Targeted Axillary Dissection for Breast Cancer

(TAD Trial)

Overseen By Maynela Quinones Mendez

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Miami

Disqualifiers: Allergy to mapping agents, Pregnancy

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: Day 1 (Day of Surgery)

45 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this research is to evaluate how to manage the axillary lymph nodes in patients with breast cancer. The investigators will determine if a sampling of the lymph nodes under the arm will give the information necessary to determine if fewer lymph nodes can be removed.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, since it mentions the receipt of standard chemotherapy and targeted therapy, you might need to continue those treatments if applicable.

What data supports the effectiveness of the treatment Axillary Dissection, Axillary Lymphadenectomy, Axillary Node Dissection, ALND for breast cancer?

The research suggests that Axillary Lymph Node Dissection (ALND) is often recommended for breast cancer patients with certain conditions, such as clinically node positive disease, but its effectiveness in improving outcomes is still uncertain. Some studies question its routine use, as it may not significantly change treatment decisions or improve survival. ^{1 2 3 4 5}

Is axillary lymph node dissection (ALND) generally safe for humans?

Axillary lymph node dissection (ALND) is known to have significant complications, including issues with arm movement and swelling, but it is a common procedure in breast cancer treatment. The American College of Surgeons Oncology Group trial Z0011 found that for some early-stage breast cancer patients, it is safe to skip ALND, suggesting that while it can be safe, it may not always be necessary. ^{1 6 7 8 9}

How is the treatment Targeted Axillary Dissection different from other treatments for breast cancer?

Targeted Axillary Dissection is unique because it combines a sentinel lymph node biopsy with the removal of specific lymph nodes that were identified as involved during the initial staging, which helps improve accuracy and reduce unnecessary surgery compared to traditional axillary lymph node dissection. ^{1 7 10 11 12}

Research Team

Susan Kesmodel, MD

Principal Investigator

University of Miami

Eligibility Criteria

This trial is for adults with invasive adenocarcinoma of the breast, who have certain levels of axillary lymph node involvement and are candidates for surgery. They must have completed standard chemotherapy +/- targeted therapy and not be pregnant or allergic to specific mapping agents used in the study.

Inclusion Criteria

My cancer's spread to nearby lymph nodes was checked by physical exam and scans.

My biopsy shows cancer in my axillary lymph nodes.

I have received standard chemotherapy, with or without targeted therapy, based on my cancer type.

Exclusion Criteria

Pregnancy

You have had allergic reactions to radioactive lymph node mapping agents or blue dye in the past.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo standard of care surgery with targeted axillary dissection and complete removal of axillary lymph nodes

Day 1 (Day of Surgery)

1 visit (in-person)

Follow-up

Participants are monitored for treatment-emergent adverse events and accuracy of imaging studies

Up to 3 weeks

Treatment Details

Interventions

• Axillary Dissection

Trial Overview The study is testing a procedure called Targeted Axillary Dissection (TAD) to see if sampling fewer lymph nodes can effectively manage cancer spread in patients with breast cancer, instead of removing more nodes which has been common practice.

Participant Groups

Group I: Targeted Axillary Dissection (TAD) Experimental Treatment 1 Intervention

During standard of care (SoC) surgery to remove breast cancer, study participants will undergo a sampling of lymph nodes in the axilla first and then complete removal of axillary lymph nodes under the arm.

Axillary Dissection is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Axillary Lymphadenectomy for:

• Breast cancer
• Melanoma
• Squamous cell carcinoma

Approved in United States as Axillary Dissection for:

• Breast cancer
• Melanoma
• Squamous cell carcinoma

Approved in Canada as Axillary Lymph Node Dissection for:

• Breast cancer
• Melanoma
• Squamous cell carcinoma

Who Is Running the Clinical Trial?

University of Miami

Lead Sponsor

Trials

976

Recruited

423,000+

Findings from Research

In a study of 292 breast cancer patients with clinically node-positive disease treated with neoadjuvant therapy, axillary lymph node dissection (ALND) did not significantly improve axillary recurrence rates or overall survival compared to targeted axillary surgery (TAS).

Five-year axillary recurrence-free survival was 100% for TAS and 90% for ALND, indicating that TAS may be a safer option without compromising outcomes, as ALND did not show a clear benefit in preventing recurrence or enhancing survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of axillary surgery on outcome of clinically node positive breast cancer treated with neoadjuvant chemotherapy. Dux, J., Habibi, M., Malik, H., et al.[2023]

In a study of 1,178 breast cancer patients, only 5% had sentinel lymph node micrometastases, and those who did not undergo axillary lymph node dissection (ALND) showed no cases of axillary recurrence after a median follow-up of 60 months.

The findings suggest that ALND may be safely omitted in patients with sentinel node micrometastases, provided they receive appropriate adjuvant systemic treatment, although further research is needed for confirmation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avoiding axillary treatment in sentinel lymph node micrometastases of breast cancer: a prospective analysis of axillary or distant recurrence. Pernas, S., Gil, M., Benítez, A., et al.[2022]

In a study of 389 breast cancer patients with one or two positive sentinel lymph nodes, 44.7% showed axillary lymph node metastasis, highlighting the prevalence of this condition in this patient group.

Younger age (under 60 years), a higher ratio of positive to total sentinel lymph nodes, and occupations involving manual labor were identified as significant risk factors for axillary lymph node metastasis, which could help determine which patients may not need axillary lymph node dissection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Independent risk factors for axillary lymph node metastasis in breast cancer patients with one or two positive sentinel lymph nodes. Zhang, W., Xu, J., Wang, K., et al.[2020]

Axillary lymph node dissection (ALND) may not be necessary for many breast cancer patients, especially ER-negative women, as it provides little benefit in guiding adjuvant therapy decisions.

The decision model indicates that ALND offers significant benefits primarily to ER-positive women with small tumors, but it may negatively impact quality of life, suggesting a need to reassess its routine use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is axillary lymph node dissection indicated for early-stage breast cancer? A decision analysis. Parmigiani, G., Berry, DA., Winer, EP., et al.[2022]

In a study of 102 breast cancer patients with positive sentinel lymph node (SLN) biopsies, 46% were found to have additional metastasis in non-sentinel lymph nodes during axillary lymph node dissection (ALND).

Three mathematical models (from MSKCC, Stanford, and Cambridge) were evaluated for predicting non-SLN metastasis, but none showed strong predictive power for the Japanese population, although they may still assist in tailoring surgical decisions when the risk of further metastasis is low.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three models for predicting the risk of non-sentinel lymph node metastasis in Japanese breast cancer patients. Sasada, T., Kataoka, T., Shigematsu, H., et al.[2022]

In a study of 96 women with breast cancer undergoing axillary lymph node dissection (ALND), 42% experienced complications post-surgery, with numbness and seroma being the most common issues reported.

ALND was effective in retrieving at least 10 lymph nodes in 81.3% of patients, and nodal metastasis was found in 62.5%, indicating its importance in cancer staging and treatment despite the associated risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axillary Lymph Node Dissection for Breast Cancer: Efficacy and Complication in Developing Countries. Abass, MO., Gismalla, MDA., Alsheikh, AA., et al.[2019]

A multicenter randomized study showed that using Axillary Reversed Mapping (ARM) during axillary lymph node dissection (ALND) in breast cancer patients can lead to fewer reported complaints of lymphedema compared to standard ALND, suggesting a reduction in postoperative morbidity.

Despite no significant differences in volumetric measurements of lymphedema between the two groups, patient-reported outcomes indicate that ARM-ALND is a valuable surgical refinement that may improve quality of life for patients undergoing surgery for clinically node negative, sentinel node positive early breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A patient- and assessor-blinded randomized controlled trial of axillary reverse mapping (ARM) in patients with early breast cancer. Beek, MA., Gobardhan, PD., Klompenhouwer, EG., et al.[2020]

In a study of 28,631 women with early-stage breast cancer, older patients (70 years and older) were more likely to receive sentinel lymph node biopsy (SLNB) alone instead of axillary lymph node dissection (ALND), indicating a trend towards less invasive surgery in this age group.

The study found that younger patients and those with HER2+ or triple-negative breast cancer were less likely to receive SLNB alone, suggesting that tumor subtype and age influence surgical decisions, even as the adoption of SLNB increased over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient Age and Tumor Subtype Predict the Extent of Axillary Surgery Among Breast Cancer Patients Eligible for the American College of Surgeons Oncology Group Trial Z0011. Ong, CT., Thomas, SM., Blitzblau, RC., et al.[2019]

The MSKCC Additional Nodal Metastasis Nomogram effectively identifies patients with invasive breast cancer who have a low risk of additional axillary metastases, potentially allowing them to avoid unnecessary Axillary Lymph Node Dissection (ALND).

In a study of 175 patients, the nomogram demonstrated high sensitivity (92.3%) and specificity (81.4%), indicating it is a reliable tool for predicting axillary lymph node status in patients with sentinel node macrometastasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Application of a predictive model of axillary lymph node status in patients with sentinel node metastasis from breast cancer. A retrospective cohort study. Vieni, S., Graceffa, G., La Mendola, R., et al.[2018]

In a study of 32 breast cancer patients who received neoadjuvant chemotherapy, targeted axillary dissection demonstrated a high detection rate of 100% for the clipped node, indicating its effectiveness in accurately staging axillary lymph nodes.

The false negative rate (FNR) for targeted axillary dissection was low at 5.0%, which is comparable to the 5.3% FNR for sentinel lymph node biopsy, suggesting that this method is a reliable approach for assessing nodal status after chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of targeted axillary dissection for de-escalation of surgical treatment after neoadjuvant chemotherapy in breast cancer. Aragón-Sánchez, S., Ciruelos-Gil, E., López-Marín, L., et al.[2022]

In a study of 129 female patients with early-stage breast cancer, targeted axillary sampling (AS) showed comparable oncological outcomes to conventional axillary lymph node dissection (ALND), indicating it may be a safe alternative.

The 5-year outcomes for targeted AS were not inferior to those of ALND, regardless of whether patients received additional radiotherapy, suggesting that AS could reduce postoperative morbidities associated with ALND.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

5-year oncological outcomes of targeted axillary sampling in pT1-2N1 breast cancer. Lee, J., Jung, JH., Kim, WW., et al.[2019]

In a study of 60 breast cancer patients undergoing neoadjuvant chemotherapy, several factors were identified as independent predictors of positive axillary lymph node dissection (ALND) results, including tumor size, number of suspicious nodes, HER2 positivity, clinical-radiological response to treatment, and positive targeted axillary dissection (TAD).

A predictive score for positive ALND was developed, showing high accuracy (AUC = 0.93) and could potentially help in safely omitting unnecessary ALND in patients with a low risk of metastasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of a predictive score of axillary lymph node dissection based on targeted axillary dissection in patients with breast cancer diagnosis, affected lymph nodes, and neoadjuvant treatment. Flores-Funes, D., Aguilar-Jiménez, J., Martínez-Gálvez, M., et al.[2022]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Impact of axillary surgery on outcome of clinically node positive breast cancer treated with neoadjuvant chemotherapy. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Avoiding axillary treatment in sentinel lymph node micrometastases of breast cancer: a prospective analysis of axillary or distant recurrence. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Independent risk factors for axillary lymph node metastasis in breast cancer patients with one or two positive sentinel lymph nodes. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Is axillary lymph node dissection indicated for early-stage breast cancer? A decision analysis. [2022]

5. Japan pubmed.ncbi.nlm.nih.gov

Three models for predicting the risk of non-sentinel lymph node metastasis in Japanese breast cancer patients. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Axillary Lymph Node Dissection for Breast Cancer: Efficacy and Complication in Developing Countries. [2019]

7. England pubmed.ncbi.nlm.nih.gov

A patient- and assessor-blinded randomized controlled trial of axillary reverse mapping (ARM) in patients with early breast cancer. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Patient Age and Tumor Subtype Predict the Extent of Axillary Surgery Among Breast Cancer Patients Eligible for the American College of Surgeons Oncology Group Trial Z0011. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Application of a predictive model of axillary lymph node status in patients with sentinel node metastasis from breast cancer. A retrospective cohort study. [2018]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Feasibility of targeted axillary dissection for de-escalation of surgical treatment after neoadjuvant chemotherapy in breast cancer. [2022]

11. Netherlands pubmed.ncbi.nlm.nih.gov

5-year oncological outcomes of targeted axillary sampling in pT1-2N1 breast cancer. [2019]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Development of a predictive score of axillary lymph node dissection based on targeted axillary dissection in patients with breast cancer diagnosis, affected lymph nodes, and neoadjuvant treatment. [2022]