Abstract textIn the first part of this presentation, the definition of Locally Advanced Breast Cancer (LABC) will be discussed. A short review will be given on the distribution of locoregional recurrences after a modified radical mastectomy (MRM) in the absence of radiation treatment (RT), to identify regions with the highest risk on a recurrence. From these data the choice for target volumes of post mastectomy radiotherapy (PMRT) will become clear. In the second part, replacing an axillary lymph node dissection (ALND) by axillary RT (ART) is discussed, which may result in some specific situations where regional RT is applied without chestwall (CW)-RT.
Definition of LABC and distribution of locoregional recurrences: The term LABC usually describes a breast cancer that has progressed locally but has not yet spread outside the breast and local lymph nodes. The exact definition varies from Stage III breast cancer1 to patients with ≥cT3, and/or ≥cN22 disease, to even patients with only cT1-2N+ patients. In most guidelines, locoregional treatment of LABC consists of breast surgery, usually MRM including an ALND, and at least CW-RT, but mostly locoregional RT. The CW is always included in the target volume, since several studies have shown that after MRM the risk on developing CW-recurrences is the highest, compared to nodal recurrences: in an analysis of 1099 patients treated with an MRM and systemic treatment in four ECOG trials where adjuvant RT was not allowed, Recht et al3 found a 10 year CW-recurrence rate of 12%, with 8% in the supraclavicular nodes, 4% in the axillary nodes, and only 0.2% in the internal mammary chain. Manounas et al4 found similar results in an analysis of the NSABP 18&27 trials: in 513 cT3 patients treated with systemic treatment and an MRM without PMRT, they found 50 (10%) CW-recurrences and only 14 (3%) regional recurrences at 10 years after diagnosis. For the 609 patients with cT1-2 tumours a similar pattern was seen, although less pronounced: 38 (6%) CW-recurrences vs 24 (4%) regional recurrences. Although these studies thus also included patients with stage II disease, they strongly support the fact that if RT is indicated, it should at least consist of CW-RT.
Replacing ALND by ART: However, it can be wondered whether these conclusions also hold true in the absence of an ALND. Since the publication of the ACOSOG Z0011 trial5, the IBSCG 23-016 trial and the AMAROS7 trial, tables have turned with respect to axillary treatment: the AMAROS trial showed that an ALND can safely be replaced by ART in case a positive sentinel node (SN) and pT1-2 disease, with significant less lymphedema after ART than after an ALND7; the Z0011 and IBSCG 23-01 trials suggest that axillary treatment is not required at all in case of ≤2 macrometastases (Z0011) or micrometastases (IBSCG 23-01) in the SN, in patients with pT1-2 disease. It should be noted however that the majority of these patients was treated with breast conserving therapy, including breast RT and adjuvant systemic treatment. Although the Z0011 trial has Although the Z0011 trial has been critized8, most authors agree that there is probably a subset of patients with a positive SN, in whom axillary treatment can be omitted. How to identify these patients is however still not yet clear. Haffty et al9 suggested to replace an ALND by less or more extensive regional RT, dependent on the estimated risk group. Similarly, current Dutch guidelines recommend to apply axillary treatment in patients with a positive SN according to three risk groups: low, intermediate and high risk, with no axillary treatment in the low risk group, treatment of axilla level 1&2 in the intermediate risk group either by ART or ALND, and to add RT of axilla level 3 and 4 in combination with the CW-RT to treatment of axilla level 1&2 (again: either RT or ALND) in the high risk group. Especially in this intermediate risk group, there is a subset of patients in whom CW-RT is not clearly indicated after an ALND, i.e. the subgroup of patients that was eligible for the SUPREMO trial, where the additional value of CW-RT is being investigated. In this specific risk group, replacement of an ALND by ART, regional RT without CW- RT can be considered. A similar situation may occur in patients with cT1-2N0, ypT1-2N1mi(SN) luminal A breast cancer without risk factors.
In conclusion: Although CW-RT is indicated in the majority of patients with LABC, there may be a small selected group of patients where regional RT may be considered without CW-RT.
1. http://www.nccn.org/professionals/physician_gls/pdf/breast.pdf
2. Simos D et al. Curr Opin Support Palliat Care 2014;8:33–8.
3. Recht A et al. JCO 1999: 17(6):1689-700.
4. Mamounas EP et al. JCO 2012: 30(32):3960-6.
5. Giuliano et al. JAMA 2017: 318(10): 918–26.
6. Galimberti et al. Lancet Oncol 2018; 19: 1385–93.
7. Donker et al. Lancet Oncol 2014: 15(12): 1303–10.
8. Kühn & Poortmans, Breast Care 2011;6:154–57.
9. Haffty BG et al. JCO 2011: 29(34):4479-81.