Surgical trauma and postoperative immune suppression in breast-conserving surgery versus mastectomy: a pilot study

Despite extensive research, breast cancer is still the number one cause of
cancer-related deaths in women. The landmark trials of the 1980s revealed that
survival after breast-conserving surgery followed by radiation treatment (RT)
is similar to survival after radical mastectomy. At that time, radiation,
chemotherapy and endocrine therapy were infrequently used. Over the last years,
several large population based retrospective trials investigated whether
survival between breast conserving surgery and mastectomy remains comparable
with the current treatments and expertise. However, most of these trials report
superior survival in the breast-conserving surgery group when compared to
mastectomy. This discovery is not geographically bound (Denmark, Norway,
California, the Netherlands), not age dependent and corrected for all tumour-
and patient variables available in the cancer registration database. There is
no straightforward explanation as to why limited surgery for early stage breast
cancer could be superior to mastectomy. A possible contributing factor is
radiotherapy, as the majority of breast-conserving surgery patients receive
radiotherapy in contrast to few patients after mastectomy. Undoubtedly, on the
other hand, there is a larger degree of surgical trauma in mastectomy, which is
associated with more complications. A plausible hypothesis emerging in recent
literature is that more extensive surgical trauma leads to an altered immune
response. Uncontrolled damage to cells as occurs during trauma or surgery leads
to the release of danger-associated molecular patterns (DAMPs), substances that
are either actively released by cells under threat, or components of the cell
or extracellular matrix that are exposed upon cell damage. These DAMPs function
as ligands for immune receptors that, upon binding, induce an anti-inflammatory
immune response characterized by the release anti-inflammatory interleukin-10
(IL-10), decreased monocytic HLA-DR expression and reduced production of
pro-inflammatory cytokines TNFa and IL-6 upon ex vivo lipopolysaccharide (LPS)
stimulation. Fragidiakis et al describe a strong correlation between immune
status and recovery from surgery. In trauma patients, the suppressed immune
state has been linked to infectious complications and mortality. Moreover, a
recent study by Máca et al. shows DAMPs reflect the degree of surgical trauma
and predict morbidity and mortality after major abdominal surgery. Several
studies suggest a relationship between postoperative complications and the
eventual incidence of metastasis. However, comparing study results remains
challenging due to heterogeneity in reports and no clear definition of
complications. This pilot study will further explore the role of DAMPs and
immune suppression after breast cancer surgery. We hypothesize that more
extensive surgical trauma of mastectomy is associated with a higher release of
DAMPs and subsequent immune suppression, which in turn may lead to
postoperative complications.

Comparing the release of DAMPs and subsequent immune suppression after
breast-conserving surgery versus mastectomy.

A mono-centre prospective observational pilot study (n=40)

Patients already scheduled to undergo either breast-conserving surgery or
mastectomy will be asked to participate in the study, participating does not
alter or delay their treatment in any way. If a patient decides to participate,
a small amount of blood will be collected before surgery, 1 hour- and 1 day
after surgery. Where possible, this will be combined with routine laboratory
assessment to avoid unnecessary extra vena puncture. Baseline-, tumour- and
treatment characteristics, perioperative parameters and complications will be
extracted from the patient*s medical file only with informed consent.