Many clinical studies on breast cancer confirm the significance of the prophylactic irradiation of supraclavicular lymph node drainage areas. It not only reduces the local recurrence rate but also significantly improves overall survival [2,3,4]. With the development of radiotherapy technology, radiotherapy of the supraclavicular region has changed from traditional two-dimensional radiotherapy to three-dimensional conformal radiotherapy, followed by the modern intensity-modulated radiotherapy. Radiotherapy planning with CT simulation for positioning is increasingly applied in radiotherapy for breast cancer. Currently, universal guidelines for delineating supraclavicular lymph node target volumes include those of the Radiation Therapy Oncology Group (RTOG) [10], a relatively accessible reference template for delineating breast/chest wall and regional lymph node radiotherapy targets in clinical trials. Relevant retrospective clinical studies include those of Mayo Clinic and the Chinese Academy of Medical Sciences Cancer Hospital [6, 7]. This study aimed to be distinct in terms of the enrolled population, distribution of lymph nodes, and CTV delineation of supraclavicular lymph nodes in breast cancer.

We enrolled patients with breast cancer who were newly diagnosed with supraclavicular lymph node metastasis. All patients had not received local or systemic treatment at the time of enrollment. Thus, the distribution of lymph nodes truly reflected the biological behaviour of supraclavicular lymph node metastasis in breast cancer. Other studies [5,6,7, 11], including those of Mayo Clinic, the Netherlands, and the Chinese Academy of Medical Sciences Cancer Hospital, included not only patients with breast cancer and supraclavicular lymph node metastases but also some patients with supraclavicular lymph node recurrence after initial treatment, particularly axillary/supraclavicular lymph node dissection. The metastatic pattern of supraclavicular lymph nodes differ between untreated and newly treated patients, because the latter experience a disrupted lymphatic return. Therefore, we optimized the enrolled population to accurately reflect the rule of supraclavicular lymph node metastasis in breast cancer.

The lymph node metastasis rule is based on blood vessel distribution. Previous studies have characterized the general region of supraclavicular lymph node metastasis in breast cancer but have not explained the metastasis rule in depth. Jumping metastasis of lymph nodes is rare in breast cancer. The most common route of metastasis is from the axillary to the subclavicular and then supraclavicular region. Extensive axillary lymph node metastasis significantly increases the probability of lymph node metastasis in the supraclavicular region. We observed that metastatic lymph nodes were present at the back of the neck (level V) in cases of extensive axillary lymph node metastasis. Notably, this exceeded RTOG’s definition for supraclavicular metastasis [10]. The subclavian vein drains the blood flow of the transverse jugular vein. The distribution of many axillary lymph nodes along the subclavian vein will cause a portion of the lymph fluid to flow backward to the back of the neck (level V), enlarging the lymph nodes in this area. This is the anatomical basis of lateral supraclavicular lymph node metastasis. Additionally, enlarged lymph nodes were occasionally present in the venous angle region (medial supraclavicular group) when clinical data suggested significantly enlarged lymph nodes in the internal mammary region. The internal mammary vein drains to the subclavian vein, and the lymph nodes in the venous angle can be transferred along the internal mammary lymph chain. This is an anatomical basis of medial supraclavicular lymph node metastasis. Based on the data at our institution, observed clinical phenomena, and anatomical knowledge, this study proposed two courses of supraclavicular lymph node metastasis to reinterpret the rule of supraclavicular lymph node metastasis in breast cancer: distribution along the posterolateral border of the internal jugular vein (medial supraclavicular group) and distribution along the transverse cervical vessels (lateral supraclavicular group).

Based on the above mentioned rules of supraclavicular lymph node metastasis, we optimized the delineation of supraclavicular lymph node target volume in breast cancer. The superior border comprised the lower edge of the cricoid cartilage. If the metastatic axillary lymph node is extensive, then the superior border of the supraclavicular region should be moved upward appropriately. The inferior border comprised the level where the clavicular head disappeared, followed by the target volume of chest wall/breast. The medial border comprised the scalene muscle bundle and lateral border of cervical vessels (carotid artery and internal jugular vein). The lateral border comprised the medial border of the sternocleidomastoid/omohyoideus muscle and superficial layer of the deep cervical fascia. The anterior border was posterior to internal jugular vein, and the posterior border was anterior to the trapezius muscle border. According to randomized controlled trials by the European Organization for Research and Treatment of Cancer 22922 [12] and National Cancer Institute of Canada Clinical Trials Group MA.20 [13], addition of regional lymph node irradiation on the basis of whole breast irradiation reduces regional lymph node recurrence. This emphasizes the importance of adequate coverage of nodal regions. The main difference between our recommended target volume and that of the RTOG [10] is our inclusion of level V (behind the neck) to the lateral and posterior borders, which was consistent with the recommendation of the Chinese Academy of Medical Sciences Cancer Hospital [7]. If the axillary lymph node metastasis is extensive, the superior border of the supraclavicular area should be moved upward appropriately.

This study had the following limitations: first, we employed a retrospective design. Thus, selection bias may have occurred. Second, the sample size was small. Thus, it may not fully reflect the rule of lymph node metastasis in the supraclavicular region. Third, the enrolled patients were either locally advanced or metastatic breast cancer, therefore, the conclusion of the suggested improved delineation is applicable to high-risk patients, not to low or moderate risk population. Lastly, some cases of clinically significant regional lymph node metastases may not have been detected or may have been detected only after the occurrence of distant metastases. Thus, future large-scale, prospective clinical trials are needed to further guide treatment.