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mastectomy. The 18-gene classifier was found to be an
independent predictor of LRR in multivariate analysis
regardless of ER status and nodal stage. The performance
of the classifier has been tested in 87 patients treated
with BCT, but the index is not yet validated and holds no
predictive information in terms of postmastectomy
radiotherapy (PMRT). The DBCG-RT profile has, however,
been found to hold both prognostic information in terms
of LRR and predictive impact in regard to PMRT. The gene
profile was derived from a training set 191 high-risk breast
cancer patients treated with mastectomy and randomized
to PMRT or not, and independently validated in another
112 patients. Among non-irradiated patients in the
training set, the profile attained prognostic impact by
identifying two groups with a significant 6-fold difference
in LRR risk. Furthermore, the DBCG-RT profile showed a
predictive impact, since PMRT could be seen to reduce the
risk of LRR in the “High LRR risk” patients, whereas the
“Low LRR risk” patients experienced no additional benefit
from PMRT. More recently, a radiation sensitivity
signature has been derived from breast cancer cell lines,
and has been found to accurately identify patients with
LRR among 185 breast cancer patients. The latter two
signatures have been found to be independent of the
intrinsic subtypes.
Finally, exploring the heterogeneity of the
tumormicroenvironment may lead to targets that can
affect radiosensitivity or reverse radioresistance. Hypoxic
areas may leave possibilities for potential therapeutic
targets, and a more profound understanding of the
interaction between the immune system and RT (including
different treatment schemes) may lead to an increased
understanding of non-targeted effects.
The progress towards integrating molecular profiling into
precision radiation oncology is currently in its infancy, but
recent discoveries have been promising. The identification
and validation of prognostic and predictive genes and gene
profiles needs, however, to take into account the various
treatment regimes as the prognostic information may
potentially not be applicable in all treatment settings.
SP-0477 Where should we place radiotherapy: before
or after surgery?
L.J. Boersma
1
, S. Lightowlers
2
, B.V. Offersen
3
, A.N.
Scholten
4
, N. Somaiah
5
, C. Coles
6
1
MAASTRO Clinic, Dept. Radiation Oncology, Maastricht,
The Netherlands
2
Cambridge University NHS Foundation Trust, Oncology
Centre, Cambridge, United Kingdom
3
Aarhus University Hospital, Oncology, Aarhus, Denmark
4
Antoni van Leeuwenhoek Hospital, Dept. Radiation
Oncology, Amsterdam, The Netherlands
5
The Institute of Cancer Research and The Royal
Marsden, Clinical Oncology, Sutton, United Kingdom
6
Cambridge University NHS Foundation Trust, Clinical
Oncology, Cambridge, United Kingdom
Introduction
Traditionally, radiotherapy (RT) for breast cancer has
been largely delivered after surgery. Pre-operative (pre-
op RT) with or without chemotherapy has usually been
limited to patients with inoperable locally advanced
breast cancer. More recently, pre-op RT is being
investigated in early stage breast cancer for both whole
and partial breast irradiation.
Clinical data on pre-operative radiotherapy
The clinical data on pre-operative RT are sparse. There
are some older series of pre-op RT in locally advanced
disease showing varying response rates. The older studies
also suggest an increased post-operative complication rate
and increased acute toxicity, possibly due to older
techniques. More recently, data are emerging on pre-
operative partial breast irradiation with promising results
both on local control (although follow-up is still short),
toxicity and on post-operative complication rate. Several
fractionation schedules are being used, which mirrors
partial breast irradiation in the post-operative setting.
Pros and cons of post-operative radiotherapy
The advantage of post-operative RT (post-op RT) is the
availability of post-operative pathology characteristics, in
combination with a huge amount of follow-up data,
supporting the indication for RT. However, since patients
are increasingly treated with primary systemic treatment,
the value of post-operative pathology to decide on post-
op RT has become less clear. Another problem with post-
op RT in breast conserving treatment is that the target
volume of the tumor bed is extremely difficult to
determine, as is clear from the inter-observer-variation
when delineating the tumor bed. In addition, when the RT
indication is clear prior to mastectomy, some oncoplastic
surgeons prefer to delay breast reconstruction until after
the post-mastectomy RT.
Potential pros and cons of pre-operative radiotherapy
The obvious disadvantages of pre-op RT are loss of post-
operative pathologic characteristics to guide treatment
and the lack of strong and long term clinical follow-up
data, similar to our experiences with primary systemic
treatment. However, the advantages of pre-op RT are also
likely to be similar to primary systemic treatment: it
allows evaluation of the effect of RT with or without
additional agents, directly on the tumor. In addition, it
may downstage the tumor and thereby facilitate surgery:
in case of inoperable locally advanced disease, the tumor
may become resectable; patients with large tumors likely
to require mastectomy, may become eligible for breast
conserving treatment after pre-op RT, especially those
patients who have luminal A type tumors not responding
to primary chemotherapy. Another advantage is the
possibility of using tumor response as a surrogate endpoint
for local control, although, as with primary systemic
therapy, pathological response may be highly dependent
on tumor type. Time for regression following RT may also
be an important factor determining pathological response
rates, especially for strongly estrogen receptor positive
tumors. If pathological response following RT proves to be
a valid surrogate endpoint, then this is very attractive for
future trial designs; for example, fewer patients will be
needed, the primary outcome will be sooner and there is
huge potential for developing translational radiobiology
research. Due to the better visibility of the target volume,
a reduction in inter observer variation has been shown
when delineating the tumor for breast conserving therapy,
resulting in smaller irradiated (boost) volumes. Finally, it
may facilitate routine immediate breast reconstruction,
sparing the patient not only a second operation, but also
sparing the patient an awkward time without a breast.
Future developments
As is clear from the above mentioned pros and cons, pre-
op RT potentially has several advantages above post-op
RT. To investigate whether these potential advantages can
be exploited in clinical practice, several trials are
currently ongoing. In the presentation an overview of
ongoing trials will be given.
SP-0478 Radiation therapy after complete response
after primary systemic therapy. Is it needed?
P. Poortmans
1
1
UMC St Radboud Nijmegen, Department of Radiation
Oncology, Nijmegen, The Netherlands
Radiation therapy (RT) improves disease-free and overall
survival in the framework of breast conserving therapy
(BCT) and when regional lymph nodes are involved.
Outcomes improved a lot following progress in diagnosis
and in loco-regional and systemic therapies. This has lead,
among others, to the introduction of primary systemic
therapy (PST) to reduce the delay in initiation of systemic
therapy in high-risk patients as well as to improve an
unfavourable tumour/breast size ratio for BCT purposes.
The outcome in terms of disease-free and overall survival