Breast cancer is the most commonly diagnosed cancer worldwide, with an estimated 2.3 million new cases and 685 000 deaths in 2020, representing a significant global health burden. Advances in surgical management have shifted treatment from radical mastectomy to more conservative approaches, such as breast-conserving surgery and sentinel lymph node biopsy, especially for early-stage, node-negative disease.1 However, axillary lymph node dissection (ALND) remains essential for patients with advanced-stage or node-positive breast cancer to accurately assess disease extent and guide therapy.2

Despite its clinical value, ALND is associated with several complications, including seroma, lymphedema, shoulder dysfunction, and sensory disturbances. One key contributor to postoperative morbidity is injury to the intercostobrachial nerve (ICBN), which can result in chronic pain, paresthesia, and numbness in the axilla and upper arm (Figure 1).3 Recent large studies and meta-analyses indicate that preserving the ICBN during ALND significantly reduces the incidence of sensory disturbances and postoperative pain, thereby improving patient quality of life.4

Early breast cancer encompasses stages I and II, which are characterized by small tumors (T0–T2) with limited or no spread to the lymph nodes (N0–N1), as well as large operable breast cancers (T3N0). Locally advanced breast cancer (LABC) includes stage IIIA–C and refers to tumors that are larger and have spread to the regional lymph nodes, without distant metastasis. LABC includes a heterogeneous group of tumors, usually larger than 5 cm, involving the skin, along with regional nodal metastasis (axillary, supraclavicular, infraclavicular, and internal mammary nodes).6 Inflammatory carcinoma is also included in this stage. Stage IV is classified as metastatic breast cancer. Early-stage breast cancer can be managed through the standard approach, which involves surgery followed by additional treatment. However, in certain cases of early breast cancer with aggressive characteristics, as well as in large operable breast cancers, neoadjuvant chemotherapy (NACT) may be preferred to enable breast conservation. NACT is also considered a standard treatment procedure for patients with LABC.7

Advancements in molecular biology have led to the molecular classification of breast cancer, aiding in decision-making for systemic therapy and prognosis. The 4 main molecular subtypes are luminal A, luminal B, ERBB2 (formerly HER2) overexpression, and basal-like triple-negative breast cancer (TNBC).8 The molecular subtypes of breast cancer provide valuable information for determining treatment options and predicting prognosis. Estrogen receptor (ER)/progesterone receptor (PR)–positive tumors are generally considered to have favorable biology, whereas ERBB2-positive and TNBC tumors are considered to have more aggressive biology. According to the Nottingham Modification of the Bloom-Richardson grading system (Figure 2), the histological grade of the tumor is determined by evaluating 3 key morphological features: tumor differentiation (extent of tubule formation), nuclear pleomorphism, and proliferative activity (mitotic count).9

NACT is the standard treatment for LABC.10 It is used for the management of early-stage cancer and is also preferred for large operable cases where breast conservation is desired. It has the potential to eliminate micro metastatic disease effectively. Moreover, it aids in determining systemic therapy associated with the residual disease.11 ALND has traditionally been recommended for patients with positive lymph nodes, particularly those with 3 or more involved nodes or larger tumors (T3).6 However, recent studies such as ACOSOG Z0011 have shown that ALND may not be necessary in all cases of lymph node positivity. For selected patients undergoing breast-conserving surgery with limited nodal involvement treated with radiation therapy and systemic therapy, sentinel lymph node biopsy alone may suffice.12 This shift reflects a growing emphasis on minimizing surgical morbidity without compromising oncological outcomes.

The objective of this study is to compare postoperative clinical outcomes, specifically pain, paresthesia, and anesthesia, in patients undergoing ALND with and without ICBN preservation and to document anatomical differences of the ICBN in the study population. The preservation of ICBN is not standard practice during axillary dissection. We hypothesized that the incidence of pain, paresthesia, and anesthesia of the ipsilateral arm would be significantly lower with ICBN preservation. Because preservation of ICBN and its clinical outcomes have not been studied widely, the aim of the present research is to investigate ICBN preservation and postoperative clinical outcomes.

A total of 147 patients were enrolled in the study.

In a study reviewing 30 observational studies involving 19 813 patients,15 it was concluded that ALND is related to a 21% high risk for persistent postsurgical pain (PPSP). There is evidence that the preservation of ICBN minimizes the incidence of PPSP associated with axillary clearance.

A single-center, small-scale randomized controlled study involving 309 patients16 assessed the effect of ICBN preservation vs sacrifice during breast cancer surgery. The findings indicated that division of the ICBN was associated with a higher risk of postoperative sensory deficits. Additionally, nerve preservation was found to increase operative time by approximately 5 minutes. In a similar context, Taira et al17 reported that preserving the ICBN significantly reduced the area of hypoesthesia over time when compared with nerve division, although it did not have a significant effect on health-related quality of life. Similarly, a meta-analysis by Warrier et al.18 confirmed that ICBN preservation decreases sensory disturbances such as hypoesthesia and anesthesia, reinforcing its clinical relevance.

If the entirety of the observed effect of axillary dissection on PPSP is attributable to the lack of ICBN preservation, the potential absolute reduction in PPSP rates would be substantial. Additionally, nerve-sparing techniques do not require specialized equipment, suggesting that implementation on a larger scale would be highly feasible. In this study, preoperative sensory evaluations showed no significant differences between the 2 groups. However, on the first postoperative day, there was a significant difference observed in the objective sensory testing. Interestingly, when patients were asked about any sensory abnormalities in the ipsilateral upper arm as part of the subjective evaluation, they did not report any abnormalities. This lack of subjective perception could be attributed to postoperative pain, which may have masked or overshadowed any sensory changes that were present. While the subjective evaluation did not show any significant differences between the groups, there was a significant difference observed during objective evaluations using cotton wool and a 10-g monofilament.

These findings suggest that there may be subtle sensory changes in the preservation group that were detectable through objective testing but were not subjectively perceived by the patients. The presence of postoperative pain might have influenced the patients' subjective experience and their ability to accurately report sensory abnormalities. During the postoperative period, specifically on day 18, a significant number of patients in the ICBN sacrificed group reported sensory abnormalities characterized by decreased sensation or anesthesia in the ipsilateral upper medial arm. This observation was consistent with the objective testing using cotton wool and a 10-g monofilament. Patients became more conscious of these sensory changes once the surgical pain subsided, allowing them to better perceive the paresthesia and anesthesia. In contrast, all patients in the ICBN preservation group had preserved sensory function as demonstrated by objective testing. These differences between the 2 groups were statistically significant. Supporting evidence from randomized clinical trials reinforces the feasibility of preserving ICBN without significantly extending surgical time or compromising lymph node clearance. Chirappapha et al14 found that preservation improved physical function and reduced sensory disturbances without increasing surgical complexity. Salama et al.19 also reported that ultrasonic dissection techniques facilitated ICBN preservation while ensuring effective lymphatic sealing. These findings suggest that nerve-sparing techniques are practical and beneficial.

A similar trend was observed on postoperative day 60, with some patients in the ICBN preservation group exhibiting a response to the 10-g monofilament but not to the cotton wool stimulus. This discrepancy was more pronounced on postoperative day 180, potentially due to the completion of adjuvant radiation therapy approximately 6 months after surgery. The effect of radiation therapy might have altered the fine touch sensation in the ipsilateral upper medial arm. However, the patients in the preservation group still had preserved pain sensation as indicated by the 10-g monofilament. Overall, the majority of patients who had ICBN preservation demonstrated preserved sensory function based on both subjective and objective evaluations, and these differences were statistically significant when compared with those who had their ICBN sectioned during surgery. These findings emphasize the benefits of ICBN preservation in maintaining postoperative sensory function. It is important to consider the potential long-term effects of adjuvant treatments such as radiation therapy on sensory outcomes and further investigate the clinical implications of these findings.

A study by Torresan et al.13 aligns with these findings. This prospective, randomized, double-blind intervention was conducted at the State University of Campinas in Brazil from January 1999 to July 2000. A total of 85 patients were divided into 2 groups based on whether the ICBN was preserved. All surgeries were performed by the same surgeons using a consistent technique. Postoperative assessments were carried out at 2 days, 40 days, and 3 months.

In the arm, pain sensitivity was evaluated using a questionnaire for subjective evaluation as well as a neurological examination for objective evaluation. The present study found that preserving the ICBN was associated with a noteworthy reduction in pain sensitivity, as assessed both subjectively and objectively. The subjective evaluation after 3 months revealed that 61% of the patients in the ICBN preservation group were asymptomatic, compared with 28.6% in the nerve section group (P < 0.01). Similarly, in the objective evaluation, 53.7% of patients in the ICBN preservation group had a normal neurological examination, compared with only 16.7% in the nerve section group (P < 0.01). Additionally, a randomized clinical trial by Melhem et al.20 showed that ICBN preservation significantly reduced paresthesia and chronic pain at 6 months postoperatively.

The study did not observe any significant difference in the total duration of surgery (P = 0.76) or the number of dissected nodes between the 2 groups (P = 0.59). This suggests that preserving the ICBN during the surgical procedure was feasible without affecting the surgical time or the extent of lymph node dissection. The present study showed that the group of patients who had the ICBN preserved had a higher proportion of asymptomatic individuals and a lower incidence of sensory disturbances or pain compared with the group where the ICBN was sectioned. These differences were statistically significant and were observed in all postoperative evaluations. The objective neurologic examination of the arm also revealed a similar pattern of sensitivity differences between the 2 groups.

Although preserving the ICBN extended surgical time slightly—by a mean of 6.3 minutes—this difference was not statistically significant. Anatomical evidence from existing studies,21,22 involving a total of 1567 axillae, indicates that the ICBN is present in 98.4% of individuals and typically originates from fibers at the T2 spinal level (90.6%). The nerve exhibits 2 common branching patterns: a single trunk in 47.0% of cases and a bifurcating pattern in 42.2%. In cases with a bifurcating pattern, the division is usually unequal (63.4%). Although fewer in number, most preserved ICBNs were single nerves. Consistent with these findings, a meta-analysis by Al-Dardery et al4 confirmed that the ICBN is present in 98.4% of individuals, typically originates from T2 fibers, and most commonly follows either a single trunk or bifurcating pattern.

However, it should be noted that the present study has some limitations. This study is a prospective observational study without randomization, which may introduce bias. Additionally, the surgeries were performed by 3 different surgeons, which could have resulted in variations in nodal yield and surgical duration, although these differences were not statistically significant. Also, subjective evaluation might not capture all sensory losses, particularly in older patients who may not report them. Furthermore, the present study did not have long-term follow-up data to assess the safety aspects of ICBN preservation regarding disease-free survival and overall survival.

These limitations should be considered when interpreting the results. Further research, ideally through a randomized clinical trial, is warranted to validate these findings and provide more comprehensive insights into the benefits and safety of ICBN preservation during axillary lymphadenectomy.

This study demonstrates that ICBN preservation during axillary lymphadenectomy is a feasible approach that positively affects postoperative outcomes by reducing variations in arm pain sensitivity. Importantly, this nerve preservation technique did not affect the total duration of the surgery or the number of dissected nodes. These findings suggest that preserving the ICBN is a viable approach that can potentially improve patients' clinical outcomes.