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Introduction: Long QT syndrome is a common cardiotoxic side effect of various anti-tumor drugs. Previous cardiological monitoring of oncological patients is primarily complex and requires for non-internal oncologists a consultation. Therefore, the QTc-Tracker smartphone APP was developed, which enabled a tele-cardiological diagnosis of the QTc time with standard single-lead ECG devices. As a result, diagnosis times could already be reduced by 99%. The further development examined an automatic determination of the QT time using the smartphone APP. However, since single-lead ECG devices are significantly more susceptible to interference, the determination of the QT time is more complex than with 12-lead ECGs. Methods: The QTc-Tracker smartphone APP was developed to determine the QT time. Self-tracker single-lead ECG devices were used to record the lead I signal. The ECG recordings were analyzed in the APP and passed on to an external cardiologist as reference. The APP used artificial intelligence and was trained in the first phase and validated in the second phase. The first phase aimed to improve QT time detection. The results of the APP were compared with the findings of the external cardiologist. In both phases, ECGs from breast cancer patients receiving ribociclib were used. Results: A total of 1889 single-lead ECGs were carried out. 248 of these could not be evaluated (13%). QTc prolongation, according to CTCAE, was diagnosed in 41 cases (2.5%). 878 of the evaluable ECGs were used for the training phase and 763 for the evaluation phase. In the first group (before the improvement), the sensitivity to automatically detect a prolongation of the QT time was 36%, and the specificity was 96%. In the evaluation collective (after the training), the sensitivity went up to 85%, and the specificity was unchanged at 96%. Conclusions: The trained method of the QTc tracker is able to reliably detect a QT time lengthening even without a cardiological diagnosis only by using single-lead self-tracker ECG’s. In the rare cases in which an elongation was not detected, the cardiac diagnosis was only a few milliseconds above the threshold value. This artificial intelligence-based smartphone APP is not intended to replace the cardiological diagnosis, but it can simplify routine processes and help to decide which patients need a cardiological examination more urgently. Citation Format: Timo Schinköthe, Christian Horst Tonk, Nadia Harbeck, Vanda Carmelo, Joana Gomes Feliciano, Rachel Wuerstlein, Sherko Küemmel, Annette Schmidt. AI-Based Smartphone App Using a Single-Lead ECG for Automated QTc Diagnostics in Oncology [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-05-36.

Zusammenfassung Hintergrund Umfangreiche Daten aus prospektiven klinischen Studien liefern einen hohen Evidenzgrad für den Einsatz von CDK4/6-Hemmern in Kombination mit einer endokrinen Therapie (CDK4/6i + ET) als Standard bei der First-Line-Behandlung von metastatischem HER2-negativen hormonrezeptorpositiven (HER2−/HR+) Brustkrebs. Reale Daten von Patientinnengruppen, die damit in der Praxis behandelt wurden, liefern Erkenntnisse über Veränderungen von Patientenmerkmalen und Prognosen im Laufe der Zeit. Methoden Die Daten wurden dem prospektiven praxisbezogenen PRAEGNANT-Register (NCT02 338 167) entnommen. Die eingeschlossenen Patientinnen hatten fortgeschrittenen primären und metastasierten HER2−/HR+ Brustkrebs. Die gewählten Therapien, das progressionsfreie Überleben und das Gesamtüberleben der jeweiligen Therapie sowie die Zeitspanne, während der die Behandlung erfolgte, werden dargelegt. Ergebnisse Nachdem CDK4/6-Hemmer erstmals im November 2016 eingesetzt wurden, stieg die Häufigkeit ihres Einsatzes schnell an. In den letzten Jahren (2018–2022) wurden ca. 70–80 % aller Patientinnengruppen mit CDK4/6-Hemmern behandelt; eine endokrine Monotherapie wurde rund 10 % und eine Chemotherapie ungefähr 15 % aller Patientinnen verabreicht. Die schlechteste Prognose hatten Patientinnen, die eine Chemotherapie erhielten. Seit Kurzem erhalten hauptsächlich Patientinnen mit guter Prognose eine endokrine Monotherapie; Patientinnen, die eine Chemotherapie erhalten, haben eine ungünstigere Prognose. Das progressionsfreie Überleben und das Gesamtüberleben von mit CDK4/6i + ET behandelten Patientinnen blieb über einen längeren Zeitraum ähnlich, obwohl sich die Patientenmerkmale änderten. Schlussfolgerung Die Behandlung mit CDK4/6i + ET entwickelte sich rasch zum First-Line-Therapiestandard für Patienten mit fortgeschrittenem Mammakarzinom. Seit der Einführung von CDK4/6i + ET wird die endokrine Monotherapie nur bei Patientinnen mit einer sehr günstigen Prognose eingesetzt, während Chemotherapie meist nur an Patientinnen verabreicht wird, die eine eher ungünstige Prognose haben. Veränderungen der Patientenmerkmale scheinen die Prognose von mit CDK4/6i + ET behandelten Patientinnen nicht zu beeinflussen.

Background Comprehensive data from prospective clinical trials have led to a high level of evidence establishing CDK4/6 inhibitors in combination with endocrine treatment (CDK4/6i + ET) as a standard for the treatment of HER2-negative, hormone receptor-positive (HER2− HR+) breast cancer patients in the first-line advanced therapy setting. Data on patient populations that have been treated in the real-world setting may provide an insight into changes of patient characteristics and prognosis over time. Methods The data were extracted from the prospective real-world registry PRAEGNANT (NCT02338167). Patients had to have HER2− HR+ advanced breast cancer in the first-line metastatic setting. The chosen therapies were described as well as progression-free survival (PFS) and overall survival (OS) in relation to the given therapies and time periods during which they were indicated. Results CDK4/6 inhibitors have been rapidly implemented since their introduction in November 2016. In recent years (2018 – 2022), about 70 – 80% of the patient population have been treated with CDK4/6 inhibitors, while endocrine monotherapy was given to about 10% and chemotherapy to about 15% of all patients. The prognosis was worst in patients treated with chemotherapy. Recently, mainly patients with a good prognosis are being treated with endocrine monotherapy, and patients who are treated with chemotherapy have an unfavorable prognosis. The PFS and OS of patients treated with CDK4/6i + ET have remained similar over time despite changes in patient characteristics. Conclusion A treatment with CDK4/6i + ET has rapidly become the therapy standard for patients in the first-line advanced breast cancer setting. After the implementation of CDK4/6i + ET, endocrine monotherapy is only given to patients with a very favorable prognosis, while chemotherapy is provided to patients with a rather unfavorable prognosis. These changes in patient characteristics did not seem to influence the prognosis of patients treated with CDK4/6i + ET.

Purpose In 2016, the University of Munich Molecular Tumor Board (MTB) was implemented to initiate a precision oncology program. This review of cases was conducted to assess clinical implications and functionality of the program, to identify current limitations and to inform future directions of these efforts. Methods Charts, molecular profiles, and tumor board decisions of the first 1000 consecutive cases (01/2016–03/2020) were reviewed. Descriptive statistics were applied to describe relevant findings. Results Of the first 1000 patients presented to the MTB; 914 patients received comprehensive genomic profiling. Median age of patients was 56 years and 58% were female. The most prevalent diagnoses were breast (16%) and colorectal cancer (10%). Different types of targeted or genome-wide sequencing assays were used; most of them offered by the local department of pathology. Testing was technically successful in 88%. In 41% of cases, a genomic alteration triggered a therapeutic recommendation. The fraction of patients receiving a tumor board recommendation differed significantly between malignancies ranging from over 50% in breast or biliary tract to less than 30% in pancreatic cancers. Based on a retrospective chart review, 17% of patients with an MTB recommendation received appropriate treatment. Conclusion Based on these retrospective analyses, patients with certain malignancies (breast and biliary tract cancer) tend to be more likely to have actionable variants. The low rate of therapeutic implementation (17% of patients receiving a tumor board recommendation) underscores the importance of meticulous follow-up for these patients and ensuring broad access to innovative therapies for patients receiving molecular tumor profiling.

Objective The aim of this study was to assess eHealth usage among oncology patients undergoing infusion therapy. Methods We used an extended version of the validated 21-item questionnaire “Use of information and communication technologies questionnaire (ICT)” developed by Seifert et al., in order to assess patient-reported information related to general internet abilities including health-related applications. Results 303 patients participated. 299/303 participants reported regular internet usage. 72.6% (217/299) use the internet to search for health-related information and 79.1% (235/297) expressed readiness to communicate digitally with health care providers. Decreasing age and higher internet literacy correlated with a more frequent use of eHealth applications (p

Supplementary Tables and Figures

The SARS-CoV-2 pandemic significantly affected oncology practice across the globe. There is uncertainty as to the contribution of patients' demographics and oncologic features to severity and mortality from COVID-19 and little guidance as to the role of anticancer and anti–COVID-19 therapy in this population. In a multicenter study of 890 patients with cancer with confirmed COVID-19, we demonstrated a worsening gradient of mortality from breast cancer to hematologic malignancies and showed that male gender, older age, and number of comorbidities identify a subset of patients with significantly worse mortality rates from COVID-19. Provision of chemotherapy, targeted therapy, or immunotherapy did not worsen mortality. Exposure to antimalarials was associated with improved mortality rates independent of baseline prognostic factors. This study highlights the clinical utility of demographic factors for individualized risk stratification of patients and supports further research into emerging anti–COVID-19 therapeutics in SARS-CoV-2–infected patients with cancer.Significance:In this observational study of 890 patients with cancer diagnosed with SARS-CoV-2, mortality was 33.6% and predicted by male gender, age ≥65, and comorbidity burden. Delivery of cancer therapy was not detrimental to severity or mortality from COVID-19. These patients should be the focus of shielding efforts during the SARS-CoV-2 pandemic.This article is highlighted in the In This Issue feature, p. 1426

Supplementary Figure 2 shows association between RNA signatures and ypT0/is ypN0

Supplementary Table 6 shows multivariate logistic regression models for predicting pCR (ypT0/is ypN0)

Purpose:Although optimal treatment in early triple-negative breast cancer (TNBC) remains unclear, de-escalated chemotherapy appears to be an option in selected patients within this aggressive subtype. Previous studies have identified several pro-immune factors as prognostic markers in TNBC, but their predictive impact regarding different chemotherapy strategies is still controversial.Experimental Design:ADAPT-TN is a randomized neoadjuvant multicenter phase II trial in early patients with TNBC (n = 336) who were randomized to 12 weeks of nab-paclitaxel 125 mg/m2 + gemcitabine or carboplatin d 1,8 q3w. Omission of further (neo-) adjuvant chemotherapy was allowed only in patients with pathological complete response [pCR, primary endpoint (ypT0/is, ypN0)]. Secondary invasive/distant disease-free and overall survival (i/dDFS, OS) and translational research objectives included quantification of a predictive impact of markers regarding selection for chemotherapy de-escalation, measured by gene expression of 119 genes (including PAM50 subtype) by nCounter platform and stromal tumor-infiltrating lymphocytes (sTIL).Results:After 60 months of median follow-up, 12-week-pCR was favorably associated (HR, 0.24; P = 0.001) with 5y-iDFS of 90.6% versus 62.8%. No survival advantage of carboplatin use was observed, despite a higher pCR rate [HR, 1.04; 95% confidence interval (CI), 0.68–1.59]. Additional anthracycline-containing chemotherapy was not associated with a significant iDFS advantage in pCR patients (HR, 1.29; 95% CI, 0.41–4.02). Beyond pCR rate, nodal status and high sTILs were independently associated with better iDFS, dDFS, and OS by multivariable analysis.Conclusions:Short de-escalated neoadjuvant taxane/platinum-based combination therapy appears to be a promising strategy in early TNBC for using pCR rate as an early decision point for further therapy (de-) escalation together with node-negative status and high sTILs.See related commentary by Sharma, p. 4840

Supplementary Data from De-escalated Neoadjuvant Chemotherapy in Early Triple-Negative Breast Cancer (TNBC): Impact of Molecular Markers and Final Survival Analysis of the WSG-ADAPT-TN Trial

Supplementary Figure from De-escalated Neoadjuvant Chemotherapy in Early Triple-Negative Breast Cancer (TNBC): Impact of Molecular Markers and Final Survival Analysis of the WSG-ADAPT-TN Trial

Purpose:To identify associations of biological signatures and stromal tumor-infiltrating lymphocytes (sTIL) with pathological complete response (pCR; ypT0 ypN0) and survival in the Phase II WSG-ADAPT HER2+/HR− trial (NCT01817452).Experimental Design:Patients with cT1-cT4c, cN0–3 HER2+/HR− early breast cancer (EBC) were randomized to pertuzumab+trastuzumab (P+T, n = 92) or P+T+paclitaxel (n = 42). Gene expression signatures were analyzed in baseline biopsies using NanoString Breast Cancer 360 panel (n = 117); baseline and on-treatment (week 3) sTIL levels were available in 119 and 76 patients, respectively. Impacts of standardized gene expression signatures on pCR and invasive disease-free survival (iDFS) were estimated by logistic and Cox regression.Results:In all patients, ERBB2 [OR, 1.70; 95% confidence interval (CI), 1.08–2.67] and estrogen receptor (ER) signaling (OR, 1.72; 95% CI, 1.13–2.61) were favorable, whereas PTEN (OR, 0.57; 95% CI, 0.38–0.87) was unfavorable for pCR. After 60 months median follow-up, 13 invasive events occurred (P+T: n = 11, P+T+paclitaxel: n = 2), none following pCR. Gene signatures related to immune response (IR) and ER signaling were favorable for iDFS, all with similar HR about 0.43–0.55. These patterns were even more prominent in the neoadjuvant chemotherapy-free group, where additionally BRCAness signature was unfavorable (HR, 2.00; 95% CI, 1.04–3.84). IR signatures were strongly intercorrelated. sTILs (baseline/week 3/change) were not associated with pCR or iDFS, though baseline sTILs correlated positively with IR signatures.Conclusions:Distinct gene signatures were associated with pCR versus iDFS in HER2+/HR− EBC. The potential role of IR in preventing recurrence suggests that patients with upregulated IR signatures could be candidates for de-escalation concepts in HER2+ EBC.

Supplementary Table from De-escalated Neoadjuvant Chemotherapy in Early Triple-Negative Breast Cancer (TNBC): Impact of Molecular Markers and Final Survival Analysis of the WSG-ADAPT-TN Trial

Background Anthracycline/cyclophosphamide-taxane-containing chemotherapy (AC-T) is the standard of care in the adjuvant treatment of HER2-negative early breast cancer (EBC), but recent studies suggest omission of anthracyclines for reduced toxicity without compromising efficacy. Methods Based on individual patient data (n = 5924) pooled from the randomised Phase III trials PlanB and SUCCESS C, we compared disease-free survival (DFS) and overall survival (OS) between intermediate to high-risk HER2-negative EBC-patients treated with either six cycles of docetaxel/cyclophosphamide (TC6) or an AC-T regime using univariable and adjusted multivariable Cox regression models. Results AC-T conferred no significant DFS or OS advantage in univariable (DFS: hazard ratio (HR) for TC vs. AT 1.05, 95% confidence interval (CI): 0.89–1.24, P = 0.57; OS: HR 1.00, 95% CI: 0.80–1.26, P = 1.00) and adjusted multivariable analysis (DFS: HR 1.01, 95% CI: 0.86–1.19, P = 0.91; OS: HR 0.97, 95% CI: 0.77–1.22, P = 0.79). Patients receiving TC6 had significantly fewer grade 3–4 adverse events. Exploratory subgroup analysis showed that AC-T was associated with significantly better DFS and OS in pN2/3 patients, specifically in those with lobular histology. Conclusion For most patients with HER2-negative EBC, AC-T is not associated with a survival benefit compared to TC6. However, patients with lobular pN2/pN3 tumours seem to benefit from anthracycline-containing chemotherapy.

Introduction: This project aimed to identify the frequency of a switch of hormone receptor (HR) and/or HER2 status after neoadjuvant chemotherapy (NAC) for early breast cancer. Methods: Tumor samples from patients without pathological complete response (non-pCR) were evaluated. Pathological complete response (pCR) was defined as no invasive tumor in breast and lymph nodes (ypT0/is ypN0). HR and HER2 status determined before NAC was compared with the corresponding receptor status determined in the surgical specimen after NAC. Results: 245 consecutive patients with primary invasive breast cancer, treated with NAC with/without targeted therapy between January 1, 2016 and December 31, 2019, at the LMU Breast Center, Munich, Germany, were identified. In 128 patients (52%), surgery revealed non-pCR after completed NAC. In 35 cases (27%), a switch of either HR and/or HER2 status between the initial biopsy and the surgical specimen was detected. Twenty cases had a switch in HR status, while 15 cases had a switch in HER2 status. Conclusion: In a substantial number (27%) of non-pCR cases, a switch in biomarker status after completed neoadjuvant treatment was detected. These results are consistent with prior evidence. Yet, routine reevaluation of HR and HER2 status is not recommended in guidelines so far. Future research needs to address the impact of HR and HER2 status switch on therapy adaptation and on subsequent patient outcome. Particularly, in view of the recent therapy advances, it will be critical to evaluate whether individualization of treatment concepts based on the biology of the non-pCR specimens is preferable to the initial therapy concept based on the pathology at primary diagnosis.

Background COVID-19 sequelae can affect about 15% of patients with cancer who survive the acute phase of SARS-CoV-2 infection and can substantially impair their survival and continuity of oncological care. We aimed to investigate whether previous immunisation affects long-term sequelae in the context of evolving variants of concern of SARS-CoV-2. Methods OnCovid is an active registry that includes patients aged 18 years or older from 37 institutions across Belgium, France, Germany, Italy, Spain, and the UK with a laboratory-confirmed diagnosis of COVID-19 and a history of solid or haematological malignancy, either active or in remission, followed up from COVID-19 diagnosis until death. We evaluated the prevalence of COVID-19 sequelae in patients who survived COVID-19 and underwent a formal clinical reassessment, categorising infection according to the date of diagnosis as the omicron (B.1.1.529) phase from Dec 15, 2021, to Jan 31, 2022; the alpha (B.1.1.7)-delta (B.1.617.2) phase from Dec 1, 2020, to Dec 14, 2021; and the pre-vaccination phase from Feb 27 to Nov 30, 2020. The prevalence of overall COVID-19 sequelae was compared according to SARS-CoV-2 immunisation status and in relation to post-COVID-19 survival and resumption of systemic anticancer therapy. This study is registered with ClinicalTrials.gov, NCT04393974. Findings At the follow-up update on June 20, 2022, 1909 eligible patients, evaluated after a median of 39 days (IQR 24-68) from COVID-19 diagnosis, were included (964 [ 50 center dot 7%] of 1902 patients with sex data were female and 938 [49 center dot 3%] were male). Overall, 317 (16 center dot 6%; 95% CI 14 center dot 8-18 center dot 5) of 1909 patients had at least one sequela from COVID-19 at the first oncological reassessment. The prevalence of COVID-19 sequelae was highest in the prevaccination phase (191 [19 center dot 1%; 95% CI 16 center dot 4-22 center dot 0] of 1000 patients). The prevalence was similar in the alpha-delta phase (110 [16 center dot 8%; 13 center dot 8- 20 center dot 3] of 653 patients, p=0 center dot 24), but significantly lower in the omicron phase (16 [6 center dot 2%; 3 center dot 5-10 center dot 2] of 256 patients, p

Background Whereas the genomic landscape of endocrine‐resistant breast cancer has been intensely characterized in previously treated cases with local or distant recurrence, comparably little is known about genomic alterations conveying primary non‐responsiveness to endocrine treatment in luminal early breast cancer. Methods In this study, 622 estrogen receptor‐expressing breast cancer cases treated with short‐term preoperative endocrine therapy (pET) from the WSG‐ADAPT trial (NCT01779206) were analyzed for genetic alterations associated with impaired endocrine proliferative response (EPR) to 3‐week pET with tamoxifen or aromatase inhibitors. EPR was categorized as optimal (post‐pET Ki67, Early recognition of endocrine resistance could be enabled by impaired suppression of proliferation after short‐term preoperative endocrine therapy (pET). Impaired endocrine proliferative response (EPR, post‐pET Ki67 ≥10%) sorts out cancers carrying TP53 mutations.

Purpose With the beginning of 2021, the world has been suffering from the COVID-19 pandemic for more than 1 year. More and more, we are able to evaluate side effects of the pandemic in the healthcare sector. A negative impact on cancer diagnoses is one of them. Careful observation of trends in an academic gyneco-oncological context appears important to identify potential negative developments. Methods We analyzed the case number of gynecologic and breast cancer diagnoses in the period from January to June 2020 compared to 2019 and during the period of the first general German lockdown (March 22nd until May 5th 2020). Patients were characterized by age, tumor type, FIGO or TNM stage and presence of symptoms at initial hospital presentation. Results The frequency of newly diagnosed gynecologic and breast cancer cases from beginning of January until end of June changed by − 10% and by − 12% during the lockdown in 2020 compared to 2019. In both periods, reduction of breast cancer cases was relatively larger than decrease of gynecologic cancers. Moreover, median patient age decreased. For the first half of 2020, we found a shift towards higher tumor stages (N+/M1 or FIGO III–IV). During the lockdown period, the appearance of tumor-associated symptoms at diagnosis increased by about 12%. Conclusion This analysis illustrates the anticipated general decrease in diagnoses of primary cancers during the lockdown periods in 2020 due to COVID-19 pandemic for gynecologic and breast cancer cases.

Purpose Assessment of HER2 overexpression using immunohistochemistry (IHC) and/or in situ hybridisation (ISH) for the detection of HER2 amplifications is standard to identify patients for established HER2-directed treatments. Patients with lower HER2 expression levels have recently also become candidates for novel therapies targeting HER2. This study aimed to assess tumour and patient characteristics and prognosis in patients with advanced breast cancer (aBC), relative to low HER2 expression levels. Methods PRAEGNANT is a prospective aBC registry (NCT02338167), focusing on molecular biomarkers. Patients in all therapy lines receiving any kind of treatment are eligible. This analysis includes patients with conventionally HER2-negative aBC. Clinical outcome was compared in the groups with no (IHC score 0) or with low HER2 expression (IHC 1+, or IHC 2+/ISH negative). Results Low HER2 expression levels in triple-negative aBC patients did not influence progression-free survival. Overall survival appeared poorer in patients with IHC 2+ compared with patients with no HER2 expression in the unadjusted analysis (hazard ratio 2.24, 95% confidence interval 0.1.12–4.47). However, this effect was not maintained in the adjusted analysis. In HER2-negative, hormone receptor–positive patients, low HER2 expression appeared to have no effect on prognosis, neither progression-free survival nor overall survival. Conclusions We could not demonstrate that HER2 expression at a low level and assessed in clinical routine can differentiate patients into prognostic groups. However, the prevalence of patients with a low expression makes this population interesting for clinical trials with potentially active treatments using HER2 as a target.

Purpose This study examines congruence between self-reported and device-measured physical activity data in women with early breast cancer and compares trajectories under different treatments. Methods Women with non-metastatic breast cancer were recruited before primary therapy. In four weeks distributed over six months after treatment start, patients reported time spent on work, transport, chores and sports via diary and wore Garmin® vivofit 3 accelerometers to assess steps taken. Associations between these measures and agreement regarding guideline adherence were tested with Spearman’s Correlation Coefficient and Weighted Kappa statistic. Effects of time and treatment were evaluated using mixed analyses of variance. Results Ninety-nine participants (median age = 50) were treated with adjuvant (N= 23), neoadjuvant (N= 21) or without chemotherapy (N= 55). Coherence between self-report and device data was strong (r = 0.566). Agreement about reaching recommendations was only “fair” (kappa coefficient = 0.321 and 0.249, resp.). Neither treatment or week nor their interaction had effects on step counts (all p > 0.05). Self-reported activity time was lower for patients with chemotherapy than for those without (adjuvant: ∆ = 69min, p= 0.006, neoadjuvant: ∆ = 45min, p= 0.038) and lower in week 18 than in week 3 (∆ = 43min, p= 0.010). Conclusion Results show that consumer-grade activity monitors and self-reports correlate but show different perspectives on physical activity in breast cancer patients. In general, patients perceive some decline regardless of primary treatment regimen. Those affected should be offered assistance to gain the benefits of activity. Accelerometers may help professionals to identify these individuals and patients to verify appraisal of their activity levels.

Background Recent advances in the treatment of human epidermal growth factor receptor positive (HER2+) early breast cancer (eBC) have led to a reduction in recurrence risk; still a relevant percentage of patients relapses over time, predominantly presenting with distant recurrence. Neratinib is registered in Europe as extended adjuvant treatment for adult patients with HER2+, hormone receptor positive (HR+) eBC, who completed adjuvant trastuzumab-based therapy within one year prior to start of neratinib. In the ExteNET study, neratinib improved the absolute 5-year invasive disease-free survival (iDFS) rate by 5.1% versus placebo in this population (90.8% vs. 85.7%; HR 0.58 [95% CI 0.41-0.82]), mainly by reducing the rate of distant metastases. According to explorative analyses from ExteNET, the effect may be even more pronounced in patients with non-pCR after neoadjuvant trastuzumab treatment and/or in patients completing the full duration of neratinib therapy (i.e. ≥11 months of neratinib treatment). Diarrhea, the most common grade 3 adverse event (neratinib: 39% without primary diarrhea prophylaxis, median cumulative duration 5 days; placebo: 1%; no grade 4 events) can generally be managed through adequate prophylaxis and treatment management. ELEANOR is the first non-interventional study (NIS) of real-world use of neratinib and its management in eBC patients in Germany, Austria and Switzerland. Methods Enrollment of 300 adult female patients with HER2+/HR+ eBC is planned in accordance with the SmPC specifications. Primary endpoint is the rate of patients adherent to neratinib treatment (i.e. neratinib use for ≥75% of treatment days). Secondary objectives include characterization of patients scheduled to receive neratinib, details on neratinib treatment, recurrences, safety/tolerability, and health-related quality of life (HRQoL). CANKADO, an eHealth application developed to support patient/physician communication, is an integral part of the NIS. Here, we report results of the preplanned interim analysis based on 200 enrolled patients. Results At data cut-off (May 2022), 202 patients had been observed for 3 months; patient enrollment is ongoing. Median age was 53.0 years and 66.3% of patients were at increased risk of disease recurrence (defined as non-pCR or AJCC stage > I). Most patients had received prior neoadjuvant treatment (79.7%). Post-neoadjuvant treatment included dual HER2 blockade with trastuzumab and pertuzumab (38.8%/23.9% of pCR/non-pCR patients) and trastuzumab-emtansine (T-DM1, 53.5% of non-pCR patients). Neratinib treatment had been documented for 187 patients, treatment was ongoing for 46.0% of patients. Diarrhea was the most common adverse event (78.6% any grade, 19.3% grade 3, 2 patients grade 4), but was markedly lower when indirectly compared to ExteNET (39% grade 3). The neratinib dose escalation schedule was chosen for 36.4% of patients and led to a decreased incidence of severe diarrhea (16.2% grade 3, no grade 4 events). 93.9% (95% CI: 87.9-97.5%) of 115 evaluable patients adhered to neratinib treatment. Conclusion The results of this preplanned interim analysis reflect the current treatment landscape in Germany, Austria and Switzerland. These results confirm, in line with the observed adherence data, that extended adjuvant neratinib use is feasible in typical clinical practice settings. Furthermore, treatment management strategies such as diarrhea prophylaxis or neratinib dose escalation are routinely used and can increase treatment tolerability markedly. The study is funded by Pierre Fabre Pharma GmbH (Freiburg, Germany), Pierre Fabre Pharma Austria (Wels, Austria) and Pierre Fabre Pharma AG (Allschwil, Switzerland). Citation Format: Rupert Bartsch, Nadia Harbeck, Denise Wrobel, Matthias Zaiss, Jürgen Terhaag, Dagmar Guth, Andrea Distelrath, Rachel Wuerstlein, Mark-Oliver Zahn, Diana Lüftner, Michael Schwitter, Marija Balic, Christian Jackisch, Volkmar Müller, Gabriel Rinnerthaler, Marcus Schmidt, Khalil Zaman, Timo Schinköthe, Anna Resch, Urs Breitenstein. Interim analysis (n=200) from ELEANOR: a multi-national, prospective, non-interventional study among patients with HER2+ and HR+ early breast cancer treated with extended adjuvant neratinib in the clinical routine [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-01-01.

Introduction: This study aimed at identification of breast cancer patients with a switched hormone- or HER2 receptor status after neoadjuvant chemotherapy. Therefore, patients without pathological complete response (pCR) were evaluated. The hormone and HER2 receptor status determined prior to neoadjuvant chemotherapy was compared with the corresponding receptor status determined in the surgical specimen after neoadjuvant chemotherapy. Methods: Clinicopathological data of 249 patients, who received neoadjuvant treatment between 2016 and 2019 at the LMU breast center, Munich were reviewed. Among those, 129 patients (52%) with non-pCR were identified. Of those, 11 patients had a residual positive lymph node only. pCR was defined as absence of invasive tumor in breast and lymph node (ypT0/is; ypN0). According to German clinical guidelines, specimens were labeled hormone receptor positive, if ≥1% of tumor nuclei were reported estrogen receptor positive or ≥10% of tumor nuclei were reported progesterone receptor positive. Tumors were labeled HER2-positive if immunohistochemistry showed strong complete circular membrane staining of >10% of invasive cells or if in-situ-hybridization showed HER2 positivity. Surgical specimens of patients with non-pCR were pathologically evaluated in order to 1) detect a receptor status switch compared to the analysis prior to neoadjuvant chemotherapy and 2) to see whether additional post neoadjuvant treatment options become available. Results: The following results apply exclusively to non-pCR cases. Median age at diagnosis was 51 years, 27 patients were younger than 40. One male patient is included.A total of 36 cases (28%) switched either hormone- or HER2-status, including two cases of a simultaneous switch. In 19 cases, the hormone receptor status switched. 3 patients switched from hormone receptor negative to positive, while 16 switched from hormone receptor positive to negative. A total of 17 cases showed a switch in HER2 receptor status. 6 patients switched from HER2-negative to HER2-positive, while 11 switched from HER2-positive to HER2-negative. Due to technical limitations, HER2 status was not evaluable in two cases, and hormone receptor status in one case. See table below. Conclusion: Our results illustrate, that a biomarker status switch after neoadjuvant treatment occurs in almost a third (28%) of cases. Reassessment of hormone- and HER2-receptor status subsequent to neoadjuvant treatment is still under discussion, with regard to post-neoadjuvant treatment. Nevertheless, it may have potential benefits for patients regarding individualization of treatment and potentially even patient outcome. At present, only gain of receptors should impact treatment concepts; in case of loss of receptors, treatment should not be changed as results in the residual tumor tissue may not reflect receptor status on disseminated tumor cells. Biomarker status in patients with non-pCRBiomarrker status in patients with non-pCRStatus at initial diagnosisStatus in surgical non-pCR specimenCases with switch in biomarker status after NACHR positive99 (77%)85 (66%)3HR negative30 (23%)43 (34%)16HR total12912819 (15%)HER2 positive35 (27%)28 (22%)6HER2 negative94 (73%)99 (78%)11HER2 total12912717 (13%)Cases with switch in biomarker status36 (28%) Citation Format: Moritz Dimpfl, Tom Degenhardt, Doris Mayr, Elisa Schmoeckel, Nadia Harbeck, Rachel Wuerstlein. Hormone- and HER2 receptor change in non-pCR breast cancer specimens after neoadjuvant treatment [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-32.

Purpose Comprehensive genomic profiling identifying actionable molecular alterations aims to enable personalized treatment for cancer patients. The purpose of this analysis was to retrospectively assess the impact of personalized recommendations made by a multidisciplinary tumor board (MTB) on the outcome of patients with breast or gynecological cancers, who had progressed under standard treatment. Here, first experiences of our Comprehensive Cancer Center Molecular Tumor Board are reported. Methods All patients were part of a prospective local registry. 95 patients diagnosed with metastatic breast cancer or gynecological malignancies underwent extended molecular profiling. From May 2017 through March 2019, the MTB reviewed all clinical cases considering tumor profile and evaluated molecular alterations regarding further diagnostic and therapeutic recommendations. Results 95 patients with metastatic breast or gynecological cancers were discussed in the MTB (68% breast cancer, 20% ovarian cancer, 5% cervical cancer, 3% endometrial cancer and 4% others). Genes with highest mutation rate were PIK3CA and ERBB2. Overall, 34 patients (36%) received a biomarker-based targeted therapy recommendation. Therapeutic recommendations were implemented in nine cases; four patients experienced clinical benefit with a partial response or disease stabilization lasting over 4 months. Conclusion In the setting of a multidisciplinary molecular tumor board, a small but clinically meaningful group of breast and gynecological cancer patients benefits from comprehensive genomic profiling. Broad and successful implementation of precision medicine is complicated by patient referral at late stage disease and limited access to targeted agents and early clinical trials. Trial registration number 284-10 (03.05.2018).

Although SARS-CoV-2 vaccines immunogenicity in patients with cancer has been investigated, whether they can significantly improve the severity of COVID-19 in this specific population is undefined.Capitalizing on OnCovid (NCT04393974) registry data we reported COVID-19 mortality and proxies of COVID-19 morbidity, including post-COVID-19 outcomes, according to the vaccination status of the included patients.2090 eligible patients diagnosed with COVID-19 between 02/2020 and 11/2021 were included, of whom 1930 (92.3%) unvaccinated, 91 (4.4%) fully vaccinated and 69 (3.3%) partially vaccinated. With the exception of a higher prevalence of patients from the UK (p = 0.0003) and receiving systemic anticancer therapy at COVID-19 diagnosis (p = 0.0082) among fully vaccinated patients, no demographics/oncological features were associated with vaccination status. The 14-days case fatality rate (CFR) (5.5% vs 20.7%, p = 0.0004) and the 28-days CFR (13.2% vs 27.4%, p = 0.0028) demonstrated a significant improvement for fully vaccinated patients in comparison with unvaccinated patients. The receipt of prior full vaccination was also associated with reduced symptomatic COVID-19 (79.1% vs 88.5%, p = 0.0070), need of COVID-19 oriented therapy (34.9% vs 63.2%, p 0.0001), complications from COVID-19 (28.6% vs 39.4%, p = 0.0379), hospitalizations due to COVID-19 (42.2% vs 52.5%, p = 0.0007) and oxygen therapy requirement (35.7% vs 52%, p = 0.0036). Following Inverse Probability Treatment Weighting (IPTW) procedure no statistically significant difference according to the vaccination status was confirmed; however, all COVID-19 related outcomes were concordantly in favour of full vaccination. Among the 1228 (58.8%) patients who underwent a formal reassessment at participating centres after COVID-19 resolution, fully vaccinated patients experienced less sequelae than unvaccinated patients (6.7% vs 17.2%, p = 0.0320).This analysis provides initial evidence in support of the beneficial effect of SARS-CoV-2 vaccines against morbidity and mortality from COVID-19 in patients with cancer.

The omicron (B.1.1.529) variant of SARS-CoV-2 is highly transmissible and escapes vaccine-induced immunity. We aimed to describe outcomes due to COVID-19 during the omicron outbreak compared with the prevaccination period and alpha (B.1.1.7) and delta (B.1.617.2) waves in patients with cancer in Europe.In this retrospective analysis of the multicentre OnCovid Registry study, we recruited patients aged 18 years or older with laboratory-confirmed diagnosis of SARS-CoV-2, who had a history of solid or haematological malignancy that was either active or in remission. Patient were recruited from 37 oncology centres from UK, Italy, Spain, France, Belgium, and Germany. Participants were followed up from COVID-19 diagnosis until death or loss to follow-up, while being treated as per standard of care. For this analysis, we excluded data from centres that did not actively enter new data after March 1, 2021 (in France, Germany, and Belgium). We compared measures of COVID-19 morbidity, which were complications from COVID-19, hospitalisation due to COVID-19, and requirement of supplemental oxygen and COVID-19-specific therapies, and COVID-19 mortality across three time periods designated as the prevaccination (Feb 27 to Nov 30, 2020), alpha-delta (Dec 1, 2020, to Dec 14, 2021), and omicron (Dec 15, 2021, to Jan 31, 2022) phases. We assessed all-cause case-fatality rates at 14 days and 28 days after diagnosis of COVID-19 overall and in unvaccinated and fully vaccinated patients and in those who received a booster dose, after adjusting for country of origin, sex, age, comorbidities, tumour type, stage, and status, and receipt of systemic anti-cancer therapy. This study is registered with ClinicalTrials.gov, NCT04393974, and is ongoing.As of Feb 4, 2022 (database lock), the registry included 3820 patients who had been diagnosed with COVID-19 between Feb 27, 2020, and Jan 31, 2022. 3473 patients were eligible for inclusion (1640 [47·4%] were women and 1822 [52·6%] were men, with a median age of 68 years [IQR 57-77]). 2033 (58·5%) of 3473 were diagnosed during the prevaccination phase, 1075 (31·0%) during the alpha-delta phase, and 365 (10·5%) during the omicron phase. Among patients diagnosed during the omicron phase, 113 (33·3%) of 339 were fully vaccinated and 165 (48·7%) were boosted, whereas among those diagnosed during the alpha-delta phase, 152 (16·6%) of 915 were fully vaccinated and 21 (2·3%) were boosted. Compared with patients diagnosed during the prevaccination period, those who were diagnosed during the omicron phase had lower case-fatality rates at 14 days (adjusted odds ratio [OR] 0·32 [95% CI 0·19-0·61) and 28 days (0·34 [0·16-0·79]), complications due to COVID-19 (0·26 [0·17-0·46]), and hospitalisation due to COVID-19 (0·17 [0·09-0·32]), and had less requirements for COVID-19-specific therapy (0·22 [0·15-0·34]) and oxygen therapy (0·24 [0·14-0·43]) than did those diagnosed during the alpha-delta phase. Unvaccinated patients diagnosed during the omicron phase had similar crude case-fatality rates at 14 days (ten [25%] of 40 patients vs 114 [17%] of 656) and at 28 days (11 [27%] of 40 vs 184 [28%] of 656) and similar rates of hospitalisation due to COVID-19 (18 [43%] of 42 vs 266 [41%] of 652) and complications from COVID-19 (13 [31%] of 42 vs 237 [36%] of 659) as those diagnosed during the alpha-delta phase.Despite time-dependent improvements in outcomes reported in the omicron phase compared with the earlier phases of the pandemic, patients with cancer remain highly susceptible to SARS-CoV-2 if they are not vaccinated against SARS-CoV-2. Our findings support universal vaccination of patients with cancer as a protective measure against morbidity and mortality from COVID-19.National Institute for Health and Care Research Imperial Biomedical Research Centre and the Cancer Treatment and Research Trust.

Introduction: Breast cancer (BC) is the most common cancer in women worldwide. Despite screening and information efforts, about 10% of patients present with tumor size T3 or T4 at primary diagnosis. Late presentation is associated with more advanced tumor stage and consecutively with worse survival rates. Objective: This study aimed to evaluate whether patients with a late presentation at primary BC diagnosis differ in their personality from those with early diagnosis. Methods: In this bicentric, observational study, personality traits, positive and negative affectivity, anxiety, spirituality, illness beliefs, and sociodemographic characteristics were assessed in BC patients who presented with T-stages 3 or 4 (late presenters) and T-stages 1 or 2 (controls) at initial diagnosis. Results: Forty patients (20 controls, 20 late presenters) were interviewed. “Late presenters” perceived their disease as long lasting and had significantly more “positive affectivity” in the current trait. Although no significant associations were found, there was a trend for late presenters to have higher education levels, less spiritual longing, less accurate explanation of their illness, less anxiety in the trait scale, and more conscientiousness than the controls. Conclusion: As patients with late presentation for BC differ in specific psychological and sociodemographic characteristics from patients with early BC, the findings of this pilot project warrant additional investigations to identify further specific characteristics and motivations. Identifying patients at risk for late presentation and encouraging them to accept an earlier diagnosis could help to improve their therapy and, finally, their outcome.