A single arm phase II study using magnetic resonance imaging (MRI) to select patients with early breast cancer for omission of post-operative radiotherapy (ANZ 1002 PROSPECT)

Funding

Other Collaborative groups,Breast Cancer Trials

Scientific enquiries

Prof Bruce Mann

Brief Summary

This study aims to determine if some women with early breast cancer can avoid radiotherapy treatment after breast surgery. If radiotherapy treatment can be omitted without there being any more than a very small risk of the cancer coming back in the same breast, more women may be able to avoid radiotherapy in the future. This means that these women would avoid 5 weeks of daily radiotherapy and the possible short term side effects; including, fatigue, skin redness, discomfort. Radiotherapy is asso .... This study aims to determine if some women with early breast cancer can avoid radiotherapy treatment after breast surgery. If radiotherapy treatment can be omitted without there being any more than a very small risk of the cancer coming back in the same breast, more women may be able to avoid radiotherapy in the future. This means that these women would avoid 5 weeks of daily radiotherapy and the possible short term side effects; including, fatigue, skin redness, discomfort. Radiotherapy is associated with long term side effects which also may be avoided: discomfort in the breast, thickening of breast tissue, and very occasionally possible lung problems (pneumonitis and lung scarring), heart problems and a very small risk of radiation-induced cancer. Who is it for? This study is for women with early breast cancer that must be positive for the oestrogen receptor and/or progesterone receptor and/or human epidermal growth factor receptor. Prior to entering the main study, patients must have a magnetic resonance imaging (MRI) scan. All treatment is standard treatment except that radiotherapy after surgery to remove the breast cancer will not be given. Trial Details The study will use magnetic resonance imaging (MRI) to select women with early breast cancer for whom radiotherapy is not needed because the risk of a local recurrence (cancer coming back in the same area) is low. We are investigating whether the abnormalities found by MRI are in fact the reason that local recurrence sometimes occurs, so if nothing is found on MRI, radiotherapy may not be required.
Read more

Key Inclusion Criteria

1. Female patients >=50 years old with histologically confirmed, unifocal*, unilateral invasive breast cancer 2. In good health and suitable for prolonged follow up with a life expectancy of at least 5 years 3. Breast conserving surgery with invasive primary tumour (including any surrounding DCIS) <=20 mm 4. Resection margins must be >= 2 mm clear of any invasive cancer and >=2 mm clear of any DCIS. However, superficial or deep margins of <2 mm for invasive cancer and DCIS are allowed if all bre .... 1. Female patients >=50 years old with histologically confirmed, unifocal*, unilateral invasive breast cancer 2. In good health and suitable for prolonged follow up with a life expectancy of at least 5 years 3. Breast conserving surgery with invasive primary tumour (including any surrounding DCIS) <=20 mm 4. Resection margins must be >= 2 mm clear of any invasive cancer and >=2 mm clear of any DCIS. However, superficial or deep margins of <2 mm for invasive cancer and DCIS are allowed if all breast tissue from the subcutaneous tissue or pectoralis fascia respectively was removed and radial margins are >=2 mm for invasive cancer and DCIS 5. pN0 by sentinel node biopsy and/or axillary dissection 6. Mammogram must have been performed within 3 months prior to first excisional surgery for breast cancer and must show unifocal* breast cancer 7. Pre-operative MRI must be performed after the patient and the investigator sign screening consent and no more than 6 weeks prior to the first excisional surgery for breast cancer 8. Radiological imaging (Ultrasound, Mammogram and MRI) must be made available for central review as part of the quality control measures for this trial. In the event of an interpretation discrepancy between the local site and the central review, the central review interpretation will be used to determine eligibility. 9. Parenchymal enhancement on pre-operative MRI must be defined as nil/minimal or mild. In the event of an interpretation discrepancy between the local site and the central review, the central review interpretation will be used to determine eligibility 10. Pathology material from any ipsilateral recurrence (invasive tumour and/or DCIS) must be available for submission for central review as part of the quality control measures for this trial. 11. ECOG performance status 0-1 12. Written informed consent must be signed and dated by the patient and the investigator prior to registration to the trial 13. Patients must be informed of and agree to data and tissue material transfer and handling, in accordance with national data protection guidelines 14. Patients must be registered within 8 weeks after final breast surgery and be accessible for long term follow up 15. Patients must cease all hormonal contraceptives and hormone replacement therapies within 4 weeks following histological diagnosis of invasive breast cancer 16. Patients must agree to comply with systemic treatment recommendations (e.g. hormonal therapy for ER+/PR+ tumours, trastuzumab for HER2 positive cancers) * Where histopathology is unable to identify a ‘bridge’ of tumour tissue joining two or more apparent invasive cancer foci the following will be used to confirm unifocal disease: - All foci must be of the same histology - All foci must have the same hormone (ER and PR) and HER2 neu status - In relation to criteria 3: the overall tumour size (including additional foci of DCIS) must remain <=20 mm. The tumour size is defined as the longest distance between the outer most edges of all foci, the space between the two or more foci is included in the overall size: Size = (‘Foci A + Foci B + ‘the distance between A and B’).
Read more

Key Exclusion Criteria

1. Diagnostic MMG shows prominent calcification in the index lesion. 2. Triple negative cancers (ER-ve and PR-ve and HER2-ve) where ER and PR positivity is defined as >=1% staining on IHC 3. Previous in-situ or invasive breast cancer 4. Patients who have had a mastectomy 5. Extensive DCIS (Extensive Intraductal Component (EIC)). Extensive DCIS is defined as invasive carcinoma with the following three components: a. DCIS is present within the invasive tumour; and b. DCIS within invasive tumour co .... 1. Diagnostic MMG shows prominent calcification in the index lesion. 2. Triple negative cancers (ER-ve and PR-ve and HER2-ve) where ER and PR positivity is defined as >=1% staining on IHC 3. Previous in-situ or invasive breast cancer 4. Patients who have had a mastectomy 5. Extensive DCIS (Extensive Intraductal Component (EIC)). Extensive DCIS is defined as invasive carcinoma with the following three components: a. DCIS is present within the invasive tumour; and b. DCIS within invasive tumour comprises more than 25% of the invasive tumour volume; and c. DCIS exists beyond the margin of the invasive tumour 6. Lymphovascular invasion; Multifocal/multicentric breast cancer; Distant metastasis at diagnosis or bilateral breast cancer 7. HER2 positive patients who will not receive trastuzumab as part of adjuvant systemic therapy 8. Gene carriers (BRCA 1,2) or those whose family history of breast cancer reaches the high-risk category of the Cancer Australia 9. Contraindication to MRI scanning (estimated glomerular filtration rate (eGFR) <30 ml/min/1.73m^2, pacemaker, implanted non MRI compatible devices, cochlear implants, neurostimulators, insulin infusion pumps, pregnancy or lactation) 10. Moderate or marked background parenchymal enhancement on pre-operative MRI. In the event of an interpretation discrepancy between the local site and the central review, the central review interpretation will be used to determine eligibility. 11. Concurrent illness/conditions which limits life expectancy to 5 years
Read more