Sofia Karageorgopoulou

Background: Breast cancer and gynecological malignancies, including cervical, ovarian, and endometrial cancers, remain leading causes of cancer incidence and mortality among women worldwide. This study investigated hereditary predisposition rates in women diagnosed with breast or gynecological cancer, focusing on the effect of age on germline pathogenic/likely pathogenic (P/LP) variant detection. We sought to determine whether younger age at diagnosis should be used as a criterion for patient selection for genetic testing. Methods: A total of 9084 consecutive females with breast cancer or gynecological tumors underwent germline NGS-based genetic testing (52 cancer-relevant genes) at Genekor laboratory from 2020–2026. Multivariable logistic regression evaluated factors associated with P/LP variant detection, adjusting for tumor type and family history. Results: Overall P/LP prevalence was approximately 20% (one in five patients), with tumor-specific rates of 19.24% in breast cancer, 27.59% in ovarian cancer, and 26.67% in endometrial cancer. P/LP prevalence declined significantly with age from 24.37% in patients p < 0.001), driven predominantly by high-risk genes (13.87% in BRCA1 showed stronger age enrichment than BRCA2 (8.14% vs. 3.16% in <40 y; median diagnosis 43 vs. 45 years). Age remained independently associated with P/LP detection in multivariable analysis, with an 18% reduction in odds per 10-year increase for any P/LP (OR 0.82, 95% CI 0.78–0.86) and a stronger 28% reduction for high-risk variants (OR 0.72, 95% CI 0.67–0.78). Family history also independently predicted P/LP detection (OR 1.40, 95% CI 1.19–1.66). Conclusions: Although derived from a referral-based (and thus selected) population, these findings show that while younger patients have a higher prevalence of high-risk P/LP variants, clinically actionable findings are present across all age groups, including those ≥70 years. These results suggest that reliance on age alone to determine eligibility for genetic testing may be insufficient. Broadening access to testing beyond strict age-based criteria could improve the identification of hereditary cancer risk and inform patient management, although further evaluation in less selected populations is warranted.

Background: Breast cancer and gynecological malignancies, including cervical, ovarian, and endometrial cancers, remain leading causes of cancer incidence and mortality among women worldwide. This study investigated hereditary predisposition rates in women diagnosed with breast or gynecological cancer, focusing on the effect of age on pathogenic/likely pathogenic (P/LP) variant detection. We sought to determine whether younger age at diagnosis should be used as a criterion for patient selection for genetic testing. Methods: A total of 9084 consecutive females with breast cancer or gynecological tumors underwent NGS-based genetic testing (53 cancer-relevant genes) at Genekor laboratory from 2020-2026. Multivariable logistic regression evaluated factors associated with P/LP variant detection, adjusting for tumor type and family history. Results: Overall P/LP prevalence was approximately 20% (one in five patients), with tumor-specific rates of 19.24% in breast cancer, 27.59% in ovarian cancer, and 26.67% in endometrial cancer. P/LP prevalence declined significantly with age from 24.37% in patients <40 years to 15.90% in those ≥70 years, while VUS remained stable (40-43%). P/LP patients had earlier diagnosis (median 45 vs 46 years, p<0.001), driven predominantly by high-risk genes (13.87% in <40y vs 7.11% in ≥70y). BRCA1 showed stronger age enrichment than BRCA2 (8.14% vs 3.16% in <40y; median diagnosis 43 vs 45 years). Age remained independently associated with P/LP detection in multivariable analysis, with an 18% reduction in odds per 10-year increase for any P/LP (OR 0.82, 95% CI 0.78-0.86) and a stronger 28% reduction for high-risk variants (OR 0.72, 95% CI 0.67-0.78). Family history also independently predicted P/LP detection (OR 1.40, 95% CI 1.19-1.66). Conclusions: While younger patients have a higher prevalence of high-risk variants, clinically actionable findings were identified across all age groups, including patients ≥70 years These findings indicate that focusing on age to determine eligibility for genetic testing is insufficient. Expanding testing accessibility to individuals regardless of their age at diagnosis may enhance the identification of genetic cancer risk and optimize patient management.

Background/Objectives: This study aimed to assess real-world toxicity and efficacy data of patients with early and advanced breast cancer (BC) who received treatment with abemaciclib. Methods: This was a prospective/retrospective multi-institutional collection of clinicopathological, toxicity, and outcome data from patients with early or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative BC who received treatment with abemaciclib in combination with endocrine therapy in departments of oncology in Greece. Treatment combinations of abemaciclib with any endocrine therapy were accepted. The primary end point was toxicity rate in all patients of the study. Results: From June/2021 to May/2024, 245 women received abemaciclib/endocrine combination therapy; the median age was 57 years. Of these, 169 (69%) received abemaciclib as adjuvant therapy for early-stage disease, while 76 (31%) were treated for advanced BC. At the time of the data cutoff, 133 (84.7%) patients remained in the 2-year treatment period. The most common adverse event (AE) was diarrhea (51%), primarily Grade ≤ 2. Dose modifications due to AEs were required in 19.2% of cases, while treatment discontinuation occurred in 5.1%. There was no difference in dose modification/discontinuation rates between older patients (>65 years) and the remaining patients. For early-stage BC patients, the 2-year DFS and OS rates were 90.8% and 100%, respectively. In patients with advanced cancer (70, 30.8%), 1-year PFS and OS rates were 78% and 96.3%, respectively. Conclusions: This study confirms the safety and effectiveness of abemaciclib in alignment with registrational trials offering valuable insights into toxicity management and clinical outcomes in routine practice without identifying new safety concerns. Clinical Trial Registration: ClinicalTrials.gov NCT04985058.

Background: Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) and adjuvant chemotherapy is a therapeutic choice for women with advanced ovarian cancer. Whether NACT affects the tumor’s molecular profile has not been determined. Methods: This was a retrospective study of patients with advanced-stage epithelial ovarian cancer treated with NACT at oncology departments affiliated with the Hellenic Cooperative Oncology Group (HeCOG). Tumor molecular profiling was performed on formalin-fixed and paraffin-embedded (FFPE) tumor pre- and post-NACT tissues. Homologous recombination deficiency (HRD), tumor-infiltrating lymphocytes (TILs), tumor molecular alterations, and tumor mutational burden (TMB) via next-generation sequencing analysis were assessed. Results: Overall, tumors from 36 patients were assessed, and molecular profiling was evaluated in 20 paired tumor samples. HRD positivity exhibited no significant change between pre- and post-NACT tumors. The BRCA1/2 mutational status remained constant, irrespective of the treatment administration. Pre-NACT tumors tended to exhibit a lower percentage of intratumoral TILs compared to post-NACT tumors (p = 0.004). Differences in the mutation profile between pre- and post-treatment tissue were observed in 33.33% (6/18) of the cases. The mean tumor cell content (TCC) (p-value: 0.0840) and the mean genomic instability score (p-value: 0.0636) decreased slightly numerically after therapy. A moderate inverse relationship was observed between the pre-NACT TMB and the chemotherapy response score (p-value: 0.038), indicating this correlation is statistically significant. Conclusion: This study provides insights into the effect of NACT on the tumor molecular landscape. While BRCA1/2 and HRD status remained stable, an increase in TIL proportion and changes in the mutational profiles were observed post-treatment.

Early-onset breast cancer constitutes a major criterion for genetic testing referral. Nevertheless, studies focusing on breast cancer patients (≤30 years) are limited. We investigated the contribution and spectrum of known breast-cancer-associated genes in 267 Greek women with breast cancer ≤30 years while monitoring their clinicopathological characteristics and outcomes. In this cohort, a significant proportion (39.7%) carried germline pathogenic variants (PVs) distributed in 8 genes. The majority, namely 36.7%, involved BRCA1, TP53, and BRCA2. PVs in BRCA1 were the most prevalent (28.1%), followed by TP53 (4.5%) and BRCA2 (4.1%) PVs. The contribution of PVs in CHEK2, ATM, PALB2, PTEN, and RAD51C was limited to 3%. In the patient group ≤26 years, TP53 PVs were significantly higher compared to the group 26–30 years (p = 0.0023). A total of 74.8% of TP53 carriers did not report a family history of cancer. Carriers of PVs receiving neoadjuvant chemotherapy showed an improved event-free survival (p < 0.0001) compared to non-carriers. Overall, many women with early-onset breast cancer carry clinically actionable variants, mainly in the BRCA1/2 and TP53 genes. The inclusion of timely testing of TP53 in these patients provides essential information for appropriate clinical management. This is important for countries where reimbursement involves the cost of genetic analysis of BRCA1/2 only.

Cancer-related fatigue (CRF) is a common distressing complaint of breast cancer (BC) patients treated with chemotherapy. Nutritional quality plays a pivotal role in CRF, while increased interest towards new pharmacological agents has been observed. Melatonin, an endogenous hormone that regulates the human sleep–wake cycle, could alleviate CRF. In the present randomized, placebo-controlled 3-month trial, we investigated the effects of melatonin intake (i.e., 1 mg/day) vs. placebo in BC patients on CRF. In both arms, the Mediterranean diet (MD) was implemented. Medical history, anthropometry and blood withdrawal were performed. CRF was evaluated by the Functional Assessment of Chronic Illness Therapy—Fatigue questionnaire and MD adherence by the MedDietScore. In total, 49 BC women (median age 52 years) were recruited, namely N = 23 in the intervention arm and N = 26 in the placebo arm. At baseline, CRF was positively associated with body mass index (BMI), even when adjusted for age, waist circumference and blood indices related to disease prognosis (beta = −0.882, p = 0.003). At 3 months, both groups showed a BMI decrease (p < 0.05), but only the intervention group improved CRF compared to baseline (p = 0.003). No differences in CRF were observed between the groups. In conclusion, melatonin oral supplementation could ameliorate CRF in BC patients.

Our aim was to evaluate the concordance between the Myriad MyChoice and two alternative homologous recombination deficiency (HRD) assays (AmoyDx HRD Focus NGS Panel and OncoScan™) in patients with epithelial ovarian cancer (EOC). Tissue samples from 50 patients with newly diagnosed EOC and known Myriad MyChoice HRD status were included. DNA aliquots from tumor samples, previously evaluated with Myriad MyChoice and centrally reassessed, were distributed to laboratories to assess their HRD status using the two platforms, after being blinded for the Myriad MyChoice CDx HRD status. The primary endpoint was the concordance between Myriad MyChoice and each alternative assay. Tumor samples were evaluated with an AmoyDx^® HRD Focus Panel (n = 50) and with OncoScan™ (n = 43). Both platforms provided results for all tumors. Analysis showed that correlation was high for the Myriad MyChoice GI score and AmoyDx^® HRD Focus Panel (r = 0.79) or OncoScan™ (r = 0.87) (continuous variable). The overall percent agreement (OPA) between Myriad MyChoice GI status (categorical variable) and each alternative assay was 83.3% (68.6–93.3%) with AmoyDx and 77.5% (61.5–89.2%) with OncoScan™. The OPA in HRD status between Myriad MyChoice and AmoyDx was 88.6% (75.4–96.2). False-positive rates were 31.6% (6/19) for AmoyDx GI status and 31.9% (7/22) for OncoScan™, while false-negative rates were 0% (0/28, AmoyDx) and 11.1% (2/18, OncoScan™) compared with the Myriad MyChoice GI status. While substantial concordance between Myriad MyChoice and alternative assays was demonstrated, prospective validation of the analytical performance and clinical relevance of these assays is warranted.

Background: Hereditary cancer predisposition syndromes are responsible for approximately 5–10% of all diagnosed cancer cases. In order to identify individuals at risk in a cost-efficient manner, family members of individuals carrying pathogenic alterations are tested only for the specific variant that was identified in their carrier relative. The purpose of this study was to investigate the clinical use and implementation of cascade family testing (CFT) in families of breast cancer patients with pathogenic/likely pathogenic variants (PVs/LPVs) in cancer-related predisposition genes. Methods: Germline sequencing was carried out with NGS technology using a 52-gene panel, and cascade testing was performed by Sanger sequencing or MLPA. Results: In a cohort of 1785 breast cancer patients (families), 20.3% were found to have PVs/LPVs. Specifically, 52.2%, 25.1%, and 22.7% of patients had positive findings in high-, intermediate-, and low-penetrance breast cancer susceptibility genes, respectively. Although CFT was recommended to all families, only 117 families (32.3%) agreed to proceed with genetic testing. Among the first-degree relatives who underwent CFT, 70.3% were female, and 108 of 121 (89.3%) were cancer free. Additionally, 42.7%, 36.7%, and 20.6% were offspring, siblings, and parents of the subject, respectively. Our data suggest that CFT was mostly undertaken (104/117, 88.8%) in families with positive findings in high-risk genes. Conclusions: Cascade family testing can be a powerful tool for primary cancer prevention by identifying at-risk family members. It is of utmost importance to implement genetic counseling approaches leading to increased awareness and communication of genetic testing results.

The oral problems of 24 cancer patients on immunotherapy between 2017–2022 and referred by their oncologists, were reported. The age range was 49–80 years, and the median was 64 years. Lung cancer was the most common disease. Three patients a had history of autoimmune disease prior to cancer diagnosis. Patients received immunotherapy for two to 48 months. Prior to immunotherapy, 17 patients received cytotoxic chemotherapy, five angiogenesis inhibitors and one1 radiotherapy to head/neck. During immunotherapy, four patients received chemotherapy, one received bevacizumab, and eight received bone targeting agents, either alone or in combination. Presenting symptoms were oral pain (18 patients, 75%), dental pain (five patients), xerostomia (five patients), burning/itching (seven patients), bleeding (three patients), swelling (three patients), and taste problems (dysgeusia) (three patients). One patient was asymptomatic. Immune-related lesions were observed in 15 patients (62.50%), of which three were exacerbations of prior autoimmune disease. Three patients reported severe deterioration and itching after using a mouthwash. We also observed six (25%) infections (four candidiasis and two herpes simplex), and six (25.00%) cases of medication-related osteonecrosis of the jaw (MRONJ). Five of those MRONJ cases developed among the eight patients with the administration of bone targeting agents and one in a patient with bevacizumab. Two patients presented with more than one lesion. In conclusion, immune-related lesions were most common; oral infections and MRONJ were also observed. Various oral complications might be related to the interplay between immunotherapy and other therapies prior or concurrent to immunotherapy.