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Utility of Internal Mammary Lymph Node Removal When Noted by Intraoperative Gamma Probe Detection

From the H. Lee Moffitt Cancer Center and Research Institute at the University of South Florida, 12902 Magnolia Drive, Tampa, Florida 33612-9497

Correspondence: Address correspondence and reprint requests to: Elisabeth Dupont, MD, Assistant Professor of Surgery, Comprehensive Breast Cancer Program, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Dr., Suite 3157, Tampa, FL 33612; Fax: 813-979-7287; E-mail: dupontel{at}moffitt.usf.edu

	ABSTRACT

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Background: Lymphatic mapping (LM) for breast cancer has made internal mammary node (IMN) detection practical and dependable. This study demonstrates the necessity of IMN removal when suggested by intraoperative radioguided surgery detection.

Methods: From April 1998 to July 2000, 1273 patients underwent LM for breast cancer. LM was performed using the combined dye and radiocolloid technique. Patients were scanned operatively with a gamma probe over the IMN area, and most underwent preoperative lymphoscintigraphy. Nodes were removed from patients in whom radioactivity was detected in the internal mammary area.

Results: Thirty of the 1273 (2.4%) patients mapped had at least one IMN removed. Twenty-two of 30 (73.3%) had inner quadrant lesions. Five of 30 (16.7%) patients had IMNs that were positive for metastatic disease. Three of these five had no metastatic spread to the axillary sentinel lymph node (SLN). One of thirty (3.3%) patients with IMN localization had neither hot nor blue nodes detected in an SLN procedure.

Conclusions: Radioguided SLN detection should be attempted in the IMN basin with all tumors. If an IMN is identified, it should be removed. IMN biopsy is a feasible, low-risk procedure when directed by radioguided LM and provides a guide for radiotherapy for patients with positive IMNs.

Key Words: Breast Cancer • Internal Mammary • Sentinel Lymph Node Biopsy

	INTRODUCTION

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The technique of lymphatic mapping and sentinel lymph node biopsy (SLN) in breast cancer has been shown to be an effective alternative to complete axillary lymph node dissection. Increased sensitivity and specificity have given researchers an increased ability to understand the significance of nonaxillary lymph node involvement. Indeed, in the last 5 years there has been a resurgence in research on the internal mammary node (IMN) chain. Data from this research highlight the importance of the IMN chain as diagnostically important to the accurate staging of the regional lymph nodes.

In 1898, Halsted identified the internal mammary chain as a route for metastasis of carcinoma of the breast. The internal mammary lymphatics may provide the primary drainage for approximately one quarter of the lymph from the breast.¹ Handley found that patients with central or medial tumors, as well as patients with axillary node metastases, exhibited internal mammary nodal metastases more often.² Li and Shen³ reported a large study that corroborated Handley’s findings for the increased risk for IMN metastases associated with centromedial primary tumors and axillary nodal metastases. Cox and Buxton⁴ reported an incidence similar to this report of nodal positivity in internal mammary nodes—in their study, 3 of 28 (10.7%) patients were noted to have positive IMN metastases.

Veronesi’s⁵ results, however, contrast with Handley’s. Veronesi demonstrated that the frequency of metastases to an IMN is slightly increased when the primary tumor is located in the central quadrant (22%) compared with inner (19.1%) and external lesions (18%). This study contrasts with the accepted theory that IMN metastases are common for primary tumors of the inner quadrants and rare for external quadrant tumors. Veronesi also reported that the presence or absence of axillary metastases is predictive of internal mammary nodal involvement. That is, in 563 cases without axillary metastases, 51 (9.1%) patients demonstrated internal mammary involvement, whereas 162 (29.1%) of 556 patients with axillary node metastases had internal mammary node involvement.⁵ Currently, the incidence of internal mammary node involvement established with lymphatic mapping of the breast has been reported to be between 1% and 6%, based on radioactivity detected along the internal mammary location.⁶

Standard treatment of IMN metastases is dissection of obvious lymph nodes in the ipsilateral second, third, and fourth intercostal spaces in combination with localized radiotherapy to the parasternal region for incomplete dissections.⁷ Chemotherapy in node-negative patients and radiotherapy to the IMNs for medial quadrant tumors have been used, precluding the need for node dissections and biopsies.

Detection of IMNs has been the subject of ongoing debate concerning which methodology can predict the outcome of IMN metastasis accurately. Patients with lymph node metastases are at a significantly increased risk for recurrent systemic disease; therefore, identifying the patients with these metastases ultimately will affect prognosis and permit appropriate therapeutic intervention.⁸ Our goal was to determine the utility of IMN removal when detected by intraoperative gamma probe detection.

	METHODS

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During a 26-month period from April 1998 to July 2000, 1273 patients underwent SLN biopsy at the H. Lee Moffitt Cancer Center. Our standard SLN biopsy technique has been described previously.⁶ Preoperative lymphoscintigraphy was used to assess almost all inner quadrant and central breast lesions. All internal mammary locations, specifically the second and third parasternal regions, were evaluated intraoperatively. If radioactivity was detected, an attempt was made to excise the internal mammary nodes. Exposure of the internal mammary chain was realized by parting the fibers of the pectoralis major and dividing the intercostal muscles at the parasternal location. The nodes were removed with careful dissection and use of the gamma probe to localize the sentinel IMN. When a sentinel IMN was resected, it was submitted for histologic evaluation. In case the node was later found to be positive, the location was marked with a metal hemoclip for subsequent radiotherapy.

The surgeons carefully avoided the pleural space so as to avoid a pneumothorax. Intraoperative pneumothorax, if it occurred, was treated with pleural aspiration and postoperative surveillance for the resolution of the pneumothorax. A negative finding precluded the necessity for radiation.^2,4 However, if the internal mammary node was found to be positive on pathologic evaluation, internal mammary radiotherapy was given.

	RESULTS

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Thirty of the 1273 (2.4%) patients mapped had at least one IMN removed. Inner quadrant lesions were present in 22 of the 30 (73.3%) IMN mapped patients. One of 30 (3.3%) patients with IMN localization had neither hot nor blue nodes detected in an axillary SLN, meaning there was no lymphatic drainage to the axilla from the site of the lesion. Five of the 30 (16.7%) patients had IMNs that were positive for metastatic disease. Three of these five had metastasis only to the IMN basin. Two had more than one positive internal mammary node. Four of the five with metastases to the IMN basin had lobular or mixed ductal and lobular carcinoma. The five patients had an average tumor size of 1.6 cm. Twenty-five of the 30 patients underwent preoperative lymphoscintigraphy, and internal mammary uptake was seen in 17 patients. Pneumothorax occurred in three cases. These pneumothoraces were treated with intraoperative aspiration and did not require a chest tube or an extended hospital stay.

	DISCUSSION

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The internal mammary lymphatics constitute an important route of spread for breast cancers. Hidden beneath the chest wall, internal mammary nodes elude palpation and histological examination. The most important risk factors for identifying internal mammary metastases are age of the patient, size of the primary tumor, and the presence of axillary node metastases.^9,10

Historically, the medial quadrants of the breast are thought to drain more extensively to the internal mammary nodes. However, recent studies have shown that the site of origin of the primary tumor does not correspond with lymphatic drainage to the IMN.^5,11 In our study, 22 of the 30 (73.3%) patients who mapped to the axilla had inner quadrant lesions. Additionally, all five patients with IMN metastases had tumors located in the inner quadrant of the breast. These data suggest that drainage to the internal mammary chain is more likely in a medial quadrant tumor, agreeing with Handley’s findings, but further studies are necessary to confirm this hypothesis. In any case, the internal mammary chain should not be ignored even with outer quadrant tumors.

Originally, lymphatic mapping and SLN biopsy of the internal mammary chain were not performed routinely. However, radioguided lymphatic mapping allows for easy evaluation of nonaxillary basins. Of the 30 patients that mapped to at least one IMN, five (16.7%) contained metastases. Lymphatic mapping eliminated unnecessary sternoradiotherapy in 25 of 30 (83.3%) patients, therefore. Sternoradiation has known complications, such as pneumotitis.¹² Furthermore, three of the 30 patients (10%) had metastases only to the IMN basin. This result indicates a somewhat higher IMN metastatic frequency without axillary metastases than those some authors^2,5,13 have reported. Thus, the IMN basin should be investigated with the gamma probe in all patients, not only when axillary metastases are present. All breast cancer patients must be considered at risk, regardless of lesion location, presence of axillary metastases, and tumor size.

Preoperative lymphoscintigraphy was used to evaluate lymphatic drainage in almost all inner quadrant and central breast lesions. Lymphoscintigraphy can alert the surgeon to that subset of patients in whom the IMN should be pursued aggressively.^14,15 It is interesting that of the 30 patients who showed radioactive uptake in the internal mammary region with the gamma probe, only 17 showed localization to an IMN on lymphoscintigraphy. All five patients with positive nodes did show IMN uptake on lymphoscintigraphy. This suggests that lymphoscintigraphy may aid in the detection of lymphatic drainage to the IMN, but should not be relied upon exclusively for detection of the IMN. Further studies are needed to establish whether lymphoscintigraphy is able to aid in the prediction of node status in the internal mammary basin.

It may seem that IMN dissection is unnecessary, because only five of 1273 (0.4%) total patients actually benefited from the removal of the IMN. However, because it is possible to identify intraoperatively the subset of patients who have lymphatic drainage from the tumor site to the internal mammary chain, it is possible to remove only those nodes that may contain metastases, thus limiting unnecessary morbidity. These results also show a lower percentage of patients with lymphatic drainage to the internal mammary chain than previously reported by other researchers.^16–18 This disparity may be because of different injection techniques or differences in how thoroughly individual surgeons pursue an IMN. Also, an IMN was only excised if a well-defined hot spot was found in the internal mammary basin with the gamma probe.

	CONCLUSIONS

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Lymphatic mapping improves the detection and removal of IMNs likely to have metastatic disease. Internal mammary node mapping should be attempted in all patients undergoing lymphatic mapping and SLN biopsy. In addition, lymphatic mapping of the internal mammary region precludes unnecessary radiotherapy to the sternal region for inner quadrant node-negative patients and reduces the attendant risk of morbidity.⁴ Furthermore, in those patients without documented drainage to the axilla but with documented IMN metastasis, a mapping failure is avoided and a complete axillary lymph node dissection therefore is unnecessary. Disease stage also is accurately assessed. Preoperative lymphoscintigraphy can alert the surgeon to that subset of patients in whom the IMN should be aggressively pursued. When the gamma probe localizes an IMN, it should be excised, because these results show that about 16.7% of the nodes will harbor metastases, substantially altering staging and postoperative treatment. With the advent of radioguided SLN biopsy, the detection of patients with internal mammary chain drainage has become a practical, minimal risk procedure.

	Acknowledgments

 
This study was supported by the McDonnell Douglas Research Fund, Department of Defense grant DAMD 17–97–7209, and the Joy McCann Culverhouse Surgical Oncology Professorship of the University of South Florida Foundation (Tampa, FL).

Received for publication March 17, 2001. Accepted for publication July 25, 2001.

	REFERENCES

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