HER2-positive early breast cancer Cancer Malignant neoplasm of breast
Conditions
Interventions
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 ad
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 ac
Sponsors
Institute of Cancer Research
Eligibility
Sex/Gender
All
Age
16 Years to 120 Years
Inclusion criteria
Inclusion criteria: 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 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. Study consent =6 weeks after completing breast cancer surgery 10. 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 11. Provision of written informed consent to participate in HER2-RADiCAL
Exclusion criteria
Exclusion criteria: 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 occur within 3 weeks of the last dose of trastuzumab. 16. Clinically significant cardiac disease within 12 months of starting trastuzumab, including unstable angina, acute myocardial infarction, New York Heart Association Class III or IV congestive heart failure, cerebral vascular accident, or cardiac arrhythmia associated with haemodynamic instability 17. Left ventricular ejection fraction (LVEF) less than 50% on most recent cardiac imaging 18. History of interstitial lung disease 19. Any medical or other contra-indication to continuing trastuzumab Previous exclusion criteria: 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. Any planned further resectional surgery for breast cancer (including re-excision, mastectomy, or axillary surgery) 4. HER2-negative invasive breast carcinoma 5. Breast cancer with clinical stage of T=3 at diagnosis 6. Evidence of scarring (or other pathological features consistent with previous malignant involvement) in >4 axillary nodes or clinical nodal stage N=2 at any time 7. Positive SLNB pre-neoadjuvant systemic therapy as this precludes determination of pCR 8. Pregnant and/or lactating women 9. F
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Relapse-free-interval (RFI), defined as time from registration to invasive local or distant relapse or death from breast cancer in the absence of a previously identified relapse (intercurrent deaths and second primary cancers censored). The primary timepoint of interest will be 3 years. | — |
Secondary
| Measure | Time frame |
|---|---|
| Efficacy: 1. Relapse-free-survival (RFS) defined as time from registration to invasive local or distant relapse or death from any cause (second primary cancers censored) 2. Invasive breast cancer-free survival (iBCFS) defined as time from registration to invasive local or distant relapse or ipsilateral or contralateral invasive second primary breast cancer (non-breast second primary cancers censored) or death from any cause 3. Invasive disease-free survival (iDFS) defined as time from registration to invasive local or distant recurrence, new invasive second cancer or death from any cause 4. Distant recurrence-free interval (DRFI) defined as time from registration to distant recurrence or death from any cause (second primary cancers and intercurrent deaths censored) 5. Breast cancer-free interval (BCFI) defined as time from registration to invasive local or distant relapse, or ipsilateral or contralateral invasive second primary breast cancer or DCIS or death from breast cancer in the absence of a previously identified relapse (intercurrent deaths and second primary cancers censored) 6. Overall survival defined as time from registration to death from any cause Other: 1. Treatment pathway adherence: non-adherence is defined as the proportion of patients who receive >9 cycles of trastuzumab or who receive further adjuvant systemic anti-HER2 treatment (e.g. pertuzumab) or chemotherapy prior to recurrence or second primary 2. Cost-effectiveness: quality-adjusted life-years derived from a health economic model developed using clinical trial and real-world data at 3 and 5 years after study entry | — |
Countries
England, Northern Ireland, Scotland, United Kingdom, Wales
Outcome results
None listed