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Background: Breast cancer is traditionally classified into three clinical subtypes based on hormone receptor and HER2 status (i.e., luminal-like, HER2-positive, and triple negative). Each subtype has distinct clinical-pathological and molecular characteristics and requires tailored treatments. Recent research efforts have been focusing on a new classification, identifying the so-called "HER2-low" category, including tumors characterized by a low level of HER2 expression (immunohistochemistry score 1+ or 2+ without in situ hybridization amplification). Emerging evidence shows that patients with HER2-low tumors can derive benefit from selected anti-HER2 therapies. This represents a major advancement in the field of breast oncology, where a broader proportion of patients with breast cancer can ultimately benefit from new effective targeted treatment strategies., Summary: The antibody-drug conjugate trastuzumab deruxtecan has proven impressive efficacy in patients with HER2-low breast cancer, and several other drugs are currently under investigation in this subset of patients. Additional investigation is needed to address open issues that exist in this field, including appropriate pathological assessment of HER2-low status, clarification of its prognostic implications, and global access to newly approved drugs., Key Message: Our review aims to summarize the available evidence regarding HER2-low breast cancer, illustrating the current challenges that are being addressed and the future perspectives in this exciting new field., Competing Interests: Dr. Molinelli received honoraria from Novartis and Lilly outside the submitted work. Dr. Jacobs declares no conflicts of interest. Dr. Agostinetto received consultancy fees or honoraria from Eli Lilly and Sandoz and support to attend medical conferences from Roche, Novartis, Eli Lilly, and Genetic, Istituto Gentili (all disclosures are outside the submitted work). Dr. Marchiò received honoraria from Bayer, Roche, AstraZeneca, and Daiichi Sankyo. Dr. De Azambuja received honoraria and/or participated to advisory board from Roche/GNE, Novartis, Seattle Genetics, Zodiac, Libbs, and Pierre Fabre; received travel grants from Roche/GNE and GSK/Novartis; and received research grant to his institution from Roche/GNE, AstraZeneca, GSK/Novartis, and Servier. Dr. Schettini received personal fees from Novartis for educational material. Dr. Lambertini played an advisory role for Roche, Lilly, Novartis, Astrazeneca, Pfizer, Seagen, Gilead, MSD, and Exact Sciences and received speaker honoraria from Roche, Daiichi Sankyo, Lilly, Novartis, Pfizer, Sandoz, Libbs, and Takeda and travel grants from Gilead outside the submitted work., (Copyright © 2022 by S. Karger AG, Basel.)

Objective: The outcome of advanced ovarian cancer patients has not significantly improved since the introduction of platinum. One of the major reasons for this failure is the lack of an effective second-line treatment. In this phase II trial we tested the combination of gemcitabine and etoposide in 2 different groups of patients. Group 1 consisted of patients showing disease progression or relapse within 6 months of first-line platinum-based chemotherapy. Group 2 comprised heavily pretreated patients showing progression during the last chemotherapy attempt., Methods: Thirty-four patients were enrolled. Gemcitabine was administered at a dose of 1,000 mg/m(2) on days 1 and 8 and etoposide was administered orally at 100 mg/day on days 8-12 for 6 courses., Results: Eighteen patients (52.9%) had an objective response and the median duration of the response was 10.3 months. Our chemotherapy regimen showed a low toxicity and good patient compliance. In 5 patients the treatment had to be delayed and in only 2 patients it was discontinued., Conclusions: The combination of gemcitabine and oral etoposide seems to be a safe and effective second-line treatment for platinum-resistant ovarian cancer patients. Additional data on larger series are warranted to better define the activity of this combination regimen., (Copyright © 2011 S. Karger AG, Basel.)

Background: Five randomized studies have demonstrated a beneficial effect of adding cisplatin-based chemotherapy to radiation therapy in the treatment of cervical carcinoma. In the present phase II study, we evaluated the response and toxicity of cisplatin-Taxol chemotherapy combined with concomitant radiotherapy in patients with locally advanced cervical carcinoma (LACC) and locally recurrent cervical carcinoma (LRCC)., Patients and Methods: In 2000, this phase II study was initiated with a chemotherapy regimen of cisplatin (75 mg/m(2)) and Taxol (175 mg/m(2)) every 21 days, for four cycles, concomitant with external radiotherapy and high-dose-rate brachytherapy. Pelvic radiotherapy was started 2 weeks after the first chemotherapy cycle, while the first brachytherapy insertion was carried out during the fourth chemotherapy cycle. SCC marker was determined before treatment and after every chemotherapy cycle., Results: All of the 27 patients treated achieved a complete clinical response. Two patients with LACC experienced distant recurrence 22 and 24 months after complete response, respectively, and 1 patient with LRCC had local progression 6 months after the end of radiotherapy. Although generally tolerable, neutropenia grade 3-4 in 4 patients and anemia grade 3 in 2 patients were observed, and 1 patient experienced grade 2 neurotoxicity; toxicity due to radiotherapy was moderate., Conclusions: Concomitant cisplatin-Taxol chemoradiotherapy seems to be well tolerated, and results, even in this small series, are encouraging., (Copyright 2006 S. Karger AG, Basel.)