Triple-negative breast cancers (TNBCs) are defined by the absence of estrogen and progesterone receptors and the absence of HER2 overexpression. These cancers represent a heterogeneous breast cancer subtype with a poor prognosis. Few systemic treatment options exist besides the use of chemotherapy (CT). The heterogeneity of the disease has limited the successful development of targeted therapy in unselected patient populations. Currently, there are no approved targeted therapies for TNBC. However, intense research is ongoing to identify specific targets and develop additional and better systemic treatment options. Standard adjuvant and neoadjuvant regimens include anthracyclines, cyclophosphamide, and taxanes. Platinum-based CT has been proposed as another CT option of interest in TNBC. We review the role of this therapy in general, and particularly in patients carrying BRCA germ-line mutations. Available data concerning the role of platinum-based CT in TNBC were acquired primarily in the neoadjuvant setting. The routine use of platinum-based CT is not yet recommended by available guidelines. Many studies have reported the molecular characterization of TNBCs. Several actionable targets have been identified. Novel therapeutic strategies are currently being tested in clinical trials based on promising results observed in preclinical studies. These targets include androgen receptor, EGFR, PARP, FGFR, and the angiogenic pathway. We review the recent data on experimental drugs in this field. We also discuss the recent data concerning immunologic checkpoint inhibitors.

In this article, we focus on the subtype of estrogen receptor (ER)-positive, human epidermal growth factor 2 (HER2)-positive breast cancer (BC). Preclinical and clinical data indicate a complex molecular bidirectional crosstalk between the ER and HER2 pathways. This crosstalk probably constitutes one of the key mechanisms of drug resistance in this subclass of BC. Delaying or even reversing drug resistance seems possible by targeting pathways implicated in this crosstalk. High-risk patients currently receive anti-HER2 therapy, chemotherapy and endocrine therapy in the adjuvant setting. In metastatic cases, most patients receive a combination of anti-HER2 therapy and chemotherapy. Only selected patients presenting more indolent disease are candidates for combinations of anti-HER2 therapy and endocrine therapy. However, relative improvements in progression-free survival by chemotherapy-based regimens are usually lower in ER-positive patients than the ER-negative and HER2-positive subgroup. Consequently, new approaches aiming to overcome endocrine therapy resistance by adding targeted therapies to endocrine therapy based regimens are currently explored. In addition, dual blockade of HER2 or the combination of trastuzumab and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOP) inhibitors targeting the downstream pathway are strategies to overcome resistance to trastuzumab. This may lead in the near future to the less frequent use of chemotherapy-based treatment options in ER-positive, HER2-positive BC.

Everolimus combined with exemestane is an important treatment option for patients suffering from estrogen receptor-positive, human epidermal growth factor receptor 2-negative, advanced breast cancer (ABC) who have been previously treated with a nonsteroidal aromatase inhibitor (NSAI). After presentation of phase III registration trial BOLERO-2, several phase IIIb trials have been started to evaluate this regimen in a more real-world setting. Here, we review the efficacy and safety data published or presented at selected international meetings. These studies confirmed the outcome observed in the BOLERO-2 trial. Patient acceptance rate is also discussed by focusing on the permanent everolimus discontinuation rate in these trials. Factors influencing the safety profile are also reported, including the impact of age. The optimal sequence of combined therapy approaches associating targeted and endocrine therapy (ET) has yet to be determined as new treatment options such as cyclin-dependent kinase inhibitors become available. However, everolimus–exemestane remains an important treatment option with a major impact on progression-free survival (PFS) and an acceptable safety profile.

Background: The impact of coronavirus disease 2019 (COVID-19) on cancer patients is still unknown. We aimed to describe the clinical characteristics and 28-day mortality among patients with solid cancers (SC) and COVID-19.Methods: This single-center retrospective study included all adult patients with SC and RT-PCR confirmed COVID-19 between March 12, 2020 and April 30, 2020. Both oncological and COVID-19-related clinical data were collected. COVID-19 severity was defined according to Chinese CDC criteria. In-hospital and 28-day mortality were estimated. Multivariate analysis was adjusted for age, sex and COVID-19 severity. Results: We included 58 (2.7%) of 2130 patients with COVID-19 diagnosed in our hospital; 37 (63.8%) were males. Median age was 68.5 years (IQR, 61-75). Main comorbidities were hypertension (28 [48.3%]) and overweight/obesity (23 [39.7%]). Most common SC were prostate (12 [20.7%]), lung (10 [17.2%]) and breast (10 [17.2%]). Overall, 48 (82.8%) patients had previous ECOG PS of 0-1; 26 (44.8%) were stage IV and 32 (57.1%) were undergoing cancer treatment. Fifty-six (96.5%) patients were admitted. Most frequent COVID-19 symptoms were fever (40 [69.0%]), cough (35 [62.5%]) and dyspnea (27 [48.2%]). Hydroxychloroquine and azithromycin were used in 40 (69.0%) and 38 (65.5%) patients, respectively; only 3 (5.2%) patients received tocilizumab. Eighteen patients (32.1%) had severe/critical COVID-19. Major complications were respiratory failure (33 [57.9%]), sepsis (14 [24.6%]) and acute kidney injury (13 [22.4%]). Four (6.9%) patients were admitted to ICU. In-hospital and 28-day mortality were 17.2% (10/58) and 24.1% (14/58), respectively. In the multivariate analysis, only dyspnea at diagnosis (hazard ratio [HR]: 6.71, 95% CI 1.40-32.25, p¼0.017) and ECOG PS of 2-3 (HR: 4.17; 95% CI: 1.13-15.30, p¼0.031) were independent risk factors for 28-day mortality.Conclusions: In our patients with SC and COVID-19, 32.1% had a severe/critical disease and 24.1% died within 28 days from diagnosis. Dyspnea at diagnosis and previous ECOG PS of 2-3 were the major predictors for 28-day mortality. Cancer treatment and stage were not associated with mortality.Legal entity responsible for the study: The authors.