The treatment of breast cancer with thermal ablation: a pilot study

Breast cancer is the most common type of cancer among women in the Netherlands.
Each year, nearly 15.000 new patients are diagnosed with breast cancer. Almost
half of these women have a tumour smaller than 2 cm. With standard breast
conserving surgery (BCS) and adjuvant therapy, these women have an excellent
prognosis and a five year survival rate of 98-99%. In these women treatment
could presumably be less invasive and surgery could even be avoided,
percutaneous thermal ablation (TA) could be the suitable technique for this.
Overall, radiofrequency ablation (RFA), microwave ablation (MWA) and
cryoablation seem to be the most promising thermal ablation techniques but
among these the success rate varies from 50-100%. Preliminary results from
cohort studies with RFA and cryoablation show local recurrence rates of 0-0.6%,
comparable to the recurrence rate after BCS. Although all three techniques
appear safe and effective, based on current literature, technique selection is
not possible because of limited evidence and lack of knowledge regarding
complete ablation rate when tested under comparable circumstances, the immune
response, patient satisfaction and follow up imaging.

Both immediate and late effects occur after TA and the area of definite cell
death can expand up to months after ablation. In previous studies resection and
pathology are mostly done 1-4 weeks after TA with a maximum of 2 months. The
three techniques are never tested under the same conditions with determination
of the complete ablation rate after more than two months.

An activation of the immune system after thermal ablation is scientifically
proven in mice studies and other types of cancer. However, this immune response
has never been investigated in patients with breast cancer, treated with
thermal ablation. The initiated immune response can presumably prevent micro
metastases and local recurrences but could also provide new insights and leads
for immunotherapy.

Patient satisfaction and cosmetic outcome are in most studies briefly described
but outcomes of validated questionnaires are currently lacking in literature.

A randomized pilot study with all three of the techniques under comparable
conditions will provide more insight in which technique has the most potential
for treating early stage breast cancer without jeopardizing treatment
effectiveness compared to standard of care, i.e. surgery.

The primary objective is to investigate if thermal ablation of breast tumors
less than 2cm with < 25% DCIS is effective in terms of the number of tumors in
which complete ablation is found on pathology result.

An open 3-arm randomized controlled pilot trial.

Ultrasound guided percutaneous RFA, MWA or cryoablation will be performed 1-2
weeks after diagnosis. Surgical resection will take place about 3 months after
diagnosis. The type of surgical resection will be based on the Dutch guideline
and will not be influenced by the type of thermal ablation.will be based on the
Dutch guideline and will not be influenced by the type of thermal ablation.

The burden of the patient is mostly based on the additional treatment (thermal
ablation) and the blood samples. All interventions will be combined with
regular follow-up visits with the physician. For example the procedure will be
combined with localisation of the tumor. This way the patient anesthetic is
only once indicated. The possible benefit for the patient is the possible
immune response that will occur and the tumor will in most of the time be
treated within 1-2 weeks, although surgery is still necessary after this.
Mainly it will be for a greater good, to minimize the burden of the patients in
the future who will not need a surgery when this treatment is as effective as
expected. This could optimize patient reported satisfaction, cosmetic outcome
and experienced illness.