although the emergence of molecular biology and new techniques in imaging raise new challenges in SLNB [5.43]. In 2009, at the 11th International St. Gallen Breast Cancer Conference [5.44], several meta-analyses and guidelines were presented on the application of SLNB after neoadjuvant therapy and in cases of micrometastases. In 2010, an international expert consensus on the current recommendations of locoregional treatment in breast cancer elaborated on several recommendations regarding the assessment of axillary LNs [5.45].
The indications and recommendations for SLNB are summarized in Table 5.1 [5.24].
5.3.2. Controversial indications
Some studies maintain that previous plastic surgery does not contraindicate SLNB. Plastic surgery with breast augmentation or reduction requires major tissue movements, but the SLN is consistently identified also in these patients, irrespective of the technique used [5.46]. Current data indicate that SLNB should be considered to be standard in patients who have undergone previous breast surgery, with accuracies comparable to the results obtained in the general population of breast cancer patients. Indeed, the lymph drainage pattern may change in patients who have undergone prior procedures, as non-axillary drainage has been identified more often in reoperative SLNB than in primary SLNB.
In 73% of such patients, radiocolloid migration to the regional nodal drainage basins has been noted in ipsilateral axillary, supraclavicular, internal mammary, interpectoral and contralateral axillary nodes [5.47].
Multifocal breast cancer is defined as separate foci of ductal carcinoma more than 2 cm apart within the same quadrant, while multicentric breast cancer indicates the presence of separate independent foci of carcinoma in different quadrants [5.48]. Until recently, SLNB was contraindicated in patients with multicentric and multifocal breast cancer because it was believed that it was difficult to localize the true SLN, and a negative SLNB would not exclude the possibility of positive LN metastasis in basins draining from other regions of the breast. However, most of the mammary gland can actually be considered as a single unit with lymph drainage to only a few designated LNs in the axilla [5.49, 5.50]. In this regard, the efficacy of SLNB in patients with multifocal/multicentric cancer has been shown to be equal to that in patients with unicentric breast cancer. Nevertheless, it should be noted that the presence of nodal metastasis is significantly higher in SLNs as well as in non-SLNs in patients with multicentric breast cancer; however, sensitivity, false negative rate and overall accuracy of SLNB are similar in both situations, although with some discordant results among different groups of investigators [5.51–5.53].
TABLE 5.1. RECOMMENDATIONS FOR SLNB (adapted from Ref. [5.24])
Clinical circumstance Use of SLNB
T1 or T2 tumours Acceptable
T3 or T4 tumours Not recommended
Multicentric tumours Acceptable
Inflammatory breast cancer Not recommended
DCIS with mastectomy Acceptable
DCIS without mastectomy Not recommended except for large DCIS (>5 cm) on core biopsy or with suspected or
proven microinvasion Suspicious, palpable axillary nodes Not recommended
Older age Acceptable
Obesity Acceptable
Male breast cancer Acceptable
Pregnancy Not recommended
Evaluation of internal mammary LNs Acceptable Prior diagnostic or excisional breast biopsy Acceptable
Prior axillary surgery Not recommended
Prior non-oncological breast surgery Not recommended After pre-operative systemic therapy Not recommended Before pre-operative systemic therapy Acceptable
Note: DCIS: ductal carcinoma in situ; LN: lymph node; SLNB: sentinel lymph node biopsy.
Early studies showed great variation in the frequency of lymphoscintigraphic visualization of the internal mammary chain during SLNM. It was later found that the internal mammary SLN detection rate is significantly affected by the depth of the radiocolloid injection. It is generally recognized that mapping of the internal mammary node (IMN) requires deep radiocolloid injection, either peritumoural or intratumoural [5.54–5.56]. Nevertheless, the rates of detection and intraoperative harvesting of IMN LNs are much lower than those for axillary LNs. Visualization of the IMN LNs has been detected in approximately one third of patients with breast cancer, of which approximately 63%–92% could be harvested during surgery; 11%–27% of these SLNs had metastases [5.55–5.58].
However, the significance of IMN SLNB is still being debated. There is evidence that IMN mapping leads to upstage migration and modification of treatment planning with respect to radiotherapy and systemic therapy, but evidence does not support that IMN mapping will improve the outcome of treatment and overall survival [5.59]. Debate is ongoing on whether SLNB is accurate enough after neoadjuvant chemotherapy, or whether it should be performed before starting neoadjuvant chemotherapy. Performing SLNB before or after primary systemic treatment has advantages and disadvantages in both cases. Before neoadjuvant chemotherapy (accepted in ASCO guidelines), SLNB yields a more precise axillary staging, with useful information about possible LN metastasis.
Nevertheless, the procedure can delay the beginning of the treatment, and two operations can be necessary. On the other hand, SLNB performed after primary chemotherapy can assess the response at lymphatic level in the axilla, but may lead to underestimation of the initial stage [5.60]. After neoadjuvant chemotherapy, the SLN detection rate decreases, the false negative rate increases and the long term local recurrence rate in patients in which LDN has not been performed has not yet been determined. This group of patients was previously regarded as ineligible for SLNB because the lymph drainage pattern evaluated after chemotherapy may not represent the lymph drainage in the tumour basin before chemotherapy, therefore possibly leading to false negative results.
Available data show that there are no significant differences in the success rate of SLNB according to clinical tumour size or clinical nodal status, and that the false negative rate is not affected by tumour response to chemotherapy. In particular, a systematic review of 24 clinical trials of SLNB in patients with breast carcinoma after neoadjuvant chemotherapy was undertaken. Metastatic LN involvement was found in 37% of patients, the global SLN identification rate was 89.6% and the overall false negative rate was 8.4% [5.61–5.63].
Until approximately ten years ago, pregnancy was considered to be a contraindication to performing SLNB; however, the radiation dosimetry burden to patients is very low and the overall benefit should be considered in those patients presenting early lesions. Pregnant patients with early lesions and clinically/US
negative axilla should therefore be offered the possibility of performing a 1 d procedure including SLNB (with a low amount of radiotracer) and breast surgery.
In this regard, SLNB can be applied safely and successfully in pregnant women with breast cancer, with minimal risk to the fetus [5.64, 5.65]. The radiation exposure of the fetus from radiocolloids is very low and does not increase the risk of prenatal death, congenital malformation or mental impairment. On the other hand, blue dyes should not be used in pregnant patients [5.42].
Finally, some conditions that were previously considered to be formal contraindications to SLNB have changed to possible applications, on a patient to patient basis [5.43–5.45]. These conditions include large or locally advanced invasive breast cancers (T3), in situ ductal carcinoma, prior non-oncological breast surgery or axillary surgery, and the presence of suspicious palpable axillary LNs.