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Patient Selection for Internal Mammary Node Irradiation: Lymphoscintigraphy Can Help

Publication: Journal of Clinical Oncology

To the Editor:

Thorsen et al1 reported long-term outcomes from the Danish Breast Cancer Group Internal Mammary Node study cohort. This prospective nationwide cohort study allocated 3,089 women with node-positive early breast cancer to adjuvant radiotherapy with or without internal mammary node irradiation (IMNI) depending on cancer laterality. Patients with right-sided cancer received IMNI while patients with left-sided cancer were treated without IMNI to avoid risk of radiation-induced heart disease. Overall survival was significantly better in patients receiving IMNI. The 15-year overall survival rates were 60.1% with IMNI versus 55.4% without IMNI (adjusted hazard ratio [HR] for death 0.86; P = .007).1 Patients with tumor in outer quadrants and only 1-to-3 positive axillary nodes seemed to have a lower absolute benefit from IMNI, but this analysis was exploratory.1 In a small randomized trial, that also included only node-positive patients (n = 735), the 7-year disease-free survival was 85.3% with IMNI versus 81.9% without (HR, 0.80; P = .22).2 However, subgroup analysis showed greater benefit among patients with mediocentrally located tumors, with a 7-year disease-free survival rate of 91.8% with IMNI versus 81.6% without (HR, 0.42; P = .008).2
As Thorsen et al1 stated, there might be a risk of overtreatment if IMNI is applied to all patients with node-positive disease—better tools for patient selection to IMNI are clearly needed. Indeed, IMNI carries a small risk of pulmonary and late cardiac toxicity,3 and breast cancer patients are usually exposed to additional potentially cardiotoxic agents.4 There is currently substantial national and international variability regarding criteria for IMNI.5 A better selection is needed so that the benefit from IMNI would outweigh potential toxicity, including in patients with left-sided breast cancer. Selection on the basis of medial/central versus lateral tumor location is suboptimal as it does not consider the actual specific drainage pattern of the tumor in a given patient.6 When lymphoscintigraphy is performed for axillary sentinel node (SN) biopsy and the radiotracer is injected peritumorally, lymphoscintigraphy not only identifies axillary SNs but also depicts drainage to the internal mammary (IM) basin, present in about 20% of patients.6,7 The probability of lymphatic flow toward the IM basin is approximately 10% for tumors of the upper outer quadrant and 30% for all other sites. Thus, contrarily to a common belief, the probability of IM drainage for tumors of the lower outer quadrant is as high as for tumors in medial or central breast.6,7 Importantly, an analysis of studies with IM node biopsy showed that when patients have IM drainage and a positive axillary SN, the risk of concomitant IM invasion exceeds 40% (75 of 183 patients).8 Thus, the presence of IM drainage in patients with SN-positive axilla should be sufficient to offer IMNI. In addition, the absence of IM drainage would allow avoiding IMNI in 80% of axillary node-positive patients.8
Relying on lymphoscintigraphy to decide on IMNI would require some standardization of the technical aspects, including peritumoral injection—most authors used 99mTc-Nanocoll (technetium-99m-albumin colloid) in a small tracer volume, to reflect physiological drainage, with peritumoral injection in breast parenchyma at the same depth as the tumor.8 This standardization can be easily done through collaboration between radiation oncologists and nuclear physicians. Lymphoscintigraphy performed with peritumoral injection offers all necessary information needed by the breast surgeon for axillary SN identification while also providing information on IM drainage that would be later helpful to the radiation oncologist for decisions regarding IM radiation.7,8 In total, lymphoscintigraphy can identify among node-positive patients, those 20% with IM drainage, who are at greatest risk of concomitant IM invasion, while allowing to avoid IMNI in the others.

Authors' Disclosures of Potential Conflicts of Interest

Patient Selection for Internal Mammary Node Irradiation: Lymphoscintigraphy Can Help

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to or
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No potential conflicts of interest were reported.


Thorsen LBJ, Overgaard J, Matthiessen LW, et al: Internal mammary node irradiation in patients with node-positive early breast cancer: Fifteen-year results from the Danish Breast Cancer Group Internal Mammary Node study. J Clin Oncol 10.1200/JCO.22.00044 [epub ahead of print on April 8, 2022]
Kim YB, Byun HK, Kim DY, et al: Effect of elective internal mammary node irradiation on disease-free survival in women with node-positive breast cancer: A randomized phase 3 clinical trial. JAMA Oncol 8:96-105, 2022
Poortmans PM, Struikmans H, De Brouwer P, et al: Side effects 15 years after lymph node irradiation in breast cancer: Randomized EORTC trial 22922/10925. J Natl Cancer Inst 113:1360-1368, 2021
Greenlee H, Iribarren C, Rana JS, et al: Risk of cardiovascular disease in women with and without breast cancer: The Pathways Heart Study. J Clin Oncol 40:1647-1658, 2022
Duane FK, McGale P, Teoh S, et al: International variation in criteria for internal mammary chain radiotherapy. Clin Oncol (R Coll Radiol) 31:453-461, 2019
Byrd DR, Dunnwald LK, Mankoff DA, et al: Internal mammary lymph node drainage patterns in patients with breast cancer documented by breast lymphoscintigraphy. Ann Surg Oncol 8:234-240, 2001
Hindié E, Groheux D, Brenot-Rossi I, et al: The sentinel node procedure in breast cancer: Nuclear medicine as the starting point. J Nucl Med 52:405-414, 2011
Hindié E, Groheux D, Hennequin C, et al: Lymphoscintigraphy can select breast cancer patients for internal mammary chain radiotherapy. Int J Radiat Oncol Biol Phys 83:1081-1088, 2012

Information & Authors


Published In

Journal of Clinical Oncology
Pages: 3669 - 3670
PubMed: 35786962


Published online: July 05, 2022
Published in print: November 01, 2022


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Elif Hindié, MD, PhD, Department of Nuclear Medicine, Bordeaux University Hospital, Bordeaux, France; and David Groheux, MD, PhD, Department of Nuclear Medicine, Saint-Louis Hospital, Paris, France
David Groheux, MD, PhD
Elif Hindié, MD, PhD, Department of Nuclear Medicine, Bordeaux University Hospital, Bordeaux, France; and David Groheux, MD, PhD, Department of Nuclear Medicine, Saint-Louis Hospital, Paris, France


Corresponding author: Elif Hindié, MD, PhD, Service de Médecine Nucléaire, Hôpital Haut-Lévêque—CHU Bordeaux, Ave Magellan, 33604 Pessac, France; e-mail: [email protected].

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Journal of Clinical Oncology 2022 40:31, 3669-3670

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