The article by Manjeet Chadha and Deborah Axelrod on routine axillary
dissection in invasive breast cancer (11: 1463-1468, 1997) is a
well-presented discussion of a timely subject. The authors make a
good case that nodal disease (pN+) is no longer the sole prognostic
indicator for adjuvant systemic therapy. They present data showing
that axillary radiation, delivered at the time of breast radiation,
achieves similar local control rates with much less cost and
morbidity. In selected cases with a low probability of pN+, watchful
waiting may be appropriate and pose no significant risk to the the
patients overall survival.
I would like to comment on other issues that the authors and
reviewers did not discuss. These are:
Axillary node sampling error;
False pathologically negative axillary nodes (pN0); and
The systemic benefits of nodal radiation, which is deterred by
One of the foundations of cancer management is the search for and
treatment of nodal metastases. Fisher delineated the diagnostic role
of nodal disease in breast cancer, while Halsted highlighted its
therapeutic significance. The importance of nodal disease was
similarly defined for all other solid tumors.
Over the years, the relevance of nodal spread has not changed, but
the role of surgical treatment of the nodes has declined. Also,
routine surgical staging has been eliminated as a separate diagnostic
procedure--except in breast cancer. In many cases, including some
breast cancers, neoadjuvant therapy is undertaken prior to surgery.
Sampling Errors and False-Negative Rates
The number of nodes removed at axillary dissection has varied.
Intergroup trials do not require a full axillary dissection and set a
criterion of six nodes for evaluation. However, inadequate axillary
dissection has a 10% to 45% sampling false pN0 rate. A sampling
level I axillary dissection, including sentinel node biopsy, does not
evaluate all of the first-echelon nodes. These include level II,
interpectoral, and internal mammary nodes. The rate of internal
mammary nodal metastases ranges from 11% to 43%, depending on the
size and location of the primary and status of the axillary nodes.
Studies using immunochemical stains indicate the high incidence of
occult metastases in nodes previously classified as pN0 after routine
hematoxylin and eosin staining. The false pN0 rate ranges from 15% to
25%, with several papers reporting a false-negative rate as high as
30%. Sampling and pathologic false pN0 rates are of concern both
for prognostic reasons in individual patients and in an academic
discussion of data and results. The uncertainties also apply to pN+
when stratification and therapy are based on the number of involved nodes.
Systemic Benefits of Nodal Radiation
The authors discuss local control of subclinical nodal disease with
radiation, which yields results similar to those of axillary
dissection. Radiation controls disease in the axilla, including the
apex and infraclavicular and supraclavicular regions. When indicated,
the internal mammary nodes can be included in the radiation field.
The systemic benefits of nodal radiation have been documented in the
past and have been confirmed recently.[3-5] Randomized and
nonrandomized series report a significant improvement in distant
disease-free survival afforded by nodal treatment with or without
adjuvant systemic therapy. The reduction in the rate of systemic
recurrence ranges from 20% to 30% at 10 to 15 years, and is
irrespective of the number of nodes involved.
In patients with clinical stage I and II disease who are treated with
nodal radiation but without axillary dissection, the disease-free
survival rate is 80% at 10 years. The 10-year systemic recurrence
rate of 20% in the Yale series is better than would appear at first
glance. One expects a 20% to 30% risk of pN+ disease in clinical T1
N0 M0 disease and a risk of 30% to 40% in T2 N0 M0 disease. These
assumptions would predict a recurrence rate of 25% to 30% for the
series. Inclusion of these patients at high risk for metastases
suggests a systemic benefit of nodal radiation in patients with
clinically negative axillary nodes.
For patients with tumors > 2 cm (clinical T2-3 N0 M0), the tumor's
virulence and metastatic potential are evident without further
invasive or noninvasive tests. These patients would be better served
with treatment to the local, regional, and systemic components of the
disease. For patients with T1 N0 M0 tumors, such information as tumor
size, grade, receptor status, and results of other noninvasive tests
may help separate the two extremes for which axillary dissection will
not affect decisions about adjuvant therapy.
In the subset of patients in whom axillary dissection will define
adjuvant therapy, sentinel node biopsy should definitely be
performed. For metastases, nodal radiation would be therapeutic,
together with systemic therapy. Axillary dissection is recommended
for patients with palpable axillary disease.
1. Moffat F, Senofsky G, et al: Axillary node dissection for early
breast cancer: Some is good, but all is better. J Surg Oncol 5:8-13, 1992.
2. Dowlatshahi K, Fan M, Snider HC, et al: Lymph node micrometastases
from breast carcinoma: Reviewing the dilemma. Cancer 80:1188-1197, 1997.
3. Overgaard M, Hansen SP, Overgaard J, et al: Postoperative
radiotherapy in high-risk premenopausal women with breast cancer who
receive adjuvant chemotherapy. N Engl J Med 337:949-955, 1997.
4. Ragaz J, Jackson SM, Le N, et al: Adjuvant radiotherapy and
chemotherapy in node-positive premenopausal women with breast cancer.
N Engl J Med 337(14):956-962, 1997.
5. Haffty BG, Ward B, Pathare P, et al: Reappraisal of the role of
axillary lymph node dissection in the conservative treatment of
breast cancer. J Clin Oncol 15:691-700, 1997.