The HER2-RADiCAL study (Response ADaptive CAre pLan) – tailoring treatment for HER2 positive early breast cancer
HER2-positive early breast cancer
Current interventions as of 21/12/2023: Patients taking part in the study will continue treatment with trastuzumab until 9 cycles have been completed (rather than 18 cycles), including those cycles administered prior to study entry. No more pertuzumab will be given after study registration, and patients will not receive chemotherapy after surgery. Some patients may not receive a type of chemotherapy called an anthracycline if this was being deferred to after surgery. Any other treatment that might have been recommended (like hormone therapy or radiotherapy) will be given as normal. Trastuzumab (original or biosimilar) should be given every 3 weeks to complete a total of 9 cycles including those cycles administered prior to study entry; the number of cycles given within the HER2-RADiCAL study is altered according to the number of cycles received prior to study entry. Trastuzumab may be administered via IV or subcutaneous routes in accordance with the standard practice at the site and will be administered as per the SmPC and local guidelines. Subcutaneous trastuzumab is administered at a dose of 600 mg every 3 weeks. Intravenous trastuzumab is administered at a dose of 6 mg/kg body weight every 3 weeks (with a loading dose of 8 mg/kg if required). No dose reductions are permitted. Previous interventions: Patients taking part in the study will continue treatment with trastuzumab until 9 cycles have been completed (rather than 18 cycles), including those cycles administered prior to study entry. No more pertuzumab will be given after study registration, and patients will not receive a type of chemotherapy called an anthracycline, or any other type of chemotherapy, after surgery. Any other treatment that might have been recommended (like hormone therapy or radiotherapy) will be given as normal. Trastuzumab (original or biosimilar) should be given every 3 weeks to complete a total of 9 cycles including those cycles administered prior to study entry; the number of cycl
Current inclusion criteria as of 21/12/2023: 1. Female or male, age ≥16 years 2. Histologically confirmed invasive breast cancer that is HER2-positive (IHC3+, and/or ISH positive/amplified) as determined by the local laboratory in accordance with national guidelines 3. Has received neoSACT chemotherapy with concomitant trastuzumab and pertuzumab 4. pCR (ypT0/is ypN0) in breast and sampled regional lymph nodes as per local pathology reporting 5. Imaging of breast and axilla prior to initiation of neoSACT and either: 5.1. Breast primary radiological measurement ≤20 mm prior to neoSACT and limited nodal involvement (cN1) confirmed by axillary core biopsy or FNA (cT1N1) OR 5.2. Breast primary radiological measurement >20 mm but ≤50 mm and node-negative (cT2N0) or limited nodal involvement (cT2N1) 6. Multiple ipsilateral cancers are permitted provided at least one meets the tumour size and axillary node inclusion criteria and none meet any of the exclusion criteria 7. Bilateral cancers are permitted provided at least one meets the tumour size and axillary node inclusion criteria and none meet any of the exclusion criteria 8. Pre-treatment diagnostic breast tumour biopsy sample available 9. Patient must be fit to continue treatment with trastuzumab and have no concomitant medical, psychiatric or social problems that might interfere with informed consent, adherence to the reduced treatment pathway or follow-up 10. Provision of written informed consent to participate in HER2-RADiCAL Previous inclusion criteria: 1. Female or male, age ≥16 years 2. Histologically confirmed invasive breast cancer that is HER2-positive (IHC3+, and/or ISH positive/amplified) as determined by the local laboratory in accordance with national guidelines 3. Has received neoSACT with a non-anthracycline chemotherapy regimen with at least 3 cycles of concomitant trastuzumab and pertuzumab 4. pCR (ypT0/is ypN0) in breast and sampled regional lymph nodes as per local pathology reporting 5. Imaging of b
Current exclusion criteria as of 21/12/2023: 1. Evidence of metastatic disease at any time since diagnosis 2. Any residual invasive disease following neoSACT. This includes isolated tumour cells in axillary nodes or tissue or evidence of lymphovascular invasion in the breast. Persistent ductal or lobular non-invasive disease (DCIS or LCIS) is permitted. Resection margins must be deemed clear of any residual DCIS according to local MDT protocol 3. Breast-conserving primary surgery where it is known that breast irradiation will not be administered (e.g. due to contraindication or patient preference) 4. Intraoperative assessment of post-neoSACT axillary SLN using one-stop nucleic acid amplification (OSNA) 5. Any planned further resectional surgery for breast cancer (including re-excision, mastectomy, or axillary surgery) 6. HER2-negative invasive breast carcinoma 7. Breast cancer with clinical stage of T≥3 at diagnosis 8. Evidence of scarring (or other pathological features consistent with previous malignant involvement) in >4 axillary nodes or clinical nodal stage N≥2 at any time9. Positive SLNB pre-neoadjuvant systemic therapy as this precludes determination of pCR 10. Pregnant and/or lactating women 11. Female patient of child-bearing potential, unwilling to use an effective form of contraception during trastuzumab treatment and for 7 months after their last dose of trastuzumab 12. Previous diagnosis of invasive breast carcinoma 13. Previous diagnosis of any other (non-breast) malignancy unless disease-free for at least 5 years and considered to be at low risk of recurrence or treated basal cell or localised squamous cell carcinoma of the skin or cervical intraepithelial neoplasia 14. Chemotherapy administered following surgery (NB. Pertuzumab and/or trastuzumab may have been continued after surgery as per local practice prior to study entry) 15. Has received >9 cycles trastuzumab. In the event a patient has received 9 cycles prior to study entry then consent must o