Clinical trial NCT06039956: De-escalating Axillary Surgery in Breast Cancer Patients in Nigeria
Official title: De-escalating Axillary Surgery After Neoadjuvant Chemotherapy in Node Positive Breast Cancer Patients in Nigeria
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Breast Cancer
Axilla; Breast
Keywords: neoadjuvant
de-escalation
breast cancer
axillary lymph node staging
Lead sponsor: Nova Scotia Health Authority
Sponsor class: OTHER
Collaborators: name: Obafemi Awolowo University
First posted: 2023-09-15
Enrollment: 100
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: In sub-Saharan Africa, breast cancer patients often present with advanced disease. In my previous research which evaluated over 600 patients from a prospective institutional data base, about 64% of women with a new diagnosis of breast cancer presented with locally advanced disease, including clinically positive axillary adenopathy. Our data also suggests that similar to African American women, triple negative breast cancer (TNBC) is common in Nigeria (43.5%).

The overall goal of the project is to evaluate the ability of existing technology in Nigeria to safely de-escalate axillary surgery in the management of locally advanced breast cancer patients. Currently, the standard-of-care for breast cancer patients with palpable axillary adenopathy (clinical N1 disease without evidence of distant metastases) at presentation in Nigeria is neoadjuvant systemic therapy followed by a modified radical mastectomy. This includes a complete axillary lymph node dissection (ALND). However, data from high-income countries however show that up to 85% of patients initially presenting with cN1 disease can be converted to cN0 (i.e. no palpable adenopathy) following NAC. These patients can thus safely undergo sentinel lymph node biopsy (SLNB) with up to 50% of these having pathologic complete response in the lymph nodes. In this patient population, both methylene blue and radio-isotope localization with Tc-99 sulphur colloid are required to ensure adequate performance of the SLNB to stage the axilla(i.e. false negative rate ≤10%). Although widely available in high-income countries, radio-isotope localization is not readily available in Nigeria. This project will explore an alternative to dual agent SLNB localization using readily available resources and multi-disciplinary collaboration in a lower-income environment. De-escalation of axillary surgery in high-income countries has significantly decreased operative morbidity and improved patient reported outcomes without compromising survival. However, context specific research and data from resource limited environments is needed to translate the benefit of de-escalation to sub-Saharan Africa.

Detailed description: The overall goal of my research is to promote the delivery of guideline-concordant breast cancer care to Nigerian breast cancer patients in a pragmatic manner. This project is novel in that the investigators are challenging the existing paradigm of dual agent localization, which is appropriate for a high-income setting, but completely out of reach and thus inapplicable in Nigeria despite the obvious need. I will leverage the African Research Group for Oncology (ARGO) breast cancer data base at OAUTHC and other existing research infrastructure to pursue the following specific aims: Aim 1: Determine the false negative rate of of axillary Ultrasound + single agent sentinel Lymph node biopsy in staging the axilla in cN1 patients who become cN0. The investigators will consent patients with complete clinical complete response (clinical assessment and targeted US) following NAC, for SLNB followed by immediate ALND. Presence or absence of residual disease will be reported separately for the SLNB and the ALND specimens. Positive axillary disease will be defined in a binary manner as any invasive disease (including isolated tumor cells) or not. Using ALND reporting as the gold standard, the investigators hypothesize a FNR of less than 10% following SLNB. Aim 2: To determine the proportion of patients with complete axillary LN Clinical \&Pathological cR post NAC. The proportion of patients who return negative for cancer cells following SLNB and or ALND will be determined based on the number of patients with preoperative node positive disease. Both overall pCR and subgroup analysis based on receptor status will be done. The investigators will also assess the concordance of pre-operative clinical and radiographic (i.e. targeted axillary US) assessment of lymph node status with and pathologic lymph node status after NAC. The investigators hypothesize a pCR rate of 50% following completion of NAC

This study will build on the peer-reviewed analysis of our own prospective data demonstrating a high incidence of locally advanced disease and chemo-sensitive subtypes (i.e. TNBC), which suggest that a large proportion of our patients may be candidates for de-escalation. The impact of de-escalation would be profound. Preliminary research into lymphedema as a result of ALND in our patient population suggest an incidence of \> 35%. The proposed study will provide a strong foundation for future studies evaluating the implementation of this strategy and other resource compatible interventions on breast cancer outcomes in Nigeria.

Eligibility criteria: Inclusion Criteria:

* Eligible to receive systemic chemotherapy

Must include all the following:

* Tany, cN1 at presentation
* Biopsy proven pN1 disease after axillary US
* cN0 after neoadjuvant chemotherapy

Exclusion Criteria:

* Previous / recurrent breast cancer
* Previous axillary and/or breast surgery
* Inflammatory breast cancer
* N2 disease or Stage IV disease

Primary outcomes:
measure: False-negative rate
timeFrame: immediately after surgery
Secondary outcomes:
measure: pathologic complete response rate
timeFrame: immediately after surgery
measure: radiographic and clinical concordance
timeFrame: immediately after surgery
measure: Sensitivity of pre-operative axillary US
timeFrame: immediately after surgery
measure: Specificity of pre-operative axillary US
timeFrame: immediately after surgery
measure: False negative rate of pre-operative axillary US
timeFrame: immediately after surgery
measure: Sensitivity of single-agent sentinel lymph node biopsy
timeFrame: immediately after surgery
measure: Specificity of single-agent sentinel lymph node biopsy
timeFrame: immediately after surgery
measure: False negative rate of single-agent sentinel lymph node biopsy
timeFrame: immediately after surgery
Other outcomes:
Locations:
Study officials:
affiliation: Obafemi Awolowo University
name: Olalekan Olasenhinde, MD
role: PRINCIPAL_INVESTIGATOR
References: