Early Breast Cancer: Should Axillary Surgery Be Performed Solely to Decide on a CDK4/6 Inhibitor?
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A New Conflict in Axillary Management: Less Surgery or More Staging Information?
The underarm lymph nodes, or axilla, were considered critical for both staging and local control in breast cancer for many years. Axillary lymph node dissection was previously used more extensively. Over time, however, it became clear that this approach could cause substantial morbidity, including lymphedema, pain, numbness, restricted shoulder movement and loss of quality of life.
Sentinel lymph node biopsy was a major step in reducing this burden. Subsequently, studies such as SOUND and INSEMA took de-escalation further by showing that even sentinel lymph node biopsy could be omitted in highly selected patients with early, clinically node-negative disease, most of whom had HR+/HER2-negative cancer.
Brief Concept Note: What Are De-escalation, SLNB and cALND?
De-escalation is an approach that reduces the burden of cancer treatment without compromising efficacy. SLNB stands for sentinel lymph node biopsy; it involves removing and examining the few lymph nodes to which the tumor may spread first. cALND stands for completion axillary lymph node dissection; it means removing additional underarm lymph nodes according to sentinel node positivity or risk.
However, adjuvant CDK4/6 inhibitors have complicated the equation. The use of drugs such as abemaciclib and ribociclib in early breast cancer requires more precise assessment of a patient's recurrence risk. In some situations, lymph node positivity can be an important criterion for eligibility for these drugs. This creates a new tension: we want to reduce axillary surgery, but also want lymph node information to guide the systemic treatment decision.
The Central Clinical Question of This Analysis
The analysis asks: if axillary surgery could otherwise safely be omitted in a patient, is performing SLNB or cALND solely to determine eligibility for a CDK4/6 inhibitor clinically worthwhile?
The researchers measured this using a “number needed to diagnose and treat” approach. In other words, how many axillary operations must be performed to identify patients who will consequently receive a CDK4/6 inhibitor and prevent one invasive disease-free survival, distant disease-free survival or overall survival event over 5 years?
Brief Concept Note: What Is a CDK4/6 Inhibitor?
CDK4/6 inhibitors are drugs that inhibit the proteins CDK4 and CDK6, which regulate the cell cycle. They can slow cancer cell proliferation in HR+/HER2-negative breast cancer. While they have long been used in metastatic disease, trials such as monarchE and NATALEE have also brought them into adjuvant treatment for high-risk early disease.
The Shared Question Across Five Randomized Trials
The analysis by Pfob and colleagues brought together data from five large randomized trials: SOUND, INSEMA, SENOMAC, monarchE and NATALEE. Some of these studies had evaluated the safety of reducing axillary surgery, while others had assessed the contribution of adjuvant CDK4/6 inhibitors in early breast cancer.
This pooled analysis brought two distinct fields together within the same clinical question: reducing axillary surgery and selecting systemic adjuvant treatment. A total of 19.541 patients were evaluated. The median follow-up was 57,2 months .
| Study | Main area | Patient context | Contribution to this analysis | Clinical message |
|---|---|---|---|---|
| SOUND | De-escalation of axillary surgery | Clinically node-negative, small early breast cancer | Provides evidence on the safety of omitting SLNB | Axillary surgery can be reduced in selected patients. |
| INSEMA | De-escalation of axillary surgery | Clinically node-negative early breast cancer with planned breast-conserving surgery | Provides large-scale evidence on the safety of omitting SLNB and reducing morbidity | Even SLNB may be unnecessary in some selected patients. |
| SENOMAC | Reducing completion axillary dissection | Sentinel node-positive early breast cancer | Provides evidence on the safety of omitting cALND | A positive sentinel node may not always require full axillary dissection. |
| monarchE | Adjuvant abemaciclib | HR+/HER2-negative, high-risk, node-positive early breast cancer | Evaluates abemaciclib benefit and eligibility criteria | CDK4/6 inhibition may reduce recurrence risk in high-risk patients. |
| NATALEE | Adjuvant ribociclib | HR+/HER2-negative stage II-III early breast cancer | Evaluates ribociclib benefit in a broader early-stage patient population | The adjuvant CDK4/6 strategy has extended to a broader risk group with ribociclib. |
Brief Concept Note: What Are Adjuvant Treatment, IDFS, DDFS and OS?
Adjuvant treatment is systemic treatment given after surgery to reduce the risk of recurrence. IDFS means invasive disease-free survival; it is the time without events such as invasive recurrence, a new cancer or death. DDFS means distant disease-free survival; it focuses on time without distant metastasis or death. OS means overall survival; it evaluates death from any cause.
The Number of Operations Needed to Prevent One Event Is Very High
The analysis's most striking finding is the apparently low clinical efficiency of axillary surgery performed solely to determine eligibility for a CDK4/6 inhibitor. When SLNB was performed to determine eligibility for ribociclib, the estimated number of axillary surgery-diagnosis-treatment pathways needed to prevent one invasive disease-free survival event over 5 years was 123 . To prevent one distant disease-free survival event, this number was 129, and to prevent one overall survival event it was 345 .
The picture was even more striking in the completion axillary dissection and abemaciclib scenario. To prevent one invasive disease-free survival event, the number was 106; to prevent one distant disease-free survival event it was 119; and to prevent one overall survival event, the reported number of completion axillary dissection-diagnosis-treatment pathways was 807 .
Brief Concept Note: What Does Number Needed to Diagnose and Treat Mean?
Number needed to diagnose and treat is a measure of how many people must undergo a diagnostic procedure, with eligible individuals then treated, to achieve a particular clinical benefit. In this analysis, the question is: how many axillary operations are needed to identify enough patients to receive a CDK4/6 inhibitor and prevent one recurrence or death event over 5 years? The higher the number, the less efficient the strategy.
What Do These Numbers Tell Us?
- The number is high even for SLNB: Determining ribociclib eligibility requires 123 SLNB procedures to prevent one invasive event over 5 years.
- The overall survival gain is even more limited: In the ribociclib scenario, 345 SLNB procedures are needed to prevent one OS event.
- The balance is less favorable for cALND: For abemaciclib eligibility, a very high number of 807 completion axillary dissections is reported to prevent one OS event.
- Morbidity must not be forgotten: These procedures do more than gather information; they also carry risks of lymphedema, pain, numbness and loss of shoulder function.
More Aggressive Axillary Investigation Solely for Systemic Treatment Eligibility Does Not Seem Balanced
The strongest patient-centered message from this analysis is this: if reducing axillary surgery is oncologically safe, investigating the axilla with more aggressive surgery solely to determine eligibility for a CDK4/6 inhibitor does not seem reasonable. Many patients may be exposed to surgical morbidity in exchange for a limited absolute benefit.
This is particularly important for completion axillary dissection. Even sentinel lymph node biopsy is not risk-free, but cALND carries a higher risk of lymphedema and functional impairment. A strategy requiring 807 completion axillary dissections to prevent one overall survival event deserves very careful scrutiny from a patient-centered care perspective.
Truecheck Note: This Analysis Is Not Against CDK4/6 Inhibitors
This study does not reject the value of abemaciclib or ribociclib in adjuvant treatment. monarchE and NATALEE have shown that CDK4/6 inhibitors can reduce recurrence risk in eligible patient groups. The question here is different: is it necessary to perform axillary surgery that could otherwise be omitted to determine eligibility for a CDK4/6 inhibitor? The analysis suggests that surgery for this purpose is not an efficient strategy.
| Decision area | Potential gain | Potential cost | Message of the analysis | Practical interpretation |
|---|---|---|---|---|
| Performing SLNB | Nodal status becomes known; ribociclib eligibility may change in some patients | Pain, seroma, infection, sensory changes and a risk of lymphedema, albeit low | The number needed to prevent one event is high | Performing SLNB solely for a CDK4/6 decision may be poorly justified in many patients. |
| Performing cALND | More precise information on nodal burden; abemaciclib eligibility may become clearer in some patients | Lymphedema, restricted shoulder movement, chronic pain and loss of quality of life are more pronounced | The number needed for one OS event is very high, at 807 | Performing cALND solely for abemaciclib eligibility does not appear to favor the patient. |
| Reducing surgery | Morbidity and loss of quality of life decrease | Nodal information may be reduced; systemic treatment and radiation field decisions may become more uncertain | The overall balance may favor reducing surgery in selected patients | The decision should incorporate clinical factors, biology and patient preferences. |
Axillary Surgery in Breast Cancer Has Progressively Decreased; the New Question Is Systemic Treatment Selection
The main direction of breast cancer surgery over the past half-century has been toward less morbid but equally safe treatment. An evolution has taken place from radical mastectomy to breast-conserving surgery, from axillary dissection to sentinel lymph node biopsy, and then to omitting even sentinel biopsy in selected patients.
The underlying philosophy is this: surgical information that does not benefit the patient is not valuable if it causes substantial morbidity. The axilla is no longer simply the answer to “how many nodes are positive?”; it is where quality of life, local control, the radiotherapy plan and systemic treatment decisions intersect.
| Period / approach | Traditional rationale | New approach | Patient benefit | Influence on today's debate |
|---|---|---|---|---|
| The axillary dissection era | Obtaining the most detailed lymph node information | Transition to more limited surgery | Reducing lymphedema and shoulder morbidity | The question arose: “Is every piece of information worth its surgical cost?” |
| Sentinel lymph node biopsy | Examining the first draining nodes instead of removing the entire axilla | Omitting cALND when the sentinel node is negative | Less morbidity, adequate staging | SLNB became the standard method of axillary staging. |
| De-escalation of cALND | Removing more nodes when the sentinel node is positive | Omitting cALND in selected patients | Substantially reducing lymphedema risk | Sentinel node positivity does not always require full dissection. |
| Trials of SLNB omission | Performing SLNB in every clinically node-negative patient | Omitting SLNB in selected patients with small, early cancers, mostly HR+/HER2- | Minimal surgery, better quality of life | The question arose of how missing nodal information affects systemic treatment decisions. |
| The CDK4/6 eligibility debate | Lymph node information determines some adjuvant treatment decisions | Questioning axillary surgery solely for CDK4/6 eligibility | Preventing unnecessary surgical morbidity | This Lancet Oncology analysis shows that increasing surgery solely for drug eligibility is inefficient. |
Abemaciclib and Ribociclib Are Valuable, but Is More Surgery Essential to Determine Eligibility?
Adjuvant CDK4/6 inhibitors are an important advance in early HR+/HER2-negative breast cancer. The monarchE trial showed that abemaciclib + endocrine treatment reduced recurrence risk in high-risk node-positive patients. NATALEE evaluated ribociclib + an aromatase inhibitor in a broader stage II-III patient population and demonstrated an invasive disease-free survival benefit.
However, the value of these drugs does not mean that more surgery is needed to initiate them. Treatment decisions should increasingly be based on tumor biology, clinical risk, genomic risk, tumor size, grade, Ki-67, age, menopausal status, comorbidities and patient preferences.
Brief Concept Note: What Are Genomic Risk, Grade and Ki-67?
Genomic risk is determined by tests that attempt to estimate recurrence risk using a tumor's gene expression profile. Grade describes how aggressive cancer cells appear under the microscope. Ki-67 is a marker of the rate of tumor cell proliferation. These parameters contribute to treatment decisions alongside nodal information or, in some circumstances, partly compensate for its absence.
Nonsurgical Layers of Information for the CDK4/6 Decision
- Tumor size: Larger tumors may indicate higher clinical risk.
- Histological grade: Grade 3 disease indicates more aggressive biology.
- Ki-67: High proliferation may be associated with higher recurrence risk, but is not a perfect decision tool on its own.
- Genomic tests: Oncotype DX and similar tests help with chemotherapy and long-term risk assessment.
- Menopausal status: The benefit of systemic treatment may be interpreted differently in premenopausal and postmenopausal patients.
- Patient priorities: The balance between the wish to reduce recurrence risk, drug toxicity and quality of life should be discussed openly with the patient.
An Important Balance
If a patient's clinicopathological features already clearly indicate high risk in relation to a CDK4/6 inhibitor, the need for additional surgical information may decrease. Conversely, if the patient is low-risk and axillary surgery could normally be safely omitted, performing nodal staging solely to prove drug eligibility may upset the benefit-morbidity balance.
Underarm Surgery Is Not Just an “Information-Gathering Procedure”
For patients, the most important cost of axillary surgery is long-term quality of life. Lymphedema, arm swelling, heaviness, restricted movement, pain, numbness and infection risk can affect a patient's everyday life for years. Expanding axillary surgery solely to determine systemic treatment eligibility therefore requires a very strong clinical justification.
This analysis shows that such a justification is weak for most patients. The need for hundreds of axillary operations to prevent one overall survival event raises a question in patient-centered care: Is this information really worth this surgical cost?
How Should We Discuss This with the Patient?
“Examining the underarm lymph nodes can provide information for some treatment decisions. However, these procedures can have adverse effects such as lymphedema, pain and restricted arm movement. New analyses show that additional lymph node surgery solely to determine whether we can give a CDK4/6 inhibitor provides limited benefit for most patients. A more balanced approach may be to assess the treatment decision together with the tumor's biology, size, grade, genomic risk and your priorities.”
More Surgical Information Does Not Always Mean Better Treatment
Academic Assessment
This study carries a highly valuable, patient-centered de-escalation message, showing that we need to reconsider the boundaries of axillary surgery in early breast cancer.
Lymph node surgery solely to determine eligibility for a CDK4/6 inhibitor does not appear reasonable, because it can impose substantial morbidity on the patient in exchange for a limited gain.
Future adjuvant treatment decisions will be shaped by more refined, personalized models that evaluate tumor biology, molecular risk and the patient's quality of life together, rather than gathering more surgical information.
Base the Decision on Multilayered Risk, Not a Single Piece of Lymph Node Information
This analysis shows that multidisciplinary decisions in early breast cancer need to become more refined. The surgeon, medical oncologist and radiation oncologist should jointly ask: will information from axillary surgery genuinely change this patient's treatment decision, and will that change provide meaningful clinical benefit?
If the answer is uncertain, a more balanced decision based on tumor biology, clinical risk and patient preferences may be more appropriate than increasing surgical morbidity. Further investigation of the axilla can sometimes clarify a systemic treatment decision; however, if this clarity does not provide a meaningful survival or recurrence-prevention gain for the patient, the procedure's value becomes debatable.
Practical Decision Questions
- Can axillary surgery normally be omitted? Criteria for omitting SLNB should be assessed in clinically node-negative patients with small, low-risk disease.
- Will nodal information genuinely change the treatment decision? If the CDK4/6 inhibitor decision is already clear from clinical and biological risk, additional surgery may be unnecessary.
- How does the patient view surgical morbidity? Lymphedema and loss of arm function should be discussed alongside the patient's life priorities.
- What are the genomic and pathological risks? Tumor size, grade, Ki-67, genomic score and menopausal status should be considered together.
- Will the radiotherapy plan be affected? The effect of missing nodal information on radiation field decisions should be discussed by the multidisciplinary team.
Truecheck Note
This analysis does not conclude that “axillary surgery is now unnecessary.” Axillary surgery remains valuable for staging, local control and treatment planning in many patients. The analysis makes a more specific point: performing axillary surgery solely to determine eligibility for an adjuvant CDK4/6 inhibitor requires very high numbers, adds morbidity and provides limited absolute benefit in overall survival.
Moving from Lymph Node Counts to Tumor Biology
The future of breast cancer treatment is moving toward decisions based on tumor biology rather than anatomical stage alone. Lymph node information remains valuable, but is no longer the sole center of treatment decisions. Genomic scores, molecular subtypes, proliferation markers, treatment response, ctDNA and AI-assisted risk models will become increasingly important.
This new analysis is an important caution about systemic treatment decisions in the era of reducing axillary surgery. Reducing surgery should not mean reducing treatment quality. Instead, it should mean reducing unnecessary morbidity and providing smarter systemic treatment to patients with genuine risk.
Brief Concept Note: What Are Morbidity and Lymphedema?
Morbidity refers to the unwanted health burden caused by a treatment or disease. Lymphedema is chronic arm swelling, heaviness, pain and susceptibility to infection caused by impaired lymphatic flow. Lymphedema risk generally increases as axillary surgery becomes more extensive.
More Extensive Axillary Investigation Solely for CDK4/6 Eligibility Does Not Appear to Favor Patients
This pooled analysis published in The Lancet Oncology answers a very important question at the intersection of axillary surgery and adjuvant CDK4/6 inhibitor decisions in early breast cancer. Performing SLNB or completion axillary dissection solely to determine eligibility for a CDK4/6 inhibitor requires a very high number of operations to prevent one event.
For ribociclib, 123 SLNB procedures are needed to prevent one invasive disease-free survival event and 345 SLNB procedures to prevent one overall survival event. For abemaciclib, a very high number of 807 completion axillary dissections is reported to prevent one overall survival event. Considered alongside the burden of lymphedema, pain, functional impairment and reduced quality of life caused by axillary surgery, these figures suggest that more aggressive surgery solely for drug eligibility is not a balanced strategy.
The most appropriate future approach is to use axillary surgery where needed, while increasingly making systemic treatment decisions together with tumor biology, genomic risk, clinical risk and patient preferences. Good care in early breast cancer is not about gathering more surgical information; it is about delivering the right treatment to the right patient with the least morbidity.
Sources
- Pfob A, Pham TH, de Boniface J et al. Lymph node surgery and CDK4/6 inhibitors in early breast cancer: a pooled analysis from five randomised trials. The Lancet Oncology. 2026;27(5):604-613.
- PubMed. Lymph node surgery and CDK4/6 inhibitors in early breast cancer: a pooled analysis from five randomised trials.
- The ASCO Post. Lymph Node Surgery and CDK4/6 Inhibitor Treatment in Early Breast Cancer. 29 May 2026.
- Reimer T et al. Axillary Surgery in Breast Cancer. New England Journal of Medicine. 2025. INSEMA primary results.
- The ASCO Post. ASCO Guideline Update Calls for Omission of SLNB in Select Patients With Early-Stage Breast Cancer. 2025.
- Rastogi P et al. Adjuvant Abemaciclib Plus Endocrine Therapy for HR+, HER2−, Node-Positive, High-Risk Early Breast Cancer: monarchE. Journal of Clinical Oncology. 2024.
- ClinicalTrials.gov. monarchE: Endocrine Therapy With or Without Abemaciclib in High-Risk Early Breast Cancer. NCT03155997.
- ClinicalTrials.gov. NATALEE: Ribociclib With Endocrine Therapy as Adjuvant Treatment in HR+/HER2− Early Breast Cancer. NCT03701334.
- Crown J et al. 5-year follow-up of NATALEE efficacy outcomes and safety in early breast cancer. ESMO Open. 2025.
- drozdogan.com. Is Removing Underarm Lymph Nodes Essential in Breast Cancer? An Approach That Reduces Lymphedema Risk. 13 December 2025.
- drozdogan.com. CDK4/6 Inhibitors in Early Breast Cancer: Responding to Criticism and the Current Situation. 10 December 2025.
- drozdogan.com. How Can We Identify Patients Who Will Not Need Chemotherapy after Breast Cancer Surgery?
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