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"Leinert, Elena"
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Effect of histological breast cancer subtypes invasive lobular versus non-special type on survival in early intermediate-to-high-risk breast carcinoma: results from the SUCCESS trials
by
Lukac, Stefan
,
Rack, Brigitte
,
Friedl, Thomas W. P.
in
Adjuvant treatment
,
Biomedical and Life Sciences
,
Biomedicine
2023
Background
Invasive lobular breast carcinomas (ILC) have different histological features compared to non-special type carcinomas (NST), but the effect of histological subtypes on survival is controversial. In this study, we compared clinicopathological characteristics and outcomes between ILC and NST based on a large pooled data set from three adjuvant breast cancer trials (SUCCESS A, B, and C) and investigated a potential differential effect of recurrence risk related to nodal stage on survival.
Methods
From 2005 to 2017, the large randomized controlled SUCCESS A, B, and C trials enrolled 8190 patients with primary, intermediate-to-high-risk breast carcinoma. All patients received adjuvant chemotherapy, and endocrine and/or HER2-targeted treatment was given where appropriate. Survival outcomes in terms of disease-free survival (DFS), overall survival (OS), breast cancer-specific survival (BCSS), and distant disease-free survival (DDFS) were estimated using the Kaplan–Meier method and analyzed using log-rank tests as well as univariable and adjusted multivariable Cox regression models.
Results
In the SUCCESS trials, 6284 patients had NST and 952 had ILC. The median follow-up time was 64 months. ILC patients were older, more likely to receive mastectomy, and more likely to have larger tumor sizes, lymph node infiltration, hormone receptor-positive, HER2neu-negative, and luminal A-like tumors than NST patients. In the overall cohort, no significant differences between ILC and NST were detectable regarding the four survival endpoints, with hazard ratios obtained in adjusted multivariable cox regressions of 0.96 (95% CI 0.77–1.21,
p
= 0.743) for DFS, 1.13 (95% CI 0.85–1.50,
p
= 0.414) for OS, 1.21 (95% CI 0.89–1.66,
p
= 0.229) for BCSS, and 0.95 (95% CI 0.73–1.24,
p
= 0.689) for DDFS. However, a differential effect of nodal stage on survival was observed, with better survival for ILC patients with pN0/pN1 tumors and worse survival for ILC patients with pN2/pN3 tumors compared to NST patients.
Conclusions
Our results revealed that ILC was associated with worse survival compared to NST for patients at high risk of recurrence due to advanced lymph node infiltration. These findings should be taken into account for treatment decisions and monitoring.
Journal Article
Prevalence of pathogenic BRCA1/2 germline mutations among 802 women with unilateral triple-negative breast cancer without family cancer history
by
Weber, Bernhard H. F.
,
Bartram, Claus R.
,
Wieacker, Peter
in
Biomedical and Life Sciences
,
Biomedicine
,
BRCA1
2018
Background
There is no international consensus up to which age women with a diagnosis of triple-negative breast cancer (TNBC) and no family history of breast or ovarian cancer should be offered genetic testing for germline
BRCA1
and
BRCA2
(gBRCA) mutations. Here, we explored the association of age at TNBC diagnosis with the prevalence of pathogenic gBRCA mutations in this patient group.
Methods
The study comprised 802 women (median age 40 years, range 19–76) with oestrogen receptor, progesterone receptor, and human epidermal growth factor receptor type 2 negative breast cancers, who had no relatives with breast or ovarian cancer. All women were tested for pathogenic gBRCA mutations. Logistic regression analysis was used to explore the association between age at TNBC diagnosis and the presence of a pathogenic gBRCA mutation.
Results
A total of 127 women with TNBC (15.8%) were gBRCA mutation carriers (
BRCA1
:
n
= 118, 14.7%;
BRCA2
:
n
= 9, 1.1%). The mutation prevalence was 32.9% in the age group 20–29 years compared to 6.9% in the age group 60–69 years. Logistic regression analysis revealed a significant increase of mutation frequency with decreasing age at diagnosis (odds ratio 1.87 per 10 year decrease, 95%CI 1.50–2.32,
p
< 0.001). gBRCA mutation risk was predicted to be > 10% for women diagnosed below approximately 50 years.
Conclusions
Based on the general understanding that a heterozygous mutation probability of 10% or greater justifies gBRCA mutation screening, women with TNBC diagnosed before the age of 50 years and no familial history of breast and ovarian cancer should be tested for gBRCA mutations. In Germany, this would concern approximately 880 women with newly diagnosed TNBC per year, of whom approximately 150 are expected to be identified as carriers of a pathogenic gBRCA mutation.
Journal Article
Effect of adjuvant radiotherapy in elderly patients with breast cancer
by
Leinert, Elena
,
Bartmann, Catharina
,
Stueber, Tanja Nadine
in
Aged
,
Aged, 80 and over
,
Breast cancer
2020
Radiotherapy (RT) is of critical importance in the locoregional management of early breast cancer. Although RT is routinely used following breast conserving surgery (BCS), patients may occasionally be effectively treated with BCS alone. Currently, the selection of patients undergoing BCS who do not need breast irradiation is under investigation. With the advancement of personalized medicine, there is an increasing interest in reduction of aggressive treatments especially in older women. The primary objective of this study was to identify elderly patients who may forego breast irradiation after BCS without measurable consequences on local tumor growth and survival.
We analyzed 2384 early breast cancer patients aged 70 and older who were treated in 17 German certified breast cancer centers between 2001 and 2009. We compared RT versus no RT after guideline adherent (GA) BCS. The outcomes studied were breast cancer recurrence (RFS) and breast cancer-specific survival (BCSS). Low-risk patients were defined by luminal A, tumor size T1 or T2 and node-negative whereas higher-risk patients were defined by patients with G3 or T3/T4 or node-positive or other than Luminal A tumors. To test if there is a difference between two or more survival curves, we used the Gp family of tests of Harrington and Fleming.
The median age was 77 yrs (mean 77.6±5.6 y) and the median observation time 46 mths (mean 48.9±24.8 mths). 950 (39.8%) patients were low-risk and 1434 (60.2%) were higher-risk. 1298 (54.4%) patients received GA BCS of which 85.0% (1103) received GA-RT and only 15% (195) did not. For low-risk patients with GA-BCS there were no significant differences in RFS (log rank p = 0.651) and in BCSS (p = 0.573) stratified by GA-RT. 5 years RFS in both groups were > 97%. For higher-risk patients with GA-BCS we found a significant difference (p<0.001) in RFS and tumor-associated OS stratified by GA-RT. The results remain the same after adjusting by adjuvant systemic treatment (AST) and comorbidity (ASA and NYHA).
Patients aged 70 years and older suffering from low-risk early breast cancer with GA-BCS can avoid breast irradiation with <3% chance of relapse. In the case of higher-risk, breast irradiation should be used routinely following GA-BCS. As a side effect of these results, removing the entire breast of elderly low risk patients to spare them from breast irradiation seems to be not necessary.
Journal Article
Does chemotherapy improve survival in patients with nodal positive luminal A breast cancer? A retrospective Multicenter Study
by
Curtaz, Carolin
,
Blettner, Maria
,
Leinert, Elena
in
Adjuvant chemotherapy
,
Aged
,
Biology and Life Sciences
2019
In this study based on the BRENDA data, we investigated the impact of endocrine ± chemotherapy for luminal A, nodal positive breast cancer on recurrence free (RFS) and overall survival (OS). In addition, we analysed if tumor size of luminal A breast cancer influences survival in patients with the same number of positive lymph nodes.
In this retrospective multi-centre cohort study data of 1376 nodal-positive patients with primary diagnosis of luminal A breast cancer during 2001-2008 were analysed. The results were stratified by therapy and adjusted by age, tumor size and number of affected lymph nodes.
In our study population, patients had a good to excellent prognosis (5-year RFS: 91% and tumorspecific 5-year OS 96.5%). There was no significant difference in RFS stratified by patients with only endocrine therapy and with endocrine plus chemo-therapy. Patients with 1-3 affected lymph nodes had no significant differences in OS treated only with endocrine therapy or with endocrine plus chemotherapy, independent of tumor size. Patients with large tumors and more than 3 affected lymph nodes had a significant worse survival as compared to the small tumors. However, despite the worse prognosis of those, adjuvant chemotherapy failed in order to improve RFS.
According to our data, nodal positive patients with luminal A breast cancer have, if any, a limited benefit of adjuvant chemotherapy. Tumor size and nodal status seem to be of prognostic value in terms of survival, however both tumor size as well as nodal status were not predictive for a benefit of adjuvant chemotherapy.
Journal Article
Negative Effect of Intravenous Antibiotics on Survival in Patients with Triple-Negative Breast Cancer
by
Lukac, Stefan
,
Rack, Brigitte
,
Friedl, Thomas Wolfram Paul
in
Adjuvant treatment
,
Antibiotics
,
Body mass index
2025
Background: The anti-tumor response of the immune system is pivotal for treating triple-negative breast cancer (TNBC), particularly as targeted therapies are limited. However, the impact of immune-modulating factors such as the application of granulocyte-stimulating factors (G-CSFs) or infections, including febrile neutropenia, prophylactic or therapeutical application of oral antibiotics (OABs), and the need for intravenous antibiotics (IABs), on survival outcomes remains unclear. Methods: 1583 patients with early-stage TNBC enrolled in the SUCCESS A or C study underwent primary surgery, adjuvant chemotherapy, and radiotherapy if indicated. All patients had Eastern Cooperative Oncology Group (ECOG) status ≤ 2. The effects of G-CSF, OAB, and IAB application on overall survival (OS), invasive disease-free survival (iDFS), breast cancer-specific survival (BCSS), and distant disease-free survival (DDFS) were assessed. Results: Only IAB treatment was significantly associated with decreased survival in univariable analyses (OS: p = 0.003; iDFS: p = 0.036; BCSS: p = 0.011; DDFS: p = 0.044), while G-CSF and OAB administration were not. Adjusted multivariable Cox regressions including febrile neutropenia and dose reduction/shift, ECOG, age of patients, and other clinicopathological parameters confirmed a significant negative effect of IABs on OS (p = 0.020), BCSS (p = 0.018), and DDFS (p = 0.044). Conclusions: In summary, IABs during adjuvant chemotherapy seems to be a risk factor for inferior OS, BCSS, and DDFS in TNBC patients, possibly by affecting microbiome-related immune response modulation. Hence, preventive measures to avoid the need for IABs should be considered in these patients.
Journal Article
ChatGPT, Google, or PINK? Who Provides the Most Reliable Information on Side Effects of Systemic Therapy for Early Breast Cancer?
by
Lukac, Stefan
,
Heitmeir, Benedikt
,
Leinert, Elena
in
Artificial intelligence
,
Breast cancer
,
Cancer therapies
2025
Introduction: The survival in early breast cancer (BC) has been significantly improved thanks to numerous new drugs. Nevertheless, the information about the need for systemic therapy, especially chemotherapy, represents an additional stress factor for patients. A common coping strategy is searching for further information, traditionally via search engines or websites, but artificial intelligence (AI) is also increasingly being used. Who provides the most reliable information is now unclear. Material and Methods: AI in the form of ChatGPT 3.5 and 4.0, Google, and the website of PINK, a provider of a prescription-based mobile health app for patients with BC, were compared to determine the validity of the statements on the five most common side effects of nineteen approved drugs and one drug with pending approval (Ribociclib) for the systemic treatment of BC. For this purpose, the drugs were divided into three groups: chemotherapy, targeted therapy, and endocrine therapy. The reference for the comparison was the prescribing information of the respective drug. A congruence score was calculated for the information on side effects: correct information (2 points), generally appropriate information (1 point), and otherwise no point. The information sources were then compared using a Friedmann test and a Bonferroni-corrected post-hoc test. Results: In the overall comparison, ChatGPT 3.5 received the best score with a congruence of 67.5%, followed by ChatGPT 4.0 with 67.0%, PINK with 59.5%, and with Google 40.0% (p < 0.001). There were also significant differences when comparing the individual subcategories, with the best congruence achieved by PINK (73.3%, p = 0.059) in the chemotherapy category, ChatGPT 4.0 (77.5%; p < 0.001) in the targeted therapy category, and ChatGPT 3.5 (p = 0.002) in the endocrine therapy category. Conclusions: Artificial intelligence and professional online information websites provide the most reliable information on the possible side effects of the systemic treatment of early breast cancer, but congruence with prescribing information is limited. The medical consultation should still be considered the best source of information.
Journal Article
Survivors of primary breast cancer 5 years after surgery: follow-up care, long-term problems, and treatment regrets. Results of the prospective BRENDA II-study
2020
PurposeThis study aims to answer the questions where breast cancer patients in Germany receive follow-up care (with what types of doctors) and what are the long-term problems and treatment regrets of breast cancer patients.MethodsIn the prospective multicenter cohort study BRENDA II (“Breast Cancer under Evidence-Based Guidelines”), 456 patients with primary breast cancer were sampled consecutively over a period of 4 years (2009–2012) and contacted again 5 years after surgery. Long-term problems were elicited on a 4-point Likert scale ranging from 0 (‘not at all’) to 3 (‘very much’).Results82% of the patients receive follow-up (FU) at the private practice gynecologist. In 22%, the initial treating hospital is involved in the FU, and in 20% the general practitioner does this (multiple answers possible). Long-term problems attributed to the treatment were most often related to endocrine therapy (mean 1.29) and to chemotherapy (mean 0.94).Most of the patients were happy to have had radiotherapy (95%). For chemotherapy, endocrine therapy, and antibody therapy, the satisfaction for the treatment decision was 87%, 87%, and 84% respectively. Among patients who reported they regretted having undergone a recommended treatment, it was most often for endocrine therapy (5%) and chemotherapy (4%).ConclusionIn Germany, different specialists are involved in the patients’ FU care for BC. The detection of long-term problems due to BC treatment is an essential part of FU care.
Journal Article
Cardiac health in breast cancer (CHiB): protocol for a single-centre, randomised controlled trial
2024
The incidence of breast cancer has increased from 900 000 to 2.3 million new annual cases over the last 25 years. The 5-year survival rate has markedly risen to over 90% worldwide due to significant therapeutic advancements. Longer survival in patients with breast cancer means more patients may experience long-term effects of their treatments, including cancer therapy-related cardiac dysfunction (CTRCD). To date, there is no established primary prevention to minimise CTRCD. The Cardiac Health in Breast Cancer study is a two-arm, single-centre, randomised controlled trial investigating the impact of an exercise programme on cardiac changes in patients with breast cancer undergoing cardiotoxic cancer therapy. 48 females with breast cancer will be randomised to either a 12-month intervention group (IG) or a control group (CG). The IG will receive a combination of supervised high-intensity interval training (HIIT) and high-intensity resistance training (HIRT) for 6 months, while the CG will follow WHO guidelines for physical activity independently. All participants will undergo transthoracic echocardiography, cardiac magnetic resonance (CMR) imaging and cardiopulmonary exercise testing at baseline, after 6 months and after 12 months. The primary endpoint is the occurrence of symptomatic or asymptomatic CTRCD at the time points of examination, detected by cardiac imaging, which may be mitigated by structured physical exercise. Secondary endpoints include assessments of cardiac inflammation as detected by CMR, mitochondrial dysfunction, health-related quality of life, the occurrence of fatigue, depression and anxiety, as well as exercise capacity, average heart rate, heart rate variability and daily physical activity.
Journal Article
Evaluating ChatGPT as an adjunct for the multidisciplinary tumor board decision-making in primary breast cancer cases
by
Lukac, Stefan
,
Rack, Brigitte
,
Heitmeir, Benedikt
in
Breast cancer
,
Cancer therapies
,
Chatbots
2023
BackgroundAs the available information about breast cancer is growing every day, the decision-making process for the therapy is getting more complex. ChatGPT as a transformer-based language model possesses the ability to write scientific articles and pass medical exams. But is it able to support the multidisciplinary tumor board (MDT) in the planning of the therapy of patients with breast cancer?Material and MethodsWe performed a pilot study on 10 consecutive cases of breast cancer patients discussed in MDT at our department in January 2023. Included were patients with a primary diagnosis of early breast cancer. The recommendation of MDT was compared with the recommendation of the ChatGPT for particular patients and the clinical score of the agreement was calculated.ResultsResults showed that ChatGPT provided mostly general answers regarding chemotherapy, breast surgery, radiation therapy, chemotherapy, and antibody therapy. It was able to identify risk factors for hereditary breast cancer and point out the elderly patient indicated for chemotherapy to evaluate the cost/benefit effect. ChatGPT wrongly identified the patient with Her2 1 + and 2 + (FISH negative) as in need of therapy with an antibody and called endocrine therapy “hormonal treatment”.ConclusionsSupport of artificial intelligence by finding individualized and personalized therapy for our patients in the time of rapidly expanding amount of information is looking for the ways in the clinical routine. ChatGPT has the potential to find its spot in clinical medicine, but the current version is not able to provide specific recommendations for the therapy of patients with primary breast cancer.
Journal Article
Supporting SURgery with GEriatric Co-Management and AI (SURGE-Ahead): A study protocol for the development of a digital geriatrician
by
Zengerling, Friedemann
,
Swoboda, Walter
,
Leinert, Christoph
in
Activities of daily living
,
Adults
,
Artificial intelligence
2023
Geriatric co-management is known to improve treatment of older adults in various clinical settings, however, widespread application of the concept is limited due to restricted resources. Digitalization may offer options to overcome these shortages by providing structured, relevant information and decision support tools for medical professionals. We present the SURGE-Ahead project (Supporting SURgery with GEriatric co-management and Artificial Intelligence) addressing this challenge.
A digital application with a dashboard-style user interface will be developed, displaying 1) evidence-based recommendations for geriatric co-management and 2) artificial intelligence-enhanced suggestions for continuity of care (COC) decisions. The development and implementation of the SURGE-Ahead application (SAA) will follow the Medical research council framework for complex medical interventions. In the development phase a minimum geriatric data set (MGDS) will be defined that combines parametrized information from the hospital information system with a concise assessment battery and sensor data. Two literature reviews will be conducted to create an evidence base for co-management and COC suggestions that will be used to display guideline-compliant recommendations. Principles of machine learning will be used for further data processing and COC proposals for the postoperative course. In an observational and AI-development study, data will be collected in three surgical departments of a University Hospital (trauma surgery, general and visceral surgery, urology) for AI-training, feasibility testing of the MGDS and identification of co-management needs. Usability will be tested in a workshop with potential users. During a subsequent project phase, the SAA will be tested and evaluated in clinical routine, allowing its further improvement through an iterative process.
The outline offers insights into a novel and comprehensive project that combines geriatric co-management with digital support tools to improve inpatient surgical care and continuity of care of older adults.
German clinical trials registry (Deutsches Register für klinische Studien, DRKS00030684), registered on 21st November 2022.
Journal Article