International Journal of Radiation Oncology*Biology*Physics
Clinical InvestigationsShould internal mammary lymph nodes in breast cancer be a target for the radiation oncologist?
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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