Abstract
Background
Emerging research has suggested that axillary staging can be avoided in breast cancer patients in certain conditions.
Objective
To highlight these conditions and explore the evidence of such a practice.
Methods
We conducted a narrative review of the scenarios in which axillary staging is accepted to be omitted.
Results
The first and oldest condition where sentinel lymph node biopsy (SLNB) can be omitted is Ductal Carcinoma in Situ (DCIS). Studies have shown that for DCIS patients who are prepared for breast-conserving surgery (BCS), SLNB is not necessary. Secondly, the Choosing Wisely guidelines recommend against SLNB for patients over 70 years old with early-stage, Luminal, HER2-negative, node-negative breast cancer as the likelihood of lymph node involvement is low, making SLNB unnecessary. In addition, The SOUND trial further supports the omission of SLNB in certain situations. This trial focused on small, early-stage breast cancer (T1) and negative axillary imaging findings. The results indicated that skipping SLNB was as effective as performing the procedure, suggesting that axillary surgery can be safely avoided in these cases. Another scenario where SLNB may be omitted is in patients with tubular breast carcinoma (TBC), which has a favorable prognosis with minimal lymph node involvement.
Conclusions
In summary, although SLNB remains a useful tool for managing breast cancer in many cases, omitting it in some patient populations could help avoid unnecessary treatment with its subsequent—even if minimal—potential morbidity.
Introduction
Up until now, surgical treatment of breast cancer has seen significant improvements including the surgery of the axilla. 1 The earliest method of axillary staging was axillary lymph node dissection (ALND), a technique that emerged in the late 1800s. 2 This operation aimed to control diseases in the region by providing staging information. 3 In axillary lymph node dissection, all tissues in the triangle formed by the chest wall, the lateral edge of the latissimus dorsi, and the axillary vein are removed. 4 Typically, 10–40 lymph nodes are removed in one piece. However, there is a higher chance of side effects like lymphedema, restricted shoulder motion, and neuropathic pain with axillary surgery. 5
Because of that, the SLNB technique has gained attention due to the need to reduce these risks while maintaining accurate nodal staging. The node is called sentinel because it is the first nodal station into which the cancer spreads. As part of this technique, a blue dye or a radioisotope is injected. The blue nodes or the nodes with high radioactivity are then removed and checked to see if the cancer has spread to other body parts. 6 Many trials have shown that SLNB is similar to ALND in terms of survival and recurrence rates. 6 Several major criteria influenced the change from SLNB to no axillary surgery. The first is accuracy. Advances in imaging now allow doctors to check lymph nodes without surgery. The second is safety. Studies showed that skipping axillary surgery doesn’t affect survival for patients.7–9
These developments have led to the adoption of less invasive approaches that preserve patient outcomes and minimize both the physical and emotional burdens of surgery. As research continues to progress, the criteria for safely omitting axillary surgery are likely to become even better.
The aims of this literature review are as follows: (1) Exploring ways to minimize surgical interventions to the axilla aiming to improve patients’ Quality of Life (QoL), (2) identifying low-risk patients who may safely omit axillary surgery to avoid overtreatment while maintaining effective cancer control, and (3) encouraging clinicians to adhere to current clinical guidelines that prioritize effective and appropriate medical care.
Methods
We conducted a narrative review on the omission of axillary surgery in specific breast cancer patient groups. The review was performed by searching peer-reviewed articles and guidelines from Google Scholar, PubMed, Scopus, and Cochrane Library. Search terms included combinations of “axillary surgery omission,” “breast cancer,” “DCIS,” “tubular carcinoma,” “elderly patients,” “low-risk tumors,” “Choosing Wisely”, “sentinel lymph node,” and “SOUND trial.” Articles published till July 2024 were also included. References from key studies and guidelines were reviewed to identify additional relevant publications. Studies were included based on their relevance to the topic and quality of evidence. The review emphasized clinical trials, meta-analyses, systematic reviews, and guideline updates. Key findings were summed up to highlight current evidence supporting the omission of axillary surgery in selected patient populations.
Results
Our literature review concluded that in the following situation, axillary staging can be safely omitted.
Ductal carcinoma in situ (DCIS)
Despite being categorized as non-invasive, the current therapeutic approach for DCIS has not been shown to reduce mortality. A less invasive strategy for managing DCIS must be implemented because of the growing concerns regarding the risks of overdiagnosis and overtreatment. 10
Research indicates that DCIS typically remains localized within the ducts, which supports the argument for conservative treatment methods. For instance, findings from Silverstein et al. found that the chance of metastasis rate is less than 1% when axillary lymph node dissection (ALND) is done. 11 This suggests that many DCIS patients may not need extensive surgery, making it clear how important it is to select treatment approaches that lower patient risk while still successfully treating the condition.
Current guidelines like the National Comprehensive Cancer Network (NCCN) recommend against routine SLNB for pure DCIS patients undergoing breast-conserving surgery. 12 However, SLNB may be considered in high-risk cases, including those with comedo necrosis, large tumors, or suspicion of invasive cancer. 13
On the other hand, it is highly advised to undergo SLNB for DCIS patients getting a mastectomy due to two main reasons: (i) There’s a risk of finding invasive cancer after mastectomy and (ii) the need to avoid more complicated lymph node surgery in the future. 14
At first, there’s a small but significant chance that invasive cancer might be found during the pathology review after a mastectomy, so performing SLNB during the mastectomy allows immediate evaluation of cancer spread to the sentinel nodes. 15 Second, performing SLNB later can be challenging due to the absence of breast tissue needed for lymph node drainage mapping; hence, SLNB during initial surgery can prevent the need for more complicated procedures later. 16
Research has shown that DCIS diagnosed by core needle biopsy (CNB) has varying rates of SLNB positivity which raises important considerations regarding the necessity and frequency of SLNB in these patients. For example, in one study of 170 patients with DCIS undergoing total mastectomy and SLNB, the frequency of positive results was 4.2%. 17 Another analysis of a national database involving 1787 DCIS patients found that 4% had lymph node positivity, 0.8% had large metastases, 2.4% had small metastases, and 0.8% had isolated tumor cells. 18 A meta-analytic pooled data from 15 trials revealed that rates of SLNB positivity for DCIS detected via CNB were uniformly less than 5%, suggesting potential overuse of SLNB in such circumstances. 19
In summary, while routine SLNB is generally unnecessary for DCIS, it may be warranted in specific high-risk situations as mentioned. Decisions regarding SLNB should be made based on the patient’s clinical and pathological characteristics to avoid unnecessary procedures while ensuring optimal patient management.
Elderly patients with low-risk tumors
Choosing Wisely recommendations were initiated by the American Board of Internal Medicine (ABIM) 12 years ago to cut down on pointless examinations, surgeries, and treatments. The main goal of Choosing Wisely is to promote shared decision-making that puts the needs of the patient first and evidence-based medicine. 20 This patient-centered approach allows patients and physicians to collaboratively discuss the need for SLNB based on the best available evidence, ensuring that decisions prioritize the patient’s quality of life and treatment needs. This objective is further supported by AJCC and NICE, which recommend not performing SLNB in certain patients without negatively affecting the outcomes.21,22
Five recommendations were released based on multiple trials indicating that SLNB did not affect local recurrence or mortality related to breast cancer. The first recommendation is “Don’t routinely use SLNB for women over 70 years old who have early-stage, hormone receptor-positive, HER2-negative invasive breast cancer and no signs of cancer in the lymph nodes.” Studies show that for older patients with operable breast cancer and early-stage tumors, axillary surgery and SLNB might not lead to better long-term results. Martelli et al.’s trials showed no survival benefit from axillary surgery in patients over 70 receiving adjuvant endocrine therapy, with low rates of axillary disease over 15 years. 23 Chung et al.’s study reinforced that nodal status did not impact outcomes significantly, with favorable survival rates and non-breast cancer causes of mortality being more common concerns. 24
Additionally, findings from CALGB 9343 provide reassurance, highlighting that skipping axillary surgery or radiation did not raise the recurrence rate in old-age patients. Specifically, there was only a 3% recurrence in patients skipping axillary surgery compared to 0% in those who underwent radiation alone. These studies suggest that omitting SLNB may be safe for this specific population, potentially reducing unnecessary procedures without compromising patient outcomes. 25
Furthermore, the IBCSG 10-93 trial investigated the quality of life following the skipping of axillary surgery in old-age patients. Although initial quality of life issues were observed post-surgery, they improved within a year. After 6 years, follow-up found that avoiding axillary surgery had no negative impact on long-term survival outcomes and led to improved early quality of life (QoL). 26
Welsh et al. found that the lymph node positivity rate was 15.3% among those who underwent axillary staging. Additionally, it was suggested that SLNB can be skipped for older patients with low-risk tumor characteristics, as they found only a 7.8% positive lymph node rate in low-risk cases compared to 22.3% in high-risk. 27
Although the findings are compelling, several studies have shown slow adoption of Choosing Wisely. For example, Wang et al. studied four unnecessary breast cancer surgeries highlighted by Choosing Wisely. They found that while procedures such as ALND and lumpectomy reoperation decreased over time, the rates of prophylactic removal of the healthy breast and SLNB in older women went up. 28 Barriers to adherence include patients’ expectations for comprehensive treatment and a lack of awareness of these guidelines. Providing more education and tools could help doctors and patients talk about which treatments are truly needed. 29
After the application of the recommendation, Tonneson et al. who studied 70-year-old patients with hormone receptor-positive found that SLNB rates decreased significantly from 90.6% (2010–2016) to 62.8%. This decline was particularly notable in breast-conserving surgery (BCS), dropping from 88.2% to 46.7%. 30
In summary, the Choosing Wisely recommendations, along with those from organizations such as the National Comprehensive Cancer Network (NCCN) and the European Society for Medical Oncology (ESMO), suggest a similar approach to SLNB in patients with low-risk breast cancer. The European SENOMAC trial provides further evidence that omitting SLNB in some cases does not affect long-term outcomes. 31 These recommendations, along with the combined studies, aim to reduce unnecessary procedures and ultimately improve patients’ QOL.
Sentinel node versus observation after axillary ultra-sound (SOUND) in patients with T1 breast cancer
The Z0011 Trial, which examined the necessity of further axillary dissection in patients with 1–2 positive sentinel nodes, led to significant discussions in the surgical community.
Therefore, the SOUND trial was initiated to determine whether axillary surgery is needed in small breast cancers and negative axillary lymph node ultrasound results. 32
The SOUND trial was a Phase 3 randomized clinical trial involving 1463 patients with early-stage invasive breast cancer and clinically negative axillary nodes. Participants were randomized to either undergo sentinel lymph node biopsy or no axillary surgery, 33 comparing outcomes between those who had SLNB and those who skipped surgery altogether. The primary goal was to assess whether skipping axillary surgery is as effective as doing SLNB in achieving 5-year distant disease-free survival (DFS). Eligibility criteria required the participants to be adults who had received or were set to receive systemic therapies, with cancer-free sentinel nodes if SLNB was performed. To take part, patients must be capable of providing informed consent and meeting the study’s requirements. Individuals were excluded if they had positive axillary lymph nodes, previous axillary surgery or radiation, non-invasive cancer (e.g., DCIS), severe, uncontrolled medical disorders were excluded, concurrent malignancies, or were pregnant or lactating. 33
The study is based on several key concepts. The first is recognizing the potential role of imaging in axillary staging. The second concept focuses on making treatment plans based on how well patients might respond rather than prognosis, as this approach increases the likelihood of the patient benefiting from a specific treatment. Finally, the goal is to improve patients’ quality of life by using less invasive surgery. 34
For instance, radiation therapy is typically given after BCS if there is lymph node involvement. For patients over 65 years old without lymph node involvement, skipping radiation therapy generally does not impact survival.35,36 Despite its limitations, the ultrasound (US) effectively identified important lymph nodes that might be missed during clinical evaluation.
Regarding adjuvant treatment recommendations as a secondary endpoint, the study found no notable differences between the two groups, even when SLNB pathological details were available, suggesting that SLNB information didn’t change the treatment decisions. The SOUND trial supports making treatment choices based on biological factors, such as genetics or tumor features, rather than just the T or N status. 37
In terms of QoL, the trial indicates that skipping axillary surgery can maximize QoL, which is a primary reason for discontinuing SLNB in this context. Gentilini et al. analyzed side effects and their impact on physical function. 34 They used the QuickDASH (Disability Arm and Shoulder) questionnaire to analyze the first 180 patients from the SOUND trial to assess upper-limb physical function. Patients who had SLNB experienced higher disability scores 1 week post-operative than those who did not have SLNB. However, after 6 and 12 months, the scores for both groups returned to levels like baseline. In contrast, patients who underwent ALND (N = 5) had consistently higher disability rates throughout follow-up.
Overall, the SOUND trial demonstrated that not performing axillary surgery is as effective as performing SLNB, with 5-year DFS rates of 97.7% for the SLNB group and 98.0% for the no-surgery group. The two groups also had similar 5-year disease-free survival (DFS) and overall survival (OS). The SENOMAC trial further supports the SOUND trial’s findings, further confirming that skipping ALND in low-risk patients does not compromise disease-free or overall survival. 31
Tubular breast carcinoma
Tubular breast carcinoma (TBC) is an uncommon subtype of invasive ductal carcinoma (IDC), characterized by its distinct tubular formations. It makes up about 1%–2% of all invasive breast cancers and is associated with a favorable prognosis.38,39 Considering its slow growth and minimal risk of lymph node spread, it questions the need for routine surgery of the axilla.
Tumors that can be found in TBC are generally small, low in grade, and have a specific subtype, especially the luminal A. In comparison to other breast cancer subtypes, research shows that TBC is less likely to metastasize. A study by Hetelekidis et al. found lymph node involvement in TBC to range between 4 and 7%, which is notably lower than in other invasive ductal carcinomas. Despite its favorable prognosis, postoperative endocrine therapy, SLNB, and breast-conserving radiotherapy are often recommended for TBC.40,41 However, a recent study showed that TBC had a limited response to endocrine and radiation therapy. 42
A recent retrospective review of 32 TBC patients found that accurate preoperative and verified pathological diagnosis may prevent postoperative endocrine and radiation treatment, as well as SLNB. In another study, they compared the overall survival (OS) and lymph node metastasis rate in DCIS, TBC, and IDC estrogen receptor-positive type using the Kaplan–Meier technique. The focus was on exploring treatment de-escalation, addressing concerns of treatment overload from previous studies. 43 Based on the findings, TBC showed more favorable rates for lymph node metastasis, OS, and DFS than not otherwise specified (NOS) cases. 10 Yamane et al. similarly observed comparable survival outcomes between TBC and DCIS, with no significant difference in OS and DFS, highlighting the favorable prognosis of TBC. 43
These findings suggest that TBC presents a suitable option for reducing the need for surgical axillary staging, given its minimal lymph node metastasis and outstanding long-term survival results. This strategy is in line with the objectives of personalized medicine, which seeks to decrease unnecessary surgical procedures while maintaining a high survival rate.
Limitations
This study has potential limitations. First, this review is not systematic and no meta-analysis was performed. Second, when applying the conclusions we should consider that the information gathered from trials like SOUND may not apply to all patient groups, especially those considered high-risk. Additionally, while TBC and DCIS were highlighted, there is still insufficient data especially on other special subtypes (e.g., papillary or mucinous carcinoma), restricting a thorough examination of all uncommon subtypes. Long-term outcome data after the study period is still necessary for improvements in DFS and recurrence rates. The way Choosing Wisely guidelines are applied varies between the doctors, and it is difficult to see how these recommendations affect patients’ overall QoL.
Conclusion
Although BC patients commonly undergo SLNB for axillary node staging, its necessity can be questioned since it is primarily used for staging without curative intent. The increasing trend of avoiding axillary surgery in DCIS patients highlights the importance of choosing treatment according to the patient’s preferences, goals, and health using the latest evidence to provide the best care. Findings from Choosing Wisely recommendations suggest that avoiding axillary surgery may benefit elderly patients with small BC and clinically negative nodes, while the SOUND trial showed that skipping axillary surgery was just as successful as SLNB. Additionally, TBC is a good candidate to skip axillary surgery due to its minimal axillary lymph node involvement. As a result, the number of surgeries that are performed currently can be reduced to improve patients’ overall health.
In a nutshell, the combination of the Choosing Wisely guidelines, insights into DCIS, findings on tubular breast carcinoma, and results from the SOUND trial indicates a shift towards reduced side effects and enhanced patient quality of life, while having minimal impact on survival rates. Ongoing research and monitoring are necessary to continue validating and refining these methods, ensuring they benefit a broader group of patients.
