Is Axillary Dissection Always Indicated in Invasive Breast Cancer?
Is Axillary Dissection Always Indicated in Invasive Breast Cancer?
The article written by Chadha and Axelrod provides a timely discussion of several critical issues in the current debate over the use of axillary lymph node dissection in early-stage breast cancer. As new information and techniques become available, they and others have reassessed the value of axillary lymph node dissection in four key areas:
- local control in the axilla,
- survival benefit,
- determining the role of systemic therapy, and
- assessing prognosis.
Axillary lymph node dissection has been clearly shown to decrease the risk of recurrence in the axilla. However, nodal irradiation offers an alternative to lymph node dissection with comparable axillary control rates. Thus, given the increasing frequency of mammographically detected lesions, small primaries (less than 0.5 cm) have become more common and the likelihood of nodal involvement of these lesions is slight, making the usefulness of any axillary therapy increasingly less clear.[1-4]
A survival advantage from axillary lymph node dissection has not been established. Long-term follow-up series of node-positive patients treated with axillary lymph node dissection without systemic therapy have shown that a substantial minority survive more than 20 years, suggesting that axillary lymph node dissection might provide a small survival advantage.[5,6] The National Surgical Adjuvant Breast Project (NSABP) B-04 trial did not demonstrate an overall survival benefit with primary axillary lymph node dissection, but this trial did not have sufficient statistical power to detect a small survival advantage.
Systemic Therapy and Nodal Status
In the past, the information obtained at axillary lymph node dissection was critical to making recommendations regarding systemic therapy. However, the impact of that information has diminished substantially with the recent publication of several trials indicating that recommendations for systemic therapy may be made independent of nodal status. Based on the results of the last published overview analysis, systemic therapy is now routinely offered to patients with tumors measuring 1 cm or greater regardless of lymph node status. Results from the recent NSABP B-20 trial demonstrate a significant benefit in disease-free survival for estrogen-receptor (ER)-positive, node-negative patients who receive chemotherapy and tamoxifen (Nolvadex) vs tamoxifen alone. These determinations will further reduce the impact of information obtained at lymph node dissection on treatment decisions. Axillary lymph node dissection was previously needed to establish nodal status before enrollment in National Cancer Institutesponsored clinical trials. However, sentinel node biopsies are currently being accepted as evidence of pathologically uninvolved lymph nodes.
The prognostic information obtained from axillary lymph node dissection may offer a substantial psychological benefit to patients, even if it has no effect on management of their disease. However, in the current atmosphere of medical cost containment, one must consider the cost of axillary dissection. To date, a detailed cost-effectiveness analysis has not been performed. Without such an analysis, any comparison of the costs of axillary lymph node dissection and the costs of other methods for managing the axilla (such as third-field irradiation or sentinel node biopsy) would have no validity.
Given the available data, we agree with Drs. Chadha and Axelrod that the recommendations for management of the axilla should now be tailored to the specific clinical features and preferences of the individual patient. The various potential benefits of axillary lymph node dissection need to be considered relative to the morbidity of the procedure, which is not not insignificant. More than 40% of patients experience some degree of upper arm dysfunction at 1 year and 80% experience loss of sensation.
When considering the options available for management of the axilla, physicians must take into account the impact of information obtained at axillary lymph node dissection on recommendations for systemic therapy and the unique preferences of the individual patient. How information obtained at axillary lymph node dissection affects recommendations for systemic therapy is a complex process. It requires estimating the risk of nodal involvement, the likelihood that nodal status would alter systemic therapy recommendations, and, ultimately, the magnitude of the impact of systemic therapy on survival.
The authors suggest using several parameters identified on pathologic review of the lumpectomy specimen to estimate the risk of nodal involvement, including tumor size, lymphovascular invasion, ER status, DNA flow cytometry, and measurements of ploidy and S-phase fraction. Of these factors, however, only tumor size has been consistently reproducible as a prognostic factor.[10-12] The authors offer bone marrow aspiration as a more reliable, less invasive, and less morbid prognostic alternative to axillary lymph node dissection. However, it is worth noting that efforts to obtain prognostic information from bone marrow are still experimental. For T1a cancers, the likelihood of lymph node involvement is less than 5%,[1-4] and axillary lymph node dissection might reasonably be omitted in these patients. For T1b cancers, the likelihood of lymph node involvement is 10% to 15%.[1-4]
Treatment of T1b Breast Cancer
Would the presence of histologically positive lymph nodes in a patient with a T1b breast cancer change the recommendations for systemic therapy? The results of a recent decision analysis suggest that, for a 60-year-old woman with a 0.75-cm ER-positive tumor, axillary lymph node dissection has a negligible effect on quality-adjusted life-years. On the other hand, for a 30-year-old woman with a 0.75-cm tumor, the degree of benefit may be greater. Another question to consider is whether or not the presence of 10 or more positive lymph nodes would alter recommendations for systemic therapy. The answer to that dilemma may come when the results of trials testing high-dose therapy in patients with 10 or more positive nodes become available.
Selecting Local Therapy
An additional consideration in the use of axillary lymph node dissection is what form of local therapy should be selected. For patients treated with mastectomy, we favor a node dissection (or sentinel node biopsy where available), except for those with T1a cancers or ductal carcinoma in situ. For those receiving breast-conserving therapy, radiation can be effectively used to treat the axilla. This has traditionally been accomplished by the use of a third field, but may be feasible in selected pa-tients using tangential fields alone.
In counseling patients on the options for managing the axilla, the physician must also help the patient assess the value of prognostic information obtained at axillary lymph node dissection. Knowing nodal status and overall prognosis may be important to some patients even if this information does not change treatment. The same holds true for patients with noncancer diagnoses.[15,16] We are currently conducting a study to measure the extent to which patients value prognostic information that would not alter treatment recommendations. All of these factors must be weighed when deciding how to manage the axilla in patients with early-stage breast cancer.
1. Carter CL, Allen C, Henson DE: Relationship of tumor size, lymph node status and survival in 24,740 cases of breast cancer. Cancer 63:181-187, 1989.
2. Bradley J, Powers C, Heimann R: The risk of axillary node involvement is low in small breast cancer (abstract). Proc Am Soc Clin Oncol 16:163a, 1997.
3. Silverstein MJ, Gierson ED, Waisman JR: Axillary lymph node dissection for T1a breast carcinoma. Cancer 73: 664, 1994.
4. 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, 1997.
5. Joensuu H, Toikhanen S: Cured of breast cancer?. J Clin Oncol 13:62, 1995.
6. Quiet CA, Ferguson DJ, Weichselbaum RR, et al: Natural history of node-positive breast cancer: The curability of small cancers with a limited number of positive nodes. J Clin Oncol 14: 3105, 1996.
7. Early Breast Cancer Trialists Collaborative Group: Systemic treatment of early breast cancer by hormonal, cytotoxic, or immune therapy. Lancet 339:1-71, 1992.
8. Fisher B, Dignam J, Decillis A, et al: The worth of chemotherapy and tamoxifen over TAM alone in node-negative patients with estrogen-receptor positive invasive breast cancer (abstract). Proc Am Soc Clin Oncol 16:1a, 1997.
9. Hladiuk M, Huchcroft S, Temple W, et al: Arm function after axillary dissection for breast cancer: A pilot study to provide parameter estimates. J Surg Oncol 50:47, 1992.
10. McGuire WL: Breast cancer prognostic factors for breast cancer. Breast Cancer Res Treat 30:117, 1994.
11. Caparini G, Pozza F, Harris AL, et al: Evaluating the potential usefulness of new prognostic and predictive indicators in node-negative breast cancer patients. J Natl Cancer Inst 85:1206, 1993.
12. Clark GM: Prognostic and predictive factors, in Harris JR, Lippman M, Morrow M, et al (eds): Diseases of the Breast, pp 462-464. Philadelphia, Lippincott-Raven, 1996.
13. Parmigiani G, Winer E, Prosnitz L, et al: Decision model for assessing the benefits of axillary lymph node dissection (ALND) (abstract). Proc Am Soc Clin Oncol 16: 139a, 1997.
14. Wong JS, Recht A, Beard CJ, et al: Treatment outcome after tangential radiation therapy without axillary dissection in patients with early stage breast cancer and clinically-negative axillary nodes. Int J Radiat Oncol Biol Phys, 1997 (in press).
15. Berwick D, Weinstein M: What do patients value? Willingness to pay for ultrasound in normal pregnancy. Med Care 23:881, 1985.
16. Asch DA: Knowing for the sake of knowing: The value of prognostic information. Med Decis Making 10: 47, 1990.