefit from axillary treatment by either surgery or radiotherapy, but this issue remains controversial. In general, the standard treatment of the axilla is surgical clearance of nodes from level I and II (partial ALND). If these nodes are involved, the clearance of level III nodes (complete ALND) is indispensable from the viewpoint of local control. Because a high rate of adverse events is observed, the extent of ALND should be determined by considering the balance between side effects and therapeutic benefit on a case-by-case basis. For the management of internal mammary nodes, most reports on randomized trials indicate that neither surgical treatment nor radiotherapy influences survival. However, the prognostic significance of internal mammary node status is high and a selected biopsy of lymph nodes with adenopathy should be considered for staging purposes. The significance of local control in this region is still controversial at present. About 30% to 40% of all invasive breast cancers are node positive. Thus, in most cases, the potential morbidity of ALND could be avoided if the status of the axillary nodes was ascertained with a less invasive procedure. The technique of sentinel lymph node biopsy may eventually prove to decrease the need for standard ALND. The randomized trial NSABP-B32 is ongoing and the results should indicate the clinical need for ALND. ---------------------------------------------------------------- Surg Clin North Am 1999 Oct;79(5):1061-73 Management of the axilla in primary breast cancer. Jatoi I. Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA. Treatment of the axilla with either radiotherapy or surgery remains an integral part of the management of patients with invasive breast cancer. In general, the standard treatment of the axilla involves a partial ALND (surgical clearance of axillary nodes from levels I and II). There is as yet no evidence that axillary treatment improves survival, but the issue remains controversial. Axillary lymph node dissection is an effective staging procedure and is essential for local control of disease in the axilla, although, with increased emphasis on mammographic screening and early detection, the incidence of node-positive breast cancers is decreasing. Today, only about 30% to 40% of all invasive breast cancers are node-positive. Thus, in most cases, the potential morbidity of ALND could be avoided if the status of the axillary nodes were ascertained with a less invasive procedure. The SLNB may eventually prove to be a preferred alternative to routine ALND. It must first be demonstrated, however, that SLNB (without completion ALND) does not adversely affect outcome. Randomized controlled trials must address these concerns, and surgeons must await completion of these studies before accepting SLNB as the standard of care. ------------------------------------------------------------------------------ Langenbecks Arch Surg 2000 Jul;385(4):236-45 Lymph-node dissection in breast cancer. Bembenek A, Schlag PM. Surgery and Surgical Oncology, Robert-Rossle-Klinik, Charite Humboldt-University, Berlin, Germany. BACKGROUND: Along with the ongoing modifications in treatment of primary breast cancer, the purpose and extent of lymph-node dissection has changed. The following is an overview of the current knowledge and practice of lymph-node dissection in breast cancer, with special regard to expected developments in the near future. Axillary dissection is described as a ten-step procedure, including dissection of level-I and -II and Rotter's nodes, without level-III nodes, providing at least ten lymph nodes for accurate staging information. DISCUSSION: Axillary dissection still offers the most efficient local control in node-positive patients, whereas, in primarily node-negative patients, irradiation seems to be equally effective. In general, lymph-node dissection does not alter overall survival but there is no doubt that surgical therapy still contributes to cure in early-breast-cancer patients and seems to be curative for certain patients with stage-I carcinoma. The lymph node status of the axilla is crucial for the indication of adjuvant therapy in early invasive breast cancer, but an increasing number of clinical node-negative patients could be managed with information based on features of the primary tumor, regardless of the nodal status. The most promising new concept for the selection of node-positive patients, while avoiding unnecessary morbidity of axillary dissection in early-breast-cancer patients, is the sentinel-node concept. The principle is based on the identification of the first "sentinel" lymph node reached by lymphatic flow. Thus, only proven node-positive patients undergo axillary dissection. Local failure of internal mammary lymph nodes is rarely recognized; however, internal mammary lymph nodes seem to have an underestimated prognostic significance in about 10-20% of axillary node-negative patients. This may lead to the withholding of systemic therapy for patients with early breast cancer. Nevertheless, there is no indication for a routine parasternal dissection today. The sentinel-node concept may also support the selection of diagnostic internal lymph-node biopsy and subsequent adjuvant therapy in cases with no axillary lymph-node metastases but with internal lymph-node metastases. ----------------------------------------------------------- Am Surg. 2003 Mar;69(3):209-11; discussion 212. Sentinel lymph node biopsy lowers the rate of lymphedema when compared with standard axillary lymph node dissection. Golshan M, Martin WJ, Dowlatshahi K. Department of Surgery, Rush University, Rush Presbyterian St. Luke's Medical Center, Chicago, Illinois, USA. Arm edema occurs in 20 to 30 per cent of patients who undergo axillary lymph node dissection (ALND) for carcinoma of the breast. Sentinel lymph node biopsy (SLNB) in lieu of ALND for staging of breast cancer significantly lowers this morbidity. We hypothesized that SLNB would have a lower lymphedema rate than conventional axillary dissection. Patients who underwent SLNB were compared with those who underwent level I and II axillary node dissection. A total of 125 patients were evaluated with 77 patients who underwent SLNB and 48 patients who underwent ALND. The arm circumference 10 cm above and 10 cm below the olecranon process was measured on both arms. In this series a difference in arm circumference greater than 3 cm between the operated and nonoperated side was defined as significant for lymphedema. Lymphedema was seen in two of 77 (2.6%) patients in the SLNB group as compared with 13 of 48 (27%) ALND patients. Given the above data patients who underwent sentinel lymph node biopsy show a significantly lower rate of lymphedema than those who had axillary lymph node dissection. This has an important impact on long-term postoperative management of patients with breast cancer. ------------------------------------------------------ Cancer. 2005 Feb 1;103(3):492-500. Predicting the status of axillary sentinel lymph nodes in 4351 patients with invasive breast carcinoma treated in a single institution. Viale G, Zurrida S, Maiorano E, Mazzarol G, Pruneri G, Paganelli G, Maisonneuve P, Veronesi U. Department of Pathology and Laboratory Medicine, European Institute of Oncology and University of Milan, Milan, Italy. BACKGROUND: Reliable predictors of metastatic involvement would enable a better selection of candidate patients for sentinel lymph node biopsy (SLNB) and possibly allow identification of patients with such a lowrisk of axillary sentinel lymph node (SLN) involvement to be even spared SLNB. METHODS: The authors evaluated 4351 consecutive patients surgically treated for breast carcinoma who also underwent SLNB. Clinicopathologic features significantly associated with SLN metastases by univariate analysis wereincluded in a multivariate model. RESULTS: By multivariate analysis, the prevalence of SLN metastaseswas associated directly with tumor size, multifocality, and with the occurrence of peritumoral vascular invasion (PVI; all P < 0.0001), and was associated inversely with a favorable histotype (P = 0.0007) and lackof progesterone receptors (P = 0.004). A predictive model based on the features more closely associatedwith SLN status documented that the patients with a favorable tumor type </= 1 cm in size and without PVI(n = 178 [4% of the population]) had the lowest risk of SLN metastases (9.5%) whereas patients with tumors >2 cm and with PVI (n = 250 [5.7% of the population]) had the highest risk (77.2%) of SLN involvement. CONCLUSIONS: Tumor size and PVI emerged as the most powerful independent predictors of SLN metastases. Although no combination of features identified patients with a 9.5% risk of SLN metastases,the current data may be used to tailor the management of patients with breast carcinoma with the aim of minimizing as much as possible the diagnostic and therapeutic procedures, thus improving the quality of life of the patients without any adverse effect on their survival rates. (c) 2004 American Cancer Society |
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