Return of individual genomic research results within the PRAEGNANT multicenter registry study.

PURPOSE: The PRAEGNANT study is a registry study for metastatic breast cancer patients, focusing on biomarker detection. Recently, within this study, genetic alterations in 37 breast cancer predisposition genes were analyzed and genetic findings were detected for 396 participants. The aim of this project was to return genetic results to the physicians and to analyze actions taken (e.g., disclosure of results to patients, validation of results, clinical impact, and impact on the patient's quality of life) using a questionnaire. METHODS: 235 questionnaires were sent out to the study centers, with each questionnaire representing one patient with a genetic finding. The questionnaire consisted of twelve questions in the German language, referring to the disclosure of results, validation of test results, and their impact on treatment decisions and on the patient's quality of life. RESULTS: 135 (57.5%) questionnaires were completed. Of these, 46 (34.1%) stated that results were returned to the patients. In 80.0% (N = 36) of cases where results were returned, the patient had not been aware of the finding previously. For 27 patients (64.3%), genetic findings had not been validated beforehand. All validation procedures (N = 15) were covered by the patients' health insurance. For 11 (25.0%) patients, physicians reported that the research results influenced current or future decision-making on treatment, and for 37.8% (N = 17) the results influenced whether family members will be genetically tested. CONCLUSION: This study provides novel insights into the return of research results and into clinical and personal benefits of disclosure of genetic findings within a German registry.

Can TSH level and premenstrual spotting constitute a non-invasive marker for the diagnosis of endometriosis?

BACKGROUND: To date, there is no reliable non-invasive marker for the early detection and diagnosis of endometriosis available possibly resulting in a delayed diagnosis and consequently an unnecessary long ordeal for the individual woman. Therefore, the primary objective of the current study was to evaluate whether the combination of a thyroid-stimulating hormone (TSH) level > 2.5 µlU/ml and premenstrual spotting could serve as non-invasive markers of endometriosis. A secondary objective was to determine whether typical symptoms of endometriosis like dysmenorrhea and/or dyspareunia could increase the diagnostic reliability. METHODS: We conducted a retrospective, case-control study with 167 female patients at the Department of OB/GYN and REI (UniKiD) of the medical center of the University of Düsseldorf, between January 2015 and December 2016. 107 women with surgically confirmed endometriosis were compared to 60 without endometriosis (controls). To evaluate the diagnostic accuracy, we considered sensitivity, specificity and predictive values. In order to assess the association between the non-invasive markers and endometriosis an odds ratio (OR) with a 95% confidence interval was calculated. RESULTS: In our cohort, diagnosis of endometriosis with non-invasive markers according to their sensitivity yielded the following ranking: increased TSH level, premenstrual spotting, combination of both previous parameters, addition of dysmenorrhea, addition of dyspareunia and combination of all parameters. CONCLUSION: The existence of endometriosis should be taken into consideration when a patient suffers from thyroid dysfunction and premenstrual spotting. Apart from an increased TSH level, the presence of premenstrual spotting underlines the possible diagnosis of endometriosis with non-invasive markers and therefore, the patient´s history needs to be taken into account carefully. Trial registration The retrospective study was approved by the Ethics Committee of the medical faculty of the Heinrich-Heine University, Düsseldorf, Germany, Registration number Düsseldorf: 5371R (approved: April 04th, 2016). Since the design of the study was retrospective no written informed consent was necessary.

Gemcitabine as adjuvant chemotherapy in patients with high-risk early breast cancer-results from the randomized phase III SUCCESS-A trial.

BACKGROUND: When chemotherapy is indicated in patients with early breast cancer, regimens that contain anthracyclines and taxanes are established standard treatments. Gemcitabine has shown promising effects on the response and prognosis in patients with metastatic breast cancer. The SUCCESS-A trial (NCT02181101) examined the addition of gemcitabine to a standard chemotherapy regimen in high-risk early breast cancer patients. METHODS: A total of 3754 patients with at least one of the following characteristics were randomly assigned to one of the two treatment arms: nodal positivity, tumor grade 3, age ≤ 35 years, tumor larger than 2 cm, or negative hormone receptor status. The treatment arms received either three cycles of 5-fluorouracil, epirubicin, and cyclophosphamide, followed by three cycles of docetaxel (FEC → Doc); or three cycles of FEC followed by three cycles of docetaxel and gemcitabine (FEC → Doc/Gem). The primary study aim was disease-free survival (DFS), and the main secondary objectives were overall survival (OS) and safety. RESULTS: No differences were observed in the 5-year DFS or OS between FEC → Doc and FEC → Doc/Gem. The hazard ratio was 0.93 (95% CI, 0.78 to 1.12; P = 0.47) for DFS and 0.94 (95% CI, 0.74 to 1.19; P = 0.60) for OS. For patients treated with FEC → Doc and FEC → Doc/Gem, the 5-year probabilities of DFS were 86.6% and 87.2%, and the 5-year probabilities of OS were 92.8% and 92.5%, respectively. CONCLUSION: Adding gemcitabine to a standard chemotherapy does not improve the outcomes in patients with high-risk early breast cancer and should therefore not be included in the adjuvant treatment setting. TRIAL REGISTRATION: Clinicaltrials.gov NCT02181101 and EU Clinical Trials Register EudraCT 2005-000490-21. Registered September 2005.

Heregulin (HRG) assessment for clinical trial eligibility testing in a molecular registry (PRAEGNANT) in Germany.

BACKGROUND: Eligibility criteria are a critical part of clinical trials, as they define the patient population under investigation. Besides certain patient characteristics, clinical trials often include biomarker testing for eligibility. However, patient-identification mostly relies on the trial site itself and is often a time-consuming procedure, which could result in missing out on potentially eligible patients. Pre-selection of those patients using a registry could facilitate the process of eligibility testing and increase the number of identified patients. One aim with the PRAEGNANT registry (NCT02338167) is to identify patients for therapies based on clinical and molecular data. Here, we report eligibility testing for the SHERBOC trial using the German PRAEGNANT registry. METHODS: Heregulin (HRG) has been reported to identify patients with better responses to therapy with the anti-HER3 monoclonal antibody seribantumab (MM-121). The SHERBOC trial investigated adding seribantumab (MM-121) to standard therapy in patients with advanced HER2-negative, hormone receptor-positive (HR-positive) breast cancer and HRG overexpression. The PRAEGNANT registry was used for identification and tumor testing, helping to link potential HRG positive patients to the trial. Patients enrolled in PRAEGNANT have invasive and metastatic or locally advanced, inoperable breast cancer. Patients eligible for SHERBOC were identified by using the registry. Study aims were to describe the HRG positivity rate, screening procedures, and patient characteristics associated with inclusion and exclusion criteria. RESULTS: Among 2769 unselected advanced breast cancer patients, 650 were HER2-negative, HR-positive and currently receiving first- or second-line treatment, thus potentially eligible for SHERBOC at the end of current treatment; 125 patients also met further clinical eligibility criteria (e.g. menopausal status, ECOG). In the first/second treatment lines, patients selected for SHERBOC based on further eligibility criteria had a more favorable prognosis than those not selected. HRG status was tested in 38 patients, 14 of whom (36.8%) proved to be HRG-positive. CONCLUSION: Using a real-world breast cancer registry allowed identification of potentially eligible patients for SHERBOC focusing on patients with HER3 overexpressing, HR-positive, HER2-negative metastatic breast cancer. This approach may provide insights into differences between patients eligible or non-eligible for clinical trials. TRIAL REGISTRATION: Clinicaltrials, NCT02338167 , Registered 14 January 2015 - retrospectively registered.

Are uterine natural killer and plasma cells in infertility patients associated with endometriosis, repeated implantation failure, or recurrent pregnancy loss?

PURPOSE: Infertility is a debilitating situation that millions of women around the world suffer from, but the causal relationship between infertility and endometriosis is still unclear. We hypothesize that the immune cell populations of uterine natural killer cells (uNK) and plasma cells (PC) which define chronic endometritis could differ in patients with or without endometriosis and therefore be the link to endometriosis-associated infertility. METHODS: Our retrospective study includes 173 patients that underwent an endometrial scratching in the secretory phase of the menstrual cycle and subsequently immunohistochemical examination for uNK cells and PC. Sixty-seven patients were diagnosed with endometriosis, 106 served as the control cohort. RESULTS: The risk for an elevated number of uNK cells in women with endometriosis is not increased as compared to the control group. Our findings suggest that patients with endometriosis are 1.3 times more likely to have chronic endometritis (CE) as compared to those without and that the treatment with doxycycline might increase pregnancy rates. Endometriosis and an increased number of uNK cells seem to be unrelated. CONCLUSIONS: In contrast to the lately published connection between endometriosis, infertility and increased uNK cells, we could not find any evidence that patients with endometriosis are more prone to elevated uterine uNK cells. Counting of PC in endometrial biopsies might be a new approach in the search of biomarkers for the nonsurgical diagnosis of endometriosis since our findings suggest a connection.

Efficacy of neoadjuvant pertuzumab in addition to chemotherapy and trastuzumab in routine clinical treatment of patients with primary breast cancer: a multicentric analysis.

PURPOSE: Neoadjuvant combination treatment with chemotherapy (CTX), trastuzumab (TZM), and pertuzumab (PTZ) has been shown to result in higher pathological complete response rates (pCR) in comparison with treatment with chemotherapy and trastuzumab (CTX/TZM). This analysis was aimed at real-world validation of these results from prospective randomized trials. METHODS: In a retrospective analysis conducted in the PRAEGNANT network, patients were eligible for inclusion if they had either received neoadjuvant therapy with CTX/TZM or chemotherapy, trastuzumab, and pertuzumab (CTX/TZM/PTZ) and subsequently underwent surgery for their primary breast cancer. The effect of the two neoadjuvant regimens on pCR in addition to commonly applicable predictors of pCR was analyzed in 300 patients from three study sites, using logistic regression analyses with treatment arm, age, clinical tumor stage, grading, and hormone receptor status as predictors. RESULTS: pCR with complete disappearance of all tumor cells was seen in 30.2% (n = 58) of patients treated with CTX/TZM and in 52.8% (n = 57) of those treated with CTX/TZM/PTZ. CTX/TZM/PTZ was positively associated with pCR (adjusted odds ratio 2.44; 95% CI 1.49-4.02). Mastectomy rates were not influenced by the therapy. CONCLUSIONS: The results of clinical trials were confirmed in this dataset of patients who were treated outside of clinical trials in everyday routine work. pCR rates can be improved by 20% with pertuzumab in routine clinical use.

Translational highlights in breast cancer research and treatment: recent developments with clinical impact.

PURPOSE OF REVIEW: Over the last decades the time which is needed to translate a preclinical finding or idea in the clinic has reduced continuously. Especially but not only for breast cancer the number of tested drugs and targeted pathways have increased immensely. In addition, the introduction of immune-oncological treatments has further advanced the possibilities for future treatments. This review focuses on recent developments in the prevention and treatment of breast cancer including results from major clinical trials and recent conferences. RECENT FINDINGS: Many pathways involved in the progression or treatment of breast cancer have been also identified in the cause and pathogenesis of breast cancer. Therefore, breast cancer risk can be described in much more detail, possibly leading to new prevention strategies. In breast cancer treatment the introduction of PARP inhibitors has begun. Recent trials will lead to a better understanding whether PI3K inhibitors can be developed for application in the clinic and first large randomized trials show the superiority of anti PD-1/PD-L1 treatments. SUMMARY: Treatment strategies which were developed over the last decade are moving rapidly into the clinical use. The understanding of treatment targets and involved side effects will be important for the safe implementation of these treatments into routine practice.

Diagnostic leukapheresis for CTC analysis in breast cancer patients: CTC frequency, clinical experiences and recommendations for standardized reporting.

Diagnostic leukapheresis (DLA) is based on continuous centrifugation that collects mononuclear cells from peripheral blood with a density of 1.055-1.08 g/ml. As epithelial cells have a similar density, DLA cocollects circulating tumor cell (CTCs) along with the targeted mononuclear cells. Here, we report on our single center experience applying DLA in 40 nonmetastatic and metastatic breast cancer patients and its impact on CTC detection. We found that the use of just 5% of the DLA product (corresponding to a median peripheral blood volume of around 60 ml) in the CellSearch® assay already leads to a significant increase in CTC detection frequency and yield. The implementation of the method was unproblematic, and we did not observe any adverse events in our patient cohort. Extrapolating the CTC counts in the DLA samples to the whole DLA product indicated that enormous CTC numbers could be harvested by this approach (around 205x more CTCs than in the 7.5 ml blood sample in M1 patients). In conclusion, DLA is a clinically safe method to collect CTCs from liters of blood enabling a real liquid biopsy. Yet, further technical developments are required to process whole DLA products and exploit the full potential of this approach. As it is foreseeable that DLA will be used by several groups, and hopefully ultimately brought to the patients in a routine setting, we discuss recommendations on the minimum of required information for reporting on DLAs to allow comparison across different approaches. © 2018 International Society for Advancement of Cytometry.

Filtration based assessment of CTCs and CellSearch® based assessment are both powerful predictors of prognosis for metastatic breast cancer patients.

BACKGROUND: The assessment of circulating tumor cells (CTCs) has been shown to enable monitoring of treatment response and early detection of metastatic breast cancer (MBC) recurrence. The aim of this study was to compare a well-established CTC detection method based on immunomagnetic isolation with a new, filtration-based platform. METHODS: In this prospective study, two 7.5 ml blood draws were obtained from 60 MBC patients and CTC enumeration was assessed using both the CellSearch® and the newly developed filtration-based platform. We analyzed the correlation of CTC-positivity between both methods and their ability to predict prognosis. Overall survival (OS) was calculated and Kaplan-Meier curves were estimated with thresholds of ≥1 and ≥5 detected CTCs. RESULTS: The CTC positivity rate of the CellSearch® system was 56.7% and of the filtration-based platform 66.7%. There was a high correlation of CTC enumeration obtained with both methods. The OS for patients without detected CTCs, regardless of the method used, was significantly higher compared to patients with one or more CTCs (p < 0.001). The median OS of patients with no CTCs vs. ≥ 1 CTC assessed by CellSearch® was 1.83 years (95% CI: 1.63-2.02) vs. 0.74 years (95% CI: 0.51-1.52). If CTCs were detected by the filtration-based method the median OS times were 1.88 years (95% CI: 1.74-2.03) vs. 0.59 years (95% CI: 0.38-0.80). CONCLUSIONS: The newly established EpCAM independently filtration-based system is a suitable method to determine CTC counts for MBC patients. Our study confirms CTCs as being strong predictors of prognosis in our population of MBC patients.

Computerized patient identification for the EMBRACA clinical trial using real-time data from the PRAEGNANT network for metastatic breast cancer patients.

As breast cancer is a diverse disease, clinical trials are becoming increasingly diversified and are consequently being conducted in very small subgroups of patients, making study recruitment increasingly difficult. The aim of this study was to assess the use of data from a remote data entry system that serves a large national registry for metastatic breast cancer. The PRAEGNANT network is a real-time registry with an integrated biomaterials bank that was designed as a scientific study and as a means of identifying patients who are eligible for clinical trials, based on clinical and molecular information. Here, we report on the automated use of the clinical data documented to identify patients for a clinical trial (EMBRACA) for patients with metastatic breast cancer. The patients' charts were assessed by two independent physicians involved in the clinical trial and also by a computer program that tested patients for eligibility using a structured query language script. In all, 326 patients from two study sites in the PRAEGNANT network were included in the analysis. Using expert assessment, 120 of the 326 patients (37 %) appeared to be eligible for inclusion in the EMBRACA study; with the computer algorithm assessment, a total of 129 appeared to be eligible. The sensitivity of the computer algorithm was 0.87 and its specificity was 0.88. Using computer-based identification of patients for clinical trials appears feasible. With the instrument's high specificity, its application in a large cohort of patients appears to be feasible, and the workload for reassessing the patients is limited.

Tumor cell dissemination to the bone marrow and blood is associated with poor outcome in patients with metastatic breast cancer.

The purpose of this study was to assess the impact of disseminated tumor cells (DTCs) on progression-free and overall survival (OS) in patients with metastatic breast cancer (MBC) and to compare it to simultaneous detection of circulating tumor cells (CTCs) from the blood in a subgroup. Disseminated tumor cells were identified in bone marrow (BM) aspirates by immunocytochemistry (pancytokeratin antibody A45-B/B3) and cytomorphology prior to the beginning of a new-line therapy. CTCs were enumerated by the CellSearch® technology. BM was obtained from 178 patients with MBC; 64/178 (36 %) patients were DTC-positive. Disseminated tumor cells occurred more frequently in patients with visceral metastases (p = 0.020) and ≥2 lines of therapy (p = 0.017). CTCs were assessed in 33 of these patients and 17/33 (52 %) patients had CTC counts ≥5 CTCs/7.5 ml blood. There was no significant association between the DTC and CTC status. Univariate analysis revealed DTC detection as a significant predictor of poor OS (p < 0.001); median OS in DTC-negative versus DTC-positive patients was 52 [95 % confidence interval (CI) 38-67] versus 28 [95 % CI 19-37] months. Moreover, as described previously, patients with ≥5 CTCs/7.5 ml blood were at an increased risk of disease progression (p = 0.026) and death (p = 0.025). Disseminated tumor cells are predictors of poor prognosis in MBC, highlighting the role of tumor cell dissemination into the BM for breast cancer progression. The absence of a significant association between concurrent DTCs and CTCs suggests they might represent different aspects of systemic BC spread.

Update Breast Cancer 2024 Part 1 - Expert Opinion on Advanced Breast Cancer.

Clinical evidence is interpreted based on clinical studies and personal experience which can lead to different interpretations of data. This makes the opinions issued by panels of experts such as the Advanced Breast Cancer Panel which convened in November 2023 for the seventh time (ABC7) particularly important. At the conference, current issues around advanced breast cancer were evaluated by an international team of experts. In 2023 the data on CDK4/6 inhibitors was so extensive that the answers to questions about the sequencing of therapy and the potential use of chemotherapy as an alternative therapy were relatively clear. Moreover, data on antibody drug conjugates which provides a good overview of their uses is available for all molecular subtypes. Some therapeutic settings, including patients with brain metastases or leptomeningeal disease, older patients, locally advanced breast cancer and visceral crises, continue to be particularly important and were discussed in structured sessions. The scientific context of some of the topics discussed at ABC7 is presented and assessed here.

Correction: Long-term Follow-up and Safety of Patients after an Upfront Therapy with Letrozole for Early Breast Cancer in Routine Clinical Care - The PreFace Study.

[This corrects the article DOI: 10.1055/a-2238-3153.].

Long-term Follow-up and Safety of Patients after an Upfront Therapy with Letrozole for Early Breast Cancer in Routine Clinical Care - The PreFace Study.

Introduction: Adjuvant treatment of patients with early-stage breast cancer (BC) should include an aromatase inhibitor (AI). Especially patients with a high recurrence risk might benefit from an upfront therapy with an AI for a minimum of five years. Nevertheless, not much is known about the patient selection for this population in clinical practice. Therefore, this study analyzed the prognosis and patient characteristics of postmenopausal patients selected for a five-year upfront letrozole therapy. Patients and Methods: From 2009 to 2011, 3529 patients were enrolled into the adjuvant phase IV PreFace clinical trial (NCT01908556). Postmenopausal hormone receptor-positive BC patients, for whom an upfront five-year therapy with letrozole (2.5 mg/day) was indicated, were eligible. Disease-free survival (DFS), overall survival (OS) and safety in relation to patient and tumor characteristics were assessed. Results: 3297 patients started letrozole therapy. The majority of patients (n = 1639, 57%) completed the five-year treatment. 34.5% of patients continued with endocrine therapy after the mandated five-year endocrine treatment. Five-year DFS rates were 89% (95% CI: 88-90%) and five-year OS rates were 95% (95% CI: 94-96%). In subgroup analyses, DFS rates were 83%, 84% and 78% for patients with node-positive disease, G3 tumor grading, and pT3 tumors respectively. The main adverse events (any grade) were pain and hot flushes (66.8% and 18.3% of patients). Conclusions: The risk profile of postmenopausal BC patients selected for a five-year upfront letrozole therapy showed a moderate recurrence and death risk. However, in subgroups with unfavorable risk factors, prognosis warrants an improvement, which might be achieved with novel targeted therapies.

Attrition in the First Three Therapy Lines in Patients with Advanced Breast Cancer in the German Real-World PRAEGNANT Registry.

Background With more effective therapies for patients with advanced breast cancer (aBC), therapy sequences are becoming increasingly important. However, some patients might drop out of the treatment sequence due to deterioration of their life status. Since little is known about attrition in the real-world setting, this study assessed attrition in the first three therapy lines using a real-world registry. Methods Patients with information available on the first three therapy lines were selected from the German PRAEGNANT registry (NCT02338167). Attrition was determined for each therapy line using competing risk analyses, with the start of the next therapy line or death as endpoints. Additionally, a simple attrition rate was calculated based on the proportion of patients who completed therapy but did not start the next therapy line. Results Competitive risk analyses were performed on 3988 1st line, 2651 2nd line and 1866 3rd line patients. The probabilities of not starting the next therapy line within 5 years after initiation of 1st, 2nd and 3rd line therapy were 30%, 24% and 24% respectively. Patients with HER2-positive disease had the highest risk for attrition, while patients with HRpos/HER2neg disease had the lowest risk. Attrition rates remained similar across molecular subgroups in the different therapy lines. Conclusion Attrition affects a large proportion of patients with aBC, which should be considered when planning novel therapy concepts that specifically address the sequencing of therapies. Taking attrition into account could help understand treatment effects resulting from sequential therapies and might help develop treatment strategies that specifically aim at maintaining quality of life.

CDK4/6 Inhibition - Therapy Sequences and the Quest to Find the Best Biomarkers - an Overview of Current Programs.

In recent years, new targeted therapies have been developed to treat patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer. Some of these therapies have not just become the new therapy standard but also led to significantly longer overall survival rates. The cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) have become the therapeutic standard for first-line therapy. Around 70 - 80% of patients are treated with a CDK4/6i. In recent years, a number of biomarkers associated with progression, clonal selection or evolution have been reported for CDK4/6i and their endocrine combination partners. Understanding the mechanisms behind treatment efficacy and resistance is important. A better understanding could contribute to planning the most effective therapeutic sequences and utilizing basic molecular information to overcome endocrine resistance. One study with large numbers of patients which aims to elucidate these mechanisms is the Comprehensive Analysis of sPatial, TempORal and molecular patterns of ribociclib efficacy and resistance in advanced Breast Cancer patients (CAPTOR BC) trial. This overview summarizes the latest clinical research on resistance to endocrine therapies, focusing on CDK4/6 inhibitors and discussing current study concepts.

Systemic Therapy of Premenopausal Patients with Early Stage Hormone Receptor-Positive, HER2-Negative Breast Cancer - Controversies and Standards in Healthcare.

In patients with existing ovarian function, there are some special aspects to adjuvant endocrine therapy in premenopausal patients with hormone receptor-positive, HER2-negative (HR pos./HER2 neg.) breast cancer. Treatment options include tamoxifen with or without a GnRH analog, and aromatase inhibitors with a GnRH analog. Furthermore, ovarian function is affected by previous chemotherapy. Both aromatase inhibitors (+GnRH analogs) and GnRH analogs in combination with tamoxifen are supposed to be indicated for patients at increased risk of recurrence. However, national and international guidelines and therapy recommendations do not provide a clear definition of intermediate or high risk; as a result, therapy decisions are often made for each patient on an individual basis. This is also reflected in the considerable variability at national and international levels, e.g., with regard to the use of aromatase inhibitors + GnRH analogs. This review summarizes the data on completed studies (e.g., SOFT, TEXT, EBCTCG meta-analyses) and the current multigene testing studies (TailorX, RxPonder, ADAPT), discusses the rationale for current studies (e.g., CLEAR-B), and looks ahead to future questions.

Pembrolizumab in combination with nab-paclitaxel for the treatment of patients with early-stage triple-negative breast cancer - A single-arm phase II trial (NeoImmunoboost, AGO-B-041).

BACKGROUND: Pembrolizumab is approved for the neoadjuvant/adjuvant treatment of early triple-negative breast cancer (TNBC) patients in combination with chemotherapy. The Keynote-522 trial used platinum chemotherapy. As neoadjuvant nab-paclitaxel (nP) is also highly effective in triple-negative breast cancer patients, this study investigates the response to nP-containing neoadjuvant chemotherapy in combination with pembrolizumab. PATIENTS AND METHODS: NeoImmunoboost (AGO-B-041/NCT03289819) is a multicenter, prospective single-arm phase II trial. Patients were treated with 12 weekly cycles of nP followed by four three-weekly cycles of epirubicin/cyclophosphamide. Pembrolizumab was given three-weekly in combination with these chemotherapies. The study was planned for 50 patients. After 25 patients, the study was amended to include a pre-chemotherapy single application of pembrolizumab. The primary aim was pathological complete response (pCR), and the secondary aims were safety and quality of life. RESULTS: Of 50 included patients, 33 (66.0%; 95%confidence interval: 51.2%-78.8%) had a (ypT0/is ypN0) pCR. The pCR rate in the per-protocol population (n = 39) was 71.8% (95%confidence interval: 55.1%-85.0%). The most common adverse events of any grade were fatigue (58.5%), peripheral sensory neuropathy (54.7%) and neutropenia (52.8%). The pCR rate in the cohort of 27 patients with a pre-chemotherapy pembrolizumab dose was 59.3%, and 73.9% in the 23 patients without pre-chemotherapy dose. CONCLUSIONS: pCR rates after NACT with nP and anthracycline combined with pembrolizumab are encouraging. With acceptable side-effect profiles, this treatment might be a reasonable alternative to platinum-containing chemotherapy in cases of contraindications. However, without data from randomised trials and long-term follow up, platinum/anthracycline/taxane-based chemotherapy remains the standard combination chemotherapy for pembrolizumab.

Update Breast Cancer 2022 Part 5 - Early Stage Breast Cancer.

The treatment of patients with early stage breast cancer has changed in recent years due to the introduction of pembrolizumab, olaparib, and abemaciclib. These and other drugs with the same class of active ingredient are currently in trial for various indications. This review article summarizes the latest results that have either been presented at major conferences such as the ESMO 2022 or published recently in international journals. This includes reports on newly discovered breast cancer genes, atezolizumab in neoadjuvant therapy in HER2-positive patients, long-term data from the APHINITY study, and on how preoperative peritumoral application of local anesthetics can influence the prognosis. We also present solid data on dynamic Ki-67 from the ADAPT studies.

Update Breast Cancer 2022 Part 6 - Advanced-Stage Breast Cancer.

Large-scale study programs on CDK4/6 inhibitors, targeted therapies, and antibody-drug conjugates launched in recent years have yielded results from current studies which are now being published in journals and presented at international conferences. In this context, new results are available from the major CDK4/6 inhibitor studies. Also, an increasing amount of data is being published from large-scale genomic studies on efficacy and resistance mechanisms in patients treated with CDK4/6 inhibitors. These results now form the basis for further research plans to investigate combination therapies and treatment sequencing. Based on the latest published results, sacituzumab govitecan is now available as a second antibody-drug conjugate; this brings an advantage in terms of overall survival for patients with hormone receptor-positive (HRpos)/HER2-negative (HER2neg) breast cancer. In this review article, we summarize the latest developments and place them in context according to the current status of research.