Cutaneous metastases from breast cancer: Considerations for implementing rigorous evaluation of local therapies

To the Editor, We read the article entitled Cutaneous metastasectomy: Is there a role in breast cancer? A systematic review and overview of current treatment modalities by Huang et al. aiming to assess the role of local therapy. Skin metastases remain a troublesome occurrence worldwide for women with breast cancer, and their optimal treatment lies at the crossroads of specialities involved in the multidisciplinary team. The authors effectively convey the complexity and heterogeneity of clinical cases and, based on the literature review, highlight the lack of a “standard of care” and the controversial role of local therapy, either surgical or nonsurgical. We agree with this and believe the way forward lies in the standardisation of treatments and rigorous reporting of clinical studies in line with current recommendations. We take this opportunity to provide additional information on one of the local therapies included in the review, electrochemotherapy (ECT), to help the readers gain a more comprehensive understanding. Two meta‐analyses have confirmed the efficacy of ECT in terms of antitumour activity in 2014 and 2020. In the former, Spratt et al. assessed the efficacy of skin‐directed therapy (i.e., ECT, radiation, photodynamic, intralesional and topical therapy) in patients with cutaneous metastases and reported a complete response (CR) rate of 47.5% for ECT (11 studies, n = 176 patients, mainly with melanoma or breast cancer). In the latter, Ferioli et al. analysed 11 studies (n = 464 patients with breast cancer) and reported a CR rate of 46.2%. Although Huang et al. retrieved 16 papers on ECT in their literature search, only four of these seem to have been listed. In our opinion, a comprehensive presentation of these publications would be advisable to appreciate the status of the art in this field. To this aim, we provide an overview of the published studies in Table 1. From these, it is clear that information on tumour burden and spread, which is notoriously heterogeneous, as nicely reported by Huang et al., is generally lacking. Additionally, there are no comparative studies between local therapies; as a result, at this stage, priority should be given to their value in tolerability and contribution to preserving patient quality of life. Importantly, the ECT technique has gone through incremental steps, in 2006 first, and then in 2018, with the publication of the European Standard Operating Procedures for ECT (ESOPE) to support clinicians in the selection of treatment modalities (e.g., anaesthesia, chemotherapy, electric pulse applicator). Finally, the concept of “earlier the referral, the better the outcome” needs to be stressed. In its various forms, local therapy should be considered early in the patient journey and not only when systemic treatment has failed. For example, in patients with chest wall recurrence from breast cancer, the chance of achieving effective tumour control with ECT inversely correlates with the spread of the disease around the mastectomy scar. Huang et al. correctly remind us of the necessity of collecting good‐quality clinical data on breast cancer patients with skin metastases. We endorse this effort and, in its support, would like to mention the hypothesis‐generating study by Cabula et al. The authors of this multicentre retrospective analysis evaluated 125 breast cancer patients with skin metastases (median 1/patient, range: 1–3) treated with ECT and reported an overall response rate of 90.2% (complete response rate: 58.4%). In multivariate analysis, small tumour size, absence of visceral metastases, oestrogen receptor positivity and low Ki‐67 index were associated with CR. Dermatologic toxicity included grade‐3 ulceration (8.0%) and grade‐2 hyperpigmentation (8.8%). Importantly, this study showed, for the first time, that a subgroup of breast cancer patients (corresponding to the luminal A‐like subtype) could be particularly sensitive to ECT with bleomycin. We believe these considerations on ECT should be extended to all locoregional approaches for treating cutaneous metastases, including surgery, to allow reliable evaluations and informed discussion with patients. At specialist referral centres, patients with skin metastases arising from breast cancer are not rare, and their number persists despite the introduction of more effective systemic treatments. The experience with locoregional therapy so far highlights the importance of multi‐specialist assessment and the need for rigorous evaluation and high‐quality reporting.