Breast cancer is the most common tumor in women. Chemotherapy is the gold standard for cancer treatment; however, severe side effects and tumor resistance are the major obstacles to chemotherapy success. Numerous dietary components and phytochemicals have been found to inhibit the molecular and signaling pathways associated with different stages of breast cancer development. In particular, this review is focused on the antitumor effects of PUFAs, dietary enzymes, and glucosinolates against breast cancer. The major databases were consulted to search in vitro and preclinical studies; only those with solid scientific evidence and reporting protective effects on breast cancer treatment were included. A consistent number of studies highlighted that dietary components and phytochemicals can have remarkable therapeutic effects as single agents or in combination with other anticancer agents, administered at different concentrations and via different routes of administration. These provide a natural strategy for chemoprevention, reduce the risk of breast cancer recurrence, impair cell proliferation and viability, and induce apoptosis. Some of these bioactive compounds of dietary origin, however, show poor solubility and low bioavailability; hence, encapsulation in nanoformulations are promising tools able to increase clinical efficiency.

Oxidative phosphorylation and glycolysis are the main ATP-generating pathways in cell metabolism. The balance between these two pathways is frequently altered to carry out cell-specific activities in response to stimuli involving activation, proliferation, or differentiation. Despite being a useful tool for researching metabolic profiles in real time in relatively small numbers of cancer cells, the main Agilent Seahorse XF Pro Analyzer (Agilent Technologies, Santa Clara, CA, USA) guideline is currently not fully detailed in the distinction between suspensions vs. adherent cancer cells. This article provides step-by-step protocols for profiling metabolic fluxes in suspension vs. adherent cancer cells via Seahorse technology, including adjustments for normalisation of data on the basis of the number of viable cells or the total protein content. Owing to the adaptations of plates, reagents, cell count, and protein quantification, it is possible to (i) analyse both adherent and suspension cells with a single instrument; (ii) conduct all experiments in 96-well plates, thus using fewer cells, media, and reagents; (iii) determine the effect of a drug or compound directly on cell metabolism; (iv) normalise data on the basis of the number of viable cells or the total protein content via a spectrophotometer; and (v) achieve notable savings in cost and time.

Background/Objectives: Breast cancer is the most frequently diagnosed malignancy among women and is characterized by marked heterogeneity in treatment response. Metabolic reprogramming, particularly enhanced de novo lipogenesis, represents a hallmark of cancer progression and a promising therapeutic target. Firsocostat, a selective allosteric inhibitor of acetyl-CoA carboxylase (ACC), has previously been investigated in metabolic diseases but has never been evaluated in breast cancer models. This study aimed to assess the antitumor effects of firsocostat on breast cancer cell lines. Methods: We investigated the cytotoxic and metabolic effects of firsocostat in four breast cancer cell lines—MCF7 (luminal A HR⁺), SK-BR-3 (HER2-positive), MDA-MB-231 (triple-negative), and HCC1937 (triple-negative, BRCA1-mutated)—together with the non-tumorigenic MCF-10A line. Dose- and time-dependent responses were evaluated using phase-contrast microscopy for morphological evaluation, Trypan Blue exclusion assays, and MTS-based viability assays. Results: Firsocostat significantly reduced cell viability across all breast cancer subtypes in a concentration- and time-dependent manner, with IC₅₀ values ranging from 80 to 93 µM. In contrast, non-tumorigenic MCF-10A cells were less affected, indicating a selective cytotoxic effect toward malignant cells. Conclusions: Firsocostat exerts robust cytotoxic effects in breast cancer models, identifying it as a promising metabolism-targeting therapeutic candidate capable of selectively impairing breast cancer cell survival by disrupting fatty acid biosynthesis. These results indicate that firsocostat could represent a viable candidate as a metabolic-based therapeutic approach for breast cancer. Given its established clinical safety profile in metabolic diseases, firsocostat warrants further preclinical investigation and supports further mechanistic and preclinical evaluation.

Background: Post-surgical breast cancer (BC) survivors frequently experience clusters of persistent post-treatment physical and psychological symptoms, which can negatively affect their quality of life (QoL). Mind–body interventions such as Qigong may offer potential benefit, but evidence in oncology remains limited. Methods: We conducted a single-arm pilot feasibility study at the AMICO clinic (IRCCS-CROB, Southern Italy) to evaluate the feasibility, acceptability, safety, and exploratory pre–post symptoms associated with an 8-week Qigong programme in post-surgical BC patients. Fourteen women (aged 42–73 years; stage I–III) who reported symptom burden and emotional sensitivity attended weekly one-hour classes and were encouraged to practise at home. Feasibility outcomes included adherence, completion of post-intervention assessment, adverse events, and participant acceptability. Symptom severity was assessed at baseline and post-intervention using a 0–5 study-specific symptom questionnaire score. For the secondary descriptive prevalence analysis, scores ≥ 3 were classified as indicating moderate-to-severe symptom burden. Results: All 14 participants completed the post-intervention assessment, overall intervention adherence was 92%, and no adverse events were reported. In the secondary descriptive analysis, the prevalence of moderate-to-severe pain and mood changes decreased from 64.3% to 35.7%, fatigue from 57.1% to 28.6%, anxiety from 85.7% to 42.9%, and sleep disturbances from 35.7% to 14.3%. Hot flushes decreased from 64.3% to 42.9%. Despite the heterogeneity of individual symptom trajectories, most participants reported meaningful improvements in overall well-being. Conclusions: The 8-week programme was feasible, well tolerated, and acceptable in this small real-world cohort. Symptom burden decreased during the intervention period; however, because of the uncontrolled study design and small sample size, these changes cannot be attributed specifically to Qigong. Larger controlled studies are required to estimate treatment effects and identify potential moderators of response.

Drug repurposing and the development of novel precursors are promising strategies for overcoming therapeutic resistance in breast cancer (BC). BnpM-NH₂, a hydroxyethylamino synthetic precursor of darunavir analogues, has previously demonstrated anticancer activity in haematological malignancies; however, its effects on BC remain unknown. This study investigated the antitumour activity of BnpM-NH₂, alone and in combination with tamoxifen (TMX), across molecularly distinct BC subtypes. Human BC cell lines representing hormone receptor-positive (MCF7), HER2-positive (SK-BR-3), and triple-negative (MDA-MB-231 and HCC1937) cell lines, together with non-tumorigenic MCF-10A cells, were treated with BnpM-NH₂ and/or TMX. Cell viability, proliferation, endoplasmic reticulum (ER) stress, autophagy, mitochondrial oxidative phosphorylation (OXPHOS), Akt–mTOR signalling, and apoptosis were evaluated using MTS assays, xCELLigence, and western blotting. Molecular docking and SwissADME analyses were used to evaluate target interactions and pharmacokinetic properties. BnpM-NH₂ significantly reduced BC cell viability with limited toxicity toward MCF-10A cells. Combination treatment with TMX enhanced the antiproliferative effects more than either agent alone. Mechanistically, BnpM-NH₂ modulated ER stress (ATF4, eIF2α), altered autophagy (LC3, p62), disrupted mitochondrial homeostasis through OXPHOS complexes and TOM20, modulated Akt–mTOR and S6 signalling, and activated caspase-dependent and apoptosis-inducing factor (AIF)-mediated mechanisms. Docking suggested favourable interactions of BnpM-NH₂ and tamoxifen with mTOR and Akt, and indicated that the two ligands can be accommodated simultaneously within adjacent regions of the respective binding pockets. SwissADME predicted favourable drug-likeness and high gastrointestinal absorption. BnpM-NH₂ exhibits broad antitumour activity across multiple BC subtypes and enhances the anticancer effects of tamoxifen. The combined experimental, computational, and pharmacokinetic prediction data support further preclinical evaluation of BnpM-NH₂ as a promising candidate for combination therapy in BC. Graphical abstract