Pre-operative screening could identify who can skip post-operative radiation and pick up malignancies that might cause recurrence.
Detecting occult disease – or its absence – with MRI in women with early breast cancer could spare them radiation treatment, improve quality of life, lower costs and catch additional tumours.
“PROSPECT suggests that women with unifocal breast cancer on MRI and favourable pathology can safely omit radiotherapy,” the researchers wrote in a paper published in The Lancet.
Pre-operative MRI might also reduce recurrence by picking up on malignancies previously missed with other screening modalities, the Melbourne researchers said.
The findings, presented at the San Antonio Breast Cancer Symposium last week, also have implications for screening and challenge accepted wisdom about low breast density risk.
The PROSPECT study was a non-randomised trial looking at the impact of omitting radiation therapy for patients aged 50 and older with early stage, biopsy-proven, hormone receptor-positive or HER2-positive (non-triple-negative), apparently unifocal, and clinically T1N0 invasive breast cancer, selected based on MRI screening before surgery and pathology screening after surgery.
The hypothesis being tested by the study, which was run by independent clinical trials research group Breast Cancer Trials (BCT), was that local recurrence risk was reduced by radiotherapy because radiotherapy inadvertently treated occult malignancies that had not been picked up by the usual imaging techniques. An MRI would identify that disease and those women would have radiation treatment, but where it wasn’t present and the pathology was low risk, radiation could be omitted from treatment without increasing the risk of recurrence.
An eligible 443 patients from The Royal Melbourne Hospital (RMH) or The Women’s Hospital (in Melbourne) were given an MRI prior to breast conserving surgery to see if they had an occult malignancy (not picked up by conventional imaging) or moderate or marked background parenchymal enhancement. The 201 who had neither, and who were not then excluded following surgery because of tumour size, lymph node positivity, lymphovascular invasion, microscopic multicentricity or multifocality, extensive ductal carcinoma in situ, inadequate surgical margin, triple-negative phenotype or clinical decision, were treated without post-operative radiation therapy. The other 242 received standard therapy.
At five years, the group without radiation therapy had an ipsilateral invasive recurrence rate (IIRR) of 1%. Quality adjusted life years increased by 0·019, and the cost for each patient went down by AU$1980.
These findings did not surprise Professor Bruce Mann, who is the instigator and study chair of PROSPECT and the director of research at BCT.
“The results almost exactly matched what we predicted if the hypothesis was correct,” the director of Breast Services for the RMH and The Women’s told OR.
“In a presentation I gave almost 10 years ago, when proposing the study, I suggested that if the hypothesis is correct and that almost all the early recurrences in the absence of radiation are due to malignant disease, so cancers that were there but just not detected, and MRIs found those additional lesions and we removed them, the local recurrence rate in five years might be 1%.”
What was unexpected was that there were no distant recurrences at all from the index cancers among the whole group of more than 400 women, after they had been screened and those with occult lesions had been treated.
“The understanding is that breast cancer is systemic at the time of diagnosis. You have to assume that it’s already spread. But we had no distant recurrences in the first five years and the implications of that need to be studied,” said Professor Mann.
“It reinforces the need for early detection and emphasises that regular mammography is the best thing that someone can do, and that improving screening – and there’s a lot of work being done on that – is really important and can have additional benefits,” said Professor Mann.
“If these findings are true, then if you can find the cancers when they’re very early, the risk of metastasis may be less than what we currently believe that it is.”
Furthermore, the MRI was able to detect malignant occult lesions in 8% of participants with low breast density (BIRADS A or B).
“There’s an expectation that it’s only women with high breast density who have additional malignancies identified on MRI. It’s an accepted wisdom. What we found is that those with high breast density did have more additional malignancies found with MRI, but those with low breast density had a reasonable number found,” said Professor Mann.
“Our interpretation is that the potential benefit from the MRI is not confined to those with high breast density.”
Unlike many studies, this research focussed on women with early breast cancer, rather than a more advanced stage, and 87% of participants in the experimental arm came through the population breast screening program.
“With women whose cancers are diagnosed at this stage, the question is, how little treatment is needed in order to maintain the excellent outcomes that we get?” said Professor Mann.
Using MRI to inform treatment in this way is not yet ready for immediate use in clinical practice.
“This is the first trial that’s used this approach. The patients were largely from a single centre. We do have to be careful in extrapolating this to other centres,” he said.
Longer follow-up was needed before implementation, said Professor Mann, both for PROSPECT and other studies whose findings were presented at the symposium – IDEA and LUMINA, that looked at identifying candidates for omission of radiation treatment by analysing the tumour.
“All of those are missing the occult additional cancers. We are concerned that once a patient ceases her endocrine therapy, which may be supressing the growth of other cancers, recurrences may occur,” he said.
“Our plea is for trialists to pay attention to the importance of imaging in breast cancer,” he said.
Professor Mann also emphasised the impact that omitting the radiation component of treatment could have on patients’ quality of life.
“Those who omitted radiation as part of PROSPECT had less fear of cancer recurrence,” he said.
One theory was that it could be because one of the long-term side effects of radiation was ongoing breast tenderness, which reminded patients of their cancer.
“It was the reverse of what we anticipated,” he said.
“But our interpretation is that the patient thought to herself, well, if the doctor was happy for me not to have this treatment, clearly, they’re not worried. If they’re not worried, why should I be worried? I think it’s probably as simple as that.”
Dr Sanjeev Kumar, medical oncologist at the Chris O’Brien Lifehouse in Sydney told OR the research would “absolutely” benefit patients.
“This is another step in the pathway to appropriately de-escalating intensity of treatment in patients with low-risk disease, using both standard clinicopathological correlates as well as MRI,” said Dr Kumar.
“Data could also be analysed alongside other trials such as the Australian EXPERT study,” he added.
Low recurrence rates in patients were reassuring, said Dr Kumar.
“However, I caution by saying that we do need to wait for a longer-term readout of this study data. It is also not a randomised study, and breast MRIs are still not ubiquitously available to our patients being treated outside of tertiary metropolitan cancer centres.”
