Pathological complete response (pCR) after neoadjuvant chemotherapy in patients with early breast cancer is correlated with better survival. Meanwhile, an expanding arsenal of post-neoadjuvant treatment strategies have proven beneficial in the absence of pCR, leading to an increased use of neoadjuvant systemic therapy in patients with early breast cancer and the search for predictive biomarkers of response. The better prediction of response to neoadjuvant chemotherapy could enable the escalation or de-escalation of neoadjuvant treatment strategies, with the ultimate goal of improving the clinical management of early breast cancer. Clinico-pathological prognostic factors are currently used to estimate the potential benefit of neoadjuvant systemic treatment but are not accurate enough to allow for personalized response prediction. Other factors have recently been proposed but are not yet implementable in daily clinical practice or remain of limited utility due to the intertumoral heterogeneity of breast cancer. In this review, we describe the current knowledge about predictive factors for response to neoadjuvant chemotherapy in breast cancer patients and highlight the future perspectives that could lead to the better prediction of response, focusing on the current biomarkers used for clinical decision making and the different gene signatures that have recently been proposed for patient stratification and the prediction of response to therapies. We also discuss the intratumoral phenotypic heterogeneity in breast cancers as well as the emerging techniques and relevant pre-clinical models that could integrate this biological factor currently limiting the reliable prediction of response to neoadjuvant systemic therapy.

At diagnosis, about 35% of pancreatic cancers are at the locally invasive yet premetastatic stage. Surgical resection is not a treatment option, leaving patients with a largely incurable disease that often evolves to the polymetastatic stage despite chemotherapeutic interventions. In this preclinical study, we hypothesized that pancreatic cancer metastasis can be prevented by inhibiting mitochondrial redox signaling with MitoQ, a mitochondria-targeted antioxidant. Using four different cancer cell lines, we report that, at clinically relevant concentrations (100–500 nM), MitoQ selectively repressed mesenchymal pancreatic cancer cell respiration, which involved the inhibition of the expression of PGC-1α, NRF1 and a reduced expression of electron-transfer-chain complexes I to III. MitoQ consequently decreased the mitochondrial membrane potential and mitochondrial superoxide production by these cells. Phenotypically, MitoQ further inhibited pancreatic cancer cell migration, invasion, clonogenicity and the expression of stem cell markers. It reduced by ~50% the metastatic homing of human MIA PaCa-2 cells in the lungs of mice. We further show that combination treatments with chemotherapy are conceivable. Collectively, this study indicates that the inhibition of mitochondrial redox signaling is a possible therapeutic option to inhibit the metastatic progression of pancreatic cancer.

In oncology, the occurrence of distant metastases often marks the transition from curative to palliative care. Such outcome is highly predictable for breast cancer patients, even if tumors are detected early, and there is no specific treatment to prevent metastasis. Previous observations indicated that cancer cell mitochondria are bioenergetic sensors of the tumor microenvironment that produce superoxide to promote evasion. Here, we tested whether mitochondria-targeted antioxidant MitoQ is capable to prevent metastasis in the MDA-MB-231 model of triple-negative human breast cancer in mice and in the MMTV-PyMT model of spontaneously metastatic mouse breast cancer. At clinically relevant doses, we report that MitoQ not only prevented metastatic take and dissemination, but also local recurrence after surgery. We further provide in vitro evidence that MitoQ does not interfere with conventional chemotherapies used to treat breast cancer patients. Since MitoQ already successfully passed Phase I safety clinical trials, our preclinical data collectively provide a strong incentive to test this drug for the prevention of cancer dissemination and relapse in clinical trials with breast cancer patients.

Objectives: We report the case of a 68-year-old male who was hospitalized for suspicion of endoleak and thrombosis of an aortic endoprosthesis, arising after multiple endovascular interventions during the last few months. During the intervention, amass was discovered, and biopsies were made. The anatomopathology results were in favor of an epithelioid angiosarcoma with atypical expression of CD31 and ERG– and no amplification of c-MYC. The main objective of this review is to highlight the difficulty of differential diagnosis, but also to evaluate overall survival according to treatments. Methods: We performed a large review of the literature using PubMed for reports concerning angiosarcoma arising from Dacron grafts from 1981 to 2019. Articles presenting potentially relevant studies were read and analyzed. Results: In our review, most of the patients were male (10 cases over 11 described), with amedian age of 63 years old (50–84 years old, 11 cases described). The overall interval time for the diagnosis after the endoprosthesis placement was 7.8 years (from 3.5 years to 17 years, 10 cases with the description) and the overall survival was 5 months (from 0 to 10 months, the only patient alive is not included, and only 8 cases had the description). Conclusion: In most of the reviewed cases, there was no information concerning immunohistochemistry. Biopsies remain the standard for the diagnosis with immunochemistry and molecular test to avoid amisdiagnosis. Epithelioid angiosarcomas derived from Dacron grafts are a rare entity, which are difficult to diagnose because of the paucity of cases. Prognosis is poor, even if surgical option is possible.

Young women with breast cancer (BC) have an increased chance of carrying germline BRCA pathogenic variants (PVs). Limited data exist on the prognostic impact of tumor histology (i.e. ductal versus lobular) in hereditary breast cancer. This multicenter retrospective cohort study included women aged ≤40 years with early-stage breast cancer diagnosed between January 2000 and December 2020 and known to carry germline PVs in BRCA1/2. Histology was locally assessed in each center. The Kaplan-Meier method and Cox regression analysis were used to assess disease-free survival and overall survival. Of 4628 patients included from 78 centers worldwide, 3969 (86%) had pure ductal, 135 (3%) pure lobular, and 524 (11%) other histologies. Compared with ductal tumors, lobular tumors were more often grade 1/2 (57.7% versus 22.1%), stage III (29.6% versus 18.5%), and luminal A-like (42.2% versus 12.2%). Lobular tumors were more often associated with BRCA2 PVs (71.1% BRCA2), while ductal tumors were more often associated with BRCA1 PVs (65.7% BRCA1). Patients with lobular tumors more often had mastectomy (68.9% versus 58.3%), and less often received chemotherapy (83.7% versus 92.9%). With a median follow-up of 7.8 years, no significant differences were observed in disease-free survival (adjusted hazard ratio 1.01, 95% confidence interval 0.74-1.37) or overall survival (hazard ratio 0.96, 95% confidence interval 0.62-1.50) between patients with ductal versus lobular tumors. No significant survival differences were observed according to specific BRCA gene, breast cancer subtype, or body mass index. In this large global cohort of young BRCA carriers with breast cancer, the incidence of pure lobular histology was low and associated with higher disease stage at diagnosis, luminal-like disease and BRCA2 PVs. Histology did not appear to impact prognosis.

Ferroptosis has recently emerged as a promising strategy to combat therapy-resistant cancers. As lipid peroxidation is a key trigger of ferroptotic cell death, enhancing cancer cell susceptibility through the supply of highly peroxidisable fatty acids represents a novel therapeutic approach. Conjugated linolenic acids (CLnAs) fulfill this requirement, exhibiting a peroxidation propagation rate eight times higher than their non-conjugated counterpart, α-linolenic acid. This study evaluates jacaric acid (JA), a plant-derived CLnA, as a ferroptotic inducer, both as a monotherapy and in combination with RAS-selective lethal 3 (RSL3), a canonical ferroptosis inducer, in 2D and 3D breast cancer cell models. JA treatment significantly reduced cell viability across all models, primarily through lipid peroxidation driven by JA incorporation into cellular lipids rather than alterations in anti-ferroptotic gene expression. Moreover, JA synergistically enhanced RSL3 cytotoxicity under 2D and several 3D conditions. Similar effects were observed with punicic acid, another plant-derived CLnA isomer. Our study exploits a common feature of cancer metabolism, increased fatty acid uptake, to turn it into a vulnerability. The incorporation of JA into breast cancer cells creates a highly peroxidisable environment that increases cancer cell sensitivity to RSL3, potentially reducing required doses and minimising side effects.