title: Electrochemotherapy in the Treatment of Cutaneous Metastases from Breast Cancer: A Multicenter Cohort Analysis.
abstract: BACKGROUND
  The management of breast cancer (BC) skin metastases represents a therapeutic challenge. Electrochemotherapy (ECT) combines the administration of bleomycin with temporary permeabilization induced by locally administered electric pulses. Preliminary experience with ECT in BC patients is encouraging.
  
  
  METHODS
  A total of 125 patients with BC skin metastases who underwent ECT between 2010 and 2013 were enrolled onto a multicenter retrospective cohort study. The treatment was administered following the European Standard Operative Procedures of Electrochemotherapy. Tumor response was clinically assessed adapting the Response Evaluation Criteria in Solid Tumors, and toxicity was evaluated according to Common Terminology Criteria for Adverse Events 4.0. Cox regression analysis was used to identify predictive factors.
  
  
  RESULTS
  Response was evaluable in 113 patients for 214 tumors (median 1 per patient, range 1-3). The overall response rate after 2 months was 90.2 %, while the complete response (CR) rate was 58.4 %. In multivariate analysis, small tumor size (P < 0.001), absence of visceral metastases (P = 0.001), estrogen receptor positivity (P = 0.016), and low Ki-67 index (P = 0.024) were significantly associated with CR. In the first 48 h, 10.4 % of patients reported severe skin pain. Dermatologic toxicity included grade 3 skin ulceration (8.0 %) and grade 2 skin hyperpigmentation (8.8 %). Tumor 1-year local progression-free survival was 86.2 % (95 % confidence interval 79.3-93.8) and 96.4 % (95 % confidence interval 91.6-100) in the subgroup of those with CR.
  
  
  CONCLUSIONS
  In this study, small tumor size, absence of visceral metastases, estrogen receptor positivity, and low Ki-67 index were predictors of CR after ECT. Patients who experienced CR had durable local control. ECT represents a valuable skin-directed therapy for selected patients with BC.
authors.affiliation: Oncologic Surgery, Ospedale Oncologico A. Businco, Cagliari, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Cabula
authors.affiliation: Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.
authors.forename: L G
authors.initials: LG
authors.lastname: Campana
authors.affiliation: Breast Surgery Unit, Ospedale Le Molinette, Turin, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Grilz
authors.affiliation: Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Galuppo
authors.affiliation: Breast Surgery Unit, Ospedale Le Molinette, Turin, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Bussone
authors.affiliation: Humanitas-Centro Catanese di Oncologia, Catania, Italy.
authors.forename: L
authors.initials: L
authors.lastname: De Meo
authors.affiliation: Plastic Surgery Unit, San Gallicano Dermatologic Institute, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Bonadies
authors.affiliation: Dermatology and Plastic Surgery Department, La Sapienza University, Rome, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Curatolo
authors.affiliation: Seconda Università di Napoli, Naples, Italy.
authors.forename: M
authors.initials: M
authors.lastname: De Laurentiis
authors.affiliation: Fondazione T. Campanella, Catanzaro, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Renne
authors.affiliation: Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Valpione
authors.affiliation: Plastic Surgery Unit, IRCCS, Referral Cancer Center of Basilicata, Rionero in Vulture, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Fabrizio
authors.affiliation: Surgical Unit 1, IRCCS San Martino-IST, Genoa, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Solari
authors.affiliation: Medical Oncology Unit, Istituto dei Tumori, Bari, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Guida
authors.affiliation: Department of Medicine and Surgery, "Federico II" University, Naples, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Santoriello
authors.affiliation: Breast Surgery Unit, Istituto Nazionale Tumori "Pascale", Naples, Italy.
authors.forename: M
authors.initials: M
authors.lastname: D'Aiuto
authors.affiliation: Breast Surgery Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. roberto.agresti@istitutotumori.mi.it.
authors.forename: R
authors.initials: R
authors.lastname: Agresti
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D015331:Cohort Studies; D053672:Electrochemotherapy / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism / Q000556:secondary / Q000628:therapy*
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human