Clinical trial NCT05951699: Mini-invasive Detection of Residual Disease in Breast Cancer Patients in Remission After Primary Chemotherapy
Official title: Prospective Clinical Trial to Assess a Mini-invasive Pre-surgical Procedure to Detect Residual Breast or Axillary Disease in Patients With cT1-T2-T3 cN0/N1 Breast Cancer in Complete Clinical/Radiological Remission After Primary Chemotherapy
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Breast Cancer
Keywords: Breast cancer
Neoadjuvant chemotherapy
vacuum-assisted biopsy
Lead sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Sponsor class: OTHER
First posted: 2023-07-19
Enrollment: 105
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: cT1-cT2-cT3 cN0-cN1 breast cancer patients, either with clinical/radiological complete response, or with \<1 cm residual breast disease after systemic primary treatment

Brief summary: Breast surgery may be overtreatment when there is a complete response to systemic neoadjuvant treatment as determined clinically and by imaging. However the reliability of imaging techniques (ultrasound, mammography and magnetic resonance) in identifying complete response varies in published studies and surgery remains the preferred method of detecting residual disease.

The aims of this study are:

1. To assess the reliability of minimally invasive preoperative image-guided vacuum-assisted biopsy (VAB) in identifying residual breast in cT1-cT2-cT3, cN0-cN1 breast cancer patients, either with complete clinical/radiological response, or with residual breast disease \<1 cm, after systemic neoadjuvant treatment.
2. To assess the reliability of minimally invasive preoperative image-guided needle biopsy in identifying residual axillary disease in cT1-cT2-cT3, cN0-cN1 breast cancer patients, either with complete clinical/radiological response, or with residual breast disease \<1 cm, after systemic neoadjuvant treatment.

After neoadjuvant treatment, and evaluation with ultrasound, mammography and magnetic resonance, VAB will be performed on the breast, and needle biopsy will be performed on the axillary lymph node of pre-treatment cN1 cases, previously marked with a magnetic clip.

The biopsy findings will be compared with the surgical findings, consisting in quadrantectomy or mastectomy plus sentinel node biopsy (or separate removal of tagged lymph nodes if they do not coincide with the sentinel node(s)) to assess the ability of biopsy to identify residual disease.

Detailed description: Systemic neoadjuvant treatment was introduced in the 1990s (1,2) mainly for advanced (cT2, cT3) breast cancer to reduce the extent of disease and hence allow conservative surgery instead of mastectomy.

Studies (3-6) demonstrated that pathologic complete response (pCR) in the breast and/or axilla after neoadjuvant treatment predicted better overall survival (OS), better distant relapse-free survival (DRS), and lower mortality.

More recently, targeted neoadjuvant therapies achieve pCR in over 60% of patients (7,8) and in up to 70% of patients with HER2-positive or triple negative subtypes that are generally associated with poorer outcomes (9).

Ultrasound, mammography and magnetic resonance imaging are still imprecise in identifying surgically confirmed residual disease after neoadjuvant chemotherapy (10,11) and the sensitivity and specificity of these imaging techniques vary markedly, (12) so surgery remains the most reliable method of detecting any residual disease.

The aims of this study are

1. to evaluate the ability of minimally invasive preoperative image-guided vacuum-assisted biopsy (VAB) to identify residual breast disease in breast cancer patients with either complete clinical/radiological complete response or with residual disease \<1 cm after systemic neoadjuvant treatment; and
2. to evaluate the ability of biopsy to identify residual axillary lymph node disease in patients who are cN1 pre-treatment and whose suspicious nodes are marked with a metal clip before treatment.

The VAB/needle biopsy results will be compared to pathological findings after quadrantectomy/mastectomy or surgical removal of the sentinel axillary lymph node(s) and tagged axillary lymph node(s) (if distinct from the sentinel node(s)).

This study is being conducted with a view to performing a future clinical trial on the omission of surgery in cases with clinical/radiological complete response and negative preoperative VAB.

Eligibility criteria: Inclusion Criteria:

* Radiologically confirmed unifocal cT1-cT2-cT3 cN0-cN1 breast cancer patients indicated for primary chemotherapy
* Histologically confirmed HER2-positive, triple negative or luminal B HER2-positive invasive breast cancer
* Clinical/radiological complete response or residual breast disease \<1 cm after primary chemotherapy
* Absence of locoregional relapse or distant metastasis
* Signed informed consent to participate.

Exclusion Criteria:

* Disease surgically inoperable or surgery not performed
* Multifocal disease or presence of microcalcifications at imaging.

Primary outcomes:
measure: Evaluation of the accuracy of histological examination of the breast VAB performed pre-surgery
timeFrame: 40 days
Secondary outcomes:
measure: Evaluation of the accuracy of histological examination of the lymph node biopsy performed pre-surgery
timeFrame: 40 days
Other outcomes:
Locations:
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
Study officials:
affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori, Via G. Venezian 1, 20133 Milan, Italy
name: Gabriele Martelli, MD
role: PRINCIPAL_INVESTIGATOR
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