Breast cryoablation for the palliative treatment of indolent subtype of multicentric triple-negative breast cancer

Abstract

Breast cryoablation for palliative and curative treatment of breast cancer has been performed for decades. Although there is a recent resurgence of interest in breast cryoablation with curative intent for unifocal, hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer, this report highlights the essential role that cryoablation can play in the palliative treatment of multicentric oestrogen and progesterone receptor-negative and human epidermal growth factor receptor 2-negative (triple-negative) breast cancer, meeting the select pretreatment objectives such as breast or nipple pain relief and prevention of tumour erosion through the skin or nipple in patients who have failed or cannot tolerate the standard of care treatment.

Background

There was a resurgence of interest in breast cryoablation after the 2021 publication of the interim results of the prospective, multicenter ICE3 (Cryoablation of Low Risk Small Breast Cancer) trial (NCT02200705), which showed a success rate similar to that of breast-conserving surgery for curative-intent cryoablation of unifocal, ultrasound-visible, 1.5 cm or smaller, low-grade to intermediate-grade, hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer.^{1 2} However, breast cryoablation has been performed since the 1960s for palliative treatment of breast tumours in patients with other known tumour foci within the body with the goal of complete or partial ablation of the breast malignancy to achieve symptom relief or tumour volume reduction, demonstrating clinical efficacy and improvement of symptoms.^3–9

This report describes the palliative breast cryoablation treatments of a patient who presented with metastatic and recurrent, multicentric triple-negative breast cancer (TNBC) (negative for oestrogen receptor, progesterone receptor and HER2), and was unable to tolerate chemotherapy due to severe side effects (severe and incapacitating) and declined surgery and radiotherapy, with pretreatment objectives of breast or nipple pain control and prevention of skin or nipple erosion caused by tumour growth.

Case presentation

The patient was a woman in her 90s who presented with a new palpable breast mass 4 years after undergoing breast-conserving surgery (partial mastectomy with negative surgical margins and sentinel lymph node biopsy that revealed no lymph node metastasis) for invasive ductal carcinoma with apocrine differentiation, intermediate nuclear grade, Nottingham histologic grade 2, Ki-67 5%, androgen receptor-positive, oestrogen receptor-negative, progesterone receptor-negative and HER2-negative (TNBC). She had received no chemotherapy or radiotherapy before or after the breast-conserving surgery. Sonography and ultrasound-guided biopsy confirmed recurrent, unifocal TNBC (invasive ductal carcinoma, intermediate to high nuclear grade with no tubule formation, Ki-67 10%) with a breast tumour measuring 2.3 cm in diameter and metastases in three level I axillary lymph nodes, with the index metastatic lymph node measuring 1.8 cm (biopsy proven N1 disease). Positron emission tomography/CT revealed no evidence of distant metastasis. Neoadjuvant chemotherapy with capecitabine was initiated but was stopped after 14 days due to severe side effects (skin rash with peeling, polyuria, mucositis and vulvovaginal candidiasis). The patient was thereafter offered cyclophosphamide, methotrexate and fluorouracil chemotherapy. However, she declined additional chemotherapy treatment, surgery and radiotherapy and was referred by the breast surgery team to the breast imaging department for cryoablation 8 months after the initial diagnosis of recurrence.

Repeat breast and regional nodal (axillary levels I, II, III, supraclavicular and internal mammary) basin sonography performed in the breast imaging department demonstrated disease progression—the breast tumour size was 3.2 cm, and there was evidence of multicentric disease (additional satellite carcinomas extending towards the nipple and axillary tail) as well as new level II lymphadenopathy (one lymph node measuring 1.2 cm; N2 disease). The level I axillary lymphadenopathy remained unchanged. Palliative cryoablation of the index breast tumour with the objective of tumour debulking for volume control and prevention of skin invasion or erosion was discussed with the patient in detail. Outpatient breast cryoablation of the index tumour was performed under local anaesthesia with a single 14-gauge argon gas cryoprobe (IceForce, Boston Scientific Corporation) under ultrasound guidance (figures 1 and 2) with three freeze-thaw cycles. The patient tolerated the procedure very well and reported minimal pain from the injection of local anaesthetics during the procedure and no pain after the procedure. There were no complications. There was no change in the patient’s daily activities after the procedure, and no wound care was required.

Figure 1.

Treatment timeline and locations and sizes of ablated tumours spanning approximately 13 cm from nipple base to axillary tail.

Figure 2.

Ultrasound images of (A) the index malignancy with in situ clip (arrowheads) during cryoablation, with (B) cryoprobe through the malignancy (arrow) and (C) formation of the cryosphere (double dotted arrows), which is the ice ball enveloping the malignancy.

Follow-up imaging 3 months after cryoablation demonstrated postablation changes at the index tumour site without internal vascularity; no viable tumour was detected on imaging. However, there was evidence of disease progression towards the nipple (a 2.7 cm conglomerate of satellite masses at the 9 o’clock position extending to 1 cm from the nipple), and a biopsy of this region confirmed TNBC (invasive ductal carcinoma with apocrine features, Nottingham histologic grade 2, Ki-67 10%). Thereafter, the patient reported nipple pain, so the decision was made to proceed with a second cryoablation treatment (using the same cryoprobe and technique as the first cryoablation treatment) with the aim of achieving relief from nipple pain as well as tumour debulking for prevention of nipple invasion (figure 1). Immediately after the cryoablation procedure, the patient reported cessation of nipple pain.

Follow-up sonography 2 months after the second cryoablation treatment demonstrated significant post-treatment changes due to fat necrosis (figure 3A). MRI was performed and confirmed benign post-treatment changes without residual carcinoma at the two cryoablation treatment sites (figure 3B). Follow-up sonography 3 months after the second cryoablation treatment demonstrated the increased size of two satellite tumours at the 10 o’clock position of the breast and in the axillary tail, almost reaching the overlying skin, so a third cryoablation treatment (IcePearl, Boston Scientific Corporation, using the same technique as the first cryoablation treatment) was performed to prevent skin invasion or erosion (figure 1).

Figure 3.

Post-treatment fat necrosis after the second cryoablation treatment. (A) On sonography, fat necrosis (arrows) appears as ill-defined areas of mixed echogenicity. (B) On MRI, fat necrosis (arrows) appears as an area with no internal contrast enhancement.

Five months after the third cryoablation treatment, no residual carcinoma was identified on sonography and mammography at the four ablation sites. However, 10 months after the third cryoablation treatment, a new 1.0 cm mass at the nipple base was identified on sonography. With the goal to avoid nipple invasion and development of nipple pain, a fourth cryoablation treatment (IcePearl, Boston Scientific Corporation, using the same technique as the first cryoablation treatment) was performed, after which follow-up clinical evaluation and sonography demonstrated complete ablation of the tumour without nipple or skin invasion nor injury.

Outcome and follow-up

At the patient’s most recent follow-up at 29 months postinitial diagnosis of TNBC recurrence (20 months after the first cryoablation treatment and 2 months after the fourth cryoablation treatment), there was no clinical evidence of tumour erosion through the skin or nipple (figure 4); breast and regional nodal basin sonography showed no viable carcinoma in the breast and unchanged level I and II axillary lymphadenopathies; N2 disease; and the patient reported no breast or nipple pain.

Figure 4.

Photograph of the patient’s breast at 29 months after diagnosis of recurrent triple-negative breast cancer, 20 months after initiation of breast cryoablation treatments and 2 months after the final cryoablation treatment (fourth treatment) demonstrates no evidence of skin or nipple erosion or cryoablation injury.

During and after the multiple cryoablation treatments performed in the outpatient setting with only local anaesthesia, the patient reported only minimal pain from the injection of anaesthetics during the procedure and no pain after the procedure. She tolerated the procedures very well, experienced no cryoablation-related complications and was able to continue to live independently with an active lifestyle while maintaining a leadership role in her community.

Discussion

Breast cancer cryoablation is a minimally invasive outpatient procedure that achieves treatment objectives without significant complications and may be performed in selected patients for palliative and locoregional disease control. Although there is a significant current interest in breast cancer cryoablation for curative intent with the elimination of surgery, palliative breast cryoablation has had a longer history of clinical application for the treatment of recurrent and advanced breast cancer, including multicentric as well as breast cancer with regional nodal or distant metastatic disease.^3–10 However, cryoablation of TNBC has been rarely reported,^{7 11} and there has been no report of multiple breast cryoablation treatments of multicentric TNBC, with pretreatment objectives of breast or nipple pain control and prevention of skin or nipple erosion caused by tumour growth. After setting appropriate treatment objectives with the multidisciplinary oncology team and the patient, palliative breast cancer cryoablation may be performed with successful outcomes, not only preventing skin and nipple erosion and achieving pain control but also meeting the patient’s quality of life expectations. In addition, stabilisation of the axillary levels I and II regional nodal metastases after the initiation of breast cryoablation treatments was noted, which warrants further investigation. We hypothesise that this is the result of cryoablation’s abscopal effect, also reported in the literature.^{12 13} However, this possible abscopal effect must be further studied with additional research to confirm this potential systemic benefit of breast cryoablation. Even though breast cancer cryoablation has been performed since the 1960s, there have been no randomised controlled trials to study its use for curative and palliative treatments and no studies that confirm long-term survival benefits. More studies need to be conducted to establish cryoablation as an alternative palliative treatment modality for breast cancer.

Patient’s perspective.

I am ambulatory and very active in national and community organisations. After diagnosis of TNBC, I had a successful lumpectomy; 4½ years later, the TNBC returned with a vengeance, and my oncologist placed me on capecitabine. After 1½ weeks of the initial 2-week regimen, I developed many extremely severe side effects and suffered the remainder of the week to complete the regimen. My oncologist and I knew that I could not continue the capecitabine nor tolerate another type of chemotherapy. My life was going to end miserably and soon. I was absolutely thrilled to learn that there was a non-chemotherapy option with which there had been some success—cryoablation. I have not had pain or discomfort from the procedures I have had and have been able to maintain my normal active lifestyle. I am delighted with the outcome and highly recommend this procedure!

Learning points.

• Although there is a recent resurgence of interest in breast cancer cryoablation for curative intent, breast cancer cryoablation for palliative intent has had a longer history performed since the 1960s and demonstrates clinical efficacy and improvement of symptoms.

• Breast cryoablation is well tolerated by the patients and is performed in the outpatient setting under local anaesthesia with no significant complications.

• The benefits of breast cryoablation go beyond tumour destruction and locoregional tumour control; it allows the patients to maintain a quality of life and an independent lifestyle.

• The possible abscopal effect must be further studied with additional research to confirm this potential systemic benefit of breast cryoablation.

Ethics statements

Patient consent for publication

Consent obtained directly from patient(s).