Locally advanced breast cancer

Locally advanced breast cancer (LABC) is defined here as inoperable breast adenocarcinoma without distant metastases. Patients with LABC require a multidisciplinary approach. Given the risk of distant metastasis, staging exams are necessary. The incidence of LABC (stages IIIB and IIIC) has decreased in recent years. LABC has rarely been investigated separately: patients with LABC have participated both in clinical trials of palliative and of neoadjuvant therapy. Most trials did not analyze responses and long-term outcomes independently; thus, the treatment of patients with LABC is extrapolated from studies of patients with less or more advanced disease. Pathologic confirmation and molecular profiling are essential for the choice of neoadjuvant chemotherapy. Preoperative endocrine therapy may be considered in certain clinical situations; the addition of a CDK4/6 inhibitor is being investigated. HER2 positive LABCs are targeted with anti-HER2 agents combined with chemotherapy. PD-1 and PD-L1 antibodies in 'triple-negative' LABC are promising. Excellent responses to neoadjuvant therapy enable conservative surgery in many patients; however, inflammatory breast cancer may still indicate mastectomy. Postoperative radiotherapy is usually indicated. Target volumes include breast/chest wall, axillary, supraclavicular and internal mammary nodal basins. Preoperative radiation therapy can be useful in patients without response to systemic therapies. Palliative surgery for poor responders after neoadjuvant systemic and radiation therapy can be considered. Multidisciplinary teams can optimize local control and prevent relapses. However, modest improvement in survival was achieved between 2000 and 2014 underscoring the unmet need in patients with LABC who will benefit from specific research efforts in this disease entity.