The present investigation was undertaken in order to achieve a better understanding of the dynamics of placental villous differentiation. Villous trees from human placentas from different stages of pregnancy (first trimester to full term) were isolated and studied by light microscopy and scanning electron microscopy. For light microscopy the trees were serially sectioned and two-dimensionally reconstructed. For scanning electron microscopy complete villous trees or freeze-cracked villi were studied. The most important finding was that the mesenchymal villi are continuously newly formed out of the trophoblastic sprouts throughout pregnancy. Because of this they exist in all stages of pregnancy and have to be considered the basis for growth and differentiation of the villous trees. In the first two trimesters they are the forerunners of the immature intermediate villi, whereas in the last trimester the mesenchymal villi are transformed into mature intermediate villi. The immature intermediate villi formed during the first two trimesters are developmental steps towards the stem villi. On the other hand, the mature intermediate villi, which only are developed during the last trimester, produce numerous terminal villi. The latter are not active outgrowths caused by proliferation of the trophoblast, but rather passive protrusions induced by capillary coiling due to excessive longitudinal growth of the fetal capillaries within the mature intermediate villi.

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The 5th International Consensus Conference for Advanced Breast Cancer (ABC5) took place on November 14–16, 2019, in Lisbon, Portugal. Its aim is to standardize the treatment of advanced breast cancer based on the available evidence and to ensure that all breast cancer patients worldwide receive adequate treatment and access to new therapies. This year, the conference focused on developments and study results in the treatment of patients with hormone receptor-positive/HER2-negative breast cancer as well as precision medicine. As in previous years, patient advocates from around the world were integrated into the ABC conference and had seats on the ABC consensus panel. In the present paper, a working group of German breast cancer experts comments on the results of the on-site ABC5 consensus votes by ABC panelists regarding their applicability for routine treatment in Germany. These comments take the recommendations of the Breast Committee of the Gynecological Oncology Working Group (Arbeitsgemeinschaft Gynäkologische Onkologie; AGO) into account. The report and assessment presented here pertain to the preliminary results of the ABC5 consensus. The final version of the statements will be published in Annals of Oncology and The Breast.

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TPS598 Background: The WSG ADAPT trial program addresses the individualization of (neo)adj. decision-making in EBC. The ADAPT umbrella trial established early predictive molecular surrogate markers for response after a 3-wk endocrine treatment (ET) to omit chemotherapy (CT) in a cohort of early high-risk HR+/HER2- pts. ADAPTlate seeks to improve adj. therapy for pts. at high risk for late disease recurrence, who completed definite locoregional therapy (with / without (neo-)adj. CT) and are under adj. ET. This high-risk population does not derive optimal benefit from standard ET, develops secondary ET resistance, and late recurrences. Methods: Prospective, multi-center, interventional, two-arm, open, randomized, controlled adj. phase III trial (NCT04565054) to investigate additional benefit from 2 years of the CDK4/6-inhibitor abemaciclib combined with ET compared to ET alone in pts. with high-risk HR+/HER2- EBC. Abemaciclib demonstrated to improve outcome in metastatic BC and even in EBC when given as part of primary therapy. Primary objective is to demonstrate superiority of iDFS of abemaciclib + ET vs. standard ET. Secondary objectives include OS, dDFS, occurrence of CNS metastases, QoL, and translational research. Recruitment started in 9/2020 to screen 1250 pts. and to randomize 903 pts. in a ratio 3:2. Until date of submission, 33 pts. were screened and 22 randomized. Pre-/postmenopausal pts. with histologically confirmed invasive HR+/HER2- EBC, 2-6 y after primary diagnosis, with either known high clinical risk (c/pN 2-3 OR high CTS score in pN 0-1 OR non-pCR after neoadj. CT in cN 1 or G3 tumors OR G3 and Ki-67 ≥ 40% in pN 0-1) or known high genomic risk (RS >25 in c/pN 0, RS >18 in c/pN 1 OR high risk Prosigna, EPclin or Mammaprint in pN 0-1) or intermediate clinical, but unknown genomic risk (luminal B-like (G3 or Ki-67 ≥20%) in c/pN 0-1 AND either RS >25 in c/pN 0 or RS >18 in c/p N1 in screening) will be eligible. Treatment duration is 2 years for the abemaciclib + ET (premenopausal: AI + GnRH) arm, followed by at least 3-6 years ET alone. Pts. in control arm will receive 5-8-years ET at investigator´s choice. ePROs are collected using CANKADO. Translational analyses: Exploratory tissue biomarker research to assess alterations in molecular markers. Liquid biopsies (CTC/ctDNA/ctRNA) will be assessed for mutations and gene expression relevant for HR+/HER2- EBC using an appropriate technology at time of testing. Conclusions: ADAPTlate seeks to evaluate whether Abemaciclib + ET is superior to ET alone in pts. with clinical or genomic high-risk EBC even 2-6 years after initial diagnosis. Translational research aims at assessing potential mechanisms of resistance to endocrine and/or CDK4/6 targeted therapy. Clinical trial information: NCT04565054.

The Advanced Breast Cancer Fifth International Consensus Conference (ABC5) which focuses on the diagnosis and treatment of advanced breast cancer was held in Lisbon on November 14 – 16, 2019. The aim of the conference is to standardize the treatment of advanced breast cancer worldwide using evidence-based data and to ensure that patients with advanced breast disease anywhere in the world are treated appropriately and have access to the latest therapies. This year, the emphasis was on new developments and study results from patients with advanced breast cancer as well as precision medicine. The collaboration with patient advocates from all over the globe is also an important goal of the ABC Conference, which is why the international ABC panel also included a number of patient advocates. We present a commentary on the voting results of the ABC5 panelists in Lisbon by a working group of German breast cancer specialists together with the implications for routine clinical care in Germany. The commentary is based on the recommendations of the Breast Commission of the German Gynecological Oncology Working Group (AGO). This commentary is useful, it includes country-specific features for the ABC consensus.

ZusammenfassungVom 14. bis 16. November 2019 fand in Lissabon die fünfte internationale Konsensuskonferenz ABC5 (Advanced Breast Cancer Fifth Consensus) zu Diagnostik und Behandlung des fortgeschrittenen Mammakarzinoms statt. Ziel ist es, die Behandlung der Patientinnen mit fortgeschrittenem Mammakarzinom weltweit auf evidenzbasierter Grundlage zu standardisieren und sicherzustellen, dass Patientinnen überall auf der Welt adäquat behandelt werden und Zugang zu neuen Therapien erhalten. Ein inhaltlicher Schwerpunkt lag dieses Jahr auf neuen Entwicklungen und Studienergebnissen beim fortgeschrittenen Mammakarzinom sowie der Präzisionsmedizin. Zudem ist die Zusammenarbeit mit den Patientenvertreterinnen aus aller Welt ein wichtiges Anliegen der ABC-Konferenz, weshalb in dem international zusammengesetzten ABC-Panel auch Patientenvertreterinnen sind. Im vorliegenden Manuskript werden die Abstimmungsergebnisse der ABC5-Panelisten vor Ort durch eine Arbeitsgruppe deutscher Brustkrebsexperten für den Therapiealltag in Deutschland kommentiert. Der Kommentierung liegen die Empfehlungen der Arbeitsgemeinschaft Gynäkologische Onkologie (AGO), Kommission „Mamma“, zugrunde. Sie erscheint sinnvoll, da in den ABC-Konsensus auch länderspezifische Besonderheiten einfließen.

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