Lymphoscintigraphy and Single-Photon Emission Computed Tomography (SPECT)/CT to Determine Need for Second Sentinel Lymph Node Biopsy for Breast Cancer Recurrence Following Ipsilateral Breast/Axillary Surgery

Background

Sentinel node biopsy (SNB) has become the standard of care for patients with cN0 breast cancer, and long-term results have been obtained [1–8]. However, evidence to support the use of second SNB in patients with ipsilateral breast tumor recurrence (IBTR) following an ipsilateral breast or axillary surgery remains insufficient. The less invasive nature of second SNB is a major advantage and has no reported definite disadvantage; thus, second SNB is performed in clinical practice. The lymphatic flow is assumed to be altered by the initial surgery; hence, many lymphoscintigraphy studies have been conducted to confirm this assumption. Performing second SNB is reasonable after verifying the location of the sentinel node (SN) in advance. In this report, we describe our experience of performing lymphoscintigraphy and single-photon emission computed tomography (SPECT)/CT in advance to determine whether SNB should be performed in patients who previously underwent ipsilateral breast or axillary surgery.

Case Report

This study included 9 patients with breast cancer and a history of ipsilateral breast or axillary surgery who underwent lymphoscintigraphy and SPECT/CT between April 2020 and July 2023. Lymphoscintigraphy was performed on a different day than surgery. Planar and SPECT/CT images were taken at 15 min and 3 h after 20–25 MBq of 99mTc-phytate was injected subcutaneously into the nipple area. SNB was performed during surgery using 2 mapping techniques: with isotope and with indigo carmine.

Patients provided written consent after being informed of the purpose of the exploratory study. Data were collected retrospectively from electronic medical records, and the institutional review board approved this study.

All 9 patients aged 47–74 years (mean: 54 years) were clinically node-negative and had no metastasis. The duration after the initial surgery was 5 months to 18 years (mean: 136 months) (Table 1). Lymphoscintigraphy was performed before the surgery.

As shown in Table 2, radioisotope accumulation by lymphoscintigraphy was observed in 2 patients at 15 min and 8 patients at 3 h, while SN could not be detected in 1 patient. The accumulation sites were only the axilla in 3 patients, other sites including axilla in 3, and sites other than the axilla in 2. Intraoperative SNB was performed in 5 of the 6 patients with lymphatic flow to the axilla (Patients 3, 4, 5, 7, and 9). Although the remaining patient also had lymphatic flow to the axilla, intraoperative SNB was not performed because the nonaxillary lymph nodes were dominant. The pathological results were negative for metastasis in all cases.

Figure 1 shows the cases subjected to undergo second SNB according to the lymphoscintigraphic findings. Patient 1, who underwent breast-conserving surgery (BCS) plus SNB as an initial surgery 18 years ago, received mastectomy without second SNB according to lymphoscintigraphy, which detected ipsilateral and contralateral internal mammary lymph node (LN) dominantly and ipsilateral axillar LN at 3 h after 99mTc-phy-tate injection. A second SNB was not performed during the surgery because the axillary lymph nodes were not dominant.

Patient 2 had triple-negative breast cancer that was clinically node-negative. She had SNB initially and then neoadjuvant chemotherapy. However, the cancer progressed. Thus, the treatment was changed to surgery. Lymphoscintigraphy and SPECT/ CT were performed at first and showed no radioisotope accumulation at 15 min and at 3 h. Thus, only mastectomy was performed (Figure 2).

Patient 4 (Figure 3) underwent BCS plus SNB 14.5 years earlier. Although radiotherapy (RT) to the affected breast was recommended, consent was not obtained; thus, RT was not performed after the initial surgery. The lymphoscintigraphy and SPECT/CT showed radioisotope accumulation only in the axilla at 15 min and at 3 h. Hence, BCS plus a second SNB was performed, followed by RT to the breast.

Surgical methods were determined according to the dominant site of radioisotope accumulation for each case.

However, second SNB was not performed in 1 patient because no LN was detected, and in 3 patients because the lymphatic flow went only to the outside of the axilla.

Discussion

SNB emerged in the mid-1990s and was initially reported in many cases using lymphoscintigraphy mapping of the lymphatic flow from the breast [3,4,7,8]. Jansen et al reported that 79% of patients had SN only in level I or II axillae, 16% in axillae and nonaxillae, and only 3% in non-axillae [8]. Although SN is not noted in axillary level I and II and is sometimes detected in LNs above level III or outside of the axilla [3,6–8], gamma scintillation counters have shown a high intraoperative detection rate (over 94%) [1,2,4]. The accuracy, sensitivity, and specificity of this tool are reportedly 96% or higher, 90% or higher, and 100%, respectively. However, SNB itself is informative and less invasive; hence, it has been a standard procedure for cN0 breast cancer [1–5].

The number of long-term follow-up cases after partial mastectomy and SNB has increased, and IBTR, which is related to a new primary breast cancer and the recurrence of a positive margin (mainly ductal component), has also become prevalent [9–11]. According to the National Comprehensive Cancer Network guidelines, the consensus recommendation of the panel for most patients with local recurrence following breast-conserving therapy and sentinel LN biopsy is mastectomy and a level I/II axillary dissection, given the lack of sufficient evidence regarding detection rate, false-negative rate, and prognosis [12].

The initial surgery may have affected the lymphatic flow. In this case, the requirement of a second SNB is debatable. Regarding adverse events, SNB is less invasive than axillary lymph node dissection (ALND). In addition, second SNB allows for the reevaluation of the disease stage. Several studies have reported detection through second SNB after initial surgery [13–18].

Generally, the detection rate of second SNB is 50-65%, and mapping by lymphoscintigraphy identifies SNs at a higher rate than intraoperative search using a gamma scintillation counter. The detection rate is also higher in SNB than in ALND in the initial treatment, and without radiation therapy (RT) than that with RT. Furthermore, the regional LN recurrence rate after second sentinel LN biopsy is reported to be less than 5% [15,19].

When a second SNB is performed intraoperatively with a gamma scintillation counter, 3 patterns are possible: (1) a SN is detected only in the axilla, (2) a SN is detected outside of the axilla, or (3) no SN is detected. If a SN is detected in the axilla, SNB would be performed as usual. If a SN is detected outside of the axilla, it is often impossible to detect intraoperatively. The gamma scintillation counter in the operating room does not provide a large field of view, so the search area is limited to the axilla and internal mammary lesion. In the present study, LNs were detected, particularly the ipsilateral, and contralateral internal mammary nodes and contralateral axillary nodes. Of note, LNs outside of the axilla are not included in the scope of local treatment, and biopsy, and pathological examination of these areas would be overly invasive. Dissection is always invasive, and it would not prove the absence of metastases. If the second SN is in a different region without LN metastases, dissection is a pointless over-invasive procedure.

In clinical practice, many possible situations are expected, but SNB itself is minimally invasive; if second SN is detected in the axilla, SNB may be performed. However, it is uncertain whether the results are as accurate and prognostic as the initial SNB. This uncertainty is most likely caused by the lack of knowledge of the lymphatic flow; mapping by lymphoscintigraphy will eliminate this uncertainty.

In the present study, lymphoscintigraphy was performed to clarify this point; planar images were taken, followed by SPECT/CT, which made the LN location easily identified [9,20]. This advantage is a sufficient reason to perform second SNB for breast cancer recurrence with a history of breast or axillary surgery.

Second SNB detected no metastases in all cases. According to some reports, when SNs can be accurately assessed, appropriate adjuvant therapy can be provided [21,22].

The use of lymphoscintigraphy to determine the indication for second SNB has been widely reported [9–18]. In particular, the use of SPECT/CT helps identify the SN location and increases the detection rate [10,20], supporting the present study. We did not observe metastasis in patients who underwent second SNB. The SNARB study reported that axillary lymph node recurrence was 1.0% after a median follow-up of 4.7 years without metastases after a second SNB for IBTR [19].

However, if the SN exhibits metastasis, applying the results of the American College of Surgeons Oncology Group Z0011 (ACOSOG Z0011) trial, which showed no difference in 10-year survival between omitting and adding axillary dissection when only a few metastases were detected after sentinel node biopsy in patients with invasive breast cancer (cT1-2 and cN0), to the second SNB is debatable [23] and requires further confirmatory studies. Although the newer methods of SNB, such as ICG, SPIO, and CEUS, have been reported and compared with conventional methods [24–26], there are no reports available on their use in a second SNB. In the case of IBTR, conducting a study under uniform conditions remains difficult, given the wide variations in the location and size of the wound and postoperative treatment, such as radiotherapy and adjuvant therapy. In addition, the indications for SNB have been expanded due to fewer disadvantages. In particular, clinically node-positive cases with targeted axillary dissection/tailored axillary surgery are now being considered. Lymphatic flow might have been altered during clinical node positivity. The accuracy of the second SNB after the modification of neoadjuvant chemotherapy is uncertain.

In terms of information, lymphoscintigraphy seems to be the most informative considering that adding SPECT/CT to planar imaging provides current information on lymphatic flow and allows us to locate the SN. Although LNs outside the axilla were detected by lymphoscintigraphy and were not pathologically examined, possible systemic treatment, and RT may be considered depending on the status of the primary tumor and SNs. In addition, the SNs as the first lymphatic basin should be considered even though the LNs are anatomically distant; their progress should also be monitored.

This study has some limitations. This single-center study included a small number of patients. Furthermore, all patients who underwent a second SNB were node-negative. Long-term follow-up is required.

Conclusions

SNB is less invasive, and information can be obtained if a second SN can be detected. On the other hand, the initial surgery may have altered lymphatic flow, so it is unclear if only the axilla is examined intraoperatively. There need to be sufficient data on long-term axillary recurrence or overall survival rate. Although the situation varies in each patient, previous lymphoscintigraphy and SPECT/CT can provide information on altered lymphatic flow, which can evaluate the significance of performing a second SN and affect the choice of treatment options.

Prior lymphoscintigraphy and SPECT/CT are strongly recommended if there is a history of ipsilateral breast/axillary surgery.