Department of Molecular Oncology, John Wayne Cancer Institute, Santa Monica, California 90404, USA
Address for correspondence: Dr. Dave S. B. Hoon, Department of Molecular Oncology, John Wayne Cancer Institute, 2200 Santa Monica Boulevard, Santa Monica, CA 90404. Voice: 310-449-5267; fax: 310-449-5282.
hoon{at}jwci.org
Breast cancer is the most common malignancy affecting women.
Advances in screening have resulted in an increasing trend towards
detecting earlier stage tumors associated with a longer disease-free
survival. Because of this prolonged latency period, it is critical
to identify patients early in their disease course who are at
increased risk for recurrence, whereby treatment decisions may
be altered accordingly based on more precise information. Molecular
markers that demonstrate prognostic importance as well as utility
for assessing subclinical disease progression offer one such
approach. Specifically, circulating microsatellite alterations
that reflect those genetic events occurring in tumors and that
can be serially assessed through a minimally invasive procedure
are a logistically practical method. In this study, serum was
collected preoperatively from 56 patients with early stage breast
cancer (AJCC stages I/II) and assessed for loss of heterozygosity
(LOH) using 8 microsatellite markers. Twelve (21%) of 56 patients
demonstrated LOH in their serum for at least one marker. Histopathologic
correlation revealed an association between the presence of
circulating LOH in serum and those tumors with increased proliferation
indices as characterized by an increased diploid index, elevated
MIB-1 fraction, and abnormal ploidy. These findings demonstrate
the presence of circulating microsatellite alterations in the
serum from patients with early stage breast cancer. The association
of known poor prognostic features found in tumors with increased
nuclear activity not only suggests a possible etiology for their
presence, but also offers a potential blood-based surrogate
marker for this disease that may demonstrate clinical utility
in long-term follow-up studies.
