Triple-negative breast cancer (TNBC) accounts for 15% to 20% of all invasive breast carcinomas and is defined by the lack of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. Although TNBC is characterized by high rates of disease recurrence and worse survival, it is significantly more sensitive to chemotherapy as compared with other breast cancer subtypes. Accordingly, despite great efforts in the genomic characterization of TNBC, chemotherapy still represents the cornerstone of treatment. For the majority of patients with early-stage TNBC, sequential anthracycline- and taxane-based neoadjuvant chemotherapy (NACT) represents the standard therapeutic approach, with pathological complete response that strongly correlates with long-term survival outcomes. However, some issues about the optimal neoadjuvant regimen, as well as the effective role of chemotherapy in patients with residual disease after NACT, are still debated. Herein, we will review the current evidences that-escalation, as well as the development of new therapies. In our view, the application of multi-omics technologies, liquid biopsy assays, and machine learning algorithms are strongly warranted to pave the way toward personalized anticancer treatment for early-stage TNBC. Triple-negative breast cancer, compared with other molecular subtypes, poses particular challenges for optimizing the timing and the extent of locoregional treatments. In the past, the combination of increased rates of both locoregional and distant recurrences led to a preference of radical surgery and extensive radiation therapy; however, since the introduction of more effective chemotherapy, a sharp de-escalation in the extent of locoregional treatments followed. Current evidence confirms that less aggressive surgery in combination with tailored radiation therapy offers improved oncological outcomes combined with better quality of life. However, further research is required to optimize locoregional treatments, considering the significant heterogeneity in biological behavior and tumor response to systemic treatments. Triple-negative breast cancer, compared with other molecular subtypes, poses particular challenges for optimizing the timing and the extent of locoregional treatments. In the past, the combination of increased rates of both locoregional and distant recurrences led to a preference of radical surgery and extensive radiation therapy; however, since the introduction of more effective chemotherapy, a sharp de-escalation in the extent of locoregional treatments followed. Current evidence confirms that less aggressive surgery in combination with tailored radiation therapy offers improved oncological outcomes combined with better quality of life. However, further research is required to optimize locoregional treatments, considering the significant heterogeneity in biological behavior and tumor response to systemic treatments. Triple-negative breast cancer (TNBC) continues to represent an unmet need because of its significantly poorer outcomes, including higher relapse rates following early-stage disease and dismal survival times in the advanced setting, when compared with other breast cancer subtypes (Cancer 2012;1185463-5472). Furthermore, there remains a lack of established systemic treatment options beyond conventional cytotoxic chemotherapy, with the exception of PARP inhibitors in the small subset of patients who harbor a BRCA mutation (N Engl J Med 2018;379753; Lancet Oncol 2020;211269-1282; Ann Oncol 2019;30558-566) and recently the use of immunotherapy in the first-line metastatic setting in those who are programmed death ligand 1-positive (Lancet Oncol 2020;21(1)44-59; N Engl J Med 2018;379(22)2108-2121). Suitable biomarkers for improving prognostication and directing therapy in both the early and advanced TNBC settings are required in order for improvements in survival outcomes to be continued to be attained. Tumor-inf required in order for improvements in survival outcomes to be continued to be attained. Tumor-infiltrating lymphocytes are gaining increasing relevance as an immunological biomarker in this arena. Obesity is an increasingly prevalent state of energy imbalance that contributes to breast cancer risk and outcomes. The effects of obesity differ by breast cancer subtype and menopause. https://www.selleckchem.com/ While most studies have focused on postmenopausal hormone receptor-positive disease, less is known about the relationship between obesity and triple-negative breast cancer (TNBC). Here we will review the observations linking obesity to TNBC, the socioeconomic disparities that contribute to obesity-related TNBC, and putative biologic mechanisms. Finally, we will consider the impact of obesity on surgical and medical treatment of TNBC and novel strategies to improve energy balance after cancer diagnosis. Obesity is an increasingly prevalent state of energy imbalance that contributes to breast cancer risk and outcomes. The effects of obesity differ by breast cancer subtype and menopause. While most studies have focused on postmenopausal hormone receptor-positive disease, less is known about the relationship between obesity and triple-negative breast cancer (TNBC). Here we will review the observations linking obesity to TNBC, the socioeconomic disparities that contribute to obesity-related TNBC, and putative biologic mechanisms. Finally, we will consider the impact of obesity on surgical and medical treatment of TNBC and novel strategies to improve energy balance after cancer diagnosis. Triple-negative breast cancer accounted for 12% of breast cancers diagnosed in the United States from 2012 to 2016, with a 5-year survival 8% to 16% lower than hormone receptor-positive disease. However, preventive and screening strategies remain tailored to the demographics of less lethal luminal cancers. This review examines the ethnic, genetic, and modifiable risk factors associated with triple-negative breast cancer, which providers must recognize to address the societal disparities of this deadly disease. Most notable is that triple-negative cancers disproportionately affect African American women and carriers of germline BRCA and PALB2 mutations. Even controlling for treatment delays, stage, and socioeconomic factors, African Americans with triple-negative breast cancer remain nearly twice as likely to die of their disease. To level the playing field, we must integrate genomic predictors of disease and epidemiologic characteristics of molecular breast cancer subtypes to provide personalized risk assessment, screening, and treatment for each patient.