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Triple negative breast cancer (TNBC) is characterized by the lack of estrogen and progesterone receptor expression and lacks HER2 overexpression or gene amplification. It accounts for 10–15% of incident breast cancers and carries the worst prognosis. TNBC is overrepresented among Black and pre-menopausal women and is associated with significant psychological and treatment-related burdens, including financial toxicity. Like other breast cancers, TNBC is biologically heterogeneous, leading to diverse clinical and epidemiological behaviors, however, unlike the other clinical subtypes, in TNBC we still lack tumor-specific targeted therapy. Early TNBC outcomes have improved due to the intensification of therapies, including improvements in polychemotherapy and the addition of immunotherapy. Future efforts are needed to identify targetable aberrations for specific drug therapy, prevent immune evasion, and increase social-economic support. Given that the name TNBC illustrates its lack of specifically targeted and effective therapy, we look forward to being able to retire the name in favor of a group of targetable entities within what is now called “TNBC”.

Purpose We previously demonstrated that sex influences response to immune-checkpoint inhibitors. Here we investigate sex-based differences in the molecular mechanisms of anticancer immune-response and immune evasion in patients with NSCLC. Experimental Design We analyzed a) transcriptome-data of 2575 early-stage NSCLCs from 7 different datasets; b) 327 tumor-samples extensively characterized at the molecular level from the TRACERx lung study; c) two independent cohorts of respectively 329 and 391 patients with advanced NSCLC treated with anti-PD1/anti-PDL1 drugs. Results As compared with men, the tumor microenvironment (TME) of women was significantly enriched for a number of innate and adaptive immune cell-types, including specific T-cell subpopulations. NSCLCs of men and women exploited different mechanisms of immune evasion. The TME of females was characterized by significantly greater T-cell dysfunction status, higher expression of inhibitory immune-checkpoint molecules and higher abundance of immune-suppressive cells, including Cancer Associated Fibroblasts, MDSCs and Regulatory T-cells. By contrast, the TME of males was significantly enriched for a T-cells excluded phenotype. We reported data supporting impaired neoantigens presentation to immune system in tumors of men, as molecular mechanism explaining the findings observed. Finally, in line with our results, we showed significant sex-based differences in the association between TMB and outcome of patients with advanced NSCLC treated with anti-PD1/PDL1 drugs. Conclusions We demonstrated meaningful sex-based differences of anticancer immune response and immune evasion mechanisms, that may be exploited to improve immunotherapy efficacy for both women and men.

Background Patients with cancer have high risk for severe complications and poor outcome to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related disease (coronavirus disease 2019 [COVID-19]). Almost all subjects with COVID-19 develop anti-SARS-CoV-2 immunoglobulin-G (IgG) within three weeks after infection. No data are available on the seroconversion rates of cancer patients and COVID-19. Material and methods We conducted a multicenter, observational, prospective study that enrolled: 1) patients and oncology health professionals with SARS-CoV-2 infection confirmed by real time polymerase chain reaction (RT-PCR) assays on nasal/pharyngeal swab specimens; 2) patients and oncology health professionals with clinical or radiological suspicious of infection by SARS-CoV-2; and 3) patients with cancer who are considered at high risk for infection and eligible for active therapy and/or major surgery. All enrolled subjects were tested with the 2019-nCoV IgG/IgM Rapid Test Cassette, which is a qualitative membrane-based immunoassay for the detection of IgG and IgM antibodies to SARS-CoV-2. The aim of the study was to evaluate anti-SARS-CoV-2 seroconversion rate in patients with cancer and oncology healthcare professionals with confirmed or clinically suspected COVID-19. Results From March 30 to May 11, 2020, 166 subjects were enrolled in the study. Among them, cancer patients and health workers were 61 (36.7%) and 105 (63.3%), respectively. Overall, 86 subjects (51.8%) had confirmed SARS-CoV-2 diagnosis by RT-PCR testing on nasopharyngeal swab specimen, while 60 (36.2%) had a clinical suspicious of COVID-19. Median time between symptom onset (for cases not confirmed by RT-PCR) or RT-PCR confirmation to serum antibody test was 17 days (interquartile range, 26). In the population with confirmed RT-PCR, 83.8% was IgG positive. No difference in IgG positivity was observed between cancer patients and health workers (87.9% vs 80.5%; P = 0.39). Conclusions Our data indicate that SARS-CoV-2-specific IgG antibody detection do not differ between cancer patients and healthy subjects

Cardiotoxicity encompasses a spectrum of adverse cardiological effects experienced by cancer patients during and after receiving antineoplastic treatments. The intersection of cancer care with the management of the multiple comorbid non-communicable diseases carried by patients or related to cancer treatments motivates the need for an integrated and multidisciplinary approach to therapeutic clinical decision-making. This present review aimed to provide a perspective and an update of the current pharmacotherapy approaches for the prevention and management of cardiotoxicity from antiblastic chemotherapy; as such, it addresses myocardial, vascular, and arrhythmic disorders associated to chemotherapy, by navigating the current knowledge and clinical indications in support of the medical interventions. Clinical scenarios of pharmacological interventions take place with patients receiving anthracycline and, by extrapolation, other agents with cardiotoxic potentials and non-chemotherapy agents, including various small molecules and immunotherapy agents. Analysis of these scenarios aims to provide practical evidence-based guidance for the management of drug-induced cardiac dysfunctions. The possible role of new biomarkers for the early recognition of cardiotoxicity is mentioned across the clinical studies, with reference to the pharmacological biomarker-driven interventions delivered. To best inform survivorship care, the management and context of cardio-oncology services are discussed within the broader network of providers and settings of care.

Adjuvant endocrine therapy (AET) is generally proposed to all patients with hormone receptor-positive breast cancer to reduce the risk of recurrence and death. Adherence to therapy is crucial. However, non-adherence to AET is common, with estimates of up to 50% of patients not successfully completing a five-year course of treatment, and it is significantly associated with lower survival rates and a higher risk of recurrence. Currently, no gold standard is available to assess adherence. Several studies, most of them retrospective in nature, have used both direct and indirect methods to monitor the adherence to therapy in breast cancer. The indirect method is more widely used, and it is based on pharmacy prescription refills and patient administered questionnaires. On the other hand, direct methods such as a measurement of the level of the drug or its metabolites in blood or urine are much more precise, but more expensive and not routinely implemented. In this review, we analyzed the results of the major studies focused on the adherence to tamoxifen in breast cancer patients. We identified several factors associated with poor adherence, such as the side effects of therapy, the lack of shared decision-making between the physician and patient, the context in which the discussion takes place, and whether the patients are enrolled in a clinical trial. Moreover, we discussed possible methods to improve adherence to adjuvant therapy in breast cancer.

Purpose of review Antibody–drug conjugates (ADCs) represent an interesting new class of anticancer agents, capable of exploiting the specificity of monoclonal antibodies toward cellular-antigens for a targeted release of potent cytotoxic drugs, with a potential increased activity and reduced toxicity compared with traditional chemotherapies. The aim of this article is to review the efficacy and safety of ADCs in breast cancer. Recent findings Following the approval of T-DM1 both in early and advanced human epidermal growth factor receptor 2 (HER2)-positive breast cancer, novel anti-HER2 ADCs have been investigated. Some of these compounds, such as the recently FDA-approved trastuzumab deruxtecan, have shown relevant activity in T-DM1-pretreated patients, possibly thanks to the so-called bystander effect, namely the ability to exert cytotoxic activity also against antigen-negative cells. Such feature allows to overcome the HER2 intratumoral heterogeneity in breast cancer and could explain in the preliminary activity demonstrated also in HER2-low breast cancers. However, several ADCs targeting other cancer-associated antigens than HER2 are under development, representing a promising strategy for the treatment of triple-negative tumors, exemplified by the encouraging results of sacituzumab govitecan. Summary ADCs are innovative and effective therapeutic drugs in breast cancer. Research efforts are ongoing to identify novel targets and combination with other treatment modalities, particularly with immunotherapy, to further improve patients’ outcomes.

Background Peripheral blood parameters are correlated to immune‐checkpoint inhibitor efficacy in solid tumors, such as melanoma and non‐small cell lung cancer. Few data are currently available on the prognostic role of these immune‐inflammatory biomarkers for other solid tumors and immunotherapy combinations. Material and Methods From August 2014 to May 2019, 153 patients with metastatic solid tumors were enrolled in phase I clinical trials testing immunotherapy both as single agents and as combinations. Primary endpoint was to evaluate the impact of baseline blood parameters on progression‐free survival (PFS) and overall survival (OS). Results The most common tumor types were gastrointestinal, breast, and gynecological cancers (22.9%, 22.2%, and 15.0%, respectively). Higher lactate dehydrogenase (LDH) and derived neutrophil‐to‐lymphocyte ratio (dNLR) were independently associated with reduced PFS (hazard ratio [HR], 1.97; 95% confidence interval [CI], 1.30–2.99; p = .001, and HR, 2.29; 95% CI, 1.39–3.77; p = .001, respectively) and reduced OS (HR, 2.04; 95% CI, 1.26–3.28; p = .004, and HR, 2.06; 95% CI, 1.12–3.79; p = .02, respectively). In the subgroup analysis, (single agent vs. combination), patients at “good” (dNLR <3 and LDH < upper limit of normal [ULN]) and “intermediate and poor” (dNLR >3 and/or LDH > ULN) risk had higher and lower PFS, respectively (p for interaction = .002). Conversely, patients receiving monotherapy presented statistically significant difference in OS according to the risk group, whereas this effect was not observed for those treated with combinations (p for interaction = .004). Conclusion Elevated LDH and dNLR are associated with poorer survival outcomes in patients treated with immunotherapy in phase I clinical trials, regardless of tumor type. These parameters represent an easy tool that might be considered as stratification factors in immunotherapy‐based clinical trials. Implications for Practice In this retrospective cohort study of 153 patients with metastatic solid tumors treated with immunotherapy in the context of phase I clinical trials, elevated baseline lactate dehydrogenase and derived neutrophil‐to‐lymphocyte ratio were associated with reduced survival regardless of tumor subtype. If prospectively validated, these parameters might represent low‐cost and easy biomarkers that could help patient selection for early phase immunotherapy trials and be applied as a stratification factor in randomized studies testing immunotherapy agents.