Morbidity of Sentinel Node Biopsy in Breast Cancer: The Relationship Between the Number of Excised Lymph Nodes and Lymphedema

Morbidity of Sentinel Node Biopsy in Breast Cancer: The Relationship Between the Number of Excised Lymph Nodes and Lymphedema

biopsy in the patient with breast cancer. JAMA. 1996;276:1818-1822. 3. McMasters KM, Tuttle TM, Carlson DJ, et al. Sentinel lymph node biopsy for Mor...

70KB Sizes 2 Downloads 71 Views

biopsy in the patient with breast cancer. JAMA. 1996;276:1818-1822. 3. McMasters KM, Tuttle TM, Carlson DJ, et al. Sentinel lymph node biopsy for

Morbidity of Sentinel Node Biopsy in Breast Cancer: The Relationship Between the Number of Excised Lymph Nodes and Lymphedema Goldberg JI, Wiechmann LI, Riedel ER, et al (Memorial Sloan-Kettering Cancer Ctr, NY) Ann Surg Oncol 17:3278-3286, 2010

Background.dDespite the reduced morbidity associated with sentinel lymph node biopsy (SLNB), lymphedema remains a clinically relevant complication. We hypothesized that a higher number of lymph nodes (LNs) removed during SLNB is associated with a higher risk of lymphedema. Methods.dSix hundred patients with clinically node-negative breast cancer who underwent SLNB were prospectively studied. Circumferential bilateral upper extremity measurements were performed preoperatively and at 3e8 years after surgery. Association of lymphedema with total number of LNs excised and other clinicopathologic variables was analyzed by the Spearman rank correlation coefficient, Fisher’s exact test, Wilcoxon rank sum test, and logistic regression. Results.dAt a median follow-up of 5 years, 5% of patients had developed lymphedema. Factors associated with lymphedema included weight and body mass index. There was no association between the number of LNs removed and the change in upper extremity measurements or in the incidence of lymphedema. Among patients with

breast cancer: a suitable alternative to routine axillary dissection in multiinstitutional practice when optimal

lymphedema (n ¼ 31) compared to those without, the mean (3.9 vs. 4.2), median (4 vs. 3), and range (1e9 vs. 1e17) of number of LNs removed were similar (P ¼ 0.93). Among the 33 women with $10 LNs removed, none developed lymphedema. Conclusions.dIn this population of 600 women who underwent SLNB, there is no correlation between number of LNs removed and change in upper extremity circumference or incidence of lymphedema. These data suggest that other factors, such as the global disruption of the lymphatic channels during axillary lymph node dissection, play a larger role in development of lymphedema than does the number of LNs removed. Goldberg and colleagues prospectively studied 936 women with clinically node-negative breast cancer who underwent SLNB alone or SLNB followed by completion axillary lymph node dissection (ALND). All patients completed baseline and follow-up upper-extremity measurements of both the ipsilateral and contralateral arms. The initial analyses were published in 2008 and reported an overall rate of measured lymphedema after SLNB of 5%.1 This article represents further evaluation of this dataset and focuses specifically on the patients who underwent SLNB alone (n ¼ 600) to determine if the number of LNs excised influences the development of lymphedema. The question about the relationship between the number of LNs re-

technique is used. J Clin Oncol. 2000; 18:2560-2566.

moved and the risk of lymphedema is not a new one. It continues to be asked, partially because existing data are conflicting, with some retrospective studies finding no relationship between the number of LNs removed and the risk of lymphedema2-5 and others demonstrating an increasing risk of lymphedema as more LNs are removed.6-9 This study by Goldberg and colleagues postulates that it is not the number of LNs per se but instead the amount of dissection and disruption of the lymphatic system that results in lymphedema. The authors found no significant association between the mean, median, or number of LNs excised and lymphedema (P ¼.93). To further support their conclusions, the authors completed a subset analysis of the women who had more than 10 LNs removed at the time of SLNB. None of these women developed lymphedema. Interestingly, when this SLNB subset was compared with the women in the ALND cohort who similarly had 10 to 17 LNs removed, 11% of the ALND patients had measured lymphedema (P ¼.04). The number of LNs in a drainage basin varies from patient to patient, but most women have 15 to 25 axillary nodes. It is unlikely that surgeons intentionally remove 10 or more LNs when performing SLNB. However, it is common that a specimen thought to have 1 node may have more than 1 node at the time of final pathology. This is the likely explanation for the SLNB patients who had 10 to 17 LNs removed. The fact that these SLNB

Breast Diseases: A Year BookÒ Quarterly Vol 22 No 3 2011

293

patients did not develop lymphedema while those who had ALND did confirms the notion that the relationship between lymphedema and axillary surgery is complex and multifactorial. One could suggest that a patient with many LNs removed at SLNB and no finding of lymphedema simply had more lymphatic collaterals (or possibly a greater overall number of nodes) and therefore suffered relatively less lymphatic disruption despite a larger than “normal” number of nodes removed. Conversely, women who underwent ALND and had a relatively small number of total LNs excised may have suffered larger overall amounts of lymphatic disruption and therefore developed lymphedema. Perhaps the development of lymphedema hinges on a physiologic ratio of the number of lymphatic collaterals (possibly nodes) removed compared with the overall number of nodes in the basin. As the denominator is unknown, the number of LNs removed is, in itself, insufficient to solve the equation and therefore to determine lymphedema risk. The other possibility is that the risk of lymphedema is inversely proportional to the patient’s ability to protect or form new lymphatic collaterals during or after treatments. Lymphatic damage or disruption is not unique to surgery but can also be caused by radiation. The synergistic effect of ALND and radiation is well documented to result in a 3.5- to 10fold higher risk of lymphedema when compared with surgery alone.2,10-12 Even axillary irradiation alone is not without complication, as these patients also demonstrate a 2- to 4.5-fold increase in the risk of lymphedema.13 Although current breast cancer treatment strategies avoid direct axillary irradiation unless more than 10 LNs are involved by metastatic disease, it is clear that scattered radiation tangents may affect the lowest levels of the axilla during treatment. Considering

294

the recently published data from the American College of Surgeons Oncology Group Z0011 trial,14 the extent of whole-breast irradiation after breast-conserving surgery with SLNB is of particular interest. While the trial clearly found no difference in local recurrence after completion ALND or SLNB alone in the setting of 1 or 2 positive sentinel lymph nodes (SLNs), no data have been published regarding the specifics of the radiation fields or the morbidity of the SLN-only group. As part of the trial, radiation planning was not standardized (although the addition of third-field axillary irradiation was prohibited) and radiation oncologists were not blinded to patients’ axillary status. However, adjusting or biasing the standard breast tangents to cover more of the axilla was acceptable. Although it is likely that lymphedema rates in the SLNB-only arm will be lower than in the completion ALND arm, one cannot help wondering if, in fact, the radiation fields were biased and what effect this might have had on increasing lymphatic damage and, therefore, on lymphedema risk after SLNB alone. Finally, data from the prospective randomized After Mapping of the Axilla: Radiotherapy or Surgery? trial (European Organization for Research and Treatment of Cancer 10981) comparing axillary irradiation alone with axillary dissection will be important in determining morbidity differences between the 2 treatment modalities. Others have argued that lymphatic disruption is a causative factor for lymphedema and have suggested using the axillary reverse mapping (ARM) technique to minimize surgical injury to the lymphatics draining the upper extremity. Theoretically, protecting these arm lymphatics will maintain upper-extremity lymphatic drainage and prevent lymphedema. Although promising in concept, ARM has been cautiously adopted by clini-

Breast Diseases: A Year BookÒ Quarterly Vol 22 No 3 2011

cians into clinical practice because of altered mapping with significant axillary tumor nodal burden,15 overlapping breast and upper-extremity drainage patterns in up to 20% of women,16 and involvement of the ARM node by breast cancer in 9% to 18% of patients.16,17 Further study of and indications for this technique are needed. In conclusion, Goldberg and colleagues precisely demonstrate the absence of a relationship between the number of LNs excised and the risk of lymphedema after SLNB. They conclude instead that it is the degree of lymphatic disruption that contributes to lymphedema risk. Clearly, both surgery and radiotherapy, independently and collectively, influence lymphatic disruption. As clinicians, we must recognize these effects and seek treatment modifications that will minimize lymphatic damage. S. A. McLaughlin, MD

References 1. McLaughlin SA, Wright MJ, Morris KT, et al. Prevalence of lymphedema in women with breast cancer 5 years after sentinel lymph node biopsy or axillary dissection: objective measurements. J Clin Oncol. 2008;26:5213-5219. 2. Ozaslan C, Kuru B. Lymphedema after treatment of breast cancer. Am J Surg. 2004;187:69-72. 3. Hinrichs CS, Watroba NL, Rezaishiraz H, et al. Lymphedema secondary to postmastectomy radiation: incidence and risk factors. Ann Surg Oncol. 2004;11:573-580. 4. Sener SF, Winchester DJ, Martz CH, et al. Lymphedema after sentinel lymphadenectomy for breast carcinoma. Cancer. 2001;92:748-752. 5. Helyer LK, Varnic M, Le LW, Leong W, McCready D. Obesity is

a risk factor for developing postoperative lymphedema in breast cancer patients. Breast J. 2010;16: 48-54. 6. Herd-Smith A, Russo A, Muraca MG, Del Turco MR, Cardona G. Prognostic factors for lymphedema after primary treatment of breast carcinoma. Cancer. 2001; 92:1783-1787. 7. Kiel KD, Rademacker AW. Earlystage breast cancer: arm edema after wide excision and breast irradiation. Radiology. 1996;198:279-283. 8. Paskett ED, Naughton MJ, McCoy TP, Case LD, Abbott JM. The epidemiology of arm and hand swelling in premenopausal breast cancer survivors. Cancer Epidemiol Biomarkers Prev. 2007;16:775-782. 9. Yen TW, Fan X, Sparapani R, Laud PW, Walker AP, Nattinger AB. A contemporary, population-based study of lymphedema risk factors in older women with breast cancer. Ann Surg Oncol. 2009;16:979-988. 10. Kwan W, Jackson J, Weir LM, Dingee C, McGregor G, Olivotto IA. Chronic arm morbidity after curative

Molecular Detection of Micrometastatic Breast Cancer in HistopathologydNegative Axillary Lymph Nodes Fails to Predict Breast Cancer Recurrence: A Final Analysis of a Prospective MultiInstitutional Cohort Study Fisher CS, Cole DJ, Mitas M, et al (Med Univ of South Carolina, Charleston; et al) Ann Surg Oncol 17:S312-S320, 2010

Background.dTo address the clinical relevance of molecular detection of

breast cancer treatment: prevalence and impact on quality of life. J Clin Oncol. 2002;20:4242-4248. 11. Coen JJ, Taghian AG, Kachnic LA, Assaad SI, Powell SN. Risk of lymphedema after regional nodal irradiation with breast conservation therapy. Int J Radiat Oncol Biol Phys. 2003;55:1209-1215. 12. Kissin MW, Querci della Rovere G, Easton D, Westbury G. Risk of lymphoedema following the treatment of breast cancer. Br J Surg. 1986;73:580-584. 13. Vevers JM, Roumen RM, Vingerhoets AJ, et al. Risk, severity and predictors of physical and psychological morbidity after axillary lymph node dissection for breast cancer. Eur J Cancer. 2001; 37:991-999. 14. Giuliano AE, Hunt KK, Ballman KV, et al. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA. 2011;305:569-575. 15. Ponzone R, Cont NT, Maggiorotto F, et al. Extensive nodal disease may

occult breast cancer in sentinel lymph nodes and nonsentinel axillary lymph nodes (ALN), we initiated the Minimally Invasive Molecular Staging of Breast Cancer (MIMS) trial, a multiinstitutional prospective cohort study. This trial represents the first prospective cohort study in which a multimarker, real-time reverse transcription polymerase chain reaction (RT-PCR) analysis was applied to the detection of breast cancer micrometastases in ALN. Materials and Methods.dSentinel and/or nonsentinel ALN from 501 breast cancer subjects with T1eT3 primary tumors were analyzed by standard histo-

impair axillary reverse mapping in patients with breast cancer. J Clin Oncol. 2009;27:5547-5551. 16. Kang SH, Choi JE, Jeon YS, Lee S, Bae Y. Preservation of lymphatic drainage from arm in breast cancer surgery: is it safe? (abstract 201). Presented at: The 2008 San Antonio Breast Cancer Symposium; December 10-14, 2008; San Antonio, TX. http://cancerres.aacrjournals. org/cgi/content/meeting_abstract/ 69/2_MeetingAbstracts/201? sid¼1f780e7f-5fb8e4878-94be4392f8593109. Accessed May 17, 2011. 17. Bedrosian I, Babiera GV, Mittendorf EA, et al. A phase I study to assess the feasibility and oncologic safety of axillary reverse mapping in breast cancer patients (abstract 220). Presented at: The 2009 American Society of Clinical Oncology Breast Cancer Symposium; May 29-June 2, 2009; Orlando, FL. http://www.asco. org/ascov2/Meetings/Abstracts? &vmview¼abst_detail_view& confID¼70&abstractID¼40118. Accessed May 17, 2011.

pathology and multimarker, real-time RT-PCR analysis. Seven breast cancerassociated genes (mam, mamB, PIP, CK19, muc1, PSE, and CEA) known to be overexpressed in metastatic breast cancer compared with control lymph nodes were used. Follow-up data were collected for 5 years. Results.dOf the 501 breast cancer subjects enrolled, 348 were node negative and completed the 5-year followup. Of these patients (n ¼ 94), 27% demonstrated evidence of molecular overexpression. The 5-year relapse-free survival rate was 95.4% (95% confidence interval [95% CI], 92.4e97.2%).

Breast Diseases: A Year BookÒ Quarterly Vol 22 No 3 2011

295