乳房保留手術後局部復發患者之前哨淋巴結位於對側腋下

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1 台灣癌症醫誌 (J. Cancer Res. Pract.) 26(3), , 2010 Case Report journal homepage: Contralateral Axillary Sentinel Lymph Node Uptake for Local Recurrence of Breast Cancer after Breast Conservation Therapy Shuo-Hui Hung 1, Su-Mei Chen 2, Sheng-Huang Hsiao 3 * 1 Department of General Surgery, Renai Branch, Taipei City Hospital, Taipei, Taiwan 2 Department of Nuclear Medicine, Renai Branch, Taipei City Hospital, Taipei, Taiwan 3 Department of Neurosurgery, Renai Branch, Taipei City Hospital, Taipei, Taiwan Abstract. Following breast conservation therapy for early breast cancer, about 10% of these patients will develop an ipsilateral breast tumor recurrence (IBTR) within 10 years after diagnosis. The benefits of sentinel lymph node (SLN) biopsy for these patients are still controversial. We present two patients with IBTR and contralateral axillary sentinel lymph nodes shown by preoperative lymphoscintigraphy. Patient 1 had breast conservation therapy and axillary lymph node dissection, and patient 2 had breast conservation therapy and SLN biopsy for primary cancer surgical intervention. These findings demonstrate the importance of lymphoscintigraphy in the preoperative evaluation of IBTR. Additionally, we should maintain a high index of suspicion that axillary metastatic lymph nodes could originate from a contralateral occult breast cancer by aberrant lymphatic drainage, especially after a contralateral breast or axillary surgical intervention. 病例報告 Keywords : sentinel lymph node biopsy, lymphoscintigraphy, breast conservation, local recurrence 乳房保留手術後局部復發患者之前哨淋巴結位於對側腋下 洪碩徽 1 陳愫美 2 蕭勝煌 3 * 1 台北市立聯合醫院仁愛院區一般外科 2 台北市立聯合醫院仁愛院區核子醫學科 3 台北市立聯合醫院仁愛院區腦神經外科 中文摘要早期乳癌的病患可選擇保留乳房的手術治療方式, 但在術後十年的追蹤期間 10% 的患者有局部復發的機會 前哨淋巴結切片術是否適合這些復發的病患仍有爭議 我們提出兩個乳房保留手術後乳癌局部復發的病例, 淋巴閃爍攝影術發現其前哨淋巴結位於病灶對側的腋下 這些發現證實了淋巴閃爍攝影術對於這些患者再次手術時淋巴結診斷的重要性 此外當潛隱性乳癌的唯一症狀是腋下淋巴結轉移時, 若患者曾接受對側乳房或腋下的手術, 須高度懷疑病灶源於對側乳房的可能性 關鍵字 : 前哨淋巴結切片術 淋巴閃爍攝影術 乳房保留手術 局部復發

2 138 S. H. Hung et al./jcrp 26(2010) INTRODUCTION Breast conservation therapy (BCT) and sentinel lymph node (SLN) biopsy have comprehensively replaced modified radical mastectomy as the surgical treatment of choice for early-stage breast cancer [1,2]. Patients treated with BCT have an annual risk of about 1% for ipsilateral breast tumor recurrence (IBTR) [3,4]. The role of SLN biopsy following IBTR and previous axillary surgery is still controversial [5]. In this report, our experience with two patients with IBTR with contralateral axillary SLNs is described with the aim of highlighting the importance of lymphoscintigraphy (LSG) to identify alternative lymphatic drainage pathways of IBTR. CASE REPORT Case 1 A 46-year-old woman had a palpable mass in the lower inner quadrant of her right breast in Ultrasound imaging demonstrated this suspicious lesion in the right breast. Excisional biopsy revealed invasive ductal carcinoma, and hormone receptor assays for ER/PR were positive. The patient s work-up and treatment plan resulted in right-side breast-conserving surgery and levelⅠand II axillary dissection for a stage I (T1N0M0) invasive ductal carcinoma. The patient received adjuvant chemotherapy, radiotherapy, and tamoxifen hormone therapy. The patient remained well until 2008, when, at age 55, her yearly screening breast sonography was interpreted as suspicious for her right breast at the former lumpectomy site. American College of Radiology Breast Imaging Reporting and Data System (ACR *Corresponding author: Sheng-Huang Hsiao M.D., Ph.D. * 通訊作者 : 蕭勝煌醫師 Tel: ext.3505 Fax: daa37@tpech.gov.tw BI-RADS) category 4B was assigned due to a new hypoechoic shadow in her right breast when compared with prior studies. Ultrasound-guided core biopsies revealed invasive ductal carcinoma. Hormone receptor assays for ER/PR were positive, and Her2-neu was negative. Preoperatively, the patient received an injection of 1 mci of Tc99m sulfur colloid subdermally in the peri-areolar site of the right breast corresponding to the level of the tumor. After 10 min, the early anterior and lateral transmission LSG images showed the injection site on the right side, and uptake by the left axillary lymph nodes, as well as curvilinear lymphatic drainage from the injection site to the contralateral side (Figure 1). At 2 hours after injection, the LSG images showed tracer uptake by the previously seen node without uptake by any additional node. Using probe-guided surgery, two hot spots were identified at junction level Ⅰ and II in the contralateral axilla. At this site, two soft and enlarged axillary lymph nodes, with radioactivity counts greater than 30 counts per second, were excised. Right-side mastectomy was performed, along with contralateral SLN biopsy. Pathology revealed a 1.5-cm invasive ductal carcinoma in the right breast. The margins were histologically negative for tumor cells. The SLNs examined by immunohistochemistry and hematoxylin and eosin staining were negative for tumor cells. There was no evidence of angiolymphatic invasion. Systemic therapeutic options were discussed with the medical oncologist, and the patient chose adriamycin-based chemotherapy and aromatase inhibitor-based hormone therapy. She remained disease-free during 27 months of follow-up. Case 2 In 2008, a 42-year-old asymptomatic woman with a strong family history of breast cancer presented for her annual screening mammogram, which was reported as abnormal. A lesion with segmental pleomorphic microcalcifications was discovered in the

3 S. H. Hung et al./jcrp 26(2010) Figure 1. A preoperative lymphoscintigram of a rightside tumor recurrence. Two curvilinear lymphatic drainage ducts from the right-breast injection site to the contralateral (left) axilla were detected and communicated with the contralateral axillary sentinel lymph nodes upper outer quadrant of the left breast, and designated ACR BI-RADS category 4B. A stereotactic biopsy of this left breast mass was positive for high-grade ductal carcinoma in situ. The patient s metastasis survey was negative. LSG was performed after injection of 1 mci of Tc99m sulfur colloid subdermally in the peri-areolar site of the left breast corresponding to the level of the tumor. After 10 min, the early anterior and lateral transmission LSG images showed the injection site and uptake by several lateral axillary lymph nodes as well as curvilinear lymphatic drainage from the injection site to the (SLNs). At 2 hours after injection, the LSG images showed tracer uptake by the previously seen nodes without uptake by additional nodes (Figure 2a). Using a gamma probe, hot spots were identified at the junction of levels Ⅰ and II in the left axilla. Five SLNs and two questionable lymph nodes were excised. Left upper outer quadrant lumpectomy was performed along with the SLN biopsy. Pathology revealed stage I (pt1micn0m0), multiple-foci, high-grade, focal microinvasive (less than 1 mm), residual ductal carcinoma in situ, which was very close (less than 1 mm) to the surgical base margin. Seven excised lymph nodes showed reactive hyperplasia, but were free of metastatic cells. ER/PR assays were negative, and Her2- neu was 3+. Considering the patient s aversion to further surgical intervention and after a thorough discussion of the therapeutic options, she opted for external beam radiation therapy to a total dose of 50 Gy to the operative area with a 14-Gy boost to the tumor site. One year later, a hypoechoic shadow with an irregular margin in the left breast around her former lumpectomy site was discovered on her yearly breast screening ultrasound image. Ultrasound-guided core biopsies revealed invasive ductal carcinoma with a Nottingham score of 7/9. Hormone receptor assays for ER/PR were negative and Her2-neu was 3+. The patient underwent LSG the day before surgery according to our standard technique. At 10 min, the early anterior and lateral transmission LSG images showed the injection site on the left side and uptake by a right axillary lymph node, without definite lymph node uptake on the left side (Figure 2b). At 2 hours after injection, the LSG images showed tracer uptake by the previously seen node, without uptake by any additional node. The LSG findings suggested an SLN in the contralateral axilla on the right, which was an unexpected site, and none in the ipsilateral left axilla, which was the expected site. Left-side mastectomy was performed, but no radioisotope uptake was seen in any SLN during gamma ray probing in either axillary fossa during surgery. Pathology revealed a 0.6-cm, grade III invasive ductal carcinoma with clean surgical margins (pt1bnxmx). Systemic therapeutic options were discussed with the medical oncologist, and the patient chose adriamycin-based chemotherapy. Six months after surgery, positron emission tomography was performed to exclude the presence of occult cancer in the right breast

4 140 S. H. Hung et al./jcrp 26(2010) Figure 2. (a) Lymphoscintigram of a primary cancer shows ipsilateral axillary drainage. (b) Lymphoscintigraphy of an IBTR shows an aberrant sentinel lymph node in the contralateral axilla and the possibility of nodal or distal metastasis. The patient remained free of disease during 14 months of follow-up. DISCUSSION The results of the National Surgical Adjuvant Bowel and Breast Project (NSABP) B-21 demonstrated that postoperative irradiation significantly reduced the incidence of IBTR after BCT for early breast cancer [6]. Nonetheless, young BCT patients or those with inadequate free surgical margins are at high risk for IBTR [7,8]. Since IBTR is inevitably increasing due to the popularity of BCT, the management of local therapy failure is a serious problem that cannot be neglected. At the beginning of the SLN biopsy era, this procedure was not recommended for patients with prior breast or axillary surgery [9]. The major consideration was the possibility of a false-negative result due to lymphatic drainage interrupted by a previous operation. Various studies have now confirmed the feasibility and efficacy of performing SLN biopsy after previous breast tumor surgery, aesthetic breast surgery, and also axillary surgery [10-13]. The success rate of LSG and the incidence of aberrant drainage to lymph node basins other than the ipsilateral axilla is widespread. Port et al [14] studied the largest patient group at present and demonstrated that the success ratio for SLN biopsy was inversely related to the extent of the prior axillary surgery. At present, SLN biopsy for early breast cancer is the standard procedure in many institutions, and we believe this will increase the success rate of SLN biopsy for IBTR. Aberrant lymph node drainage was identified by LSG significantly more often in re-operative SLN than in primary SLN biopsy [14]. Tasevski et al [5] summarized other published series of re-operative SLN biopsies and found that aberrant lymph node drainage rates ranged from 30% 100%. The contralateral axilla was a possible site of aberrant lymph node drainage, and the cases of at least five patients with metastatic contralateral axillary SLNs were published. These findings demonstrate the importance of SLN mapping to evaluate possible aberrant lymph drainage and current nodal status of IBTR. Based on these encouraging data, we initiated LSG in patients with IBTR who had undergone previous BCT. We have presented two cases of IBTR,

5 S. H. Hung et al./jcrp 26(2010) both with identifiable contralateral axillary SLNs. The primary axillary interventions were axillary lymph node dissection in the first patient and SLN biopsy in the second patient. Patient 1 developed IBTR 9 years after a previous axillary lymph node dissection, and patient 2 one year after a previous SLN biopsy. While we could not identify the SLN in patient 2 during the second surgery, the aberrant pathway developed within 1 year. Further studies are necessary to investigate the time needed for formation of new lymphatic drainage pathways after surgery. In this study, we did not find evidence of metastasis in these aberrant lymph nodes. Neiweg reported that radioisotopic tracers injected in the skin or subareolar plexus may be the quickest to travel the axilla, but rarely identify sentinel nodes outside the axilla [15]. Tracers were injected in the skin or subareolar plexus of both of our patients. Thus, the effects of the injection site must be considered in the diagnosis of IBTR. The most important benefit of LSG is to identify the site of aberrant lymphatic drainage and present the real nodal status of IBTR. For patients with negative SLNs, the morbidity of axillary lymph node dissection can be avoided, and for patients with positive SLNs, complete lymph node dissection will lower the incidence of nodal failure. Additionally, aberrant lymphatic drainage reminds us of the possibility that metastasis to the axillary lymph nodes can originate from a contralateral occult breast cancer [16]. Application of breast MRI in occult breast cancer may alter locoregional treatment in these patients [17]. Careful history-taking regarding previous breast or axillary surgical interventions is essential for the success of SLN identification and biopsy. In conclusion, for patients with IBTR after BCT, using LSG to detect SLNs is a beneficial technique, not only to avoid unnecessary axillary lymph node dissection, but also to identify positive metastatic lesions requiring further intervention. REFERENCES 1. Fisher B. From Halsted to prevention and beyond: advances in the management of breast cancer during the twentieth century. Eur J Cancer 35: , Veronesi U, Paganelli G, Viale G, et al. A randomized comparison of sentinel-node biopsy with routine axillary dissection in breast cancer. N Engl J Med 349: , Stotter AT, McNeese MD, Ames FC, et al. Predicting the rate and extent of locoregional failure after breast conservation therapy for early breast cancer. Cancer 64: , Komoike Y, Akiyama F, Iino Y, et al. Ipsilateral breast tumor recurrence (IBTR) after breast-conserving treatment for early breast cancer: risk factors and impact on distant metastases. Cancer 106: 35-41, Tasevski R, Gogos AJ, Mann GB. Reoperative sentinel lymph node biopsy in ipsilateral breast cancer relapse. Breast 18: , Fisher B, Anderson S, Bryant J, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med 347: , Kroman N, Holtveg H, Wohlfahrt J, et al. Effect of breast-conserving therapy versus radical mastectomy on prognosis for young women with breast carcinoma. Cancer 100: , Singletary SE. Surgical margins in patients with early-stage breast cancer treated with breast conservation therapy. Am J Surg 184: , Lyman GH, Giuliano AE, Somerfield MR, et al. American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer. J Clin Oncol 23: , Luini A, Galimberti V, Gatti G, et al. The sentinel node biopsy after previous breast surgery: pre-

6 142 S. H. Hung et al./jcrp 26(2010) liminary results on 543 patients treated at the European Institute of Oncology. Breast Cancer Res Treat 89: , Taback B, Nguyen P, Hansen N, et al. Sentinel lymph node biopsy for local recurrence of breast cancer after breast-conserving therapy. Ann Surg Oncol 13: , Rodriguez Fernandez J, Martella S, Trifiro G, et al. Sentinel node biopsy in patients with previous breast aesthetic surgery. Ann Surg Oncol 16: , Koizumi M, Koyama M, Tada K, et al. The feasibility of sentinel node biopsy in the previously treated breast. Eur J Surg Oncol 34: , Port ER, Garcia-Etienne CA, Park J, et al. Reoperative sentinel lymph node biopsy: a new frontier in the management of ipsilateral breast tumor recurrence. Ann Surg Oncol 14: , Nieweg OE. Lymphatics of the breast and the rationale for different injection techniques. Ann Surg Oncol 8: 71S-73S, Lanitis S, Behranwala KA, Al-Mufti R, et al. Axillary metastatic disease as presentation of occult or contralateral breast cancer. Breast 18: , Bresser J, Vos B, Ent F, et al. Breast MRI in clinically and mammographically occult breast cancer presenting with an axillary metastasis: a systematic review. Eur J Surg 36: 114-9, 2010.