The role of anthracyclines in the treatment of early breast cancer (EBC) is increasingly being challenged, especially in de-escalation strategies. However, owing to their immunogenic effects, anthracyclines are promising combination partners with immunotherapies. In the randomized phase 2 trial ABCSG-52 (EudraCT no. 2019-002364-27), we investigated epirubicin plus immunotherapy in women with human epidermal growth factor receptor 2 (HER2)-positive EBC. A total of 58 patients were randomized 1:1 to two cycles of a chemotherapy-free induction phase (part 1) of dual HER2 blockade with trastuzumab and pertuzumab (TP) plus the anti-programmed death ligand 1 antibody atezolizumab (TP-A) or TP alone. Thereafter, all patients received four cycles of TP-A in combination with epirubicin (part 2). The primary endpoint, pathological complete response (pCR), was met in 35 patients (60.3%; 95% confidence interval (CI) 47.5% to 71.9%), 19 patients (65.5%) in the TP-A group and 16 patients (55.2%) in the TP group. The residual cancer burden 0/I rate and objective response rate (secondary endpoints) in all patients with evaluable data were 80.0% (n = 44/55; 95% CI 67.6% to 88.4%) and 89.3% (n = 50/56; 95% CI 78.5% to 95.0%), respectively. Grade ≥3 adverse events were reported in 17 patients (29.3%). Based on our findings, we conclude that a neoadjuvant chemotherapy de-escalation immunotherapy regimen with trastuzumab, pertuzumab, atezolizumab and epirubicin is effective and safe in patients with HER2-positive EBC.

Background: Endocrine treatment (ET) is a highly effective breast cancer treatment but can distinctly impair breast cancer patients’ quality of life (QOL). In a patient-reported outcome (PROs) study conducted by the authors in 2011, patients reported higher ET-induced symptom levels than known from the registration trials, and was underestimated. Based on these study results, we investigated the long-term sequelae of ET reported by breast cancer survivors (BCS) in a follow-up study conducted 5–10 years after an earlier assessment. Methods: BCS who had participated in the earlier study (n = 436) were approached for study participation either at one of their routine follow-up appointments or via mail; consenting patients were asked to completed the same PRO assessment used in the original study (FACT-B + ES). BCS with relapse/ progressive disease were excluded from the analysis. We compared long-term endocrine symptomatology and overall QOL outcome (i.e. FACT-G and -ES sum score). Results: A final sample of 268 BCS was included in the analysis. BCS reported a significant improvement of the overall endocrine symptomatology (baseline mean = 59 vs. follow-up mean = 62, p < 0.001), physical (baseline = 23.9 mean vs. follow-up mean = 24.8, p < 0.01) and functional well-being (baseline mean = 21.7 vs. follow-up mean = 22.7, p = 0.013) and overall QOL (mean baseline = 88.3 vs. mean follow-up = 90.9, p = 0.011). However, the prevalence of particular symptoms, well-known to be ET induced, did not change over time such as joint pain (baseline = 45.5% vs. 44.2%, n.s. difference), lack of energy (36.4% vs 33.8%, n.s. difference), weight gain (36.8% vs. 33.9%, n.s. difference) or vaginal dryness (30.2% vs. 33%, n.s. difference) and the proportion reporting lack of interest in sex increased (40.4% vs. 48.7%, p < 0.05). Conclusion: Presented results indicate that BCS recover well in terms of overall endocrine symptomatology and quality of life but experience some clinically relevant and unfavorable ET-related long-term effects.

Background/Objectives: This study aimed to demonstrate the higher efficacy of cryotherapy in temperature reduction in the upper compared to the lower extremity when used for prevention of chemotherapy-induced peripheral neuropathy (CIPN). Methods: This study was conducted between May 2020 and January 2023 at the Department of Obstetrics and Gynecology at the Medical University of Innsbruck. The analysis included all patients from the CROPSI study who received cryotherapy on their upper (UEX) and lower extremity (LEX) and had completed all assessments from start to end of chemotherapy as well as follow-up. The assessments included temperature measurements and neurological tests during CT and at follow-up after completion of CT. Results: Of the 97 patients recruited in the study, 50 completed all assessments and were therefore included in this analysis. Cryotherapy was more effective when cooling was applied to the upper extremity compared to the lower. On the upper extremity, cryotherapy achieved a cooling effect of 12.5 °C compared to 9.6 °C on the lower extremity (p < 0.001). Patients scored better in both neurological tests on their upper extremity compared to lower. Regarding side effects, there was no significant difference between upper and lower extremities. No severe side effects were reported for either location. Conclusions: Our study suggests that currently available devices for continuous cooling for cryotherapy are significantly more effective on the upper extremity.

Advances in endocrine therapies for hormone receptor (HR)-positive/HER2-negative advanced breast cancer (ABC) continue to transform care and significantly improve patient outcomes. However, the integration of molecular and clinical risk stratification into guiding individualized treatment selection remains a key challenge. We therefore evaluated whether the integration of baseline circulating tumor DNA (ctDNA)-derived tumor metrics enhances risk stratification among patients receiving early lines of treatment of HR-positive ABC in a real-world multicenter cohort of patients in Austria. Patients with HR-positive/HER2-negative ABC treated at multiple Austrian centers were included. CtDNA was analyzed using a 77-gene panel (AVENIO ctDNA Expanded Kit). Tumor fraction (TFx) was estimated via two complementary approaches: untargeted aneuploidy assessment using mFAST-SeqS, and the highest variant allele frequency (hVAF) from the AVENIO assay. Somatic variants and single, binary, and three-level composite TFx metrics were assessed for their association with progression-free and overall survival (PFS, OS). We analyzed 225 ctDNA samples from 184 patients [128 before first-line (1L) and 76 before second-line (2L) treatment], including 40 paired samples. Overall TFx was low (median z-score 2.49; range -0.5-208.3), with higher levels in 2L, although the difference did not reach statistical significance (P = 0.058). In contrast, the hVAF was significantly higher in the 2L cohort (P = 0.007). Somatic variant burden was significantly increased in 2L (P < 0.001), with notably more frequent ESR1 mutations (26.7% versus 7.1% in 1L). Median PFS was 29.2 months in 1L and 6.0 months in 2L, while median OS was 57.3 months and 16.1 months, respectively. TP53 and ESR1 mutations, and all ctDNA-based metrics were significantly associated with PFS and OS, with a three-level composite ctDNA variable showing the highest prognostic discrimination. Our findings demonstrate that integrating baseline ctDNA-derived TFx metrics with established clinical variables significantly improves risk stratification in HR-positive/HER2-negative ABC.

Background: Endocrine treatment (ET) is a highly effective breast cancer treatment but can distinctly impair breast cancer patients’ quality of life (QOL). In a patient-reported outcome (PROs) study conducted by the authors in 2011, patients reported higher ET-induced symptom levels than known from the registration trials, and was underestimated. Based on these study results, we investigated the long-term sequelae of ET reported by breast cancer survivors (BCS) in a follow-up study conducted 5-10 years after an earlier assessment.Methods: BCS who had participated in the earlier study (n=436) were approached for study participation; consenting patients were asked to completed the same PRO assessment used in the original study (FACT-B+ES). BCS with relapse/ progressive disease were excluded from the analysis. We compared long-term endocrine symptomatology and overall QOL outcome (i.e. FACT-G and -ES sum score).Results: A final sample of 268 BCS was included in the analysis. BCS reported a significant improvement of the overall endocrine symptomatology (baseline mean=59 vs. follow-up mean=62, p<0.001), physical (baseline=23.9 mean vs. follow-up mean=24.8, p<0.01) and functional well-being (baseline mean=21.7 vs. follow-up mean=22.7, p=0.013) and overall QOL (mean baseline=88.3 vs. mean follow-up=90.9, p=0.011). However, the prevalence of particular symptoms, well-known to be ET induced, did not change over time such as joint pain (baseline=45.5% vs. 44.2%, n.s. difference), lack of energy (36.4% vs 33.8%, n.s. difference), weight gain (36.8% vs. 33.9%, n.s. difference) or vaginal dryness (30.2% vs. 33%, n.s. difference) and loss of interest in sex even deteriorated over time (40.4% vs. 48.7%, p<0.05).Conclusion: Presented results indicate that BCS recover well in terms of overall endocrine symptomatology and quality of life but experience some clinically relevant and unfavorable ET related long-term effects.