Management of the axilla after neoadjuvant chemotherapy for breast cancer

Abstract

Neoadjuvant chemotherapy (NACT) is increasingly administered to women with breast cancer. Pathological complete response (pCR) rates as high as 80 per cent in the breast and axilla can be achieved in women with human epidermal growth factor receptor 2-positive (HER2+) and triple-negative tumours1. Although the advantages of breast conservation after NACT are well known and have been described extensively2, management of the axilla in the era of NACT remains controversial. Gandhi and colleagues3 recently published a multidisciplinary guideline from the UK on axillary surgery for clinical node-negative (cN0) and node-positive (cN1) tumours following NACT. These guidelines advise that sentinel lymph node biopsy (SLNB) should be done either before or after NACT in patients with cN0 disease, followed by axillary lymph node dissection (ALND) or axillary radiotherapy if the sentinel node is positive. For cN1 disease, SLNB with dual mapping should be performed, with the aim of removing at least four nodes, followed by axillary radiotherapy in pN0 disease and ALND if the nodes are positive. ALND is always advised when there is extensive axillary nodal disease after NACT. Guidelines are known to vary between countries. A number of aspects can be discussed regarding the UK guidelines. In the era of multidisciplinary treatment for breast cancer, it would perhaps be preferable to discuss axillary management rather than axillary surgery after NACT. This is underlined by the fundamental role of axillary staging and axillary radiotherapy in these women. Moreover, the focus should be not only on women with cN1 disease, but also on those with cN2 breast cancer, as axillary pCR is also seen in this group of women, in whom locoregional radiotherapy is indicated irrespective of the nodal response. However, the combination of ALND and axillary radiotherapy increases morbidity, so whether ALND improves local control in this group of patients is subject to debate. There are also other differences in the recently published UK guideline compared with the current Dutch guideline (Table 1). In the setting of primary surgery, ALND has been replaced safely by SLNB in cN0 disease4. In the UK, the POSNOC trial5 is open for women with a positive sentinel node, randomizing between adjuvant systemic treatment alone versus adjuvant systemic treatment plus ALND or axillary radiotherapy. Multiple other trials have verified that omitting ALND in cN0 disease with low-volume disease at SLNB does not increase the risk of axillary recurrence6. The American Society of Clinical Oncology7 recommends that ALND should not be offered to women with early-stage breast cancer with one or two positive sentinel lymph nodes (SLNs), who receive breast-conserving surgery and wholebreast radiotherapy with systemic treatment. The need to perform even a SLNB for cN0 disease is currently being investigated. The SOUND trial8 randomizes women with cN0 breast cancer who are treated with breast-conserving surgery and radiotherapy to SLNB with, or without ALND, or no surgical staging of the axilla. In the BOOG 2013-08 trial9, women with cT1–2 N0 disease who have breast-conserving surgery are randomized to SLNB or no SLNB. Women treated with NACT are also eligible for inclusion in this trial, regardless of the timing of SLNB. After NACT, the rate of sentinel node positivity (ypN+) is very low, especially in women with triplenegative or HER2+ disease and a complete radiological response on MRI (M. E. M. van der Noordaa et al., unpublished data presented to the European Breast Cancer Conference, March 2018) or breast pCR. Based on these data, current Dutch guidelines advise that SNLB should be performed after NACT in women with cN0 disease, whereas the UK guidelines advise SLNB may be done before or after NACT. To select women with cN+ breast cancer for whom less extensive axillary treatment is safe, adequate axillary nodal staging before and after NACT is required. Previous studies have shown that PET–CT is the optimal locoregional staging method before NACT, with a high positive predictive value for detecting axillary metastases and the ability to assess the number of fluorodeoxyglucose-avid axillary lymph nodes10. The accuracy of axillary staging after NACT has been