The Pre-DX trial is investigating pre-operative Oncotype DX testing on core biopsy for breast cancer instead of the traditional post-operative approach. Here, with an introduction from Hospital Healthcare Europe editor Helena Beer, the lead investigator of the trial, Mr Henry Cain, discusses this ‘natural next step’ in the evolution of novel approaches to breast cancer diagnostics, what the trial found and how it’s set to transform clinical practice.
When considering post-surgery adjuvant therapy for patients with oestrogen receptor (ER) positive, human epidermal growth factor receptor 2 (HER2) negative breast cancer, genetic testing has been shown to effectively guide recommendations.
Standard practice is to order the test in the post-operative setting on a specimen from the excised invasive carcinoma, but recent efforts have focused on determining whether earlier testing is possible.
Mr Henry Cain, consultant oncoplastic breast surgeon at the Royal Victoria Infirmary, part of Newcastle upon Tyne Hospitals NHS Foundation Trust, has observed meaningful improvements in the patient pathway by shifting the ordering of the test from oncologists post-surgery to surgeons immediately following the procedure. This has the benefit of shorter waiting times for adjuvant treatment.
But a group of UK researchers, led by Mr Cain, set about pushing the boundaries even further by performing the test on the diagnostic core biopsy in the pre-operative setting – the technical possibility of which had been intimated.
‘Coupled with increasing confidence in the reliability of core biopsy testing, it made sense to take this a step further and explore testing even earlier at the point of diagnostic biopsy,’ he says. ‘This shift offered the opportunity to further streamline care and potentially alleviate patient anxiety by providing crucial treatment information much earlier in the journey.’
The result was the Pre-DX trial, and its findings were recently presented at the 19th St. Gallen International Breast Cancer Conference 2025, which Mr Cain delves into here.
What were the aims and primary outcomes of the Pre-DX trial?
The primary aim was not to alter treatment sequencing, since patients in this cohort are not candidates for neoadjuvant treatment, as they typically have small cancers suitable for breast-conserving surgery. Instead, the trial sought to understand whether testing earlier in the pathway could improve efficiency within the standard treatment process and enhance the patient experience.
We aimed to reduce unnecessary appointments and deliver care more efficiently. From a patient perspective, we wanted to see whether addressing key treatment questions earlier, such as the need for chemotherapy, could reduce stress and uncertainty at a difficult time. Our hypothesis was that having this clarity earlier would positively impact patients’ emotional wellbeing.
While clinical appointments are essential, they are also resource intensive. We often see patients returning for visits where little new information is shared – appointments that could have been avoided if results had been available earlier. Reducing these touchpoints not only makes the journey less burdensome for patients but also eases pressure on breast services.
Fewer unnecessary appointments mean shorter treatment timelines and a more efficient use of NHS resources. This translates into better throughput and a less stressful care experience.
How do you interpret the notable decrease in anxiety and depression among patients in the intervention group?
The trial showed that patients who received their results earlier had lower anxiety and depression scores by the time they reached adjuvant treatment. We tracked these metrics at multiple points to ensure that we weren’t simply shifting anxiety to an earlier stage.
Patients consistently told us that their two biggest concerns at diagnosis were: “Will I need a mastectomy?” and “Will I need chemotherapy?” By answering one of those questions earlier, we helped reduce the emotional toll of uncertainty. The data confirmed what we had long heard anecdotally – that earlier clarity can significantly ease a patient’s mental burden.
What are the practical implications for using pre-operative samples routinely in clinical settings?
The good news is that integrating pre-operative genetic testing into routine practice is straightforward. The criteria remain the same – the key is accurately identifying patients who meet them at an earlier stage.
Ordering and discussing the test is no different from the post-operative setting. The only additional step is communication with pathology teams to ensure that the correct biopsy specimen – one with a minimum of 2mm tumour focus – is submitted for testing. Our trial demonstrated a test success rate of 98-99% on core biopsy, in line with traditional post-operative specimens.
In summary, the process fits seamlessly into existing workflows and offers meaningful benefits for both patients and the clinical teams.
Were there challenges in coordinating pre-operative testing among 17 different breast cancer units in the UK?
I wouldn’t say that we encountered any hurdles that were particularly difficult to overcome. In fact, the reason the trial succeeded is that it was very carefully considered and designed to fit in seamlessly with the normal clinical pathway in each unit.
The key principle we adhered to was ensuring the trial didn’t require any additional steps, biopsies or processes beyond standard practice, as we didn’t want to create any extra burdens for the units. The trial was designed with real-world application in mind from the very beginning.
Our aim was to avoid a situation where we investigated an intervention that – even if successful in the trial setting – would be incredibly difficult to implement into routine practice.
In my view, the trial exemplifies a well-considered, well-designed study, which succeeded in minimising potential logistical and technical challenges.
A small percentage of patients switched to neoadjuvant treatment after randomisation. What does this suggest about the influence of early genomic data on treatment planning?
The small number of patients who switched to neoadjuvant treatment reflects the deliberate design of the trial. Our aim was not to explore a change in treatment sequencing but to assess how early genomic testing could improve the standard surgical pathway.
We specifically targeted ER-positive, HER2-negative patients who were already scheduled for surgery, as most in this group would not typically receive neoadjuvant therapy. The low switch rate therefore validates the inclusion criteria and confirms that the pathway studied was both appropriate and consistent with real-world practice.
The trial clearly demonstrated that pre-operative genomic testing can deliver a positive impact on the standard patient pathway and experience. The findings support data from other studies demonstrating the oncological utility of the test in patients requiring downstaging, providing valuable information at the point of diagnosis.
Do you think the Covid-19 pandemic and its effects on patient flow and appointments influenced the primary outcome of clinical touchpoints?
Yes, absolutely. Covid-19 threw a spanner in the works. When we designed trials before the pandemic, we were basing our models on patients typically having six to eight appointments as part of their standard workup.
Then everything changed. Many units in the control arm ended up having only two or three appointments, as they tried to minimise face-to-face contact. This significantly affected clinical touchpoints. It became much more difficult to demonstrate a sizeable reduction, since many of those appointments had already been removed from the system.
These reductions were a response to a crisis. We may have streamlined the process, but it impacted the quality of care. A lot of results were given over the phone, often not by the treating physician. Appointments were combined and the personal touch was often lost.
Since the end of the pandemic, we have seen a rebound, with most units returning to a more standardised, face-to-face approach. However, it’s important to remember that in the Pre-DX trial, we didn’t dictate how units should use the genetic test results, it was simply another piece of data.
The trial didn’t mandate specific changes in the intervention arm. However, when this becomes standard practice, units looking to make those efficiencies will be aiming to leverage this to their benefit.
How did multidisciplinary collaboration influence the implementation and success of pre-operative genetic testing in the trial?
The trial wouldn’t have been possible without strong multidisciplinary collaboration. From the start, we needed accurate radiology to stage the patient pre-operatively. Then there were the pathological inputs and surgeons. The oncologists also needed to be comfortable with the results from the core biopsies and the plan for addressing them. It was critical to achieve the buy-in of all these groups.
The design of trial and intervention meant that no additional work was required for the healthcare professionals, which was a critical factor in winning their support. It did not require additional biopsies – only that radiologists and surgeons continued to do what they do every day, providing accurate readings and advice on biopsies.
We made the process as seamless as possible, integrating smoothly into existing workflows and creating an environment open to collaboration.
How might the findings of the Pre-DX trial inform a more personalised and efficient approach to breast cancer care?
The trial did exactly this. The test’s ability to identify patients who will and will not benefit from chemotherapy early in their diagnostic pathway allows for a radically more tailored treatment strategy.
Instead of a one-size-fits-all approach, clinicians can confidently de-escalate treatment for the approximately seven out of 10 of patients unlikely to require chemotherapy, sparing them from unnecessary side effects and improving their quality of life.
Conversely, the trial enables the early identification of the 30% of patients who do require chemotherapy, allowing for a timelier referral to oncology and potentially a shift in the treatment sequence. This proactive approach allows for earlier initiation of chemotherapy, potentially improving outcomes for this higher-risk group.
By integrating the Pre-DX findings into clinical practice, we can move towards a more efficient patient pathway, directing resources and expertise to those who need them most.
What further research would you like to see in this area, especially regarding long-term outcomes or patient-reported quality of life?
Further research should prioritise two key areas: the long-term oncological impact of early genomic testing and, crucially, the integration of patient-reported outcomes and quality of life measures directly into clinical trial design.
Regarding the oncological impact, I’d like to see continued investigation into trials that stratify patients based on clinical staging and genomic risk profiles, using tools such as the Oncotype DX test to guide treatment pathways. Specifically, the research should focus on long-term outcomes such as overall survival, recurrence rates and the ability to reduce mortality by tailoring treatment intensity based on these early genomic assessments. These studies should aim to definitively demonstrate whether early, genomically informed treatment decisions lead to improved survival and reduced recurrence compared to traditional approaches.
Equally important is a shift in how we approach patient experience within clinical trials. We need more research that illustrates that “bolting on” patient experience as an afterthought is simply not sufficient. Instead, it should be an integral component of trial design, influencing treatment decisions and endpoints alongside traditional oncological measures.
This would involve proactively assessing patient wellbeing, emotional state and quality of life at various points through the treatment journey. Trials could explore how different treatment pathways – guided by genomic risk and incorporating patient feedback – impact anxiety, depression, fatigue and overall satisfaction with care.
Ultimately, the goal is to develop treatment strategies that not only improve oncological outcomes but minimise the emotional and psychological burden on patients, ensuring they navigate their breast cancer journey as seamlessly as possible. This requires a fundamental shift in how we value and integrate patient experience into the research process, giving it the same weight as traditional oncological endpoints.
