Download metastatic breast cancer

update in
metastatic breast cancer
Dr.Mina Tajvidi
Radiation oncologist
Fewer than 10 percent of women present with
metastatic disease at the time of diagnosis
 the majority of women who relapse after
definitive therapy for early stage or locally
advanced disease will do so with disseminated
metastatic disease rather than an isolated local
recurrence
The most common sites of distant tumor
involvement are the bones, liver, and lungs.
Only 5 to 10 percent of patients with MBC
survive five or more years, and perhaps 2 to 5
percent become long-term survivors, possibly
cured of disease.
In the absence of dramatic survival benefits,
the focus of treatment in patients with MBC is
Successful palliative therapy requires a reduction
in disease-related symptoms without excessive
treatment-related toxicity.
Selection of initial therapy
Some patients are willing to accept a high
burden of toxicity for small survival benefits,
while others may only wish to be treated if
toxicity is minimal and the likelihood of
symptom control is high
Local versus systemic treatment
Women who have an isolated local recurrence or
involvement of a single metastatic site (eg, a single painful
bone lesion or evidence of impending fracture) might be
optimally palliated with local treatment alone, withholding
systemic therapy until relapse or progression
 women with widespread disease involving multiple
symptomatic sites are better served with initial systemic
treatment. Systemic and local therapy are frequently
combined.
Bone targeting radioisotopes (eg, 89-strontium, 153samarium lexodronam) are more often used in men with
advanced prostate cancer, but they can provide excellent
palliation of bone pain in women with predominantly
osteoblastic multifocal bone metastases in whom pain
control is not adequately controlled with radiation therapy,
systemic antitumor therapy or analgesics.
Endocrine therapy versus
chemotherapy for HER2-negative
disease
In general, the risk to benefit ratio is more favorable with
endocrine therapy as compared to chemotherapy, due to a
lower toxicity profile.
If a patient with slowly progressive disease, no visceral
involvement, and minimal symptoms, might be best served
with a trial of endocrine therapy, even if her tumor has low
or absent ER expression.
a patient with rapidly-growing disease, especially with
involvement of lung and/or liver, is better initially treated
with chemotherapy, which is more likely to induce a
response than endocrine therapy under these
circumstances.
Confirming the diagnosis
In general, a biopsy is indicated at the time of first
suspected recurrence in women with a prior history of
breast cancer. Solitary pulmonary nodules in particular
require biopsy, since up to 50 percent represent new
primary lung cancers, especially if there is a history of
smoking
Repeat biopsy may also permit a more precise
characterization of relevant predictive factors. As an
example, up to 20 percent of estrogen receptor (ER)
measurements may be discordant between primary and
metastatic lesions . In addition, the tumor molecular profile
is becoming increasingly important in selecting therapies,
such as trastuzumab for HER2-positive tumors
Endocrine therapy versus
chemotherapy for HER2-positive
disease
Trastuzumab is the preferred initial agent for patients with
HER2-positive tumors. For patients with relatively indolent
disease, it is reasonable to try trastuzumab alone or
trastuzumab plus endocrine therapy for a few months.
Some patients may respond and be well palliated. An
alternative for patients with symptomatic or rapidly
progressive visceral metastases is combined therapy
 Amplified/overexpressed HER2 predicts for response to
therapies that target HER2, such as the humanized
monoclonal antibody trastuzumab (Herceptin) and the
small molecule tyrosine kinase inhibitor lapatinib (Tykerb®)
 These drugs are only effective in those patients whose
tumors have high levels of HER2 overexpression (3+ by
immunohistochemistry) or gene amplification (as detected
by fluorescence in situ hybridization, FISH) of HER2
About 24 percent of IHC 2+ positive tumors have gene
amplification by FISH, and these patients have the potential
to respond to trastuzumab. some women with HER2negative primary tumors acquire HER2 protein
overexpression at recurrence
predictors of chemotherapy
response
The most consistent predictors of
poor chemotherapy response are
progression with prior chemotherapy
for advanced disease, relapse within
12 months of completing adjuvant
chemotherapy, poor performance
status, and multiple disease sites,
especially visceral involvement
bisphosphonate therapy in MBC
Among women with lytic, and probably blastic,
bone metastases, bisphosphonate therapy in
combination with either endocrine therapy or
chemotherapy prolongs the time to first skeletal
complication and decreases the proportion of
women who develop complications related to
bone metastases
The American Society of Clinical Oncology
recommends intravenous pamidronate (90 mg
over one to two hours every four weeks) in such
patients
tumor marker
Serial tumor marker assay can be particularly helpful in
confirming a clinical suspicion of a change in the biologic
course.
CA 15-3 and CA 27.29 are well-characterized assays that
detect circulating MUC-1 antigen in peripheral blood.
(ASCO), monitoring selected patients with metastatic
disease in the absence of readily measurable disease was
the sole recommended use for circulating tumor markers
including CA15-3, CA27.29, and CEA
tumor marker
If the MUC-1 assay is elevated, there is no role
for monitoring CEA, but if not, then serial CEA
levels may be useful.
 Up to 20 percent of patients successfully
treated with systemic therapy may experience a
transient increase (marker "flare") during the first
one or two months after treatment initiation,
presumably due to release of antigen by cytolysis
 Patients with abnormal liver function may also
have falsely elevated marker levels because they
are cleared by the liver
CA 15-3 levels may be aberrantly elevated in
patients with vitamin B12 deficiency and
megaloblastic anemia, as well as in patients with
thalassemia or sickle cell disease

single agents & combination
chemotherapy
We suggest therapy with serial single agents
rather than initial combination chemotherapy for
patients with nonvisceral or slowly progressive
visceral disease (G2B).
 For elderly women and those with a borderline
performance status, single agent vinorelbine is a
reasonable alternative to anthracyclines or a
taxane
single agents & combination
chemotherapy
For selected, highly symptomatic patients and
those with rapidly progressive visceral
metastases, we suggest initial combination
therapy rather than serial single agents because
of the greater likelihood of an objective response
There is no single regimen that has emerged as
superior
high dose chemotherapy
There is no proven benefit for high
dose chemotherapy with
hematopoietic stem cell support,
single agents & combination
chemotherapy
 Due to the lack of survival and QOL
benefit, we suggest serial single agents
rather than combination chemotherapy for
second, third, or fourth-line treatment for
most patients with slowly progressive,
asymptomatic disease (Grade 2B).
 For patients whose disease is rapidly
progressive or symptomatic, the risks and
benefits of combination therapy must be
discussed with the patient, and treatment
individualized.
circulating levels of the HER2 protein
extracellular domain (ECD)
Multiple studies have addressed whether
circulating levels of the HER2 protein extracellular
domain (ECD) can predict response to
trastuzumab (or lapatinib) and is generally
associated with a poorer prognosis
lapatinib
Until further information is available, we suggest
that lapatinib not be used as a first-line agent,
even in patients with brain metastases
The role of surgery in metastatic
breast cancer
Patients with metastatic breast cancer are
unlikely to be cured of their disease by any
means.
In the absence of curative treatment for the
majority of patients, the goals of therapy
typically shift from cure to palliation,
focusing on symptom control, improved quality of
life (QOL), and prolongation of survival.
There are no randomized trials showing that
resection of any metastatic site prolongs survival
compared to systemic treatment alone.
The role of surgery in metastatic
breast cancer
At least three observational studies directly comparing
outcomes of surgically treated patients with pulmonary or
hepatic metastases with those receiving chemotherapy
alone suggest a significant survival advantage for surgery
However, caution is warranted in interpreting the results
of comparative studies due to the selection bias that is
inherent in such reports.
 Patients with significant comorbidities are rarely
considered good operative candidates and are more often
recommended for nonsurgical therapies. In addition,
patients selected for surgery are often those who have
better prognostic features or indolent biologic behavior (ie,
good performance status, solitary metastases, long diseasefree interval).
The role of surgery in metastatic
breast cancer
 Most oncologists consider the presence of
disease outside one organ to be a
contraindication to metastatectomy, although
there are exceptions to this general rule
The role of surgery in metastatic
breast cancer
Patients with a history of breast cancer
and a new solitary pulmonary lesion
should be strongly considered for
resection, because of the possibility that
this represents a potentially curable
primary lung cancer.
The role of surgery in metastatic
breast cancer
Contraindications to hepatic
resection include bilobar disease,
hilar involvement, or insufficient liver
function to permit resection.
The role of surgery in metastatic
breast cancer
Craniotomy should be considered for patients
with a single accessible large or symptomatic
brain metastasis.
The role of surgery for patients with multiple
brain metastases is controversial.