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Original Article |
1 Division of Breast Surgery, European Institute of Oncology, Via Ripamonti, 435, 20141 Milan, Italy
2 Division of Nuclear Medicine, European Institute of Oncology, Via Ripamonti, 435, 20141 Milan, Italy
3 Division of Pathology and Laboratory Medicine, European Institute of Oncology, Via Ripamonti, 435, 20141 Milan, Italy
4 University of Milan School of Medicine, Milan, Italy
5 Division of Epidemiology and Biostatistics, European Institute of Oncology, Via Ripamonti, 435, 20141 Milan, Italy
Correspondence: Address correspondence and reprint requests to: Mattia Intra, MD; E-mail: mattia.intra{at}ieo.it
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMETHODSRESULTSDISCUSSIONREFERENCES |
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Methods: Between January 2000 and June 2004, 79 patients who were previously treated at our institution with breast-conserving surgery and who had a negative SLNB for early breast cancer developed, during follow-up, local recurrence that was amenable to reoperation. Eighteen of these patients were offered a second SLNB because of a clinically negative axillary status an average of 26.1 months after the primary event.
Results: In all 18 patients (7 with ductal carcinoma-in-situ and 11 with invasive recurrences), preoperative lymphoscintigraphy showed an axillary sentinel lymph node, with a preoperative identification rate of 100%, and 1 or more SLNs (an average of 1.3 per patient) were surgically removed. Sentinel lymph node metastases were detected in two patients with invasive recurrence, and a complete axillary dissection followed. At a median follow up of 12.7 months, no axillary recurrences have occurred in patients who did not undergo axillary dissection.
Conclusions: Second SLNB after previous SLNB is technically feasible and likely effective in selected breast cancer patients. A larger population and longer follow-up are necessary to confirm these preliminary data.
Key Words: Breast cancer • Axillary sentinel lymph node biopsy • Reoperative biopsy • Second biopsy • Reappearing breast cancer • Recurrence
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONREFERENCES |
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An increasing proportion of patients with early breast cancer (and candidate to SLNB) undergo breast-conserving surgery (BCS), and approximately 5% to 15% of them are at high risk of presenting with locally recurrent disease within 10 years.3,4 Although the current standard treatment in this setting is mastectomy, patients selected according to the site and size of the recurrence and the size of the breast may be offered a reoperative BCS.5 Likewise, 10% to 15% of patients with ductal carcinoma-in-situ (DCIS) treated with BCS may develop local relapse, which is invasive in approximately 50% of cases6–8 and is suitable in most cases for a new BCS.
As for the primary tumor, evaluation of the histological status of the residual axillary lymph nodes is prognostically important for patients with local recurrence after a previous BCS and SLNB. The questions then arise whether a second SLNB is anatomically and biologically feasible for these patients and whether the identification rate of sentinel lymph nodes (SLNs) is acceptable. Although a previous SLNB or any axillary operation has generally been considered a contraindication for a second SLNB, few data support this concern.
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METHODS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONREFERENCES |
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Lymphoscintigraphy
Lymphoscintigraphy was performed by using the standard technique in our institution (radiocolloid injection).9 In case of NIPT, the technique did not differ from that already described. Briefly, 10 to 12 MBq of 99mTc-labeled colloidal particles of human albumin <80 nm (Nanocoll; Nycomed Amersham-Sorin, Saluggia-VC, Italy) in .2 mL of isotonic sodium chloride solution was injected subdermally according to the skin projection of the tumor on the day before the operation or on the same day. In case of TLR, the injection technique was the same as that used in the presence of a skin scar from a previous surgical biopsy: one single subdermal injection close to the skin scar, toward the axilla. In both cases (TLR and NIPT), lymphoscintigraphy was then performed by acquiring planar images in the anterior and oblique anterior views: 150,000 counts were collected at 15 and 30 minutes after the injection. More delayed acquisition at 120 minutes was performed only if SLNs were not previously evident. The skin projection of the SLN was marked with a indelible ink pen and used as a landmark when the operation began. If the NIPT was nonpalpable, radioguided occult lesion localization was performed to localize the tumor by using 99mTc macroaggregates.10
Surgery
SLNB took place 4 to 20 hours after injection of the radiolabeled albumin nanocolloids. A gamma ray–detecting probe (Neoprobe 2000; Ethicon, Inc., Somerville, NJ) was used to locate the radioactive lymph node and facilitate its removal. In case of BCS, the second SLNB was performed through the same incision as the tumor resection whenever possible or through a separate 2- to 3-cm axillary incision if the tumor was far from the axilla. After the SLN was removed, the surgical bed was rechecked for any residual radioactivity, and, if present, additional SLNs were identified and removed. If the primary tumor was nonpalpable, the radioguided resection of the lesion10 allowed its correct removal (cluster of microcalcifications or small opacities). All nodes with radiotracer uptake were removed and sent for histopathologic examination. The SLN examination was performed as previously described, according to our standard protocol.11
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RESULTS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONREFERENCES |
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. Four of the nine patients with DCIS developed an invasive recurrence, and two of the nine patients with invasive carcinoma developed a DCIS recurrence. In total, 7 patients with DCIS and 11 with invasive recurrences underwent a second SLNB. At preoperative lymphoscintigraphy, at least 1 new axillary SLN (total, 20; average, 1.1 per patient) was visualized in all 18 cases. No other sites of drainage outside the axilla (e.g., lymph nodes of the internal mammary chain) were observed. In all patients, 1 or more SLNs were surgically removed (average, 1.3 per patient). Metastases were identified in the SLNs of two patients with invasive recurrence, and a complete axillary dissection followed. In 1 patient, the second SLN was the only metastatic lymph node, whereas in the other patient, 12 additional metastatic axillary lymph nodes were identified. Comparing the characteristics of the SLNs in the 12 TLRs and 6 NIPTs in terms of the number of SLNs visualized at lymphoscintigraphy or identified at operation and the interval between radioisotope injection and scintigraphic visualization, no differences were observed (Table 2). In particular, the SLNs were visualized at lymphoscintigraphy within 120 minutes from the radioisotope injection in all 18 cases, and no further administrations were necessary. At a median follow-up of 12.7 months, no axillary recurrences occurred in the 16 patients who did not undergo completion axillary dissection.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONREFERENCES |
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Most authors, however, still consider previous axillary surgery a definite contraindication to SLNB, but no data are currently available to support or refute this concept. In the Memorial Sloan-Kettering Cancer Center experience,19 a previous axillary operation—either a partial level I or II axillary dissection or a previous successful or failed lymph node biopsy—did not hamper the identification of an SLN, especially when fewer than 10 nodes were removed during the earlier procedure. In their series, the second SLNB was guided by using a combined dye/ isotope mapping technique; the overall identification rate was 75%, and the number of second SLNs removed was 2.3 per patient. The rate of SLN identification was significantly lower than in our series (100% of SLNs identified), probably because of the larger extent of previous surgical treatment of the axilla. In fact, when the second SLNB was performed after a level I or II axillary dissection or an inadequate axillary dissection, the identification rate was only 66.6%, whereas if the second SLNB was performed after a previous SLNB, the identification rate was higher (87.5%).
The SLN is, by definition, the first node or nodes directly draining the lymph from the breast carcinoma area. Although usually an axillary node and most commonly in the central group of level I, the SLN may be at level II (behind the pectoralis minor muscle) or level III (infraclavicular) or may even be an intramammary node, an interpectoral (Rotter’s) node, or an internal mammary node.2 To be anatomically and oncologically effective and to correctly predict the histological status of the axilla, SLNB requires, at a minimum, the presence of an intact lymphatic flow from the site of the primary tumor (or recurrence). A previous axillary operation could partially or temporarily interrupt and modify the lymphatic flow, thus complicating the correct identification of the SLN.
In case of partial interruption of the lymph flow, an axillary SLN may still be identified. In fact, several studies20,21 support the hypothesis that breast tumors drain through a few common afferent lymphatic channels to a common axillary SLN, regardless of the tumor location and number of tumor foci. The breast drains to the axilla as a single unit through few major lymphatic trunks coming from a subareolar plexus. If one or more trunks are interrupted, an alternative path to the SLN may be used successfully for radioisotope migration.
In case of complete lymphatic interruption, the physiological restoration of the anatomy of the lymphatic drainage makes the obstacle only temporary. In fact, when an adequate period of time elapses between the first axillary operation and disease recurrence, the lymphatic net has time to be rebuilt, and a new lymphatic "bridge" can connect the breast and the operated axilla. The new lymphatic pathway allows identification of a novel SLN—the true sentinel hic et nunc of the new tumor, as the first SLN was of the first carcinoma. These considerations could introduce a new dynamic concept of SLN: not "one SLN forever" but "always a new SLN." In our series, a new SLN was detected at lymphoscintigraphy in 100% of the patients after a median interval of 26.1 months (range, 4–61 months) from the primary axillary operation.
In case of NIPT, the radioisotope injection technique did not differ from the one already described8: a single subdermal injection in correspondence with the projection of the tumor. In case of TLR, the radioisotope injection technique was the same as that used in case of a skin scar from a previous surgical biopsy, i.e., one single subdermal injection close to the scar, toward the axilla. In our experience with 534 patients who underwent previous surgical biopsy, this method allowed us to identify the SLN in 98.5% of cases. Comparing the two groups of patients, no differences were observed in terms of the number of SLNs visualized at lymphoscintigraphy and the interval between radioisotope injection and scintigraphic visualization. In the NIPT group, the number of SLNs identified at operation was slightly higher than in the TLR group, but the small number of patients does not allow significant conclusions (Table 2
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Seven patients with recurrent disease had pure DCIS. Because of the low prevalence of metastatic SLN involvement (1.6%) in our previously published series on pure DCIS,22 SLNB is not considered at our institution as a standard procedure in the treatment of DCIS. SLNB is considered only in case of DCIS that has a chance of showing (micro)invasive foci at the histopathologic examination, such as large solid tumors or diffuse or pluricentric microcalcifications undergoing mastectomy.
The low rate of metastatic second SLNs (2 of 18 patients) was related to the small size of the invasive recurrences (.9 cm on average). Moreover, as expected, the 2 metastatic SLNs were observed only in the group of 11 invasive recurrences, and no meta-static SLNs occurred in DCIS recurrences.
In conclusion, we recommend the performance of lymphoscintigraphy in case of local recurrence after BCS, even if an SLNB has been previously performed. Whenever an SLN is identified at lymphoscintigraphy, the axillary dissection and its morbidity and sequelae could also be avoided in these patients without losing the important prognostic information of the axillary status. Furthermore, it should be emphasized that the lymphoscintigraphic technique adopted in our institution1 allows preoperative selection of patients for either SLNB or axillary dissection, thus programming the operation better and adequately preparing the patients for operation. In contrast, the blue dye technique provides knowledge of whether an SLN will be identified only during the operation.
Received for publication October 20, 2004. Accepted for publication June 28, 2005.
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This article has been cited by other articles:
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  E. R. Port, C. A. Garcia-Etienne, J. Park, J. Fey, P. I. Borgen, and H. S. Cody III Reoperative Sentinel Lymph Node Biopsy: A New Frontier in the Management of Ipsilateral Breast Tumor Recurrence Ann. Surg. Oncol., August 1, 2007; 14(8): 2209 - 2214. [Abstract] [Full Text] [PDF]
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