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Translational Highlights in Breast and Ovarian Cancer 2019 - Immunotherapy, DNA Repair, PI3K Inhibition and CDK4/6 Therapy


Hartkopf, Andreas D; Müller, Volkmar; Wöckel, Achim; Lux, Michael P; Janni, Wolfgang; Ettl, Johannes; Belleville, Erik; Schütz, Florian; Fasching, Peter A; Kolberg, Hans-Christian; Welslau, Manfred; Overkamp, Friedrich; Taran, Florin-Andrei; Brucker, Sara Y; Wallwiener, Markus; Tesch, Hans; Fehm, Tanja N; Schneeweiss, Andreas; Lüftner, Diana (2019). Translational Highlights in Breast and Ovarian Cancer 2019 - Immunotherapy, DNA Repair, PI3K Inhibition and CDK4/6 Therapy. Geburtshilfe und Frauenheilkunde, 79(12):1309-1319.

Abstract

In the near future, important translational questions of clinical relevance will be adressed by studies currently in progress. On the one hand, the role of PD-L1 expression must be further understood, after it was found to be relevant in the use of atezolizumab in first-line therapy of patients with metastatic triple-negative breast cancer (TNBC). No association between efficacy and PD-L1 expression was found in a neoadjuvant study that included pembrolizumab in TNBC. The pathological complete response rate (pCR) was higher in both patient groups with and without PD-L1 expression when pembrolizumab was added to chemotherapy. Another future question is the identification of further patient groups in which efficacy of PARP inhibitors is seen, which are licensed for the pBRCA1/2 germline mutation. These include, for example, patients with mutations in other genes, which are involved in homologous recombination, or patients with tumours that show an abnormality in global tests of homologous recombination deficiencies (HRD tests). The question of whether a PARP inhibitor can be given and with which chemotherapy combination partners is currently being investigated in both breast and ovarian cancer. While the data on improved overall survival are being consolidated for the CDK4/6 inhibitors, knowledge of molecular changes during the therapy and during progression on the therapy is growing. Both the accumulation of PI3K mutations and also PTEN changes might play a part in planning subsequent therapies. This review article summarises these recent developments in breast cancer and in part also in ovarian cancer.

Abstract

In the near future, important translational questions of clinical relevance will be adressed by studies currently in progress. On the one hand, the role of PD-L1 expression must be further understood, after it was found to be relevant in the use of atezolizumab in first-line therapy of patients with metastatic triple-negative breast cancer (TNBC). No association between efficacy and PD-L1 expression was found in a neoadjuvant study that included pembrolizumab in TNBC. The pathological complete response rate (pCR) was higher in both patient groups with and without PD-L1 expression when pembrolizumab was added to chemotherapy. Another future question is the identification of further patient groups in which efficacy of PARP inhibitors is seen, which are licensed for the pBRCA1/2 germline mutation. These include, for example, patients with mutations in other genes, which are involved in homologous recombination, or patients with tumours that show an abnormality in global tests of homologous recombination deficiencies (HRD tests). The question of whether a PARP inhibitor can be given and with which chemotherapy combination partners is currently being investigated in both breast and ovarian cancer. While the data on improved overall survival are being consolidated for the CDK4/6 inhibitors, knowledge of molecular changes during the therapy and during progression on the therapy is growing. Both the accumulation of PI3K mutations and also PTEN changes might play a part in planning subsequent therapies. This review article summarises these recent developments in breast cancer and in part also in ovarian cancer.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Gynecology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:December 2019
Deposited On:29 Jan 2020 14:17
Last Modified:30 Jan 2020 08:43
Publisher:Georg Thieme Verlag
ISSN:0016-5751
OA Status:Green
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1055/a-1039-4458
PubMed ID:31875860

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