CEUS & proliferation markers to characterise NACT response in TNBC
Research type
Research Study
Full title
Imaging of tumour microvasculature using high resolution contrast enhanced ultrasound (CEUS) together with markers of proliferation/ angiogenesis/ vascular mimicry to characterise response to NACT in triple negative breast cancer.
IRAS ID
301345
Contact name
Karina Cox
Contact email
Sponsor organisation
Maidstone & Tunbridge Wells NHS Trust
Duration of Study in the UK
1 years, 0 months, 0 days
Research summary
Summary of Research
Triple negative breast cancer (TNBC) accounts for around 15% of new diagnoses. Because the cancer cells don't carry oestrogen, progesterone and Her-2 receptors, common treatments to stop the supply of oestrogen to breast cancer cells or newer treatments against the HER-2 molecule can't be used. As cancerous tumours get bigger, they try to grow more blood vessels. This happens by a process called angiogenesis. Tumours can also make channels of cancerous cells to get blood into them, called vasculogenic mimicry. Increasing the blood supply may help cancer spread and vascular mimicry is linked to poorer survival.
Modern treatments of TNBC are mainly dependent upon chemotherapy first before surgery because the strong drugs shrink the cancer completely in up to half of cases. However, it is often not easy to track how the cancer is responding because current radiology tests cannot always show if the cancer is getting smaller.
New ultrasound technology using tiny injected bubbles (microbubble contrast) and high resolution hold the promise of improved monitoring by allowing the blood vessels inside the tumour to be seen. Changes in the blood vessels of the tumour during a course of chemotherapy may be able to predict if the cancer is going to get smaller.
This research aims to follow 5 TNBC patients through chemotherapy to surgery. High resolution contrast ultrasound and cancer tissue analysis will be used to assess tumour blood supply and growth at 3 time points during chemotherapy.Summary of Results
Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer that lacks common receptors targeted by many treatments, making it harder to treat. Patients typically undergo chemotherapy before surgery (neoadjuvant chemotherapy or NACT) to shrink the tumor. However, monitoring how well the treatment is working can be challenging. This study explored whether a special imaging technique, high-resolution contrast-enhanced ultrasound (CEUS), combined with laboratory tests on tumor samples, could provide better tracking of treatment response than standard methods.
Study Approach:
Two patients newly diagnosed with TNBC participated in this research. Each patient had two separate tumor areas, which were analysed individually. Researchers examined how well the treatment was working by:
• Using CEUS to track blood flow patterns around the tumor.
• Studying biological markers in tumor samples that indicate blood vessel formation (angiogenesis), tumor growth, and alternative ways tumors get oxygen (vascular mimicry).
• Checking for specific proteins linked to different TNBC subtypes.
Key Findings:
• Tumor Subtypes Matter: Testing for specific proteins (CK5, CK6, CK14) helped classify the TNBC subtype, which may be useful in future treatment decisions.
• Tracking Treatment Response: CEUS was effective in showing changes in blood vessels feeding the tumor. In one patient, these vessels disappeared by the end of treatment, matching the final laboratory results showing no remaining cancer.
• Angiogenesis and Tumor Growth: Blood vessel markers (such as VEGF and CD34) were present at the start of treatment and decreased over time, suggesting that the chemotherapy was working.
• Potential for Future Use: If CEUS can reliably track tumor response, it may reduce the need for repeat biopsies, making treatment monitoring easier for patients.
Challenges and Next Steps:
This was a small study with only two patients, and more research with a larger group is needed to confirm these findings. Future studies could involve multiple hospitals and explore how adding new drugs like pembrolizumab (an immune therapy) affects the results.
Conclusion:
The study suggests that high-resolution CEUS, combined with laboratory tests, could be a promising way to monitor TNBC treatment response. This approach may help clinicians adjust treatments more effectively and improve patient care in the future.REC name
West of Scotland REC 1
REC reference
22/WS/0045
Date of REC Opinion
18 May 2022
REC opinion
Further Information Favourable Opinion