Radiotherapy or surgery for the axilla in node-positive

Radiotherapy or surgery
for the axilla in nodepositive breast cancer?
The benefits of adjuvant radiotherapy
in positive axillary nodal regions
after breast-conserving and postmastectomy surgery have been
though sentinel lymph node
biopsy has largely replaced lymphadenectomy in the assessment
of micrometastases in sentinel
lymph nodes, it is still debated
in axillary management, owing
to the unfavourable effect of
macrometastatic sentinel lymph
nodes on breast cancer outcome.3
In the EORTC 10981-22023
AMAROS trial,4 patients with positive
sentinel lymph nodes received either
axillary radiotherapy or axillary
lymph node dissection. However, the
small number of axillary recurrences
observed in the study meant that
the test for non-inferiority was
underpowered. Axillary recurrence
occurred in four of 744 patients in the
axillary lymph node dissection group,
and in seven of 681 patients in the
axillary radiotherapy group. 5-year
axillary recurrence was 0·43% (95% CI
0·00–0·92) after axillary lymph node
dissection versus 1·19% (0·31–2·08)
after axillary radiotherapy.
The very low incidence of axillary
recurrence in both study groups
does not allow us to draw any
definitive conclusions about the best
interventional approach. Moreover,
the trial did not take into account all
the low-risk patients (probably not
negligible) that could not undergo
any intervention in the axillary region
in case of a positive sentinel lymph
node. We also have to consider the
suboptimal dose of radiotherapy
delivered in the adjuvant setting
in the presence of residual axillary
disease, and the technical challenge of
re-irradiation in cases of locoregional
recurrence in already irradiated
patients. In particular, re-irradiation Vol 16 February 2015
could affect both cosmesis and local
disease control.
Although modern radiotherapy
techniques allow the dose to organs at
risk to be decreased, while at the same
time improving target coverage, it is
well known that radiation could lead
to an increase in deaths not related
to breast cancer, mainly by induction
of pulmonary diseases, cardiac
diseases, and secondary cancers.
These radiation-related complications
probably affect the overall benefit
of radiotherapy on breast cancer
mortality after extended follow-up.
We need to continue to assess results
of the contemporary multidisciplinary
management of breast cancer to better
understand the complex interaction
between the contributions of systemic
and locoregional treatments to the
final outcome, including survival and
toxic effects.5
In our opinion, this outstanding
study cannot change clinical practice.
Conversely, it does support an
alternative for locoregional axillary
management in selected patients.
Axillary radiotherapy should be a
valid option if there is no indication
for lymphadenectomy, and it will
represent one more method in the
armamentarium of oncologists. A
multidisciplinary approach will be an
even more complex and crucial step
in the management of patients with
breast cancer.
Finally, longer follow-up of the
AMAROS trial population is strongly
needed to confirm not only the
equivalence of axillary radiotherapy in
terms of efficacy but also to determine
the early and late toxicity profiles.
We declare no competing interests.
Lorenzo Livi, *Icro Meattini
[email protected]
Department of Radiation Oncology, University of
Florence, Florence, Italy (LL, IM)
Early Breast Cancer Trialists’ Collaborative
Group (EBCTCG). Effect of radiotherapy after
breast-conserving surgery on 10-year
recurrence and 15-year breast cancer death:
meta-analysis of individual patient data for
10 801 women in 17 randomised trials. Lancet
2011; 378: 1707–16.
EBCTCG (Early Breast Cancer Trialists’
Collaborative Group). Effect of radiotherapy
after mastectomy and axillary surgery on
10-year recurrence and 20-year breast cancer
mortality: meta-analysis of individual patient
data for 8135 women in 22 randomised trials.
Lancet 2014; 383: 2127–35.
Lyman GH, Temin S, Edge SB, et al. Sentinel
lymph node biopsy for patients with earlystage breast cancer: American Society of
Clinical Oncology clinical practice guideline
update. J Clin Oncol 2014; 32: 1365–83.
Donker M, van Tienhoven G, Straver ME, et al.
Radiotherapy or surgery of the axilla after a
positive sentinel node in breast cancer (EORTC
10981-22023 AMAROS): a randomised,
multicentre, open-label, phase 3 noninferiority trial. Lancet Oncol 2014;
15: 1303–10.
Poortmans P. Postmastectomy radiation in
breast cancer with one to three involved lymph
nodes: ending the debate. Lancet 2014;
383: 2104–06.
We read Donker and colleagues’ study1
reporting the results of the AMAROS
trial with great interest. The study
confirmed that axillary radiotherapy
and axillary lymph-node dissection
(ALND) provide comparable local
control. However, despite reduced
lymphoedema in the axillary radiotherapy group, no significant
differences were recorded in range of
motion and quality of life.
The investigators postulated a bias
due to low sensitivity or a response
shift of the quality-of-life measures,
but did not discuss the potential effect
of axillary radiotherapy on range of
motion and quality of life. Restrictions
in motion were less common after
irradiation of the breast tissue alone
in patients who underwent sentinel
lymph-node biopsy compared with
those who underwent ALND.2 Since
no differences were observed in the
AMAROS trial, it is reasonable to
postulate that the dose delivered
in the axillary radiotherapy group
counteracted the benefits expected by
omitting ALND. Although irradiation
of the periclavicular area might have
affected the range of motion, the
potential morbidity of additional
axillary radiotherapy deserves further
investigation, as it can be associated
with shoulder problems and can
affect quality of life.3 In particular,
conventional breast irradiation includes