In this study, we investigated the implications of preoperative non-linear upper extremity lymphatic anatomy on the incidence of breast cancer-related lymphedema. Our findings demonstrate that patients with non-linear anatomy (1) had a higher rate of prior surgery or trauma to the limb, (2) a greater number of lymph nodes removed during preoperative sentinel lymph node biopsy, and (3) an increased incidence of lymphedema following ALND and ILR.

This study suggests a possible association between prior trauma or injury to the superficial lymphatic channels correlating with a higher risk of lymphedema following oncologic breast interventions. Understanding the association between the surgical treatment for breast cancer and the development of lymphedema is critical, as one in five patients develop upper extremity lymphedema after lymph node extraction and mastectomy [1, 23]. Our Lymphatic Center, a certified Center of Excellence, invests significant focus on researching surgical and non-invasive interventions associated with reduced rates of lymphedema, thereby allowing for robust investigations into this patient population [24]. Our center has previously observed that of the breast cancer patients who had received a successful ILR procedure after ALND by the same surgeon, 9% of the cohort went on to develop post-operative lymphedema after 11 months of followup [17]. Notably, in this study’s assessment of patients specifically with non-linear anatomy, 42% of patients developed a clinical lymphedema diagnosis with an additional 25% showing signs of lymphedema. Additionally, these patients had a shorter follow-up compared to those patients in the previous study (10.5 months compared to 17 months) [17]. As lymphedema can develop in a delayed fashion, having a larger incidence in breast cancer related lymphedema with a significantly shorter follow-up is likely to underestimate the incidence of breast cancer related lymphedema in this population. This critical difference in breast cancer related lymphedema incidence suggests that preoperative non-linear anatomy may be an independent risk factor for lymphedema.

There are known risk factors for breast cancer-related lymphedema, including (1) axillary lymph node dissection, (2) regional lymph node radiation (RLNR), and (3) high BMI [23, 25,26,27]. Other debated risk factors include (1) taxane-based chemotherapy, (2) increasing age, and (3) modified radical mastectomy [28,29,30]. Our findings suggest that prior trauma or invasive procedures to the ipsilateral arm or axillary region is an important additional risk factor for the development of breast cancer-related lymphedema. Prior trauma could incite lymphatic dysfunction that can be further perturbed with direct mechanical force or manipulation during breast cancer procedures. Further research is required to investigate the coorlation of these traumas to the lymphosomes with resultant non-linear lymaphatic anatomy [19]. These results seem to suggest that the presence of non-linear lymphatic anatomy, regardless of the cause or prior trauma history, may be a risk factor for breast cancer-related lymphedema.

These conclusions align with existing literature stating that non-linear patterns represent dysfunctional lymphatic flow [15, 16]. Furthermore, Buchan et. al found that even in patients with pre-operative linear lymphatic anatomy, lymphovenous bypass during ALND may result in changes to the lymphatic anatomy in select patients’ post-operative ICG readings [31]. The authors of this article postulate that these patients may have had risk factors such as minor trauma to the limb that could have lowered the threshould to incite post operative lymphatic flow changes. This potentially supports the theory this paper presents as trauma to the limb of interest could be a risk factor for lymphatic flow disruption.

Globally, patient accessibility to a surgeon trained to perform lymphatic surgery is limited. While lymphedema has gained increasing recognition as a major issue faced by one in five breast cancer survivors, there remains a critical deficit of trained microsurgeons able to perform risk-reducing ILR to meet the needs of these patients [32,33,34]. Therefore, research focusing on non-invasive, preventative approaches for lymphedema is imperative to target breast cancer patients without access to a lymphatic surgeon or insurance coverage for ILR. Furthermore, continuing collaboration within the fields of plastic surgery, breast surgery, oncology, radiology, and physical therapy is necessary to decrease the risk of lymphedema in this patient population.

Our results suggest that prophylactic interventions may benefit patients with preoperative non-linear lymphatic anatomy, as they appear to be at high risk for lymphedema development. At our Lymphatic Center, patients presenting with non-linear lymphatic anatomy begin prophylactic compression therapy of the affected limb immediately after ALND and ILR. This protocol aims to help target and prevent lymphedema for high-risk patients. The use of compression garments immediately after ALND has been found to significantly decrease the incidence of lymphedema in breast cancer patients, though it is well documented that compression garments have detrimental effects on patient quality of life and compliance levels can vary [35,36,37]. In institutions where ICG lymphangiography or ILR may not be available, our findings suggest that patients with previous trauma to the limb or those with a large number of nodes removed in a prior SNLB may particularly benefit from early use of compression garments prophylactically. Additionally, diligent follow-up and monitoring can aid in early detection of lymphedema, allowing for earlier intervention.

This study must be interpreted in the context of several limitations. As non-linear lymphatic anatomy on pre-operative ICG lymphography is an uncommon phenomenon, the statistical analysis is underpowered. Nevertheless, our results quantitively demonstrate an association between lymphedema development and non-linear lymphatic anatomy. Our team anticipates a steady growth in the number of patients with non-linear findings, as there is an increasing volume of patients being offered ILR at our institution and greater opportunities for detection through longer follow-up.