Search Results (80)

Background/Objectives: Cancer patients are highly susceptible to infectious diseases due to malignancy- and treatment-induced immunosuppression. The coronavirus disease 2019 (COVID-19) pandemic highlighted this vulnerability, particularly in aggressive tumors such as triple-negative breast cancer (TNBC) and clear cell renal cell carcinoma (ccRCC). However, the molecular mechanisms linking cancer progression with COVID-19 severity remain poorly defined. This study aimed to identify shared molecular signatures between COVID-19 and TNBC, breast cancer, and ccRCC using integrative bioinformatics approaches. Methods: A comprehensive in silico case–control analysis was conducted using publicly available GEO transcriptomic datasets (GSE164805, GSE139038, GSE45498, and GSE105261). Differentially expressed genes (DEGs) were identified by comparing mild and severe COVID-19 cases with each cancer type. Protein–protein interaction (PPI) networks were constructed to identify hub genes, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Regulatory networks involving microRNAs (miRNAs) and transcription factors (TFs) were also examined. Results: Shared hub genes were identified across COVID-19 and cancer datasets, including IGF1, MMP9, and NOTCH1 in TNBC; TOP2A, PXN, and CCNB1 in breast cancer; and ASPM and TTK in ccRCC. These genes are linked to immune regulation, inflammation, cell cycle control, and tumor progression. Enrichment analyses revealed convergent pathways such as MAPK signaling, cytokine–cytokine receptor interaction, Ras signaling, and proteoglycans in cancer. Key regulatory molecules, including miR-145-5p, miR-192-5p, miR-335-5p, and transcription factors NFKB1, BRCA1, and TP53, modulated both viral and oncogenic processes. Severe COVID-19 was associated with enhanced inflammatory and proliferation-related signaling across all cancer types. Conclusions: This integrative, severity-stratified analysis identifies shared molecular and regulatory features linking severe COVID-19 with aggressive cancers, highlighting persistent immune activation and altered immune communication as common underlying themes without implying causality or clinical outcome effects. These findings provide a systems-level, hypothesis-generating framework for understanding virus–cancer interactions and may inform future biomarker discovery and immune-focused therapeutic strategies in vulnerable cancer populations. Full article

Background: Triple-negative breast cancers (TNBCs) are among the most aggressive breast tumors, due not only to the absence of clinically functional biomarkers used in other molecular subtypes, but also their marked heterogeneity and pronounced migratory and invasive behavior. The search for new molecules of interest for risk prediction, diagnosis and therapy stems from the class of long non-coding RNAs (lncRNAs), which often display context-dependent (“dual”) functions and tissue specificity. Among them, lncRNA LINC01133 stands out for its dysregulation across cancer, although its molecular role in TNBC remains unclear. Methods: In the present study, we used the human TNBC cell line Hs578T to generate a cell panel comprising the parental line (Hs578T_wt), the control line (Hs578T_ctr), and the LINC01133 knockout line (Hs578T_ko). Subsequently, we performed bulk RNA-Seq to identify KO-associated Differentially Expressed Genes (DEGs) using ko_vs_ctr as the primary contrast. Functional interpretation was achieved by Over-Representation Analysis (ORA) using Gene Ontology. We then conducted a comparative patient-cohort analysis using TCGA-BRCA Basal-like/TNBC cases (TCGA/BRCA n = 1098; Basal-like/TNBC n = 199), classified with the AIMS algorithm, and evaluated concordance between KO-associated signatures and patient tumor expression patterns via trend-based analyses across the LINC01133 expression levels and associated genes. Results: A total of 265 KO-dominant DEGs were identified in Hs578T_ko, reflecting transcriptional changes consistent with tumor progression, with enrichment of pathways associated with LINC01133 knockout including cell adhesion, cell–cell interactions, epithelial–mesenchymal transition (EMT), and extracellular matrix (ECM) remodeling. The main DEGs included ITIH5, GLUL, CACNB2, PDX1, ASPN, PTGER3, MFAP4, PI15, EPHB6, and CPA3 with additional candidates, such as KAZN and the lncRNA gene SSC4D, which have been implicated in migration/invasion, ECM remodeling, or signaling across multiple tumor contexts. Translational analyses in TCGA-BRCA basal-like tumors suggested a descriptive association in which lower LINC01133 levels were accompanied by shifts in the expression trends of genes linked to ECM/EMT programs and modulation of genes related to cell adhesion and protease inhibition. Conclusions: These results suggest a transcriptional model in which LINC01133 is associated with TNBC-related gene expression programs in a concentration-dependent manner, with loss of LINC01133 being associated with a transcriptomic shift toward pro-migratory/ECM remodeling signatures. While functional validation is required to establish causality, these data support LINC01133 as a molecule of interest in breast cancer research. Full article

Objectives: The molecular characterization of male breast cancer (MaBC) has long been understudied, primarily due to its rare occurrence. Clinical management of MaBC remains profoundly challenging, with current therapeutic strategies largely extrapolated from female breast cancer protocols. Methods: Through panel-based sequencing targeting BRCA1, BRCA2, and PALB2 variants, we delineated the genomic landscape of 96 MaBC cases. Subsequent whole-exome sequencing (WES) of 84 BRCA1/2- and PALB2-mutation-negative MaBC patients, compared against 4480 healthy controls, revealed compelling findings. Results: Pathogenic variants in BRCA1/2 and PALB2 were identified in 14.6% (14/96) of MaBC cases, with BRCA2 mutations predominating at 12.5% (n = 12). Notably, one patient harbored the BRCA1 c.4015G > T stop-gained mutation, while another exhibited the PALB2 c.481_482dupGA alteration. Our analysis further uncovered 170 pathogenic/likely pathogenic mutations, with RAD50, DMD, ARSA, and ABCC6 demonstrating recurrent mutations in MaBC. Conclusions: As the inaugural germline genomic investigation of MaBC in a Han Chinese population, this work reveals clinically actionable alterations with diagnostic and therapeutic implications. These discoveries not only advance our understanding of MaBC’s molecular architecture but also underscore the critical need for dedicated research into this malignancy. Full article

Invasive lobular carcinoma (ILC) accounts for approximately 15% of breast cancers and the most common neoplasm in the female population. Cervical involvement is exceptionally rare and often underrecognized. This relationship is well-defined in the context of breast and ovarian cancer syndrome related to BRCA gene mutations. However, it is also observed in rare but underreported cases of cervical metastases originating from breast cancer. The objective of this manuscript is to describe a rare case of cervical recurrence of invasive lobular carcinoma and summarize comparable case to guide future gynecologic follow-up strategies. Therefore, we report the case of a 60-year-old woman who developed a late cervical recurrence of ILC ten years after her initial breast cancer diagnosis. The patient had previously undergone mastectomy for ER-positive, PR-positive, HER2-negative ILC, followed by five years of adjuvant endocrine therapy. She remained disease-free until presenting with post-menopausal bleeding, urinary symptoms, and acute renal failure. Pelvic examination and ultrasonography revealed an enlarged, indurated cervix with bilateral hydroureteronephrosis. Biopsy demonstrated a discohesive infiltrate consistent with metastatic lobular carcinoma, confirmed by immunohistochemistry (GATA3+, CK7+, ER/PR+, E-cadherin−, CK20−, CDX2−). Staging PET-CT showed additional metastases involving bone, peritoneum, and lymph nodes. The patient began systemic therapy with ribociclib plus letrozole, achieving radiologic improvement of the cervical lesion and abdominal disease. After a follow-up of several months, she maintains stable disease but has persistent chronic renal impairment secondary to obstructive uropathy. This case highlights the ability of ILC to recur after long latency and to metastasize to unusual gynecologic sites such as the cervix. We also review the literature on cervical recurrence from lobular carcinoma to emphasize the importance of gynecologic surveillance in breast cancer survivors and to identify areas that require further investigation. Full article

Background: Pembrolizumab has reshaped the neoadjuvant treatment landscape for triple-negative breast cancer (TNBC). However, the influence of BRCA1/2 mutational status on the efficacy of chemo-immunotherapy remains unclear, particularly in real-world settings. Since BRCA-mutated tumors exhibit homologous recombination deficiency (HRD) and high genomic instability, they may be more immunogenic and responsive to immune checkpoint inhibitors. This multicenter study investigated the association between BRCA1/2 mutations and pathologic complete response (pCR) in TNBC patients treated with pembrolizumab-based neoadjuvant chemotherapy (NACT). Methods: We retrospectively analyzed 184 patients with stage II–III TNBC treated between 2021 and 2024 across eleven Italian oncology centers. All received pembrolizumab combined with platinum- and taxane-based NACT followed by anthracyclines, according to the KEYNOTE-522 regimen. Germline BRCA1/2 status was determined by next-generation sequencing. The primary endpoint was pCR, defined as ypT0/is ypN0. Fisher’s exact test and logistic regression models were used to assess associations between clinical–pathological variables and pCR. Results: Among 184 patients, 25 (13.6%) harbored BRCA1 mutations, 12 (6.5%) BRCA2 mutations, and 147 (79.9%) were wild-type. pCR was achieved in 80.0% of BRCA1-mutated, 75.0% of BRCA2-mutated, and 61.1% of wild-type tumors. When pooled, BRCA1/2-mutated cases showed a higher likelihood of achieving pCR (78.4% vs. 61.1%; odds ratio [OR] = 2.17; 95% CI 1.01–4.97; p = 0.056). High tumor-infiltrating lymphocytes (≥30%) were also associated with increased pCR rates. The frequency of BRCA mutations (20.1%) was consistent with that reported in major TNBC series. No comparative analysis of toxicity or survival outcomes was performed due to the retrospective design and limited follow-up. Conclusions: In this multicenter real-world cohort, TNBC patients carrying BRCA1/2 mutations exhibited a trend toward higher pCR rates with pembrolizumab-based NACT compared with wild-type tumors. These findings suggest enhanced chemosensitivity and immune responsiveness in BRCA-deficient disease, warranting further validation in larger prospective studies with survival endpoints. Full article

Homologous recombination deficiency (HRD) is a clinically relevant biomarker that predicts sensitivity to PARP inhibitors and enables personalized cancer therapy. Validated local HRD testing solutions are essential to ensure timely and equitable access, ultimately improving treatment outcomes. We evaluated a shallow whole-genome sequencing (sWGS) approach for genomic instability (GI) assessment combined with a 52-gene targeted panel in ovarian cancer. Validation used reference materials and 24 archival samples with prior HRD characterization, comparing performance with the Myriad myChoice^® HRD test. A prospective cohort of 124 newly diagnosed ovarian cancer patients was then analyzed. sWGS-derived GI status showed strong concordance with the reference test (95.8% overall agreement; κ = 0.913; NPV 100%, PPV 93.3%). Pathogenic BRCA1/2 variants were detected in 30 patients (24.19%). An additional 22.76% were BRCA1/2-negative but GI-positive, giving an overall HRD prevalence of 47.15%. Platinum sensitivity occurred in 90.0% (18/20) of HRD-positive patients with follow-up. Among 12 patients assessed for PARP-inhibitor response, the overall response rate was 66.7% (95% CI 39.1–86.2) and disease control rate 83.3% (95% CI 55.2–95.3). TP53 alterations were most frequent (62.90%), followed by BRCA1 (19.35%) and BRCA2 (4.83%). Pathogenic variants in other HR-pathway genes (ATM, CHEK2, BRIP1, RAD51C, BARD1) appeared in 9.57% of BRCA-wild-type cases, with heterogeneous GI impact. Two cases showed concurrent BRCA2 variants and microsatellite instability, indicating possible eligibility for anti-PD-1/PD-L1 therapy in addition to PARPi. This first comprehensive analysis of Romanian ovarian cancer patients suggests that integrating sWGS-based genomic instability assessment with BRCA testing can improve HRD detection and reflects the heterogeneity of HR-pathway variants. Preliminary clinical observations were consistent with known HRD-associated treatment responses, although larger studies are needed to confirm these findings. Full article

Personalized cancer vaccines are a key strategy for training the immune system to recognize and respond to tumor-specific antigens. Our earlier software release, AutoEpiCollect 1.0, was designed to accelerate the vaccine design process, but the identification of tumor-specific genetic variants remains a manual process and is highly burdensome. In this study, we introduce AutoEpiCollect 2.0, an improved version with integrated genetic analysis capabilities that automate the identification and prioritization of tumorigenic variants from individual tumor samples. AutoEpiCollect 2.0 connects with RNA sequencing and cross-references the resulting RNAseq data for efficient determination of cancer-specific and prognostic gene variants. Using AutoEpiCollect 2.0, we conducted two case studies to design personalized peptide vaccines for two distinct cancer types: cervical squamous cell carcinoma and breast carcinoma. Case 1 analyzed five cervical tumor samples from different stages, ranging from CIN1 to cervical cancer stage IIB. CIN3 was selected for detailed analysis due to its pre-invasive status and clinical relevance, as it is the earliest stage where patients typically present symptoms. Case 2 examined five breast tumor samples, including HER2-negative, ER-positive, PR-positive, and triple-negative subtypes. In three of these breast samples, the same epitope was identified and was synthesized by identical gene variants. This finding suggests the presence of shared antigenic targets across subtypes. We identified the top MHC class I and class II epitopes for both cancer types. In cervical carcinoma, the most immunogenic epitopes were found in proteins expressed by HSPG2 and MUC5AC. In breast carcinoma, epitopes with the highest potential were derived from proteins expressed by BRCA2 and AHNAK2. These epitopes were further validated through pMHC-TCR modeling analysis. Despite differences in cancer type and tumor subtype, both case studies successfully identified high-potential epitopes suitable for personalized vaccine design. The integration of AutoEpiCollect 2.0 streamlined the variant analysis workflow and reduced the time required to identify key tumor antigens. This study demonstrates the value of automated data integration in genomic analysis for cancer vaccine development. Furthermore, by applying RNAseq in a standardized workflow, the approach enables both patient-specific and population-level vaccine design, based on statistically frequent gene variants observed across tumor datasets. AutoEpiCollect 2.0 is freely available as a website based tool for user to design vaccine. Full article

Breast cancer (BC) is a heterogeneous disease, and triple-negative breast cancer (TNBC) is the most aggressive and immunogenic subtype. A significant proportion of TNBC cases are linked to hereditary cancer syndromes involving pathogenic germline variants, most commonly in BRCA1/2. However, few studies have compared hereditary and sporadic TNBC in admixed populations. In this study, molecular and immunological features were analyzed through the analysis of 62 Colombian TNBC samples (20 hereditary and 42 sporadic cases) by RNA sequencing to identify molecular and immune differences. We used an external validation cohort of 16 TCGA TNBC cases (8 BRCA-mutated and 8 non-mutated) to replicate our findings. Results: We found a set of 921 differentially expressed genes (DEGs) between hereditary and sporadic TNBC. Hereditary tumors were enriched for pathways related to extracellular matrix (ECM) remodeling, structural components, and DNA damage response and exhibited a more immunologically active tumor microenvironment compared to sporadic tumors. LASSO logistic regression identified 23 genes with discriminatory potential, showing that hereditary tumors are characterized by complex immune regulation, inflammatory processes, and activation of key oncogenic pathways. Conclusions: Hereditary TNBC is characterized by molecular and biological functions linked to ECM remodeling and its constituents and an active immune microenvironment. This integrated molecular–immune profile provides insight into the distinct biology of hereditary tumors in admixed populations. Full article

Targetable gene alterations have become increasingly important in the treatment of cancers. Thirty STK11-mutated lung cancers from 199 cases with molecular profiling performed during 2016–2024 were studied for clinical, morphologic, immunohistochemical (IHC) and molecular features. Of the 30 STK11-mutated lung cancers, 29 were lung adenocarcinomas (LADCs) and 1 was large cell neuroendocrine carcinoma (LCNEC). STK11 mutation was not found in other subtypes of lung cancers. Of the 29 STK11-mutated LADCs, 6 (21%) were mucinous and 23 (79%) were non-mucinous. Of the 19 non-mucinous LADCs with sufficient material for IHC, 9 (47%) displayed acinar/papillary/lepidic patterns, 8 (42%) were poorly differentiated (solid/trabecular/basaloid/complex glandular), and 2 (11%) had mixed solid and acinar patterns. The most common concurrent altered genes were KRAS (52%), followed by TP53 (38%), KEAP1 (34%), and DNA repair genes (BRCA2/ATM) (21%). A total of 6/15 (40%) LADCs with a KRAS mutation presented with mucinous morphology. Concurrent EGFR, ROS, or ALK alterations with STK11 mutation were rare or non-existent. Of the 3 LADCs with SMARCA4 deficiency, 2 were mucinous and 1 had basaloid/adenoid cystic-like features. All the cases were microsatellite stable (MSS). The majority (55%) had low TMB (<10). Most (86%) had PD-L1 TPS 0 or <5%. Among the 14 non-mucinous LADCs with IHC performed, 5 (36%) were TTF-1-negative and all displayed poorly differentiated morphology. Overall, 8/10 (80%) of poorly differentiated components in non-mucinous LADCs were negative for TTF-1. In contrast, all LADCs with better differentiated patterns (acini/papillary/lepidic) were positive for TTF-1. The majority (14/21, 67%) of patients with available follow-up presented with metastasis. Full article

Background/Objectives: Access to genetic counselling and BRCA1/2 germline testing is standard of care for patients with high-grade serous ovarian carcinoma (HGSOC). While tumour testing reliably detects pathogenic variants in hereditary cancer genes, it cannot distinguish somatic from germline variants. Concurrent testing of non-cancerous (normal) tissue obtained during surgery may improve triage for germline testing and clinical genetics referral. This study evaluated the concordance of inherited variant detection among tumour, normal tissue, and blood to determine whether archived normal tissue can reliably identify germline pathogenic variants. Methods: Patients with HGSOC who had a pathogenic variant identified by targeted Next Generation Sequencing (NGS) tumour testing and underwent germline hereditary cancer gene panel (HCP) testing between April 2019 and November 2020 were included. HCP testing was performed on formalin-fixed, paraffin-embedded normal tissue from the original resection. Variant results were compared across tumour, normal tissue, and germline (blood) samples to determine concordance, false-negative, and false-positive rates. Results: Forty-one patients had confirmed tumour variants in BRCA1/2 or other HCP genes. Of these, 24 harboured a corresponding germline pathogenic variant. Archived normal tissue was available for 23 of these 24 cases, and all germline variants were detected in normal tissue, showing 100% concordance. Among the 17 patients without germline variants, all corresponding normal tissue samples were negative, also demonstrating 100% concordance. No false positives or negatives were identified. Conclusions: NGS testing of normal tissue at surgical resection reliably identifies germline pathogenic variants in patients with HGSOC. Incorporating this approach may help triage patients for clinical genetics assessment. Full article

Breast cancer (BC) is the most common malignancy in women worldwide, with incidence projected to rise, particularly among younger patients. In premenopausal women with hormone receptor-positive disease, ovarian suppression is an established component of systemic therapy, most often achieved pharmacologically with gonadotropin-releasing hormone agonists (GnRHas). Bilateral salpingo-oophorectomy (BSO) represents a surgical alternative that ensures definitive suppression, eliminates compliance issues, and is more cost-effective in the long term. Despite these advantages, BSO induces irreversible menopause, associated with vasomotor symptoms, cardiovascular morbidity, bone loss, cognitive decline, and reduced quality of life. Evidence suggests that BSO is most appropriate in selected cases, including women unable to tolerate or adhere to medical suppression, those with inadequate estradiol suppression, patients approaching natural menopause, individuals with metastatic hormone receptor-positive disease, and carriers of BRCA1 mutations, especially with triple-negative tumors. Conversely, data on its benefit in BRCA2 carriers remain limited. Overall, BSO provides oncologic outcomes comparable to medical suppression but at the cost of permanent systemic effects. The decision between surgical and medical ovarian suppression should be individualized, balancing oncologic efficacy, comorbidities, genetic background, and patient preference. Further studies are needed to define the optimal duration of medical suppression and clarify the role of BSO in hereditary breast cancer. Full article

Background: Copy number variations (CNVs), also referred to as large genomic rearrangements (LGRs), represent a crucial component of BRCA1/2 (BRCA) testing. Next-generation sequencing (NGS) has become an established approach for detecting LGRs by combining sequencing data with dedicated bioinformatics pipelines. However, CNV detection in formalin-fixed paraffin-embedded (FFPE) samples remains technically challenging, and there is the need to implement a robust and optimized analysis strategy for routine clinical practice. Methods: This study evaluated 40 FFPE ovarian cancer (OC) samples from patients undergoing BRCA testing. The performance of the amplicon-based NGS Diatech Myriapod^® NGS BRCA1/2 panel (Diatech Pharmacogenetics, Jesi, Italy) was assessed for its ability to detect BRCA CNVs and results were compared to two hybrid capture-based reference assays. Results: Among the 40 analyzed samples (17 CNV-positive and 23 CNV-negative for BRCA genes), the Diatech pipeline showed a good concordance with the reference method—all CNVs were correctly identified in 16 cases with good enough sequencing quality. Only one result was inconclusive due to low sequencing quality. Conclusions: These findings support the clinical utility of NGS-based CNV analysis in FFPE samples when combined with appropriate bioinformatics tools. Integrating visual inspection of CNV plots with automated CNV calling improves the reliability of CNV detection and enhances the interpretation of results from tumor tissue. Accurate CNV detection directly from tumor tissue may reduce the need for additional germline testing, thus shortening turnaround times. Nevertheless, blood-based testing remains mandatory to determine whether detected BRCA CNVs are of hereditary or somatic origin, particularly in cases with a strong clinical suspicion of inherited predisposition due to young age and a personal and/or family history of OC. Full article

Breast cancer (BC) is the most prevalent malignancy in women worldwide. Despite most cases being diagnosed in the early stages, patients typically require a multimodal treatment approach. This typically involves a combination of surgery, radiotherapy, systemic treatments (including chemotherapy or immunotherapy), targeted therapy, and endocrine therapy, depending on the disease subtype and the risk of recurrence. Moreover, patients with BC and germline mutations in the breast cancer genes 1 or 2 (BRCA1/BRCA2), (gBRCAm), who are typically young women, often require more aggressive therapeutic interventions. These mutations present unique characteristics that necessitate a distinct treatment approach, potentially influencing the side effect profiles of patients with BC. Regardless of the clear benefit observed with these treatments in terms of reduced recurrence and mortality rates, long-term, treatment-related adverse events occur that negatively affect the health-related quality of life (HRQoL) of BC survivors. Thus, long-term adverse events need to be factored into the treatment decision algorithm of patients with early BC (eBC). Physical, functional, emotional, and psychosocial adverse events can occur and represent a significant concern and a challenge for clinicians, patients, and their families. This review article provides an overview of the various long-term adverse events that patients with eBC may experience, including their associated risk factors, as well as management and prevention strategies. We also explore the evidence of the long-term impact of treatment on the HRQoL of patients with gBRCAm. By providing a comprehensive overview of current evidence and recommendations regarding patients’ HRQoL, we aim to equip clinicians with scientific and clinical knowledge and provide guidance to optimize care and improve long-term outcomes. Full article

Background and Objectives: Despite the well-established role of the BRCA and mismatch repair (MMR) genes in DNA damage repair pathways, a substantial proportion of familial cancer cases still lack pathogenic variants in those genes. Next Generation Sequencing (NGS) panels have emerged as a powerful tool to identify hereditary cancer at-risk individuals and subsequently provide them with accurate management. Materials and Methods: Families harbouring PVs in RAD50, RAD51C, RAD51D, and BRIP1 were identified by analysing a cancer-predisposing genes panel using Ion S5 system technology. A retrospective cohort of 155 families tested only for the BRCAs of MMR genes were reanalysed, prompted by an increase in familial cases or new cancer diagnoses among index cases. Results: We identified 40 families through molecular reanalysis (33 with Hereditary Breast and Ovarian Cancer (HBOC) and 7 with Lynch Syndrome (LS)), with positive test results among 155 families lacking BRCA or MMR mutations. The most frequently mutated genes after ATM and CHEK2 were BRIP1, RAD51D, and RAD51C with 16, 13, and 9 positive families, respectively. The phenotype–genotype correlations not only revealed ovarian and HER-negative breast cancer predispositions but also other cancer types, particularly lung and gastric, and individuals with a second or third distinct cancer episode. Conclusions: Broader ranges of malignancies, including gastric, lung, and bladder, have been identified among BRIP1, RAD51D, and RAD51C positive families. The results generated using NGS provide a comprehensive genetic landscape in each patient that could explain the diversity of phenotypes shown in PV families that, combined with non-genetic factors, might enable accurate surveillance and personalized treatments. NGS reanalysis doubled our diagnostic yield and was a good strategy to identify hereditary cancer families that would otherwise be overlooked. Full article

Patients with a BRCA1 germline mutation often represent a challenge for medical healthcare, since they develop malignancies that tend to be more aggressive and which need to be addressed in multidisciplinary teams with more individualized therapies. We report a case of a 37-year-old woman with a BRCA1 mutation who was diagnosed and treated for high-grade papillary serous carcinoma of the fallopian tube. Eight years later, her regular check-up imaging revealed a latero-aortic lymphadenopathy and a right breast tumor. She underwent a fine needle breast biopsy which was positive for invasive non-specific type carcinoma with negative estrogen, progesterone and Her2 receptors in immunohistochemistry tests. The patient underwent debulking surgery for metastatic lymphadenopathy, followed by chemotherapy with Carboplatin and Paclitaxel, and a modified right mastectomy with axillary lymphadenectomy. She subsequently initiated therapy with the PARP inhibitor Olaparib. No evidence of tumor recurrence was detected during the six-month postoperative follow-up period. The primary goal of this paper is to emphasize the complexity and challenges of managing patients with BRCA1 mutations who develop synchronous malignancies. This case report aims to highlight the increasing role of precision medicine and the importance of personalized, multidisciplinary therapeutic strategies, which include surgery, chemotherapy, and targeted therapies. Full article