Omission of Surgery and Sentinel Lymph Node Dissection in Clinically Low-risk HER2positive Breast Cancer With High HER2 Addiction and a Complete Response Following Standard Anti-HER2-based Neoadjuvant Therapy
This is a prospective, single arm, open-label, unicenter, exploratory study in women with primary operable HER2-positive, HER2-enriched/ERBB2-high breast cancer according to PAM50 intrinsic subtype and a ERBB2 pre-defined cutoff (high vs low ERBB2 expression), to evaluate the omission of surgery and sentinel lymph node dissection in patients with HER2-E and ERBB2 high breast cancer who achieving a complete response following standard anti-HER2-based neoadjuvant therapy with paclitaxel/trastuzumab/pertuzumab. The primary trial objective is to estimate the loco-regional invasive disease-free survival at 3-year of patients who achieve a complete response based on imaging (i.e. Magnetic resonance imaging) and a stereotactic-guided vacuum-assisted breast biopsy, and omit loco-regional surgery.
• Female participants who are at least 40 years of age on the day of signing the informed consent form with histologically confirmed diagnosis of breast cancer.
• A participant is eligible to participate if she is not pregnant, not breastfeeding.
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
• Histologically confirmed invasive adenocarcinoma of the breast, with all of the following characteristics:
‣ HER2-positive status by local determination according to 2018 ASCO/CAP guidelines.
⁃ PAM50 HER2-enriched subtype and ERBB2-high as predefined cutoff as per central determination.
⁃ Unifocal invasive carcinoma: only 1 invasive focus can be observed (the tumor focus containing or not containing an in situ component)
⁃ Tumor largest diameter ≤4 cm as defined by breast MRI.
⁃ No nodal involvement (i.e. cN0). Any suspicious axillary node by ultrasound must be biopsied. If the biopsy or the FNA is negative of tumor cells, patient is eligible.
⁃ No evidence of distant metastasis (M0) by routine clinical assessment.
• Patient must have known ER and PR status locally determined prior to study entry.
• Eligible for taxane therapy.
• Willingness of the patient to omit surgery if all criteria are met following neoadjuvant therapy.
• Estimated life expectancy of at least 5 years irrespective of the diagnosis of breast cancer.
• Breast cancer eligible for primary surgery
⁃ Have provided archival tumor tissue sample or newly obtained core. Formalin-fixed,paraffin embedded (FFPE) tissue blocks are mandatory. Available pre-treatment FFPE core biopsy evaluable for PAM50 or possibility to obtain one.
⁃ Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
⁃ Ability and willingness to comply with study visits, treatment, testing and to comply with the protocol.
⁃ Have adequate organ function.