Lancet
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Anti-HER2 treatment for HER2-positive breast cancer has changed the natural biology of this disease. This Series article reviews the main achievements so far in the treatment of both metastatic and early HER2-positive breast cancer. ⋯ With survival rates of almost 5 years in women with metastatic HER2-positive breast cancer and 75% of patients achieving a pathological complete response, new treatments in the past decade have clearly improved the prognosis of HER2-positive breast cancer. Despite these achievements, however, the persisting high toll of deaths resulting from HER2-positive breast cancer calls for continued, intensive clinical research of newer therapies and combinations.
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Triple-negative breast cancer is a heterogeneous disease and specific therapies have not been available for a long time. Therefore, conventional chemotherapy is still considered the clinical state of the art. Different subgroups of triple-negative breast cancer have been identified on the basis of protein expression, mRNA signatures, and genomic alterations. ⋯ Nevertheless, the molecular analysis of this disease has identified potential options for targeted therapeutic intervention. This has led to promising clinical strategies, including modified chemotherapy approaches targeting the DNA damage response, angiogenesis inhibitors, immune checkpoint inhibitors, or even anti-androgens, all of which are being evaluated in phase 1-3 clinical studies. This Series paper focuses on the most relevant clinical questions, summarises the results of recent clinical trials, and gives an overview of ongoing studies and trial concepts that will lead to a more refined therapy for this tumour type.
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Oestrogen-receptor-positive breast cancer is the most common subtype of breast cancer. Endocrine therapies that target the dependence of this subtype on the oestrogen receptor have substantial activity, yet the development of resistance to therapy is inevitable in advanced cancer. ⋯ A new wave of targeted therapies is being developed, including inhibitors of PI3K, AKT, and HER2, and a new generation of oestrogen-receptor degraders. Considerable challenges remain in patient selection, deciding on the most appropriate order in which to administer therapies, and establishing whether cross-resistance occurs between therapies.