Clinical Investigations
Factors associated with regional nodal failure in patients with early stage breast cancer with 0–3 positive axillary nodes following tangential irradiation alone

Presented in part at the Fortieth Annual Meeting of the American Society of Therapeutic Radiology and Oncology.
https://doi.org/10.1016/S0360-3016(99)00334-XGet rights and content

Abstract

Purpose: Recent randomized trials have suggested that improved local-regional control after radiation therapy significantly increases survival for breast cancer patients with positive axillary nodes treated with adjuvant systemic therapy 1, 2. It has been our policy to use a third radiation field only in patients with 4 or more positive nodes. The purpose of this study was to assess whether there are any clinical or pathologic factors associated with an increased risk of regional nodal failure (RNF) in patients with 0–3 positive nodes treated with tangential radiotherapy (RT) alone with or without systemic therapy.

Methods and Materials: We retrospectively analyzed the incidence of RNF for 691 patients with clinical Stage I or II invasive breast cancer treated with complete gross excision of the primary tumor and tangential RT alone between 1978–87; 12% also received systemic therapy. All had 0–3 positive nodes on axillary dissection that had histologic examination of ≥ 6 nodes, and all had potential 8-year follow-up. The median number of axillary nodes removed was 11 (range 6–36). RNF was defined as any recurrence in ipsilateral axillary, internal mammary, supraclavicular, or infraclavicular nodes in the absence of recurrence in the breast, with or without simultaneous distant metastasis. Crude rates for first sites of failure within the first 8 years after treatment were calculated. A polychotomous logistic regression was used to identify factors prognostic for RNF and other sites of first failure.

Results: Within 8 years, RNF was the first site of failure for 27 patients for a crude 8-year rate of 3.9%. Isolated axillary failure occurred in 8 patients (1.2%). Isolated supraclavicular and/or infraclavicular failure occurred in 5 (1.3%) and 3 (0.4%) patients, respectively. Isolated internal mammary node failure occurred in 2 patients (0.3%). A polychotomous logistic regression model of first site of failure (local failure, regional nodal, distant/opposite breast, dead without recurrence, no evidence of disease) within 8 years found age <50 years, moderate or marked necrosis, size greater than 1 cm, and presence of an extensive intraductal component (EIC) to be significantly correlated with site of first failure, but only the last two were associated with a significantly larger relative risk of RNF versus being no evidence of disease at 8 years. The incidence of RNF was 0.7% for patients with tumors ≤ 1 cm compared to 5.7% among patients with larger tumors. Among patients with EIC-positive tumors the incidence of RNF was 7.6% compared to 3.1% among those whose tumors were EIC-negative.

Conclusions: Although the incidence of RNF has been shown to be somewhat higher in patients with tumors measuring greater than 1 cm and those with an EIC, RNF is uncommon among all subsets of patients with negative or 1–3 positive lymph nodes treated with conservative surgery, axillary dissection, and only tangential RT fields. Therefore, giving only tangential RT (without a separate nodal field) appears generally acceptable for patients with 0–3 positive nodes.

Introduction

The optimal treatment of regional nodes in the setting of breast-conserving surgery and radiation after early stage breast cancer is unknown. Recent randomized trials have suggested that for patients treated with adjuvant systemic therapy, the addition of postmastectomy radiation substantially reduces the risk of regional nodal failure (RNF) 1, 2, 3. However, in the larger Danish trials, the extent of axillary dissection was more limited than commonly used in the United States. As a result, a median of 7 nodes were removed, and a substantial rate of axillary recurrence was seen in the unirradiated patients. Therefore, it is unclear if regional nodal irradiation in patients who have undergone an adequate axillary dissection with negative or 1–3 involved nodes would have a substantial impact on the risk of RNF. Moreover, the benefits of regional nodal irradiation must be balanced against the potential toxicities of such treatment, which include increased risks of radiation pneumonitis (4), brachial plexopathy (5), arm edema (6), long-term cardiac toxicity 7, 8, match line fibrosis (9), and second tumors 10, 11.

Until now, it has been our policy to recommend regional nodal irradiation only to patients with four or more positive nodes because of these concerns regarding toxicities. However, given the results of the randomized studies of postmastectomy radiotherapy, we decided that this question needed to be readdressed. The purpose of this study was to determine the risk of RNF in patients with 0–3 positive axillary lymph nodes treated with breast-conserving surgery, axillary dissection, and tangential radiation fields without nodal irradiation and with or without systemic therapy. We also examined whether particular clinical or pathologic factors were associated with an increased risk of RNF following such treatment.

Section snippets

Methods and materials

From July 1968 to December 1987, 2140 patients without a history of a prior malignancy (except nonmelanoma skin cancer or in situ carcinoma of the cervix) were treated at the Joint Center for Radiation Therapy (JCRT) for Stage I or II invasive breast carcinoma. Patients who presented with synchronous bilateral primary tumors or who had had prior cancer in the opposite breast were excluded from this group. For patients later developing a contralateral tumor, only the first side treated was

Results

By 8 years of follow-up, 86 patients (13%) had a local recurrence as the site of first failure, 123 (18%) had a distant or opposite breast recurrence, 34 (5%) died without recurrence, and 421 (61%) had no evidence of disease (Table 1). RNF was the first site of failure within 8 years for 27 patients (3.9%, exact Poisson 95% confidence interval of 2.65% to 5.5%) (Table 1).

Eight of the 27 patients with RNFs had simultaneous distant metastases and 19 did not (Table 3). Of the 19 patients who

Discussion

This study reports the 8-year crude incidence of regional nodal failure among patients with early stage breast cancer and 0–3 involved axillary nodes treated with breast-conserving surgery, axillary dissection, and tangential radiation without nodal irradiation. In our total cohort, the incidence of regional nodal failure for each specific regional nodal site was 2% or less. The internal mammary nodes were a less common site of failure than the axilla or supraclavicular/infraclavicular fossa

References (21)

There are more references available in the full text version of this article.

Cited by (87)

  • Breast Cancer: Stages I-II

    2015, Clinical Radiation Oncology
  • Radiotherapy After Mastectomy

    2013, Surgical Oncology Clinics of North America
View all citing articles on Scopus
1

Dr. Galper is the recipient of a Health Services Research Fellowship from the Agency for Health Care Policy and Research.

View full text