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Epithelial ovarian cancer is the most lethal gynecologic malignancy. In most women, it is diagnosed at an advanced stage, which largely explains the poor prognosis of this malignancy. Germline mutations of the genes BRCA1 and BRCA2 , which encode proteins essential for the repair of double-strand DNA breaks through homologous recombination, lead to increased cancer predisposition. BRCA mutations are present in approximately 14% of epithelial ovarian cancers. Somatic BRCA mutations have also been described. Current first-line treatment of high-grade epithelial ovarian cancer includes debulking surgery followed by combination chemotherapy, usually carboplatin and paclitaxel. Ovarian cancer is highly sensitive to chemotherapy, in particular to platinum drugs. Most patient will achieve remission with initial chemotherapy, but most will eventually experience disease recurrence. Targeted therapies, including the anti-angiogenic agent bevacizumab and oral poly (ADP-ribose) polymerase (PARP) inhibitors, have been recently approved for the treatment of ovarian cancer, based on the results from randomized clinical trials showing significant benefits in terms of progression-free survival, with acceptable tolerability and no detrimental effects on quality of life. Olaparib, the first PARP inhibitor to be granted approval, is currently indicated as maintenance monotherapy in ovarian cancer patients with relapsed disease and mutated BRCA who have achieved a complete or partial response to platinum-based chemotherapy. The analysis of BRCA mutational status has, therefore, also become crucial for therapeutic decisions. Such advances are making personalized treatment of ovarian cancer feasible. Here we briefly review treatments for platinum-sensitive, high-grade serous epithelial ovarian cancer that are currently available in Italy, with a focus on targeted therapies and the relevance of BRCA mutational analysis. Based on the evidence and on current guidelines, we propose strategies for the tailored treatment of patients with relapsed ovarian cancer that take into account BRCA mutational status and the treatment received in the first-line setting.

Breast cancer associated with BRCA1 and BRCA2 mutations presents unique therapeutic challenges, traditionally favoring mastectomy due to concerns over recurrence and new primaries. However, evolving evidence and advances in multimodal therapy have reshaped this paradigm, positioning breast-conserving surgery (BCS) as a viable option for selected carriers. This narrative review synthesizes current data from meta-analyses, retrospective cohorts, and pivotal studies, including a multicenter analysis which affirmed oncologic equivalence between BCS and mastectomy when combined with radiotherapy and systemic therapy. While meta-analyses confirm higher local events following BCS, survival remains comparable, indicating that recurrence reflects genetic predisposition rather than surgical inadequacy. Optimized systemic treatments, including chemotherapy, endocrine therapy, risk-reducing salpingo-oophorectomy, and PARP inhibitors, further mitigate recurrence risk. Meanwhile, patient-centered outcomes favor BCS: studies consistently link it to improved body image, psychosocial well-being, and quality of life, especially for younger BRCA carriers. Fertility-preserving options remain viable, with evidence supporting the safety of pregnancy, breastfeeding, and assisted reproductive technologies in BRCA-mutated survivors. These findings support individualized surgical planning for BRCA carriers within multidisciplinary care, balancing oncologic safety, systemic strategies, and psychosocial priorities. BCS should be considered a standard option for well-selected patients in hereditary breast cancer management.

The HRD (Homologous Recombination Deficiency) test is considered a genomic alteration useful for guiding therapeutic decisions in patients with ovarian cancer. Some commercial and in house alternative “academic” tests are available. Recent findings indicate that not all BRCA1/2 mutations determine the magnitude of HRD and that some patients carrying BRCA1/2 mutations may exhibit indeterminate or even negative HRD scores. Furthermore, certain therapies (e.g., olaparib and bevacizumab) offer particularly pronounced benefits for high-grade serous ovarian cancer (HGSOC) patients harboring mutations in the DNA-binding domain (DBD) of BRCA1/2. The aim of the present study is to investigate the relationship between the HRD scores and BRCA1/2 status of 51 HGSOC patients (50 BRCA1/2 mutated and 1 wild type). The HRD status was assessed by means of shallow whole-genome sequencing and BRCA1/2 status by the NGS pipeline. We did not find a correlation between the HRD status and type of BRCA1/2 alterations. A strong correlation between the HRD score and age was found. Our paper underlines the need to introduce other biological factors within the algorithms of the HRD evaluation in order to better tailor the HRD status, harmonize the metrics of the HRD assessment, and personalize therapies.

Patients with luminal breast cancer (BC) may develop central nervous system metastases in 20%–40% of cases. Radiation or surgical therapy represents the cornerstone of treating central nervous system metastases. Meanwhile, the best practice for metastatic luminal BC involves using cyclin-dependent kinase 4/6 inhibitors combined with endocrine therapy. To our knowledge, this is the first case to report a dramatic response of breast metastases to abemaciclib plus endocrine therapy without radiation therapy, particularly in a patient who presented with seizures and sudden coma. She received brain surgery to control a large bleeding metastasis. Abemaciclib was crushed and diluted in water for administration via the nasogastric tube, while an upfront fulvestrant was given since aromatase inhibitors cannot be diluted. Beyond the radiological response, the clinical improvement was notable, with complete symptom recovery to the point where she is again working. Our paper supports the activity of abemaciclib in brain metastases from luminal BC and includes a review of the medical literature. Further investigation is warranted in this clinical setting.

Mirvetuximab soravtansine-gynx (MIRV) is a first-in-class antibody–drug conjugate targeting folate receptor α (FRα), approved by the US Food and Drug Administration for the treatment of platinum-resistant ovarian cancer in the USA. Here, we report patient-reported outcomes for participants treated with MIRV compared with investigator's choice of chemotherapy from the phase 3 MIRASOL trial, which met its primary endpoint of progression-free survival and key secondary endpoints of objective response rate and overall survival. The MIRASOL trial was a confirmatory, phase 3, randomised, controlled, open-label trial, building on the phase 2 SORAYA trial which had previously demonstrated the safety and efficacy of MIRV in platinum-resistant ovarian cancer. Patients 18 years or older with a confirmed platinum-resistant, recurrent high-grade serous epithelial ovarian cancer diagnosis were recruited from 253 sites including hospitals, academic centres, and community centres in 21 countries. Patients must have received one to three previous systemic anticancer therapies, and have high FRα tumour expression (≥75% tumour cells with an immunohistochemistry score of ≥2+ membrane staining using the PS2+ scoring method), one or more lesions with measurable disease, and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1) to MIRV or investigator's choice of chemotherapy, stratified by number of previous therapy lines and the type of investigator's choice of chemotherapy. Therapies were administered in an open-label manner; MIRV was administered intravenously at 6 mg/kg of adjusted ideal bodyweight every 3 weeks. The primary endpoint was progression-free survival. Key secondary endpoints were objective response rate, overall survival, and a 15·0-point or greater improvement at week 8 or 9 in abdominal and gastrointestinal symptoms using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Ovarian Cancer Module (EORTC QLQ-OV28) in the intention-to-treat population. The MIRASOL trial was registered at ClinicalTrials.gov (NCT04209855), the Gynecologic Oncology Group (GOG 3045), and the European Network of Gynaecological Oncological Trial Groups (ENGOT-ov55), and is complete. Between Feb 3, 2020, and Aug 3, 2022, 453 patients were enrolled and randomly assigned to treatment (227 to the MIRV group and 226 to the investigator's choice of chemotherapy group). All patients were female; 301 (66%) participants were White, 53 (12%) were Asian, 13 (3%) were Black, and 86 (19%) were of another race or not reported; 27 (6%) were Hispanic or Latino. The median follow-up for the study, determined by the reverse Kaplan–Meier method, was 13·1 months (95% CI 12·1–14). QLQ-OV28 completion rates were 86% (365 of 425) at baseline and 81% (282 of 349) at week 8 or 9. 34 (21·0%; 95% CI 15·0–28·1) of 162 patients treated with MIRV reported improvement in QLQ-OV28 abdominal and gastrointestinal scores, compared with 23 (15·3%; 10·0–22·1) of 150 patients treated with the investigator's choice of chemotherapy. These differences were not statistically significant (odds ratio 1·5 [95% CI 0·8–2·6]; p=0·26). MIRV did not seem to impair or improve patient quality of life compared with investigator's choice of chemotherapy. The similar quality-of-life outcomes in the two treatment groups, combined with the previously reported higher efficacy of MIRV compared with single-agent chemotherapy, support MIRV as new treatment option for FRα-positive platinum-resistant ovarian cancer. AbbVie.

Background: Older women represent a significant and increasing population of patients with breast cancer, accounting for over 40% of new cases of breast cancer. However, this growing subgroup of patients is still underrepresented in clinical trials, and treatment is usually selected based on limited data from retrospective subgroup analyses. However, the ESMO guidelines for metastatic breast cancer (mBC) suggest that the management decision should not be based on age alone. Nab-paclitaxel (nab-P) was associated with improved efficacy and a better safety profile than solvent-based taxanes without steroid or antihistamine premedication, making this treatment appealing to elderly patients. Patients and methods: This is an observational, retrospective, multicenter study, evaluating the safety and activity of nab-paclitaxel (nab-P) in elderly patients (≥65 years old) with HER2-negative mBC from 11 Sicilian oncology centers. The primary endpoint of the study was the safety nab-P in elderly mBC patients; secondary endpoints included the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: We included 70 patients, and all were evaluable for safety and efficacy. All patients had previously been pretreated with taxane-based chemotherapy in a (neo)-adjuvant or metastatic setting. One third of the patients received nab-P as a fourth line therapy. Most of the patients were treated with nab-P at doses of 260 mg/m2 3-weekly (87.1%), and 12.9% received a nab-P dose of 125 mg/m2 weekly. Patients’ characteristics included a median age of 67 years (range 65–83 years), a median ECOG PS of 1 (range 0–2), and the following intrinsic molecular subtypes: Luminal A (18.8%), Luminal B HER-2 negative (62.5%), and triple negative (18.8%). Nab-P was administered for a median of six cycles (range 1–21), with 35.5% of patients experiencing a dose reduction, and 11.5% treatment discontinuation due to toxicity. Adverse events were mainly G2-G3 and occurred mostly in patients treated with 3-weekly nab-P (85.7%). The ORR was 31.3% (CR in 6.3% and PR in 25% of pts) and the DCR was 70.4%. Median PFS was 6 months (95% CI, 2–38), and median OS was 40.5 months (95% CI, 7–255). Conclusions: Our real-life study showed that nab-P is an effective, well-tolerated regimen in elderly mBC patients, including taxane-pretreated patients, and can be safely administered in elderly mBC patients.

Background Metastatic breast cancer (MBC) is an incurable disease and its treatment focuses on prolonging patients’ (pts) overall survival (OS) and improving their quality of life. Eribulin is a microtubule inhibitor that increases OS in pre-treated MBC pts. The most common adverse events (AEs) are asthenia, neutropenia and peripheral neuropathy (PN). Methods PAINTER is a single arm, phase IV study, aimed at evaluating the tolerability of eribulin in MBC pts. Secondary objectives were the description of treatment efficacy and safety, the assessment of the incidence and severity of PN and its association with genetic polymorphisms. Genomic DNA was isolated from blood samples and 15 Single Nucleotide Polymorphisms (SNPs) were genotyped by Taqman specific assays. The association between PN and SNPs were evaluated by Fisher exact test. Results Starting from May 2014 until June 2018 180 pts were enrolled in this study by 20 Italian centers. 170 of these pts could be evaluated for efficacy and toxicity and 159 for polymorphisms analysis. The median age of pts was 60 years old and the biological subtypes were luminal type (64.7%), Her2 positive (18.3%) and triple negative (17%). Pts were pretreated with a median of 5 lines for MBC. The median follow up of this study was 15.4 months with a median number of 4.5 cycles administered (minimum–maximum 1–23). The median overall survival was 12 months. 48.8% of pts experienced a dose reduction, mainly for neutropenia (23.9%) and liver toxicity (12%). 65 pts (38.2%) reported at least one severe toxicity. Neutropenia and neurotoxicity were the most frequent severe AEs (15.3% and 14.7%, respectively); other reported toxicities were osteo-muscular, abdominal or tumor site pain (19.4%), liver toxicity (6.6%), pulmonary toxicity (6.5%) and dermatological toxicity (3.6%). Among the 15 evaluated SNPs, an association with PN was found for rs2233335 and rs7214723. Conclusions Eribulin is a well-tolerated treatment option in MBC. Schedule and dosage modifications were common, but toxicity rarely led to treatment discontinuation. SNPs rs2233335 (G/T and T/T) in the NDRG1 gene and rs7214723 (CC and CT) in the CAMKK1 gene were associated with PN. These findings, if validated, could allow a tailored treatment with eribulin in cancer patients. Trial registration : ClinicalTrials.gov ID: NCT02864030.

A low fT3/fT4 ratio has been associated with poorer prognosis in several diseases. Inflammatory indexes (IIs) and the skeletal muscle index (SMI) are established prognostic factors in various cancer types. However, their interplay and individual contributions to the prognosis of cervical cancer remain unclear. This study aimed to evaluate the impact of these biomarkers on survival outcomes in cervical cancer patients treated with innovative immunotherapy. This retrospective study included 101 patients with cervical cancer treated with cemiplimab at 12 Italian oncology centres. Patients with thyroid comorbidities or missing fT3/fT4 ratio data were excluded. The primary endpoint was overall survival (OS) in relation to the fT3/fT4 ratio. Secondary endpoints included progression-free survival (PFS) and correlations between the fT3/fT4 ratio, ECOG Performance Status, IIs and SMI. An optimal fT3/fT4 cutoff for OS prediction was identified at 0.29. Median OS was 10.9 months for patients with a low fT3/fT4 ratio, while it was not reached for those with high fT3/fT4 levels (HR = 2.70; 95% CI: 1.17-6.22; p = 0.02). Multivariate analysis confirmed that both the fT3/fT4 ratio and ECOG PS independently influenced OS. Among the IIs analysed, the systemic inflammatory index (SII) demonstrated the strongest correlation with fT3/fT4 levels (OR = 3.82; 95% CI: 1.39-10.50; p = 0.0092). Exploratory analysis also revealed significantly lower SMI values in patients with lower fT3/fT4 ratios (p = 0.034). This study highlights the prognostic significance of the fT3/fT4 ratio, IIs, and SMI in cervical cancer patients treated with cemiplimab. Given the exploratory nature of these findings, further validation in larger, prospective cohorts is warranted to support their integration into clinical practice and the development of innovative prognostic tools.

Background: Adherence to oral anticancer therapies among breast cancer patients is an often-overlooked issue. A lack of patient compliance can be caused by several factors, and may hinder the efficacy of prescribed medication, leading to a shorter than expected survival. In this context, few data about adherence to CDK4/6 inhibitors in real-world practice are available. We report here the results of a retrospective analysis of adherence to abemaciclib plus endocrine therapy in a cohort of women with hormone receptor-positive (HR+), epidermal growth factor 2 negative (HER2−) breast cancer. Methods: Abemaciclib adherence was computed as the ratio between the total number of cycles/months that medication was supplied and the months between the first and the last prescription. The proportion of Days Covered (PDC) ranged from 0 to 1. A score of 0.8 (i.e., 80% adherence rate) was the cutoff used to classify the patients as adherent (0.8 ≤ PDC ≤ 1) or non-adherent (0 ≤ PDC < 0.8). The received dose intensity was also calculated. Results: The abemaciclib pharmacy claims of 100 women with HR+/HER2− breast cancer were retrieved. Most patients (91%) were treated in the advanced setting. Abemaciclib was more frequently taken with an aromatase inhibitor (63%) than with fulvestrant (27%). In this population, the adherence rate was high (92.25% + 1.939 SD). The proportion of non-adherent patients taking abemaciclib with PDC <0.8 was 12%. There was a significative correlation between the occurrence of side effects and the use of <5 drugs for non-oncological illnesses, probably reflecting concomitant non-oncological diseases. Conclusions: Adherence to abemaciclib-based therapy is high in a real-life setting, pending the adequate and proactive management of patients. The careful evaluation of patients and detailed information about expected adverse events are essential to ensure adherence to this antineoplastic agent.

Background: In real-world practice, eribulin mesylate provides significant survival benefit, with a manageable safety profile in heavily pretreated patients with metastatic breast cancer (MBC). Methods: In this prospective, open-label, multicentre, observational study we evaluated the effectiveness and tolerability of eribulin as third-line treatment in a homogeneous population. The primary endpoints were the safety profile and response in metastatic sites; secondary endpoints included the response in different subtypes, overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). Results: From 2013 to 2016, 118 women were treated in 21 Sicilian institutions; the median age was 58 years (range 29–79), with 69% of patients under 65. The median cycles of eribulin were 5.5 (range 1–26). The most common adverse event was neutropenia (9.3%, 3 cases of grade 3, 4 of grade 4); only 1 case of QT prolongation was reported. Eribulin was effective in controlling metastatic disease in all sites, and it achieved the highest ORR in brain (16%) and liver (14.9%). Median OS was 31.8 months (95% CI 27.9–34.4) and median PFS 5.5 months (95% CI 4.2–6.6). PFS was 5.2 months (95% CI 2.8–8.4) in patients with triple-negative subtype. Median PFS was longer in patients over 65 years (6.1 months, 95% CI 4.4–8.3). In patients who had visceral metastases PFS was 5.5 months (95% CI 95% 3.5–6.6) and OS 33.9 months (95% CI 29.8–40.8). Conclusions: Eribulin as third-line treatment shows an acceptable safety profile and a substantial antitumour activity in the treatment of MBC, even in elderly patients and in those with visceral disease.