Clinical Investigations
Should internal mammary lymph nodes in breast cancer be a target for the radiation oncologist?

https://doi.org/10.1016/S0360-3016(99)00481-2Get rights and content

Abstract

Purpose: The elective treatment of internal mammary lymph nodes (IMNs) in breast cancer is controversial. Previous randomized trials have not shown a benefit to the extended radical mastectomy or elective IMN irradiation overall, but a survival benefit has been suggested by some for subgroups of patients with medial tumors and positive axillary lymph nodes. The advent of effective systemic chemotherapy and potential for serious cardiac morbidity have also been factors leading to the decreased use of IMN irradiation during the past decade. The recent publishing of positive trials testing postmastectomy radiation that had included regional IMN irradiation has renewed interest in their elective treatment. The purpose of this study is to critically review historical and new data regarding IMNs in breast cancer.

Methods and Materials: The historical incidence of occult IMN positivity in operable breast cancer is reviewed, and the new information provided by sentinel lymph node studies also discussed. The results of published randomized prospective trials testing the value of elective IMN dissection and/or radiation are analyzed. The data regarding patterns of failure following elective IMN treatment is studied to determine its impact on local-regional control, distant metastases, and survival. A conclusion is drawn regarding the merits of elective IMN treatment based on this review of the literature.

Results: Although controversial, the existing data from prospective, randomized trials of IMN treatment do not seem to support their elective dissection or irradiation. While it has not been shown to contribute to a survival benefit, the IMN irradiation increases the risk of cardiac toxicity that has effaced the value of radiation of the chest wall in reducing breast cancer deaths in previous randomized studies and meta-analyses. Sentinel lymph node mapping provides an opportunity to further evaluate the IMN chain in early stage breast cancer. Biopsy of “hot” nodes may be considered in the future to select patients who are most likely to benefit from additional regional therapy to these nodes.

Conclusions: Irradiation of the IMN chain in conjunction with the chest wall and supraclavicular region should be considered only for those with pathologically proven IMNs with the goal of improving tumor regional control.

Introduction

The ability of breast cancer to metastasize to the internal mammary lymph node chain has long been recognized as a pattern of spread by early breast cancer surgeons. In an earlier era driven by Halsteadian principles, more aggressive regional treatment of this lymph node chain by surgery with or without radiation was tested. However, surgical oncologists abandoned the extended radical mastectomy when randomized clinical trials failed to show a significant survival benefit 1, 2. The advent of effective adjuvant systemic therapy, and the increasing acceptance of the potential systemic nature of operable breast cancer, also led to changes in the surgical treatment of breast cancer. In this environment, radiation oncologists placed less emphasis on regional node irradiation and focused more on treatment of the intact breast or chest wall after mastectomy. However, elective irradiation of the internal mammary chain was championed by some based on subgroup analyses of larger negative randomized clinical trials, retrospective series, or physician bias. Recently, there has been resurgence in the call for a return to routine elective IMN treatment primarily in postmastectomy patients 3, 4. This is due in no small part to the recent publication of positive trials of postmastectomy radiation that had included internal mammary radiation 5, 6, 7.

The purpose of this study is to critically review both historical and new evidence concerning the incidence of IMN metastases, and the results of treatment of this region from randomized clinical trials. The risk of decreased survival from cardiac complications after IMN treatment will also be discussed. The merits of their elective irradiation in today’s patients with operable breast cancer incorporating modern surgery and adjuvant systemic therapies will be discussed.

Section snippets

Incidence of positive internal mammary lymph nodes in operable breast cancer

The data commonly cited on the incidence of positive internal mammary lymph nodes in operable breast cancer are derived from series of patients treated by extended radical mastectomy (Table 1). The highest incidence of positive IMNs is in the first or second intercostal space, followed in frequency by the third, fourth, and fifth spaces 8, 9, 10. The incidence of positive IMNs is strongly associated with the pathologic status of the axilla 8, 9, 11, 12, 13, 14, 15. In these series, the risk of

Clinical incidence of internal mammary node recurrence

The clinical recurrence rate in an undissected internal mammary lymph node chain is rare with or without prophylactic radiation. In the NSABP B-04, the clinical failure rate in the undissected axilla after total mastectomy was only one-half that of the predicted rate of axillary node positivity (26). An even greater discrepancy between predicted involvement and subsequent clinical failure is observed with the IMN chain. Axillary node positive patients have rates of IMN positivity of 30% or

Results of treatment of positive internal mammary lymph nodes

The results of treatment of positive internal mammary lymph nodes by extended radical mastectomy are shown in Table 2. The results in these series were obtained by loco-regional treatment alone, with many including postoperative regional irradiation for positive nodes, but without adjuvant systemic therapy. The 10-year overall survival of patients with positive internal mammary nodes and negative axillary nodes ranges from 0–62%. In many of these series, this prognosis was similar to that of

Results of treatment of clinically negative internal mammary nodes

A single randomized trial reported by Kaae and Johansen (37) compared extended radical mastectomy to simple mastectomy and comprehensive irradiation. The study consisted of 668 patients with clinically negative IMNs treated between 1951 and 1957. There were no observed differences in the 5, 10, or 15-year crude rates of overall or recurrence-free survival. The 10-year rate of local-regional recurrence was slightly lower after radiation in the subgroup of operable clinical stage II and III

Cardiac mortality after internal mammary node irradiation

Two meta-analyses of randomized trials of postmastectomy radiation, most including IMN irradiation, showed a significant increase in non-breast cancer mortality in irradiated patients. Cuzick et al. (48) reported data on causes of death from 9 early trials of postmastectomy radiation in women surviving at least 10 years from trial entry. The cardiac-related causes of death were significantly increased in patients randomized to receive radiotherapy (p <0.001). The Early Breast Cancer Trialists’

Discussion

The renewed interest among radiation oncologists for the prophylactic treatment of the internal mammary lymph node chain is in large measure from the success of comprehensive postmastectomy radiation in recently reported large prospective randomized trials 5, 6, 7. The recent observations in patients undergoing sentinel lymph node mapping, where drainage can be localized to the IMN chain, has also revived interest in their treatment. This review does not seek to diminish the strongly positive

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