A distinctive subset of metastatic breast cancer is represented by the so called ‘oligometastatic' disease, characterized by single/few detectable metastatic lesions. A more aggressive multidisciplinary approach can be considered in this patient population: available data report favorable results of ‘radical' local therapy for limited metastatic disease at least in a subset of selected patients. Selection bias and the retrospective nature of data do not allow for generalization of the results: the use of such approaches must be individualized and managed within a multidisciplinary team of dedicated specialists. Improvement in surgical and radiation techniques, development of new tools to deliver local chemotherapy, and new procedures (i.e. cryosurgery, laser and microwave ablation) mandate careful evaluation of such single and combined modalities in controlled clinical trials. A more accurate identification of patients with limited metastases and better definition of treatment endpoints will also allow correct patient selection for locally aggressive therapies. This paper focusses on local treatment of the primary tumor and of the most frequent distant disease sites in the presence of oligometastatic disease.

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Purpose: In contrast to recurrence after initial diagnosis of stage I–III breast cancer [recurrent metastatic breast cancer (rMBC)], de novo metastatic breast cancer (dnMBC) represents a unique setting to elucidate metastatic drivers in the absence of treatment selection. We present the genomic landscape of dnMBC and association with overall survival (OS). Experimental Design: Targeted DNA sequencing (OncoPanel) was prospectively performed on either primary or metastatic tumors from 926 patients (212 dnMBC and 714 rMBC). Single-nucleotide variants, copy-number variations, and tumor mutational burden (TMB) in treatment-naïve dnMBC primary tumors were compared with primary tumors in patients who ultimately developed rMBC, and correlated with OS across all dnMBC. Results: When comparing primary tumors by subtype, MYB amplification was enriched in triple-negative dnMBC versus rMBC (21.1% vs. 0%, P = 0.0005, q = 0.111). Mutations in KMTD2, SETD2, and PIK3CA were more prevalent, and TP53 and BRCA1 less prevalent, in primary HR+/HER2− tumors of dnMBC versus rMBC, though not significant after multiple comparison adjustment. Alterations associated with shorter OS in dnMBC included TP53 (wild-type: 79.7 months; altered: 44.2 months; P = 0.008, q = 0.107), MYC (79.7 vs. 23.3 months; P = 0.0003, q = 0.011), and cell-cycle (122.7 vs. 54.9 months; P = 0.034, q = 0.245) pathway genes. High TMB correlated with better OS in triple-negative dnMBC (P = 0.041). Conclusions: Genomic differences between treatment-naïve dnMBC and primary tumors of patients who developed rMBC may provide insight into mechanisms underlying metastatic potential and differential therapeutic sensitivity in dnMBC. Alterations associated with poor OS in dnMBC highlight the need for novel approaches to overcome potential intrinsic resistance to current treatments.

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A 76-year-old woman presented with symptoms suggestive of acute sinusitis. Previously, her breast carcinoma was treated with right lumpectomy, adjuvant chemotherapy and breast radiotherapy. She remained free from recurrence for the following 8 years. After initial treatment with antibiotics, the local symptom worsened with exophthalmos, eye blindness and development of an ulceration of the hard palate. MRI showed irregular enhancement of the nasal cavity extended to the maxillary sinus and ethmoidal lamina and concomitant infiltration of the orbit and skull base. A biopsy of the palatal ulcer showed a poorly differentiated adenocarcinoma and was compared with the histology of the primary breast tumour and it was concluded for the same morphology. After discussion at the multidisciplinary team, a specific chemotherapy has been activated with an initial local response. Further surgical resection was not thought appropriate and the patient has subsequently undergone palliative radiotherapy to the right paranasal lesions to improve local disease control.