High-intensity focused ultrasound for symptomatic breast fibroadenoma

Evidence-based recommendations on high-intensity focused ultrasound for symptomatic breast fibroadenoma in adults. This involves using high-frequency sound waves to heat up the tissues in the lump.

# Recommendations
The evidence on high-intensity focused ultrasound for symptomatic breast fibroadenoma raises no major safety concerns. Evidence on its efficacy is inadequate in quantity and quality. Therefore, this procedure should only be used with special arrangements for clinical governance, consent and audit or research.
Clinicians wishing to do high-intensity focused ultrasound for symptomatic breast fibroadenoma should:
Inform the clinical governance leads in their NHS trusts.
Ensure that patients understand the uncertainty about the procedure's efficacy and provide them with clear written information. In addition, the use of NICE's information for the public is recommended.
Audit and review clinical outcomes of all patients having high-intensity focused ultrasound for symptomatic breast fibroadenoma (see section 7.1).
Patients should be informed about all the alternative treatment options, which could include conservative treatment.
Further research should include publication of patient-reported outcome measures and studies with long-term follow-up.# Indications and current treatments
Breast fibroadenomas are common benign masses that often develop during puberty, although they can occur in women of any age. The condition is rare in men. Simple fibroadenomas are usually 1 cm to 3 cm in size but giant fibroadenomas can be over 5 cm. They do not usually increase in size and some may disappear overtime. The condition is diagnosed by breast examination, and ultrasound or mammography. A needle core biopsy can be used for histological confirmation. Fibroadenomas are usually painless but can become painful and cause deformity.
If a fibroadenoma is asymptomatic, it does not need to be treated and no follow-up is necessary. However, any growth or other changes to the fibroadenoma should be reported. When symptomatic, fibroadenomas can be removed surgically or by vacuum-assisted mammotomy, which can be done under general or local anaesthesia.# The procedure
High-intensity focused ultrasound for breast fibroadenomas is a minimally invasive thermoablative technique that can be done at an outpatient clinic under local anaesthesia and sedation. A focusing ultrasound device delivers the treatment and allows for simultaneous imaging of the treatment area. The technology uses sound waves that propagate through the tissues, generating local heat and inducing coagulative necrosis, protein denaturation and cellular destruction. A strong acute inflammatory response follows. Remodelling of the chronic inflammatory response lasts for up to 3 months and involves cellular regeneration, proliferation, migration and removal of debris.
Tumour size reduction should happen gradually with no need for further intervention.# Efficacy
This section describes efficacy outcomes from the published literature that the committee considered as part of the evidence about this procedure. For more detailed information on the evidence, see the interventional procedure overview.
In a case series of 42 women (51 fibroadenomas) treated by high-intensity focused ultrasound (HIFU), 63% (29/46) of the fibroadenomas had reduced in size by 30% at 2 months, 67% (32/48) had reduced by 50% at 6 months and 87% (40/46) had reduced by 60% at 12 months. In a non-randomised controlled study of 40 women, in which 20 were treated by HIFU and 20 were in a control group, fibroadenoma size was statistically significantly reduced by 17% at 2 weeks (standard deviation  19%, p=0.021) and by 31% at 3 months (SD 53%, p=0.022) in the HIFU group. In the same study, fibroadenoma size reduction was statistically significantly different in women treated by HIFU (44%, SD 39%, p=0.016) compared with women in the control group (5%, SD 46%, p=0.53) at 6month follow-up; complete fibroadenoma reduction was reported in 33% (4/20) of women in the HIFU group at 12month follow-up. In a case series of 10 patients treated by HIFU, fibroadenoma diameter was reduced by 50% in 100% (10/10) of patients at 3month follow-up. In a case series of 9 patients treated by magnetic resonance-guided HIFU, fibroadenomas size was reduced to 1.3 cm3 (mean, SD 1.1 cm3) from a baseline of 1.9 cm3 (mean, SD 1.5 cm3) in 50% (6/12) of treatments at 6month follow-up. In a case series of 20 patients, fibroadenoma size was statistically significantly reduced in patients treated only once by HIFU from 0.78 ml (0.35 ml to 2.24 ml) at baseline to 0.35 ml (0.06 ml to 1.21 ml, p<0.001) at 2year follow-up, and in patients treated twice from 2.66 ml (0.52 ml to 3.01 ml) to 0.21 ml (0.09 ml to 1.66 ml, p=0.003) at 2year follow-up.
In the non-randomised controlled study of 40 women, 10% (2/20) of fibroadenomas treated by HIFU did not change in size at 6month follow-up.
In the case series of 9 patients treated by magnetic resonance-guided HIFU, technical failure was reported in 42% (5/12) of fibroadenoma treatments.
In the case series of 42 women, 61% (31/51) of the fibroadenomas had caused discomfort before the procedure, which had resolved in 100% of the women at 12month follow-up. In the same study, at baseline, 35% (18/51) of fibroadenomas were associated with pain, which had resolved in 100% of patients at 12month follow-up. In the non-randomised controlled study of 40 women, complete pain reduction was reported by 75% (6/8) of women treated by HIFU at 6month follow-up.
In the case series of 20 patients treated by HIFU, for symptom disappearance, 45% (9/20) of patients were completely satisfied, and satisfaction was high in 50% (10/20) and low in 5% (1/20) of patients. In the same case series, for cosmetic results, 95% (19/20) of patients were completely satisfied and satisfaction was high in 5% (1/20) of patients.
The specialist advisers listed key efficacy outcomes as reduction in lesion size, relief or resolution of symptoms, cost effectiveness, recurrence of symptoms in the short and long term, and time taken to do the procedure.# Safety
This section describes safety outcomes from the published literature that the committee considered as part of the evidence about this procedure. For more detailed information on the evidence, see the interventional procedure overview.
Discomfort or burning sensation assessed with a visual analogue scale (VAS, 0=no pain, 10=very severe pain) was reported by 90% (18/20) of women (mean score 6.4, standard deviation  3.2) treated by high-intensity focused ultrasound (HIFU) in a non-randomised controlled study of 40 women. In the same study, persistent pain assessed with a VAS was reported by 10% (2/20) of women in the HIFU group (mean score 1.6, SD 1.9) within 3 months of treatment. Pain during treatment was reported as being slight in 36% (4/11), moderate in 18% (2/11) and severe in 9% (1/11) of the procedures in a case series of 9 women (11 fibroadenomas) treated by magnetic resonance-guided HIFU. Pain after treatment measured by a VAS (0=no pain to 100=extreme pain) was 40.7 (24.6) after the first ablation and 34.9 (17.9) after the second ablation (p value not reported), in a case series of 20 patients treated by HIFU.
Numbness of the skin was reported by 1 woman of 20 treated by HIFU in the non-randomised controlled study of 40 women. Mild to moderate tenderness was reported by 45% (9/20) of patients up to 1 week after the first HIFU session, and by 57% (4/7) of patients after the second HIFU session in the case series of 20 patients.
Superficial skin burn with blistering was reported in 6% (3/51) of fibroadenomas after the procedure in a case series of 42 women (51 fibroadenomas) treated by HIFU. A first-degree skin burn was reported in 1 woman of 20 treated by HIFU in the non-randomised controlled study of 40 women. A first-degree skin burn with hyperpigmentation visible after 6 months was reported in 1 woman of 7, who had more than 1 fibroadenoma, in the case series of 20 women treated by HIFU.
Hyperpigmentation of the skin was reported in 1 woman within days after the procedure in the case series of 42 women treated by HIFU. Hyperpigmentation of the skin was reported by 30% (6/20) of women treated by HIFU at 3 months and 20% (4/20) at 6 months in the non-randomised controlled study of 40 women.
Subcutaneous induration was reported in 1 woman of 42 at 12month follow-up in the case series of 42 women treated by HIFU. Subcutaneous oedema was reported in 25% (4/20) of women in the case series of 20 women treated by HIFU.
Ecchymosis was reported by 45% (9/20) of women treated by HIFU in the non-randomised controlled study of 40 women.
Erythema was reported by 30% (6/20) of women treated by HIFU in the non-randomised controlled study of 40 women. Mild to moderate erythema that resolved within 1 week was reported by 29% (2/7) of women, who had more than 1 fibroadenoma, treated by HIFU in the case series of 20 patients.
Dimpling of the skin was reported by 1 woman of 20 treated by HIFU in the non-randomised controlled study of 40 women.
In addition to safety outcomes reported in the literature, specialist advisers are asked about anecdotal adverse events (events which they have heard about) and about theoretical adverse events (events which they think might possibly occur, even if they have never done so). For this procedure, specialist advisers listed no anecdotal adverse events. They considered that the following were theoretical adverse events: poor cosmetic outcome, infection and severe fibrosis.# Further information
This guidance requires that clinicians doing the procedure make special arrangements for audit. NICE has identified relevant audit criteria and has developed an audit tool (which is for use at local discretion).
For related NICE guidance, see the NICE website.
Patient commentary was sought but none was received.

# Information for patients
NICE has produced information on this procedure for patients and carers (information for the public). It explains the nature of the procedure and the guidance issued by NICE, and has been written with patient consent in mind.
ISBN: 978-1-4731-2679-4