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
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 axillary dissection.
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.
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.
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