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SALAMA AND CHMURA
Surgery or Ablative Radiotherapy for Breast
Cancer Oligometastases
Joseph K. Salama, MD, and Steven J. Chmura, MD, PhD
OVERVIEW
Precisely focused radiation or surgical resection of limited metastases resulted in long-term disease control and survival in multiple
studies of patients with oligometastatic breast cancer. The integration of these ablative techniques into standard systemic therapy
regimens has the potential to be paradigm shifting, leaving many patients without evidence of disease. Although an attractive treatment
option, the utility of these therapies have not been proven in controlled studies, and improved outcomes may be because of patient
selection or favorable biology alone. Ongoing studies continue to refine radiation techniques and determine the role for ablative
therapies in the management of patients with metastatic breast cancer (MBC). Additionally, patient selection for metastasis-directed
therapies is based on clinical criteria, with many not benefiting from therapies that may have substantial toxicities. Recent reports are
beginning to uncover the biology of oligometastatic cancer, but much work is needed. Current and developing trials that integrate both
clinical and translational endpoints have the potential to transform management strategies in women with limited MBC.
The use of novel surgical and radiotherapeutic techniques
for the treatment of few breast cancer metastases has been
gaining considerable interest. 1,2 For both patients and physicians,
the treatment of limited metastases, rendering a patient
without evidence of cancer and, potentially cured, is an exciting
concept. However, despite single-institution studies demonstrating
improved outcomes compared with historic series of
patients treated with systemic therapy alone, there is a lack of
evidence proving that this treatment approach will extend
progression-free survival (PFS) or overall survival (OS) for some
patients with breast cancer with limited metastatic disease.
Herein, we will review the evidence supporting the treatment of
patients with oligometastatic breast cancer with ablative (surgery
or radiation techniques). We will review what has been described
for selection of these patients and their follow-up. We
will also comment on ongoing clinical trials that may help to
elucidate some of these questions. Finally, we will review what
little is known about the biology driving the oligometastatic
state.
Breast cancer has long served as a model to understand the
mechanisms underlying the biology of metastatic cancer. Based
on clinical observations in the late 19th and early 20th century,
Halstead described an orderly and direct spread of malignancy
from the primary tumor to regional lymph nodes and then to
directly connected metastases. 3 The increase in radical and
ultra-radical en-bloc operations resulted from this philosophy,
attempting to remove all evidence of cancer. The continued evidence
of distant cancer dissemination despite aggressive surgeries
suggested a need for alternative hypotheses. The systemic
hypothesis of metastasis was fırst described by Keynes and perhaps
articulated most clearly by Fisher. 4 It suggested that widespread
dissemination of disease occurred before clinical
detection of the primary tumor. Therefore, cancers were dichotomized
into either those that were localized to the primary site
or those that were widespread. If widespread, increasing aggressive
surgeries to the primary tumor and regional lymphatics,
would not improve patient outcomes. Rather, systemic therapies
delivered adjuvantly or neoadjuvantly could reduce distant
metastases and, ultimately, have been integrated into standard
treatment regimens. However, based on the clinical observations
that not all breast cancers were widely metastatic at initial
presentation, and that some patients with metastases had long
disease-free intervals after metastasectomy and without systemic
therapy, an alternative hypothesis was called for.
Hellman advanced our understanding of the natural history
of metastasis by elucidating the spectrum hypothesis 5 in which
some breast cancers remain locoregionally confıned, others
metastatic at presentation, and the remaining subset progressing
from locoregional confınement to widespread metastases.
Soon thereafter, Hellman and Weichselbaum described the
clinically meaningful oligometastatic state, arising as a corollary
of the spectrum hypothesis, where metastases limited in number
and destination organ are unlikely to progress rapidly. 6 This was
based on successful surgical removal of metastases, reported by
Weinlechner as early as 1882, 7 and long-term survival (1939)
and cure (1947) after metastasectomy. 8 Whether arising de
From the Department of Radiation Oncology, Duke University Medical Center, Durham, NC; The University of Chicago, Chicago, IL.
Disclosures of potential conflicts of interest are found at the end of this article.
Corresponding author: Joseph K. Salama, MD, Box 3085, Duke University Medical Center, Durham, NC 27710; email: joseph.salama@duke.edu.
© 2015 by American Society of Clinical Oncology.
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