Role of Nodal
Irradiation in Breast
Cancer
Carol Marquez, M.D.
Associate Professor,
Department of Radiation Medicine
OHSU
Goals of discussion
Review of randomized literature
 Present factors associated with axillary
node involvement
 Discuss changing role of radiation in era of
sentinel lymph node biopsy (SLNB)
 Give guidelines for inclusion of nodal fields
 Explore techniques for treatment
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Review of nodal anatomy
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The primary drainage of
the breast is to the axilla,
regardless of location of
primary tumor.
Very few tumors will have
primary drainage to
internal mammary nodes.
For patients with involved
axillary nodes, risk of IMN
involvement increases,
especially with tumor in
medial location.
NSABP B-04: Randomized
management of the axilla
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Axilla treated by either
surgery, XRT or observation
in clinically negative nodes;
in clinically positive nodes,
treatment either by surgery
or XRT.
In clinically negative axilla,
40% of patients were found
to have nodal involvement
while only 18% of the TM
patients developed a clinical
axillary failure.
NSABP B-04: Results
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XRT achieved similar local control as surgery in
clinically negative axilla while it was inferior to
surgery in clinically positive axilla.
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35% of the patients randomized to the total
mastectomy arm had limited axillary dissection.
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Patients who had 6 or more nodes removed did
not have axillary recurrence.
No difference in survival with respect to
treatment in either arm.
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NSABP B-04: Late effects
Those patients treated with radical
mastectomy had almost double the risk of
lymphedema than those treated with
radiation therapy or total mastectomy.
 Increased risk of secondary lung cancers
in patients on this trial compared to those
on NSABP B-06 where nodal irradiation
was not performed.
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Incidence of lung cancer: NSABP
B04
Other randomized data: French trial
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Randomized 658 pts with clinically negative
nodes to axillary dissection (AXD) or axillary
radiation. Enrollment from 1982-87.
Fifteen year followup showed slight increase in
axillary recurrence with XRT (3% vs. 1%).
No difference in overall survival or disease free
survival.
JCO 22:97-101, 2004
What has changed since 1987?
The use of adjuvant chemotherapy
increased so the purpose of axillary
dissection shifted from therapeutic to
prognostic.
 Sentinel lymph node biopsy has largely
replaced AXD as the method of nodal
evaluation.
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What factors predict for axillary
involvement?
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Size: Any size tumor can have + nodes. Reports
show an 11% risk of + nodes in T1a tumors,
rising to 15-20% in T1b.
Age: A variety of cutoffs but the younger the
patient, the greater the chance of + nodes.
LVSI: Risk rises to 50-60% in its presence and
decreases to 15-25% without it.
Histology: Ductal and lobular appear equal
while tubular and medullary appear to have
lower risks.
Impact of sentinel lymph node
biopsy (SLNB)
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Evaluation of nodes
became “easier”, less
morbidity to patients and
less extensive surgery.
More extensive
pathologic evaluation of
nodes.
Able to get nodal
information prior to more
extensive breast surgery
(as in neoadjuvant
setting).
What has SLNB taught us? Data
from NSABP B-32
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In 61% of patients, the + sentinel node is the only +
node; therefore, even without the completion dissection,
the procedure is therapeutic in 60% of patients.
Risk of + non-sentinel node is increased by size of tumor
and presence of LVSI.
Risk of + non-sentinel node is decreased by increased
number of nodes removed (>4).
Morbidity is low and there is a learning curve that each
surgeon (institution) needs to go through.
Do not yet have results from American College of
Surgeons randomized trial of completion AXD to none.
Special type= colloid,
medullary or tubular
Doctor, What are my
chances of having a
positive sentinel node? A
Validated Nomogram for
Risk Estimation.
Bevilacqua JLB et al.
JCO 25:3670-3679, 2007.
Micromets: What to do?
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Extensive pathologic
evaluation of sentinel
node(s) has allowed for
new categories of positive
nodes.
Makes reliance on older
data difficult since these
categories did not exist.
Nomograms for predicting nonsentinel lymph node involvement
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Helpful in deciding who needs completion AXD.
Rely on information that is only available after
final pathology is complete.
Memorial-Sloan Kettering:
http://www.mskcc.org/mskcc/html/15938.cfm
Stanford: http://wwwstat.stanford.edu/~olshen/NSLNcalculator
Where does all this information
leave us?
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In the era of SLNB, most patients should have nodes
evaluated.
Purpose of nodal evaluation and removal is still both
prognostic and therapeutic.
If the patient cannot have AXD or SLNB, XRT will
provide adequate local control in the clinically negative
axilla.
The hard question: Who needs the supraclavicular
nodes radiated when the completion AXD is not done?
Who needs the supraclavicular fossa treated
if the completion AXD is not performed?
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Two retrospective reviews looking for factors predicting 4
or more nodes involved at completion dissection.
MDACC found that any patient with only 1 positive node
and no LVSI should be treated to the axilla only via
modified tangents. (IJROBP 59:1074-79, 2004)
MGH found that any patient with a micromet (<2 mm), 1
positive node, and no LVSI did not require treatment to
the supraclavicular fossa. (IJROBP 65:40-44, 2006)
Who needs the supraclavicular fossa
treated when the AXD is performed?
Any patient with 4 or more positive nodes.
 The controversial group (again) is 1-3
positive nodes in either the post
mastectomy or post lumpectomy setting.
 NCIC MA20, a trial randomizing pts with 13 positive nodes to breast or breast +
regional radiation, has closed to accrual so
results will not be available for years.
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Nodal ratios: Prognostic value for
local recurrence and survival
Nodal ratio (NR)= # of positive nodes/ # of
removed nodes.
 Allows for comparison of data across
institutions/groups where extent of surgical
dissection and pathologic evaluation of
axilla may vary.
 Generally accepted cutoff of <25%, 25<75%, >75%.
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Canadian review of nodal ratios in
T1-2 tumors with 1-3 + nodes
Cancer 103:2006-14, 2005
Use of NR to determine who will
benefit from regional XRT
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Retrospective review of 1255 node + pts with a
median of 14 nodes removed after either
lumpectomy or mastectomy.
Since retrospective, fields of XRT varied based
on discretion of physician. Chemotherapy only
used in 37%.
Found that regional XRT provided improvement
in overall and cause specific survival in pts with
medium and high nodal ratios, not for the low
nodal ratio group. (IJROBP 68:662-666, 2007)
Techniques for nodal irradiation
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“Modified” tangents to
include axilla: requires
both a raising of superior
border and expanding
posterior border.
Supraclavicular fossa:
important to do CT
planning to choose
appropriate depth for
coverage of nodes.
What do I do? No axillary surgery
If no axillary surgery, I would include axilla
in tangents if probability of nodal
involvement is above 10%.
 I would include supraclavicular fossa if
patient’s condition could tolerate fibrosis of
lung in that field.
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What do I do? SLNB but no AXD
If only 1 + node and no LVSI (especially if
>4 nodes removed in SLNB), I include the
axilla in the tangents.
 If more than 1 node and/ or LVSI, I would
include suprclavicular fossa.
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What do I do? SLNB + AXD
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If 1 + node, no regional XRT.
If >4 + nodes, XRT to axilla and supraclav.
If >4+ nodes and upper inner quadrant, XRT to
axilla, supraclav and IMN.
If 2-3 nodes positive and NR>25%, XRT to axilla
and supraclav.
Multiple nodes with micromets seems like real
cancer to me.