Breast CancerPROSPECTIVENCT06445738
Post-operative Radiotherapy Omission in Selected Patients With Early Breast Cancer Trial International VErsion (PROSPECTIVE)
A study testing Arm A: Radiotherapy Omission and Arm B: Standard Treatment in people with Breast Cancer and Breast Cancer Female, run by Breast Cancer Trials, Australia and New Zealand at 9 sites in 2 countries.
Trial summary
The PROSPECTIVE trial aims to find out if using the results of Magnetic Resonance Imaging (MRI) for early breast cancer can select people to not have radiotherapy and still have a low chance of the cancer coming back after surgery. Read more about this study
- Who is it for?
- Ages 50 years and older, women only
- Conditions the study is for
- Breast Cancer, Breast Cancer Female
- What is being tested?
- Arm A: Radiotherapy Omission and Arm B: Standard Treatment
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,400 participants
- Where
- 9 sitesin 2 countries
- Study dates
- 6 Jun 2025to Jun 2039
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- For inclusion in the study at Registration, participants must fulfil all of the following criteria:
- Has provided written, informed consent to participate in the study.
- Female participants ≥ 50 years old with histologically* confirmed ER-positive and/or HER2-positive invasive breast cancer.
- Has a life expectancy of at least 10 years and suitable for prolonged follow up for 10 years.
- Breast imaging indicating unifocal, unilateral breast cancer must have been performed before pre-registration.
- Willing/able to have surgery within 8 weeks of registration or pre-operative MRI, whichever occurs later.
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- Have ECOG performance status 0-2.
- Oestrogen receptor and progesterone receptor status of invasive cancer will be assessed by immunohistochemistry on the diagnostic core biopsy specimen. The IHC results will be reported as percentage of nuclei stained and a score of intensity from negative, weak, intermediate or high staining
- HER2 neu status will be assessed by immunohistochemistry and will be scored as follows46:
- 0 or 1+ (HER2 negative): No staining or membrane staining that is incomplete and is faint/barely perceptible and in ≤ 10% of tumour cells (0); or incomplete membrane staining that is faint/barely perceptible and in > 10% of tumour cells (1+).
- 2+ (equivocal): weak to moderate complete membrane staining observed in > 10% of tumour cells. Must order reflex test (same specimen using ISH) or order a new test (new specimen if available using HIS or ISH).
- 3+ (HER2 positive): Circumferential membrane staining that is complete, intense and in > 10% of tumour cells.
Who cannot join
- Any one of the following at Registration is regarded as a criterion for exclusion from the study:
- Triple negative breast cancer (ER-negative and PR-negative and HER2-negative) where ER and PR positivity is defined as ≥ 10% staining on IHC.
- Previous invasive breast cancer and/or DCIS in either breast.
- Prior RT to the breast or chest.
- Participants who plan to have a mastectomy for the index cancer.
- Lymphovascular invasion (LVI) reported on diagnostic core biopsy.
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- Multifocal/multicentric breast cancer on breast imaging before registration.
- Distant metastasis at diagnosis.
- Bilateral breast cancer
- Known breast cancer predisposition gene mutation carriers (BRCA1, BRCA2, PALB2, CHEK2, ATM, CDK1, p53, BARD1, RAD51C, RAD51D, CDH1, STK11, PTEN).
- Contraindication to breast MRI scanning.
- Concurrent illness/conditions which limits life expectancy to 10 years or less.
- Has moderate or marked BPE in the breast containing the index cancer (where MRI is done before registration).
- Inability to give informed consent.
- Allocation: Arm A - Radiotherapy Omission
- In addition to the above criteria, for inclusion in the omission of radiation therapy arm of the study after surgery, participants must fulfil all the following criteria. Participants not fulfilling any one of the following criterial will be allocated to Arm B:
- Has nil/minimal or mild BPE in the breast containing the index lesion on pre-operative breast MRI.
- BCS with unifocal**, invasive primary tumour (including any surrounding DCIS) ≤ 20 mm.
- 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 = ('Focus A + Focus B + 'the distance between A and B').
- Radial resection margins must be ≥ 2 mm clear of any invasive cancer and ≥ 2 mm clear of any DCIS. Superficial or deep margins of < 2 mm for invasive cancer and DCIS are allowed if there is no tumour on ink and all breast tissue from the subcutaneous tissue or pectoralis fascia respectively was removed and radial margins are ≥ 2 mm for invasive cancer and DCIS.
- pN0 (pN0 i+ is eligible for inclusion) by sentinel node biopsy and/or axillary dissection.
- Absence of LVI and extensive intraductal component (EIC) on final pathology.
- The extent of invasive cancer is at least 50% of the total tumour size (invasive cancer + DCIS).
- Have no additional BIRADS 3+ lesions not shown to be benign on pre-operative or surgical biopsy.
- Participants with Grade 3 cancer and/or HER2-positive cancer must agree to comply with systemic treatment recommendations.
- Participants must be allocated to a treatment arm within 8 weeks after final breast surgery.
- 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 histological subtype
- All foci must have the same hormone (ER and PR) and HER2 status.
- Allocation: Arm B - Standard Treatment (ineligible for RT omission on study; includes management of MRI-detected lesions)
- In addition to the above Inclusion Criteria, participants who fulfil one any of the following criteria will receive standard treatment:
- Has moderate or marked BPE in the breast containing the index lesion on pre-operative breast MRI.
- Has a biopsy-proven mOL identified on breast MRI.
- Suspicious lesion identified on CEM but not on MRI and confirmed on investigation to be a DCIS or invasive breast cancer.
- Surgical pathology does not meet the inclusion criteria. 2mm radial margins are required, as guidelines suggesting "no tumour on ink" relate to those receiving adjuvant RT.
- Clinical team meeting determination that RT be recommended.
- Participant chooses to have RT despite being eligible for RT omission.
Trial locations and contacts
9 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
9 sites in 2 countries
Australia7 sites, 7 recruiting
- Not yet recruiting
Royal Adelaide Hospital
Adelaide, South Australia, 5000
Janne Bingham, Dr
- Not yet recruiting
The Chris O'Brien Lifehouse
Camperdown, New South Wales, 2050
Sanjay Warrier, A/Prof
- Recruiting
Monash Cancer Centre (MMC Moorabbin)
Clayton, Victoria, 3168
Corinne Wei Leng Ooi, Dr
- Not yet recruiting
Lake Macquarie Private Hospital
Gateshead, New South Wales, 2290
Shanta Velaiutham, Dr
- Recruiting
The Royal Melbourne Hospital
Melbourne, Victoria, 3000
Bruce Mann, Prof
- Recruiting
Mater Hospital, Sydney
North Sydney, New South Wales, 2060
Andrew Spillane, Prof
- Not yet recruiting
Westmead Hospital
Westmead, New South Wales, 2145
Elisabeth Elder, Dr
United States2 sites, 2 recruiting
- Not yet recruiting
Baylor St Luke's Medical Centre
Houston, Texas, 77030
Alastair Thompson, Prof, +1 (713) 798 2901, alastair.thompson@bcm.edu
Alastair Thompson, Prof
- Not yet recruiting
UCSF Breast Care Center
San Francisco, California, 94158
Michael Alvarado, Prof, +1 (415) 353-7070, michael.alvarado@ucsf.edu
Michael Alvarado, Prof
About this study
Official title: A Two-arm, Non-randomised, Prospective, Multicentre Study Using Magnetic Resonance Imaging (MRI) Findings and Pathology Features to Select Patients With Early Breast Cancer for Omission of Post-operative Radiotherapy
The PROSPECTIVE trial aims to find out if using the results of Magnetic Resonance Imaging (MRI) for early breast cancer can select people to not have radiotherapy and still have a low chance of the cancer coming back after surgery.
The main question it aims to answer is:
- Will cancer come back in the same breast as the original cancer in patients who have surgery for their breast cancer, but who don't have radiotherapy afterwards because the results of an MRI before surgery showed favourable characteristics for not having radiotherapy.
Read the detailed description
Breast cancer is the most common serious malignancy in women and most patients are suitable for therapy involving surgery and adjuvant radiotherapy (RT). For most patients, there is a lack of evidence that breast conserving surgery without adjuvant RT is safe and therefore patients bear the costs, inconvenience and morbidity of RT. Prior attempts to identify large subsets of patients for whom RT can be safely omitted based on clinicopathological features of the index cancer have had limited success, and so RT is currently omitted only in some women over 65 or 70 with small low risk cancers. Identification of a much larger subset of patients in whom adjuvant RT could be safely omitted would be hugely significant, not only to the patients, but to the entire health system.
The ANZ 1002 PROSPECT study was a two-arm phase II study that used breast MRI findings and pathological features to identify a group of patients with low risk early breast cancer in whom RT may be safely omitted. The findings at the primary strongly support the hypothesis and suggest that the combination of preoperative MRI and pathological features can identify a substantial group of early breast cancer patients in whom adjuvant RT can be safely omitted.
A Health Economic analysis of PROSPECT found that the avoided costs of RT and its potential side effects is likely to substantially outweigh the extra cost of MRI scans and associated investigations. Parallel cross-sectional studies assessing Fear of Cancer Recurrence (FCR) and Health Related Quality of Life (HRQoL) in patients taking part in PROSPECT who either did or did not receive RT and a control group found a substantially lower FCR in PROSPECT patients who omitted RT as well as improved HRQoL.
The majority of screened and eligible patients (427/443 and 193/201, respectively) for PROSPECT were recruited from two Australian sites. Before the PROSPECT approach can be widely adopted, the findings need to be replicated in a multicentre, international study. In addition, patient reported outcomes and health economic assessments need to be performed prospectively and longitudinally.
PROSPECTIVE is the follow-up to PROSPECT which will address these issues, and also include translational research aspects to further study the natural history and outcomes of this group of lower risk early breast cancers.
- Conditions
- Breast Cancer, Breast Cancer Female
- Being tested
- Arm A: Radiotherapy Omission, Arm B: Standard Treatment
- Keywords
- Omission of radiotherapy, Magnetic Resonance Imaging (MRI)
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Arm A: Radiotherapy OmissionRadiation
Also called A1: Grade 1 or 2/HER2 negative; A2: Grade 3 and/or HER2 positive
Omission of radiotherapy based on pre-surgical MRI and pathology findings at surgery.
Arm B: Standard TreatmentOther
Ineligible for RT omission on study; includes management of MRI-detected lesions.
| Study group | Role | What they receive |
|---|---|---|
| Radiotherapy Omission | Experimental | Participants with nil, minimal or mild parenchymal enhancement on pre-operative MRI whose pathology meets inclusion/exclusion requirements for omission of post-operative radiotherapy will be allocated to Arm A, unless the participant prefers to receive Standard Treatment (Arm B) or following clinical team recommendation.
Arm A participants will be divided into 2 groups:
* Arm A1: Grade 1 or 2/HER2 negative ("low risk")
* Arm A2: Grade 3 and/or HER2 positive ("high risk") Receives: Radiation: Arm A: Radiotherapy Omission |
| Standard Treatment | Active comparator | Participants who are found to be ineligible for RT omission on study; includes management of MRI-detected lesions.
Participants with any of:
* Moderate or marked parenchymal enhancement on pre-operative MRI
* A malignant occult lesion identified on MRI; or
* Pathology that does not meet inclusion/exclusion criteria will receive standard multidisciplinary team recommendations to guide treatment. Participants may also be included in Arm B due to their own preference or following clinical team recommendation. Receives: Other: Arm B: Standard Treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ipsilateral Invasive Recurrence Rate (IIRR) in low-risk patients omitting RT at a median of 5 years follow up
To determine the ipsilateral invasive recurrence rate (IIRR) in lower risk patients with unequivocally unifocal breast cancer and on breast MRI and favourable clinico-pathological features.
Measured: Median of 5 years follow up (when 300th low risk patient in Arm A reaches 5 years follow up)
Secondary outcomes (24)
Ipsilateral Invasive Recurrence Rate (IIRR) in all participants omitting RT at a median of 10 years follow up after surgery.
To determine the ipsilateral invasive recurrence rate (IIRR) in patients allocated to omit radiotherapy (Arm A1).
Measured: Median of 10 years follow up after surgery.
IIRR in participants in Arm A1, Arm A2, Arm A, Arm B, and Arms A+B.
To determine the ipsilateral invasive recurrence rate (IIRR) in participants in Arm A2, Arm A, Arm B, and Arms A+B.
Measured: Median of 5 years and 10 years follow up after surgery.
Ipsilateral DCIS recurrence rate in participants in Arm A1, Arm A2, Arm A, Arm B, and Arms A+B.
To determine the ipsilateral DCIS rate in the breast in participants in Arm A1, Arm A2, Arm A, Arm B, and Arms A+B.
Measured: Median of 5 and 10 years follow up after surgery.
The combined ipsilateral DCIS and invasive recurrence rate (IRR) in participants in Arm A1, Arm A2, Arm A, Arm B, and Arms A+B.
To determine the combined ipsilateral DCIS and invasive recurrence rate (IRR) in the breast in participants in Arm A1, Arm A2, Arm A, Arm B, and Arms A+B.
Measured: Median of 5 and 10 years follow up after surgery.
Regional recurrence rate in participants in Arm A1, Arm A2, Arm A, Arm B, and Arms A+B.
To determine the regional recurrence rate in participants in Arm A1, Arm A2, Arm A, Arm B, and Arms A+B.
Measured: Median of 5 and 10 years follow up after surgery.
Distant recurrence rate in participants in Arm A1, Arm A2, Arm A, Arm B, and Arms A+B..
To determine the distant recurrence rate in participants in Arm A1, Arm A2, Arm A, Arm B, and Arms A+B.
Measured: Median of 5 and 10 years follow up after surgery.
Contralateral DCIS and invasive breast cancer rate in participants in Arm A1, Arm A2, Arm A, Arm B, and Arms A+B
To determine the contralateral DCIS and invasive breast cancer rate in participants in Arm A1, Arm A2, Arm A, Arm B, and Arms A+B.
Measured: Median of 5 and 10 years follow up after surgery.
Breast cancer specific survival (BCSS) in participants in Arm A1, Arm A2, Arm A, Arm B, and Arms A+B
BCCS rate defined as the percentage of people who have not died from breast cancer.
Measured: Median of 5 and 10 years follow up after surgery.
Overall Survival (OS) in participants in Arm A1, Arm A2, Arm A, Arm B, and Arms A+B.
OS rate defined as the percentage of people alive.
Measured: Median of 5 and 10 years follow up after surgery.
PRO: Fear of Cancer Recurrence
To determine the difference in Fear of cancer recurrence (FCR) between Arm A and Arm B measured by the Fear of Cancer Recurrence Inventory Short Form (FCRI-SF). A higher score indicates a greater fear of recurrence.
Measured: Median 24 months post-surgery
PRO: Levels of FCR and perception of risk of recurrence in Arm A over time.
To determine the difference in levels of FCR and perception of risk of recurrence in Arm A measured by the Fear of Cancer Recurrence Inventory - Short Form and 2 items adapted from Abbott et al. A higher score indicates greater fear of recurrence and greater risk perception.
Measured: At median of 24 months post-surgery
PRO: Difference in FCR and perception of risk of recurrence between Arm A and Arm B.
To determine the difference over time in FCR and perception of risk of recurrence between Arm A and Arm B over time as measured by the FCRI-SF and 2 items adapted from Abbott et al. A higher score indicates greater fear of recurrence and greater risk perception.
Measured: From allocation to 3-, 6-, 12-, 24- and 60 months median follow-up post-surgery.
PRO: Perception of risk of recurrence in Arm A and between Arm A and Arm B.
To determine the difference in perceptions of risk of recurrence in the breast and elsewhere in the body measured by 2 items adapted from Abbott et al. A higher score indicates greater risk perception.
Measured: From allocation to 3-, 6-, 12-, 24- and 60 months median follow up post-surgery
PRO: Health Related Quality of Life (HRQoL) (functional and aesthetic outcomes, fatigue, body image, financial toxicity) between Arm A and Arm B.
To determine the difference in breast-specific symptoms, cosmetic status, arm- and shoulder functional status measured by the Breast Cancer Treatment Outcomes Scale (BCTOS); and fatigue, body image, financial toxicity measured by the EORTC IL353. A higher score indicates greater morbidity, greater fatigue; greater financial toxicity; poorer body image.
Measured: At a median of 24 months post-surgery.
PRO: Health Related Quality of Life (HRQoL) (functional and aesthetic outcomes, fatigue, body image, financial toxicity) in Arm A
To determine the HRQoL (functional and aesthetic outcomes, fatigue, body image, financial toxicity), in Arm A measured by the BCTOS (breast-specific symptoms, cosmetic status, arm- and shoulder functional status) EORTC IL353 measure (custom measure for this protocol) (fatigue, body image, financial toxicity). A higher score indicates greater fatigue, poorer body image and greater financial toxicity.
Measured: From allocation to 3-, 6-, 12-, 24- and 60 months median follow up post-surgery
PRO: Difference over time in HRQoL (functional and aesthetic outcomes, fatigue, body image, financial toxicity) between Arm A and Arm B.
To determine the difference in breast-specific symptoms, cosmetic status, arm- and shoulder functional status measured by the BCTOS; and fatigue, body image, financial toxicity measured by the EORTC IL353between Arm A and Arm B.
Measured: From allocation to 3-, 6-, 12-, 24- and 60 months median follow-up post-surgery.
PRO: Quality of Life Years (QALYs) between Arms A and Arm B.
To determine the Quality of Life Years (QALYs) between Arms A and Arm B measured by the EQ-5D-5L. A high score indicates more problems.
Measured: At a median of 24 months follow up post-surgery.
PRO: Difference in QALYs over time between Arm A and Arm B.
To determine the Quality of Life Years (QALYs) between Arms A and Arm B over time measured by the EQ-5D-5L. A high score indicates more problems.
Measured: From registration to allocation, 3-, 6-, 12-, 24- and 60 months median follow-up post-surgery..
PRO: Difference in Decision Regret between Arm A and Arm B.
To determine the difference in decision regret between Arm A and Arm B measured by Decision Regret Scale. A higher score indicates more regret.
Measured: At median of 24 months follow up post-surgery.
PRO: Decision Regret in Arm A.
To determine decision regret in Arm A measured by Decision Regret Scale. A higher score indicates more regret.
Measured: At median 24 months of follow-up post-surgery.
PRO: Overall mental health and depression over time between Arm A and Arm B.
To determine the overall mental health and differences over time in depression between Arm A and Arm B. Measured by the Patient Health Questionnaire-2. A higher score indicates and greater symptom burden.
Measured: From allocation to 3-, 6-, 12-, 24- and 60 months median follow-up post-surgery.
PRO: Overall mental health and differences over time in anxiety in Arm A.
To determine the overall mental health and differences over time in anxiety in Arm A, measured by the Generalized Anxiety Disorder-2. A higher score indicates a higher symptom burden.
Measured: At 24 months median follow-up post-surgery.
PRO: Overall mental health (depression) over time between Arm A and Arm B.
To determine the overall mental health and differences over time in depression between Arm A and Arm B. Measured by the Patient Health Questionnaire-2. A higher score indicates and greater symptom burden.
Measured: From allocation to 3-, 6-, 12-, 24- and 60 months median follow-up post-surgery.
PRO: Overall mental health (anxiety) over time between Arm A and Arm B.
To determine the overall mental health and differences over time in anxiety between Arm A and Arm B. Measured by the Generalized Anxiety Disorder-2. A higher score indicates and greater symptom burden.
Measured: From allocation to 3-, 6-, 12-, 24- and 60 months median follow-up post-surgery.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2024
- Study start6 Jun 2025
- Primary completionJun 2032 (estimated)
- Study completionJun 2039 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- A two-arm, non-randomised, prospective, multicentre study using MRI findings and pathology features to select patients with early breast cancer for omission of post-operative radiotherapy.
- Masking
- None (open label)
- Enrolment
- 1,400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Breast Cancer Trials, Australia and New Zealand
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Bruce Mann, MD, Study chair, Melbourne HealthSteven David, MD, Study chair, Peter MacCallum Cancer Centre - MoorrabinAlastair Thompson, MD, Study chair, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06445738
- Sponsor's protocol ID
- BCT 2401
- Acronym
- PROSPECTIVE
- Status last verified
- Jan 2026
- First submitted
- 24 May 2024
- Last updated
- 15 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Anonymised Individual Patient Data (IPD) collected during the trial.
Study at a glance
From the registry record, last updated by the sponsor on 15 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Two-arm, Non-randomised, Prospective, Multicentre Study Using Magnetic Resonance Imaging (MRI) Findings and Pathology Features to Select Patients With Early Breast Cancer for Omission of Post-operative Radiotherapy
- ClinicalTrials.gov ID
- NCT06445738
- Acronym / sponsor ID
- PROSPECTIVE / BCT 2401
- Conditions
- Breast Cancer, Breast Cancer Female
- Keywords
- Omission of radiotherapy, Magnetic Resonance Imaging (MRI)
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 1,400 participants (estimated)
- Lead sponsor
- Breast Cancer Trials, Australia and New ZealandUniversity, hospital or other
- Study start
- 6 Jun 2025 (actual)
- Primary completion
- Jun 2032 (estimated)
- Study completion
- Jun 2039 (estimated)
- First posted
- 6 Jun 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The PROSPECTIVE trial aims to find out if using the results of Magnetic Resonance Imaging (MRI) for early breast cancer can select people to not have radiotherapy and still have a low chance of the cancer coming back after surgery.
The main question it aims to answer is:
- Will cancer come back in the same breast as the original cancer in patients who have surgery for their breast cancer, but who don't have radiotherapy afterwards because the results of an MRI before surgery showed favourable characteristics for not having radiotherapy.
Detailed description
Breast cancer is the most common serious malignancy in women and most patients are suitable for therapy involving surgery and adjuvant radiotherapy (RT). For most patients, there is a lack of evidence that breast conserving surgery without adjuvant RT is safe and therefore patients bear the costs, inconvenience and morbidity of RT. Prior attempts to identify large subsets of patients for whom RT can be safely omitted based on clinicopathological features of the index cancer have had limited success, and so RT is currently omitted only in some women over 65 or 70 with small low risk cancers. Identification of a much larger subset of patients in whom adjuvant RT could be safely omitted would be hugely significant, not only to the patients, but to the entire health system.
The ANZ 1002 PROSPECT study was a two-arm phase II study that used breast MRI findings and pathological features to identify a group of patients with low risk early breast cancer in whom RT may be safely omitted. The findings at the primary strongly support the hypothesis and suggest that the combination of preoperative MRI and pathological features can identify a substantial group of early breast cancer patients in whom adjuvant RT can be safely omitted.
A Health Economic analysis of PROSPECT found that the avoided costs of RT and its potential side effects is likely to substantially outweigh the extra cost of MRI scans and associated investigations. Parallel cross-sectional studies assessing Fear of Cancer Recurrence (FCR) and Health Related Quality of Life (HRQoL) in patients taking part in PROSPECT who either did or did not receive RT and a control group found a substantially lower FCR in PROSPECT patients who omitted RT as well as improved HRQoL.
The majority of screened and eligible patients (427/443 and 193/201, respectively) for PROSPECT were recruited from two Australian sites. Before the PROSPECT approach can be widely adopted, the findings need to be replicated in a multicentre, international study. In addition, patient reported outcomes and health economic assessments need to be performed prospectively and longitudinally.
PROSPECTIVE is the follow-up to PROSPECT which will address these issues, and also include translational research aspects to further study the natural history and outcomes of this group of lower risk early breast cancers.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- A two-arm, non-randomised, prospective, multicentre study using MRI findings and pathology features to select patients with early breast cancer for omission of post-operative radiotherapy.
| Arm | Type | Receives |
|---|---|---|
| Radiotherapy Omission | Experimental | Radiation: Arm A: Radiotherapy OmissionParticipants with nil, minimal or mild parenchymal enhancement on pre-operative MRI whose pathology meets inclusion/exclusion requirements for omission of post-operative radiotherapy will be allocated to Arm A, unless the participant prefers to receive Standard Treatment (Arm B) or following clinical team recommendation. Arm A participants will be divided into 2 groups: * Arm A1: Grade 1 or 2/HER2 negative ("low risk") * Arm A2: Grade 3 and/or HER2 positive ("high risk") |
| Standard Treatment | Active comparator | Other: Arm B: Standard TreatmentParticipants who are found to be ineligible for RT omission on study; includes management of MRI-detected lesions. Participants with any of: * Moderate or marked parenchymal enhancement on pre-operative MRI * A malignant occult lesion identified on MRI; or * Pathology that does not meet inclusion/exclusion criteria will receive standard multidisciplinary team recommendations to guide treatment. Participants may also be included in Arm B due to their own preference or following clinical team recommendation. |
Who may qualify
- Ages
- 50 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- For inclusion in the study at Registration, participants must fulfil all of the following criteria:
- Has provided written, informed consent to participate in the study.
- Female participants ≥ 50 years old with histologically* confirmed ER-positive and/or HER2-positive invasive breast cancer.
- Has a life expectancy of at least 10 years and suitable for prolonged follow up for 10 years.
- Breast imaging indicating unifocal, unilateral breast cancer must have been performed before pre-registration.
Key exclusion criteria (37 listed)
- Any one of the following at Registration is regarded as a criterion for exclusion from the study:
- Triple negative breast cancer (ER-negative and PR-negative and HER2-negative) where ER and PR positivity is defined as ≥ 10% staining on IHC.
- Previous invasive breast cancer and/or DCIS in either breast.
- Prior RT to the breast or chest.
- Participants who plan to have a mastectomy for the index cancer.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Arm A: Radiotherapy OmissionAlso: A1: Grade 1 or 2/HER2 negative; A2: Grade 3 and/or HER2 positiveOmission of radiotherapy based on pre-surgical MRI and pathology findings at surgery. | Radiation | Radiotherapy Omission |
| Arm B: Standard TreatmentIneligible for RT omission on study; includes management of MRI-detected lesions. | Other | Standard Treatment |
Primary outcome
Ipsilateral Invasive Recurrence Rate (IIRR) in low-risk patients omitting RT at a median of 5 years follow up
Time frame: Median of 5 years follow up (when 300th low risk patient in Arm A reaches 5 years follow up)
To determine the ipsilateral invasive recurrence rate (IIRR) in lower risk patients with unequivocally unifocal breast cancer and on breast MRI and favourable clinico-pathological features.
24 secondary outcomes
Ipsilateral Invasive Recurrence Rate (IIRR) in all participants omitting RT at a median of 10 years follow up after surgery.
Time frame: Median of 10 years follow up after surgery.
IIRR in participants in Arm A1, Arm A2, Arm A, Arm B, and Arms A+B.
Time frame: Median of 5 years and 10 years follow up after surgery.
Ipsilateral DCIS recurrence rate in participants in Arm A1, Arm A2, Arm A, Arm B, and Arms A+B.
Time frame: Median of 5 and 10 years follow up after surgery.
The combined ipsilateral DCIS and invasive recurrence rate (IRR) in participants in Arm A1, Arm A2, Arm A, Arm B, and Arms A+B.
Time frame: Median of 5 and 10 years follow up after surgery.
Regional recurrence rate in participants in Arm A1, Arm A2, Arm A, Arm B, and Arms A+B.
Time frame: Median of 5 and 10 years follow up after surgery.
Distant recurrence rate in participants in Arm A1, Arm A2, Arm A, Arm B, and Arms A+B..
Time frame: Median of 5 and 10 years follow up after surgery.
Contralateral DCIS and invasive breast cancer rate in participants in Arm A1, Arm A2, Arm A, Arm B, and Arms A+B
Time frame: Median of 5 and 10 years follow up after surgery.
Breast cancer specific survival (BCSS) in participants in Arm A1, Arm A2, Arm A, Arm B, and Arms A+B
Time frame: Median of 5 and 10 years follow up after surgery.
Overall Survival (OS) in participants in Arm A1, Arm A2, Arm A, Arm B, and Arms A+B.
Time frame: Median of 5 and 10 years follow up after surgery.
PRO: Fear of Cancer Recurrence
Time frame: Median 24 months post-surgery
PRO: Levels of FCR and perception of risk of recurrence in Arm A over time.
Time frame: At median of 24 months post-surgery
PRO: Difference in FCR and perception of risk of recurrence between Arm A and Arm B.
Time frame: From allocation to 3-, 6-, 12-, 24- and 60 months median follow-up post-surgery.
PRO: Perception of risk of recurrence in Arm A and between Arm A and Arm B.
Time frame: From allocation to 3-, 6-, 12-, 24- and 60 months median follow up post-surgery
PRO: Health Related Quality of Life (HRQoL) (functional and aesthetic outcomes, fatigue, body image, financial toxicity) between Arm A and Arm B.
Time frame: At a median of 24 months post-surgery.
PRO: Health Related Quality of Life (HRQoL) (functional and aesthetic outcomes, fatigue, body image, financial toxicity) in Arm A
Time frame: From allocation to 3-, 6-, 12-, 24- and 60 months median follow up post-surgery
PRO: Difference over time in HRQoL (functional and aesthetic outcomes, fatigue, body image, financial toxicity) between Arm A and Arm B.
Time frame: From allocation to 3-, 6-, 12-, 24- and 60 months median follow-up post-surgery.
PRO: Quality of Life Years (QALYs) between Arms A and Arm B.
Time frame: At a median of 24 months follow up post-surgery.
PRO: Difference in QALYs over time between Arm A and Arm B.
Time frame: From registration to allocation, 3-, 6-, 12-, 24- and 60 months median follow-up post-surgery..
PRO: Difference in Decision Regret between Arm A and Arm B.
Time frame: At median of 24 months follow up post-surgery.
PRO: Decision Regret in Arm A.
Time frame: At median 24 months of follow-up post-surgery.
PRO: Overall mental health and depression over time between Arm A and Arm B.
Time frame: From allocation to 3-, 6-, 12-, 24- and 60 months median follow-up post-surgery.
PRO: Overall mental health and differences over time in anxiety in Arm A.
Time frame: At 24 months median follow-up post-surgery.
PRO: Overall mental health (depression) over time between Arm A and Arm B.
Time frame: From allocation to 3-, 6-, 12-, 24- and 60 months median follow-up post-surgery.
PRO: Overall mental health (anxiety) over time between Arm A and Arm B.
Time frame: From allocation to 3-, 6-, 12-, 24- and 60 months median follow-up post-surgery.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jan 2026.
- Individual participant dataSharing planned: Yes. Anonymised Individual Patient Data (IPD) collected during the trial.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Bruce Mann, MD study chair
Melbourne Health
Steven David, MD study chair
Peter MacCallum Cancer Centre - Moorrabin
Alastair Thompson, MD study chair
Baylor College of Medicine
9 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Arm A: Radiotherapy Omission and Arm B: Standard Treatment in people with Breast Cancer and Breast Cancer Female, run by Breast Cancer Trials, Australia and New Zealand at 9 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Australia, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Heath Badger (+61 2 4925 5239, heath.badger@bctrials.org.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ipsilateral Invasive Recurrence Rate (IIRR) in low-risk patients omitting RT at a median of 5 years follow up (time frame: Median of 5 years follow up (when 300th low risk patient in Arm A reaches 5 years follow up)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jan 2026.