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Invited Commentary
Kirby I Bland, MD, FACS
Birmingham, Alabama
I congratulate Dr Rivadeneira and his associates from Cornell
and the Strang-Cornell Breast Cancer Center for bringing this
important study to the attention of the College. I reiterate
from the conclusions of this paper that univariate and multivariate
analyses have identified three factors that are independent predictors
of axillary lymph node metastases (ALNM): size, histologic grade,
and patient age. I concur with the authors that these factors
should be considered in selecting appropriate management of the
axilla for patients with T1 lesions that are < 1cm
in size.
Increased enphasis has recently been placed on a more conservative
approach to optimize both risk-benefit and cost-benefit in patients
with breast cancer. Debate will continue regarding the role of
axillary node dissection in the clinically negative axilla (cN0);
this is especially true for patients with minimal lesions <1cm
in size without palpable nodes, who are expected to have excellent
overall survival rates. As many are aware, the NSABP-BO4 trial
determined that axillary node dissection did not enhance overall
survival, although subsequent management of the axilla by surgical
procedures or irradiation was essential in approximately 17%
of the patients. Currently, the decision to treat with adjuvant
systemic therapy is principally determined on the basis of biologic
characteristics of the primary tumor: large size, high grade,
high S-phase fraction, aneuploidy, hormone receptor status, the
presence of various oncogene proteins, and, possibly cathepsin-D
levels.
The authors of this paper have noted two previous studies
completed at Brown University that include the state of Rhode
Island computerized tumor registry database inclusive of nine
hospitals within the Hospital Association of Rhode Island (HARI)
and the Tumor Registry at Bay State Medical Center (MA). In the
original analysis of almost 9,400 women with breast cancer reported
to HARI and an additional 2,637 women reported to the Bay State
Medical Center, we identified 2,185 patients with invasive breast
cancers < 1 cm, which comprised 18% of all breast cancers.
In an analysis similar to that performed in the current study,
we divided patients into groups based on age, tumor size, histologic
type, nuclear grade, and axillary lymph node status. The overall
frequency of axillary node positivity was 16% in the T1a and
T1b lesions, a frequency similar to that of the present study
(18%). In the Brown University study, 11% of T1a and 17% of T1b
lesions harbored axillary metastases (p = 0.02). Thirty-one percent
of patients under age 40 had positive nodes compared with 15%
of older patients (p = 0.001). Nuclear grade was available in
49% of the cases; grades 2 and 3 were associated with nuclear
involvement twice as often as grade 1 tumors (p = 0.002). The
influence of histologic type of tumor (ductal or lobular variants)
did not reach statistical significance in this analysis. Overall,
patients who had the absence of any poor prognostic factors had
a 7% chance or less of nodal involvement and patients with all
three poor prognostic indicators had a 34% chance of nodal involvement.
We concluded in these two studies, the second of which had more
than 2,100 patients, that selective nodal dissection may be possible
through risk factor analysis. The prospective
registration of complete histopathologic information allows a
more comprehensive analysis and may further enhance selective
treatment of patients with minimally invasive breast cancers.1
The arguments to reevaluate the necessity of axillary dissection
have been triggered principally by the rare incidences of nodal
metastasis reported in other sites for T1a and T1b lesions. Proponents
of a less aggressive approach for treatment point out that the
majority of these patients will undergo axillary dissection unnecessarily.
Rosen and coworkers at Memorial-Sloan Kettering
Cancer Center2 have previously demonstrated
a 20-year recurrence rate in invasive ductal and lobular cancers
<1cm with documented negative disease to be 12% with
a 10% mortality rate. Recurrence and mortality rates were 39%
and 35%, respectively, if positive nodes were present. The differentiation
of N0 from N1 disease, even among patients with minimally invasive
cancer, is essential for determination of prognosis and to make
future therapeutic decisions.
One study by my colleague Dr Cady and associates treating
72 patients with T1a and T1b lesions between 1980 and 1992 used
excision alone or additional radiation for control of disease.
The authors concluded that the incidence of local recurrence
and distant metastases are not affected with elimination of the
axillary dissection. In this study, regional nodal failure occurred
in 4.2% (3 of 72 patients) in median followup of 4 years; patients
receiving irradiation had a lower incidence of axillary nodal
failure (15% versus 2%; p = 0.05). This effect is perhaps because
of inclusion of the lower portion of the axilla in the irradiation
field. The pitfalls of this study are the small sample size and
limited followup.
Rosen has previously reported a similar frequency of nodal
metastasis in the T1a and T1b lesions as that of the current
study (11% versus 15%, respectively). These frequencies parallel
that of our own studies of the Rhode Island and Bay State Registry
Data. In the first analysis of these minimal
cancers at Brown, we did not perform survival outcomes because
previous authors have demonstrated a relationship between tumor
size, nodal status, and outcomes.3-7 Carter and colleagues8
have defined an independent, but additive, indication of prognosis
from tumor size and lymph node status. It is known that node
positivity predicts worse prognosis in individuals with T1a and
T1b cancers, but it was unclear in any studies as to whether
tumor size in minimally invasive cancers serves as an independent
prognostic variable for survival. Before
this Congress in 1997, we confirmed that small T-size does not
affect survival.9 In univariate analysis
age, grade, and nodal status were significant in their association
with cancer-specific survival, but these factors do not serve
as a surrogate for nodal status to establish prognosis.
The NSABP-BO4 suggests that axillary
dissection alone did not add therapeutic value regarding survival,
but the opposite conclusion has been revealed by Cabanes and
associates10 in a study of 658 patients
with clinically negative axillae. In these patients in which
the primary tumor was <3cm (T1 and T2), patients were randomized
to lumpectomy and irradiation with and without axillary dissection.
The study including that of our series11 noted a statistical enhancement in survival
and lower recurrence in those who have had axillary dissections
(levels I and II). Only patients who underwent axillary dissection
that were histologically proved to have nodal involvement received
adjuvant chemotherapy or tamoxifen. The study demonstrates that
adjuvant systemic therapy directed by pathologic node staging
may result in improved survival and decreased recurrences.
The model that has been proposed in the current study and
those presented formerly by us from Brown suggest that readily
available risk factors inclusive of size, histologic grade, and
age are of value in selection of patients for nodal dissection.
Risk stratification based on other characteristics such as presence
of growth factor receptors, S-phase fraction, ploidy, and oncogene
proteins does not have similar statistical power for use in prediction
of recurrences as those indicated above. A detailed molecular
or biochemical analysis of the primary tumor is often precluded
as a result of the small size of these minimally invasive cancers.
It is our hope that risk stratification models such as these
will be used as a template with other prognosticators to more
accurately predict nodal status. These approaches may allow ``highly
selective'' sentinel node biopsy to be performed with greater
precision for the population that is at greatest risk for metastatic
disease.
Again I congratulate the authors and am delighted to see that
this paper reinforces our previous analyses from the Rhode Island
and Massachusetts Tumor Registry databases.
References
1. Mustafa IA, Cole
B, Wanebo HJ, et al. Prognostic analysis of survival in small
breast cancers. J Am Coll Surg 1998;186:562-569.
2. Rosen PP, Groshen
S. Factors influencing survival and prognosis in early breast
carcinoma (T1NOMOT1N1MO): assessment of 644 patients with median
follow-up of 18 years. Sur Clin North Am 1990;70:937-962.
3. Rosen PP, Groshen
S, Kinne DW, Norton L. Factors influencing prognosis in node-negative
breast carcinoma: analysis of 767 T1N0M0/T2N0M0 patients with
long-term follow-up. J Clin Oncol 1993;11:2090-2100.
4. Rosen PP, Groshen S, Saigo PE, et
al. Pathological prognostic factors in stage I (T1N0M0) and stage
II (T1N1M0) breast carcinomas: a study of 644 patients with median
follow-up of 18 years. J Clin Oncol 1989;7:1239-1251.
5. Reger V, Beito G, Jolly PC. Factors
affecting the incidence of lymph node metastases in small cancers
of the breast. Am J Surg 1989;157:501-502.
6. Rosen PP, Saigo PE, Braun DW, et
al. Prognosis in stage II (T1N1M0) breast cancer. Ann Surg 1981;194:576-584.
7. Rosen PP, Saigo PE, Braun DW, et
al. Predictors of recurrence in stage I (T1N0M0) breast carcinoma.
Ann Surg 1981;193:15-25.
8. Carter CL, Allen
C, Henson DE. Relation of tumor size, lymph node status, and
survival in 24,740 breast cancer cases. Cancer 1989;63:181-187.
9. Mustafa IA, Cole
B, Wanebo HJ, et al. Prognostic analysis of survival in small
breast cancers. J Am Coll Surg 1998;186:562-569.
10. Cabanes PA,
Salamon RJ, Vilcoq JR, et al. Value of axillary dissecton in
additon to lympectomy and radiotherapy in early breast cancer.
Lancet 1992;339:1245-1248.
11. White RE,
Vezeridis MP, Konstadoulkis M, et al. Therapeutic options and
results for the management of minimally invasive carcinoma of
the breast: influence of axillary dissection for treatment of
T1a and T1b lesions. J Am Coll Surg 1996;183:575-582.
Introduction
| Methods
| Results
| Discussion
| References
Invited Commentary | Reply
JACS |
