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10.1245/s10434-006-9062-4
Annals of Surgical Oncology 13:1338-1343 (2006)
© 2006 Society of Surgical Oncology
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Original Article

Clinical and Therapeutic Importance of Sentinel Node Biopsy of the Internal Mammary Chain in Patients with Breast Cancer: A Single-Center Study with Long-Term Follow-Up

Paulo Carcoforo, MD1, Davide Sortini, MD1, Luciano Feggi, MD2, Carlo V. Feo, MD1, Giorgio Soliani, MD1, Stefano Panareo, MD2, Stefano Corcione, MD3, Patrizia Querzoli, MD4, Konstantinos Maravegias, MD1, Serena Lanzara, MD1 and Alberto Liboni, MD1

1 Department of Surgical, Anaesthesiological and Radiological Sciences, Section of General Surgery, University of Ferrara, C.so Giovecca 203, 44100, Ferrara, Italy
2 Department of Radiology, Unit of Nuclear Medicine, Sant’Anna University Hospital of Ferrara, C.so Giovecca 203, 44100, Ferrara, Italy
3 Department of Radiology, Unit of Radiology, Sant’Anna University Hospital of Ferrara, C.so Giovecca 203, 44100, Ferrara, Italy
4 Department of Experimental Medicine, Section of Pathological Anatomy, University of Ferrara, C.so Giovecca 203, 44100, Ferrara, Italy

Correspondence: Address correspondence and reprint requests to: Davide Sortini, MD; E-mail: srtdvd{at}unife.it


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: We evaluated the incidence of sentinel lymph nodes (SLNs) in the internal mammary chain, calculated the lymphoscintigraphy and surgical detection rates, and evaluated the clinical effect on staging and the therapeutic approach in patients with breast cancer.

Methods: The study involved 741 women diagnosed with breast cancer eligible for the SLN technique. Lymphoscintigraphy was performed on the day before the operation by peritumoral injection of 99mTc-labeled nanocolloid. During the operation, a gamma probe was used to detect the SLN, which was then removed.

Results: A total of 719 SLNs were found in the axillary chain and 72 in the internal mammary chain. Preoperative lymphoscintigraphy showed 107 hot spots in the internal mammary chain, but only 72 SLNs in 65 patients were identified by the gamma probe and then removed with no complications. Of these 65 patients, 10 had a positive internal mammary chain SLN on final pathologic examination, whereas 55 patients had ≥1 negative SLNs on final pathologic analysis. Thirty-five (53%) of 65 patients had also an axillary SLN, but only 5 patients (8%) had a positive SLN on pathologic analysis.

Conclusions: Evaluation of the SLNs in the internal mammary chain may provide more accurate staging in breast cancer patients. If an internal mammary sampling is not performed, patients may be understaged. This technique may allow better selection of those patients who will be submitted to adjuvant locoregional radiotherapy.

Key Words: Breast surgery • Sentinel node • Internal mammary chain • Lymphatic drain


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Sentinel lymph node (SLN) biopsy provides accurate staging information in women with breast cancer, thus decreasing early and late postoperative morbidity, and is progressively replacing standard lymphadenectomy in the surgical treatment of breast cancer.1 The SLN is the first node to receive lymphatic drainage from a tumor and it is considered to be the first affected by metastases.2 Although extra-axillary nodes can drain breast tumor metastatic cells, their removal has never been recommended. Lymphatic mapping offers the opportunity to visualize and identify SLNs and to assess breast lymphatic drainage patterns. Certainly, these nodes carry important prognostic information, because involvement of both axillary and internal mammary lymph nodes is associated with a worse prognosis.3,4 In addition, SLN biopsy may have an effect on the therapeutic strategy, because removal of the internal mammary chain (IMC) nodes provides more accurate staging.3 Indeed, in patients with no axillary metastases, malignant lymphatic involvement is confined to the internal mammary lymph nodes.5 IMC SLNs have been investigated in only a few studies, with conflicting results.3,6–12 In this study, a large group of patients with early-stage breast cancer was evaluated to (1) determine the incidence of IMC SLNs, (2) calculate the lymphoscintigraphy and surgical detection rates, and (3) assess the effect on staging and therapeutic strategy.


   METHODS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Patients
Between July 1999 and February 2005, 741 women with breast cancer were referred to the Nuclear Medicine Department of the Sant’Anna University Hospital of Ferrara, Italy, for SLN detection. The mean age was 60.7 ± 11.0 years (range, 29–94 years). Preoperative diagnosis was made by fine-needle aspiration or needle core biopsy. No patient had palpable axillary nodes. All 741 patients were included in the study. The primary tumor location, according to the mammary quadrant, is shown in Table 1Go. All patients underwent lymphoscintigraphy, surgical resection (i.e., quadrantectomy or mastectomy), and SLN detection. All procedures were performed by the same radiologist (C.S.) and nuclear medicine doctor (L.F.). All patients provided their informed consent for the SLN biopsy. The study protocol was approved by the ethics committee of our hospital.


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  		TABLE 1. Number of lesions draining to the internal mammary chain, depending on the quadrant of the primary tumor
 
Lymphoscintigraphy
A 2-day protocol was used; 99mTc-nanocolloid was injected peritumorally in a mean volume of .3 mL and with a mean radioactivity dose of 147.16 ± 22.8 MBq (3.83 mCi) on the day before the operation. Both palpable and nonpalpable lesions were injected under ultrasound or stereotactic radiographic guidance. Static scintigraphy imaging was performed at 30 minutes and at a mean of 19 hours after injection. A dual-head gamma camera was used to obtain both anterior and lateral images. SLNs were visualized by a hot spot on the lymphoscintigraphy (with or without the contemporary detection of any afferent lymphatic vessel); if more than one hot spot was seen, the SLN was defined as the first one identified in a sequential scan pattern. The SLNs suggested by lymphoscintigraphy were always verified and isolated during surgery by a gamma ray detection probe (Scinti Probe MR 100; Pol. Hi. Technology, Aquila, Italy). Between July 1999 and March 2001, in the first 263 patients, methylene blue in a 1-mL volume was injected into the tumor on the day of the surgical procedure. Therefore, both radiocolloid and blue dye tracers were used to identify the SLN. Specifically, blue dye was used in only the first 24 patients with SLNs in the IMC.

Surgery
All the surgical procedures were performed by the same experienced surgeon (P.C.) or by residents under his direct supervision. Extra-axillary regions were also explored in case of hot spots on lymphoscintigraphy. IMC SLNs were explored either through the same incision for tumor resection or through a small separate intercostal incision based on the probe localization of the SLN. After the pectoral muscle fibers were split, the intercostal muscles were separated from the lower rib to expose the fatty tissue along the internal mammary vessels on the surface of the parietal pleura. Rib dislocation was never required. Axillary lymphadenectomy was performed only in case of a positive axillary SLN on final pathologic analysis; in case of positive IMC SLNs, no axillary lymphadenectomy was performed.

Pathology
Before this study began, at the beginning of the experience with SLN biopsy, 50 consecutive patients underwent a complete lymphadenectomy after SLN identification, followed by histological examination. All SLNs were submitted to multilevel (100-µm interval) sectioning evaluation with hematoxylin and eosin staining and immunohistochemistry (anti-cytokeratin AE1, AE3, and PCK26 antibodies).

Follow-Up
After completion of the surgical operation and adjuvant therapy, all patients underwent follow-up with clinical examination at 6-month intervals during the first 2 years and every year thereafter and with mammography at 12-month intervals for 5 years.

Statistical Analysis
Statistical analysis was performed by using SPSS 9.0 for Windows (SPSS Inc., Chicago, IL). The Student’s t- and {chi}2 tests were used as appropriate to assess differences between the groups. P ≤ .05 was considered significant.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Lymphoscintigraphy
There were 89 patients (12%) with negative lymphoscintigraphy. In these patients, no SLN biopsy was performed, and in 39 patients (44%) with invasive carcinoma at pathologic analysis, an axillary dissection was performed. One hundred seven hot spots in the IMC were detected at preoperative lymphoscintigraphy in 95 patients, but only in 72 cases (67%), in 65 patients, was radioactivity evidenced by the probe in the operating room. In 37 (51%) of these 72 cases, the IMC SLN was the only one detected, whereas in 35 patients (49%), ≥1 axillary SLNs were associated. Table 1Go details the IMC drainage pattern according to the primary tumor location. Of the 498 lesions located in the outer quadrants, 27 (5%) drained to the IMC, whereas of 183 tumors in the inner and central quadrants, 45 (18%) drained to the IMC (P < .001).

Surgery
Seven hundred ninety-one SLN biopsies were performed in 652 patients: 719 (615 patients) in the axilla and 72 (65 patients) in the IMC, with a mean of 1.16 ± .51 lymph nodes (range, 1–5 lymph nodes) for the axilla and a mean of 1.10 ± .34 lymph nodes (range, 1–3 lymph nodes) for the IMC. Blue dye was injected in 24 (37%) of these 65 patients, but only 10 lymph nodes (42%) were dyed. Fifty-six SLNs (78%) were located in the second or third intercostal space (Fig. 1Go). Two complications (3%) were observed in 65 patients: 2 minor pleural lesions were detected and sutured with no subsequent pneumothorax or further consequences. For patients submitted to IMC SLN biopsy, the mean length of the operation was 72 ± 15 minutes, as opposed to 68 ± 16 minutes in patients submitted to axillary SLN biopsy (not significant). In patients with IMC SLN biopsy, the median postoperative hospital stay was 1 day (range, 1–4 days), versus 1 day (range, 1–3 days; not significant) in patients with axillary SLN biopsy.


Figure 1
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  		FIG. 1. Number and localization of sentinel lymph nodes in intercostal spaces.

 
Pathologic Characteristics
Among the 72 SLNs in the IMC, 62 nodes (86%) in 55 patients were negative at pathologic analysis, whereas 10 SLNs (14%) in 10 patients were positive; specifically, in 4 patients SLN macrometastases and in 6 patients SLN micrometastases were present. Five (8%) of 65 patients had a positive SLN axillary macrometastasis, and 1 patient (1.5%) had a positive SLN both in the IMC and axilla. Four patients with positive axillary SLNs showed negative IMC SLNs. In the nine patients with positive IMC SLNs, three had negative axillary SLNs, and six patients had no axillary SLN (Table 2Go). Patients with positive IMC SLNs had a mean age of 59.8 ± 11.4 years, as opposed to 55.9 ± 10.5 years in patients with negative IMC SLNs (P < .05). In patients with negative IMC SLNs, the tumor diameter was 1.2 ± .5 cm, versus 1.7 ± .9 cm (P < .001) in patients with positive IMC SLNs. The pathologic analysis and SLN status in 65 patients who underwent IMC SLN biopsy are illustrated in Table 3Go. The patient with intraductal carcinoma and positive SLNs in the IMC had negative SLNs in the axilla.


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  		TABLE 2. Drainage pattern in 65 patients with SLNs in the internal mammary chain
 

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  		TABLE 3. Relationship between pathologic diagnosis and lymph node status in internal mammary and axillary chains
 
Follow-Up
The mean follow up was 41.7 ± 15.3 months. Two (3%) of 65 patients with IMC SLNs died as a result of metastatic breast cancer 20 and 28 months after the surgical operation. Sixty-three patients (97%) are alive with no evidence of local or systemic recurrence. Both patients who died had negative SLNs, in the IMC and axilla, respectively. No false-negative SLN biopsy results have been recorded.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Axillary lymph node dissection has been considered the mainstay for surgical treatment of primary breast cancer to adequately stage the tumor and define adjuvant therapy strategies. However, IMC SLN removal is routinely performed only by a few breast surgeons.

In this study, 65 (9%) of 741 tumors showed IMC drainage. Although peritumoral injection of the tracer was used, this percentage is lower than in other studies5,8,10,11,13 (Table 4Go). Peritumoral injection visualizes both axillary and IMC drainage, as opposed to subareolar or intradermal injection.14 Preoperative lymphoscintigraphy showed 107 IMC hot spots (14%) in 95 patients, in accordance with other studies.


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  		TABLE 4. Studies evaluating SLNs in the IMC
 
In this study, SLN location, as shown by preoperative lymphoscintigraphy, was confirmed by probe scan in all cases. Superficial lymphatics have been shown to drain into the axilla, as opposed to deep lymphatics that drain into the IMC.10 Accordingly, in this study, superficial lesions localized in inner quadrants showed drainage in the axilla, whereas deep outer quadrant lesions drained toward the IMC. The intraparenchymal injection technique is also recommended when extra-axillary regions have to be evaluated.15–17 Although tumors located in the inner quadrants have shown a higher drainage rate into the IMC,10,12 cancers located in the outer quadrants may drain into the IMC.18–20 Correspondingly, in this series of patients, tumors were mostly located in the upper outer quadrant, but lesions in the inner quadrants showed the highest drainage rate to the IMC (20%–21%).

Indeed, IMC SLN biopsy may increase morbidity (e.g., pneumothorax and hemothorax) as compared with axillary node biopsy.5,9,11 In this study, only two complications (3%) were registered after IMC SLN biopsy: namely, minor pleural tears in two patients that resolved spontaneously without chest drainage. In addition, the lengths of the operation and of the hospital stay were the same in patients undergoing IMC as opposed to axillary SLN biopsy. Thus, biopsy of IMC SLNs seems to be a safe procedure, with no major complications or drawbacks.

Intraoperative blue dye injection has been advocated to guide SLN retrieval.21,22 In this series, blue dye injection was adopted in the first 263 patients, with no adverse reactions, but it was then discontinued because no advantages in SLNs localization were detected.

Patient age and the size of the primary tumor seem to be related to the frequency of IMC metastases.5,23 In this study, IMC metastases were detected in 10 (15%) of 65 patients; of note, in these 10 patients, only 1 (10%) also had axillary metastasis.

Tumor staging has been shown to be influenced by sampling the IMC lymph nodes.11 Veronesi et al.3 demonstrated in a 30-year follow-up study that patients with isolated IMC metastases had prognoses equivalent to those of patients with isolated axillary metastases. Adjuvant radiotherapy may be offered to patients with tumor-positive IMC nodes24; therefore, IMC SLN biopsy may help to select patients who will most likely benefit from additional regional therapy.6,7 In this study, one patient’s staging according to the International Union Against Cancer staging classification (latest version; 6th edition) changed from pN1a (metastasis in one to three axillary lymph nodes) to pN1c (metastasis in one to three axillary lymph nodes and in the internal mammary nodes, with microscopic disease detected by SLN dissection). More importantly, nine patients (14%) changed from pN0 (no regional lymph node metastasis histologically) to pN1, and adjuvant radiotherapy to the internal mammary region was added to conventional treatment. Indeed, only in 9 patients (1%) out of 741 was the therapeutic strategy changed, but IMC SLN biopsy was a safe procedure and may have improved prognosis in patients with breast cancer. To fully establish the effect of IMC SLN biopsy on the therapeutic strategy in patients with breast cancer, clinical trials are needed to determine whether it improves survival rates.

In conclusion, evaluation of the SLNs in the IMC may provide more accurate staging in breast cancer patients, with a potential survival benefit.

Received for publication October 19, 2005. Accepted for publication April 17, 2006.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Aarsvold JN, Alazraki NP. Update on detection of sentinel lymph nodes in patients with breast cancer. Semin Nucl Med 2005; 35:116–28.[CrossRef][Medline]
  2. Reintgen D, Cruse CW, Wells K, et al. The orderly progression of melanoma nodal metastases. Ann Surg 1994; 6:759–67.
  3. Veronesi U, Cascinelli N, Bufalino R, et al. Risk of internal mammary lymph nodes metastases and its relevance on prognosis of breast cancer patients. Ann Surg 1983; 198:681–4.[Medline]
  4. Carcoforo P, Sortini D, Soliani G, Basaglia E, Feggi L, Liboni A. Accuracy and reliability of sentinel node biopsy in patients with breast cancer. Single center study with long term follow-up. Breast Cancer Res Treat 2006; 95:111–6.[CrossRef][Medline]
  5. Farrús B, Vidal-Sicart S, Velasco M, et al. Incidence of internal mammary node metastases after a sentinel lymph node technique in breast cancer and its implication in the radiotherapy plan. Int J Radiat Oncol Biol Phys 2004; 60:715–21.[CrossRef][Medline]
  6. Freedman GM, Fowble BL, Nicolaou N, et al. Should internal mammary lymph nodes in breast cancer be a target for the radiation oncologist? Int J Radiat Oncol Biol Phys 2000; 46:805–14.[CrossRef][Medline]
  7. Allweis TM, Badriyyah M, Bar Ad V, Cohen T, Freund HR. Current controversies in sentinel lymph node biopsy for breast cancer. Breast 2003; 12:163–71.[CrossRef][Medline]
  8. Noguchi M, Tsugawa K, Miwa K. Internal mammary chain sentinel lymph node identification in breast cancer. J Surg Oncol 2000; 73:75–80.[CrossRef][Medline]
  9. Johnson N, Soot L, Nelson J, et al. Sentinel node biopsy and internal mammary lymphatic mapping in breast cancer. Am J Surg 2000; 179:386–8.[CrossRef][Medline]
  10. Estourgie S, Nieweg OE, Valdés Olmos RA, Rutgers EJ, Kroon BB. Lymphatic drainage patterns from the breast. Ann Surg 2004; 239:232–7.[CrossRef][Medline]
  11. Galimberti V, Veronesi P, Arnone P, et al. Stage migration after biopsy of internal mammary chain lymph nodes in breast cancer patients. Ann Surg Oncol 2002; 9:924–8.[Abstract/Free Full Text]
  12. Paganelli G, Galimberti V, Trifiro G, et al. Internal mammary node lymphoscintigraphy and biopsy in breast cancer. Q J Nucl Med 2002; 46:138–44.[Medline]
  13. Uren RF, Howman-Giles R, Chung D, Thompson JF. Nuclear medicine aspects of melanoma and breast lymphatic mapping. Semin Oncol 2004; 31:338–48.[CrossRef][Medline]
  14. Feggi L, Basaglia E, Corcione S, et al. An original approach in the diagnosis of early breast cancer: use of the same radio-pharmaceutical for both non-palpable lesions and sentinel node localisation. Eur J Nucl Med 2001; 28:1589–96.[CrossRef][Medline]
  15. Nieweg O, Estourgie S, van Rijk M, Kroon BB. Rationale for superficial injection techniques in lymphatic mapping in breast cancer patients. J Surg Oncol 2004; 87:153–6.[CrossRef][Medline]
  16. Ortega M, Vidal-Sicart S, Zanón G, et al. Comparative study of the different radiotracer administration route to locate the sentinel node in breast cancer. Rev Esp Med Nucl 2004; 23:153–61.[CrossRef][Medline]
  17. Tanis P, Nieweg OE, Valdés Olmos RA, Kroon BB. Anatomy and physiology of lymphatic drainage of the breast from the perspective of sentinel node biopsy. J Am Coll Surg 2001; 192:399–409.[CrossRef][Medline]
  18. Jakub JW, Cox CE, Pipas AW, Gardner M, Pendas S, Reintgen DS. Controversial topics in breast lymphatic mapping. Semin Oncol 2004; 31:324–32.[CrossRef][Medline]
  19. van der Ent FW, Kengen RA, van de Pol HA, Povel JA, Stroeken HJ, Hoofwijk AG. Halsted revisited: internal mammary sentinel lymph node biopsy in breast cancer. Ann Surg 2001; 34:79–84.
  20. Paredes P, Vidal-Sicart S, Zanon G, et al. Clinical relevance of sentinel lymph nodes in the internal mammary chain in breast cancer patients. Eur J Nucl Med Mol Imaging 2005; 32:1283–7.[CrossRef][Medline]
  21. Montgomery LL, Thorne AC, Van Zee KJ, et al. Isosulfan blue dye reactions during sentinel lymph node mapping for breast cancer. Anesth Analg 2002; 5:385–8.
  22. Simmons R, Thevarajah S, Brennan MB, Christos P, Osborne M. Methylene blue dye as an alternative to isosulfan blue dye for sentinel lymph node localization. Ann Surg Oncol 2003; 10:242–7.[Abstract/Free Full Text]
  23. Cserni G, Szekeres JP. Internal mammary lymph nodes and sentinel node biopsy in breast cancer. Surg Oncol 2001; 10:25–33.[Medline]
  24. Benamor M, Nos C, Fréneaux P, Clough KB. Impact of internal mammary sentinel node imaging in breast cancer. Clin Nucl Med 2002; 28:375–8.



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