Changes in gynecologic and breast cancer diagnoses during the first wave of the COVID-19 pandemic: analysis from a tertiary academic gyneco-oncological center in Germany.

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.

Increased risk for thromboembolic events from combination of a gynecologic malignancy with severe acute respiratory syndrome coronavirus 2 infection: a case report.

PURPOSE: During the severe acute respiratory syndrome coronavirus 2 pandemic, several patient groups are at particular risk. Mortality is higher among cancer patients and may be increased further by thromboembolic events, which are more common in coronavirus 2019 patients according to recent publications. We discuss the association of gynecologic malignancies, Severe acute respiratory syndrome coronavirus 2, and thromboembolism by reporting a case study and summarizing available literature. CASE REPORT: A 71-year-old Caucasian patient with ovarian cancer receiving first-line chemotherapy was diagnosed with deep vein thrombosis and pulmonary embolism. Routine screening revealed infection with severe acute respiratory syndrome coronavirus 2 in absence of specific symptoms. After uneventful recovery, oncologic treatment could be continued a few weeks later. METHODS: We performed a systematic review of the literature on PubMed following Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. The search included articles ahead of print, published between 1 December 2019 and 1 June 2020. Cross-searches were conducted on all relevant articles. RESULTS: We identified five articles meeting the defined criteria, including two retrospective studies, a review, a position paper, as well as a letter to the editor. CONCLUSION: Cancer patients infected with severe acute respiratory syndrome coronavirus 2 have a relatively poor outcome, which may partially be due to a higher rate of thromboembolic events. Thromboprophylaxis is recommended, and scoring systems are helpful in early detection. In cancer patients with severe acute respiratory syndrome coronavirus 2, individual risk for thromboembolic events should be taken into account when considering interruption versus continuation of antitumoral therapy. However, further data and studies are required.

Molecular Prognostic Factors for Distant Metastases in Premenopausal Patients with HR+/HER2- Early Breast Cancer.

Molecular factors that drive metastasis in premenopausal patients with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-), early breast cancer (EBC) are largely unknown. To identify markers/signatures contributing to metastasis, we analyzed molecular changes in tumors from premenopausal patients who developed metastasis (M1) and who did not (M0). Ninety-seven premenopausal patients with HR+/HER2- EBC were included (M1, n = 48, median distant metastasis-free survival (DMFS): 54 (7-184) months; M0, n = 49, median follow-up: 149 (121-191) months). Gene expression profiling on tumor RNA (Breast Cancer 360TM panel, Nanostring) was performed, followed by comprehensive bioinformatic and statistical analyses. Significantly enhanced ROR (risk of recurrence) scores and reduced signature scores of PGR (progesterone receptor), claudin-low, and mammary stemness were determined in M1. These differences were significantly associated with shorter DMFS in univariate survival analyses. Gene set enrichment analysis showed an enriched mTORC1 pathway in M1. Moreover, a metastasis signature of 19 differentially expressed genes (DEGs) that were DMFS-related was defined. Multivariate analysis including the four signatures, 19 DEGs, pN, and pT status, identified LRP2, IBSP, and SCUBE2 as independent prognostic factors. We identified prognostic gene signatures and single-gene markers for distant metastasis in premenopausal HR+/HER2- EBC potentially applicable in future clinical practice.

Updated Survival Analysis after a Median Follow-up of 12 Years of an Anthracycline-Containing Adjuvant Prospective Multicentre, Randomised Phase III Trial on Dose-Dense Chemotherapy in Primary Node-Positive, High-Risk Breast Cancer Patients.

PURPOSE: Although dose-dense (dd) chemotherapy plays a fundamental role in the treatment of breast cancer (BC), a variety of trials have presented divergent survival results. Here, we present data of patients with more than 3 positive axillary lymph nodes (+aLN) receiving dd chemotherapy after a median follow-up period of 12.3 years. METHODS: In the years 1996-2000, 231 patients with invasive BC, ≥pN2a and no evidence of distant metastases were recruited to receive treatment A, i.e. dd 3 × epirubicin (E, 90 mg/m2) + paclitaxel (P, 175 mg/m2) every 2 weeks (q2w) followed by 3 × cyclophosphamide (C)/methotrexate/5-fluorouracil (CMF, 600/40/600 mg/m2, q2w), or treatment B, i.e. 4 × E + C (C, 600 mg/m2) q3w followed by 3 × CMF q3w. RESULTS: 113 patients in arm A and 113 patients in arm B were analysed after an updated median follow-up of 12.3 years. The median age was 55 years, with a median number of 6 +aLN, 50.4% had a T2 and 79.2% hormone receptor-positive BC. The disease-free survival (DFS) rate was 53.1% in arm A and 42.5% in arm B (adjusted p = 0.027). The overall survival (OS) rate was 54.9% in arm A and 48.7% in arm B (adjusted p = 0.058). In the multivariable analysis, the tumour burden was a significant predictor for DFS and OS. CONCLUSION: The adjuvant use of dd chemotherapy led to a statistically significant improvement of DFS after a follow-up of 12.3 years.

Autologous Lipotransfer - Daily Therapeutic Practice in Breast Cancer: An Intergroup Analysis Encompassing NOGGO, WSG, GBG, AWO Gyn and DGPRÄC.

BACKGROUND: Autologous fat transfer in breast reconstruction has become increasingly important in breast reconstructive surgery. Although the indication to obtain fat, the various operative procedures, and the risks for the patient have been addressed in a large number of studies, detailed information on the everyday use of autologous lipotransfer in breast units in Germany is still lacking. METHODS: The objective of the study was to obtain primary data on the use of autologous lipotransfer to treat breast cancer patients in Germany and to determine measures for quality assurance in the daily practice. An online questionnaire concerning breast cancer and lipofilling was sent to specialists in gynecology and plastic surgery. RESULTS: Two-thirds of the specialists who responded to the questionnaire use autologous lipotransfer for breast reconstruction and did not report an increase of local recurrence following lipotransfer. There were only small differences between gynecologists and plastic surgeons regarding the procedure and indication for lipotransfer. The method is highly accepted by patients and physicians, and both gynecologists and plastic surgeons rated the improvement achieved through lipofilling as 'high'. CONCLUSIONS: The lack of randomized controlled data, especially in high-risk patients, demonstrates the necessity for a registry study on this topic. Our survey describes, in detail, the indications for lipofilling as well as its appropriate application in breast cancer patients in Germany and may thereby reduce the present therapeutic uncertainties.

Treatment of Early Breast Cancer Patients: Evidence, Controversies, Consensus: Focusing on Systemic Therapy - German Experts' Opinions for the 16th International St. Gallen Consensus Conference (Vienna 2019).

A German working group of leading breast cancer experts have discussed the votes at the International St. Gallen Consensus Conference in Vienna for the treatment of primary breast cancer with regard to the German AGO (Ar-beitsgemeinschaft Gynäkologische Onkologie) recommendations for clinical practice in Germany. Three of the German breast cancer experts were also members of this year's St. Gallen panel. Comparing the St. Gallen recommendations with the annually updated treatment recommendations of the Gynecological Oncology Working Group (AGO Mamma 2019) and the German S3 Guideline is useful, because the recommendations of the St. Gallen panel are based on expert opinions of different countries and disciplines. The focus of this article is on systemic therapy. The motto of this year's 16th St. Gallen Consensus Conference was "Estimating the magnitude of clinical benefit." The rationale behind this motto is that, for every treatment decision, a benefit-risk assessment must be taken into consideration for each patient.

Primary Therapy of Early Breast Cancer: Evidence, Controversies, Consensus: Spectrum of Opinion of German Specialists on the 16th St. Gallen International Breast Cancer Conference (Vienna 2019).

The results of the international St. Gallen Consensus Conference for the treatment of patients with primary breast cancer were discussed this year by a working group of leading breast cancer experts in view of the therapy recommendations for everyday clinical practice in Germany. Three of the breast cancer experts are also members of this year's St. Gallen panel. The comparison of the St. Gallen recommendations with the annually updated treatment recommendations of the AGO 2019 as well as the S3 guideline is useful, since the recommendations of the St. Gallen panel represent the opinions of experts from various countries and disciplines. The recommendations of the S3 guideline and AGO are based on evidence-based research of the literature. This year's 16th St. Gallen conference featured the motto "Magnitude of clinical benefit". In addition to the evidence-based data, each therapeutic decision must also undergo a benefit/risk assessment of the patient's individual situation and be discussed with the patient.

Jumping Breast Phenomenon Following Subcutaneous Mastectomy: First Description and Grading of a Well-Known Breast Deformity.

INTRODUCTION: One of the goals of breast cancer surgery is to preserve the breast. However, where this is not possible, various breast reconstructive procedures are available. The most common procedure is the immediate insertion of a subpectoral implant after removing the breast tissue. A significant challenge involving subpectoral implants is the deformation of the breast upon contraction of the pectoral muscle causing elevation of the breast and development of wrinkles or ripples in the caudal and cranial quadrants (jumping breast), especially in slim patients with a thin subcutaneous fat layer. METHODS: While the jumping breast phenomenon after augmentation is well-known in cosmetic breast surgery, it has never been systematically described. In oncologic breast surgery, this deformity, which at times can be quite severe, has been ignored thus far. RESULTS AND CONCLUSION: In this paper, we present an initial distinction of grades for the so-called jumping breast, show examples for the different grades of severity of breast deformity in response to tensing of the pectoral muscle, and further describe different primary and secondary procedures for the prevention of the jumping breast phenomenon. By means of a 2-stage procedure, we can prevent this complication and reduce the risk of breast deformity after implant-based breast reconstruction.

Using a New Marker Clip System in Breast Cancer: Tumark Vision® Clip - Feasibility Testing in Everyday Clinical Practice.

BACKGROUND: This study presents first feasibility experiences with a new 3-dimensional (3D) marker clip system in clinical practice. The rate of clinical complete responses in the treatment of breast cancer patients is increasing; additionally, a change to targeted axillary dissection is being considered after neoadjuvant chemotherapy (NACT). Consequently, marker clips are needed which are reliable and easy to handle even in the axillary lymph node system. METHODS: A total of 50 patients from the Breast Care Unit of the Kliniken Essen Mitte were included. Clip marking of all 50 primary breast cancer lesions as well as 23 lymph nodes was performed using the Tumark Vision® clip. Following application, the position and visibility of the marker clip were monitored and documented in 2 axes. RESULTS: The feasibility of the Tumark Vision clip was excellent in everyday clinical practice as none of the markers dislocated. After clip marking of the tumor region and/or suspicious lymph nodes, all Tumark Vision clips could be detected in both axes. The 3D shape could be observed in all cases after application. CONCLUSION: The new 3D-shaped marker clip seems to be a promising tool for marking breast cancer lesions and even lymph nodes before NACT. As there are many studies ongoing to prove the feasibility of a shift from standard axillary dissection after NACT towards targeted axillary dissection, the Tumark Vision clip seems to provide good visibility even in lymph nodes after NACT. Further studies are warranted.

Comparison between early and delayed systemic treatment with candesartan of rats after ischaemic stroke.

OBJECTIVE: The effects of candesartan treatment starting early (3 h) and delayed (24 h) after middle cerebral artery occlusion (MCAO) with reperfusion was investigated in normotensive rats. METHODS: Subcutaneous treatment with candesartan (0.3 and 3 mg/kg) or vehicle was initiated 3 or 24 h after the onset of MCAO and continued for seven consecutive days (n=20 per group and timepoint). Neurological outcome was evaluated daily using two different scoring systems. Infarct and oedema volumes were determined in rats 2 or 7 days after MCAO. Mean arterial, systolic and diastolic blood pressures were recorded before and after the application of candesartan. RESULTS: Mean arterial, systolic and diastolic blood pressures were markedly decreased with the high dose, but only moderately decreased with the low dose of candesartan. Vehicle-treated rats showed marked neurological deficits 24 h after MCAO, which gradually improved with time. Candesartan improved neurological outcomes at all timepoints only when treatment was started 3, but not 24 h after MCAO. The infarct volume was reduced on days 2 and 7 after MCAO in rats treated with the low but not the high dose of candesartan. CONCLUSION: The present study demonstrates that only an early but not a delayed onset of treatment with candesartan exerts neuroprotection after focal ischaemia. The degree of neurological impairments did not correlate with the infarct volume, which was reduced only after the low dose of candesartan. The high dose of candesartan failed to reduce the infarct volume, probably because of an excessive blood pressure decrease.