What are the implications of the Insema trial for an adult female with a potential interest in breast health?

INSEMA Trial: Implications for Breast Health in Adult Women

Key Finding

The INSEMA trial demonstrated that omitting sentinel lymph node biopsy (SLNB) in carefully selected early-stage breast cancer patients is non-inferior to performing SLNB, with significantly better arm and breast symptoms and no compromise in cancer outcomes. 1

Trial Design and Results

The INSEMA trial was a prospective, randomized, phase III non-inferiority study that enrolled 5,542 patients with clinically node-negative (cN0), T1 or T2 (tumor size ≤5 cm) invasive breast cancer scheduled for breast-conserving surgery. 1

Primary Outcomes

• Invasive disease-free survival (IDFS) at 5 years: 91.9% in the no axillary surgery group versus 91.7% in the SLNB group (HR 0.91; 95% CI, 0.73-1.14), confirming non-inferiority 1
• Median follow-up: 73.6 months (approximately 6 years) 1
• Upstaging rate: Only 13.1% had 1-3 positive lymph nodes and 0.6% had ≥4 positive nodes among those who underwent axillary surgery 1

Quality of Life Benefits

Patients who avoided SLNB experienced significantly and clinically meaningful improvements in arm and breast symptoms: 2

• Lymphedema: 1.8% (no surgery) versus 5.7% (SLNB) 1
• Restriction of arm/shoulder mobility: 2.0% versus 3.5% 1
• Pain with arm/shoulder movement: 2.0% versus 4.2% 1
• Arm symptom scores: Differences ≥5.0 points at all postoperative time points, with highest difference at one month 2

Patient Selection Criteria

Ideal Candidates for Omitting SLNB

The following patients are appropriate candidates based on ASCO 2025 guidelines: 1, 3

• Age: ≥65 years (strongly represented in trial) 3
• Tumor characteristics: T1 tumors, ER-positive, HER2-negative 3
• Clinical nodal status: Clinically and sonographically node-negative 1
• Planned treatment: Will receive whole-breast irradiation AND endocrine therapy 3
• Surgery type: Breast-conserving surgery 1

Patient Populations Underrepresented in INSEMA

Caution is warranted for the following groups, as they comprised small percentages of the trial: 1

• Age <50 years (10.8% in INSEMA) 1
• Grade 3 invasive carcinoma (3.6%) 1
• Ki-67 >20% (12.9%) 1
• Lobular or mixed lobular carcinoma (12.7%) 1
• HER2-positive disease (3.6%) 1
• Triple-negative breast cancer (1.2%) 1

Critical Treatment Requirements

Radiation Therapy Mandates

Patients must receive whole-breast irradiation if SLNB is omitted—this is non-negotiable: 3

• The INSEMA protocol mandated whole-breast irradiation for all patients 3
• Partial breast irradiation alone was not studied in the context of SLNB omission 1
• The incidental axillary treatment from tangential radiation fields is assumed to provide curative treatment for low-volume nodal disease 3
• At least 50% of INSEMA patients received adequate radiation dose (≥80% of prescribed breast dose) to axillary level I, even with contemporary 3D techniques 4

Absolute Contraindications to Omitting SLNB

Do not omit SLNB in the following scenarios: 3

• Patients who will not receive whole-breast irradiation 3
• Clinically suspicious axillary nodes on examination or imaging 3
• Patients undergoing mastectomy (not studied in INSEMA) 5

Clinical Decision-Making Without Nodal Staging

When SLNB is omitted, treatment decisions must rely on tumor biological parameters: 5

• Chemotherapy decisions for luminal-like tumors should be guided by tumor grade, Ki-67, Oncotype DX or similar genomic assays, and tumor size 5
• Regional nodal irradiation (excluding axilla) decisions should be based on tumor biology rather than nodal status 5
• The majority of INSEMA patients would not have required regional nodal irradiation given the low rate of positive nodes (14.9% with pN1 disease, 0.2% with pN2 disease) 1

Common Pitfalls to Avoid

Imaging Considerations

• Breast MRI was not routinely used in INSEMA but can help confirm tumor size ≤2 cm if performed 1
• Axillary ultrasound with FNA of suspicious nodes was performed in both trials 1

Patient Counseling

• Patients must understand they are forgoing knowledge of nodal status 5
• Approximately 20% of eligible patients refused the second randomization in INSEMA, indicating patient preference remains important 5
• High questionnaire completion rates (>70% at all time points) demonstrate patient engagement with quality of life outcomes 2

Radiation Planning

• Obesity significantly increases incidental axillary radiation dose 4
• Younger age, boost application, and fractionation schedule showed no impact on axillary dose distribution 4

Unanswered Questions

The INSEMA trial does not address: 5

• Whether partial breast irradiation alone is safe when SLNB is omitted in low-risk situations 5
• Whether SLNB can be avoided in patients requiring mastectomy 5
• Optimal management of premenopausal patients (only 21.3% in companion SOUND trial) 1