What are the effects of poly adenosine diphosphate-ribose polymerase (PARP) inhibitors for the treatment of locally advanced or metastatic breast cancer?

2021 ◽  
Author(s):  
Jane Burch ◽  
Agustín Ciapponi
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Adenosine Diphosphate ◽  
Parp Inhibitors

scholarly journals Update Breast Cancer 2020 Part 2 – Advanced Breast Cancer: New Treatments and Implementation of Therapies with Companion Diagnostics

2020 ◽  
Vol 80 (04) ◽  
pp. 391-398
Author(s):  
Diana Lüftner ◽  
Andreas Schneeweiss ◽  
Andreas D. Hartkopf ◽  
Volkmar Müller ◽  
Achim Wöckel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Targeted Therapy ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Parp Inhibitors ◽  
Companion Diagnostics ◽  
Molecular Tests ◽  
New Treatments ◽  
First Time

AbstractFor patients with locally advanced or metastatic breast cancer, new and effective therapies such as CDK4/6 inhibitors, PARP inhibitors and a PD-L1 inhibitor have been introduced in recent years. This review presents an update on the available studies with their data. In addition, two innovative anti-HER2 therapies are presented (trastuzumab-deruxtecan and tucatinib) for which the results from new studies have been reported. Molecular tests offer the possibility of defining patient populations or also monitoring courses of therapy. This can help identify patients with specific characteristics in order to provide them with individually targeted therapy within the framework of studies. In a large study, the benefit of such a biomarker study was able to be described for the first time.

scholarly journals Olaparib for metastatic breast cancer in a patient with a germline PALB2 variant

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Sherko Kuemmel ◽  
Hakima Harrach ◽  
Rita K. Schmutzler ◽  
Athina Kostara ◽  
Katja Ziegler-Löhr ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Parp Inhibitor ◽  
Metastatic Breast ◽  
Adenosine Diphosphate ◽  
Parp Inhibitors ◽  
Parp Inhibition ◽  
Sequence Variant ◽  
Wild Type ◽  
Genetic Changes

Abstract There is a strong biologic rationale that poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors may benefit a broader range of metastatic breast cancer (MBC) patients than covered by current approvals, which require a germline BRCA1/2 sequence variant affecting function. We report a patient with germline/somatic BRCA1/2 wild-type MBC, who had a dramatic response to the PARP inhibitor olaparib of at least 8 months’ duration. The patient is a 37-year-old woman with recurrent, hormone receptor-positive, HER2-negative MBC that had progressed despite hormonal therapy and palbociclib. Sensitivity to olaparib was likely conferred by a germline sequence variant affecting function in PALB2 (exon 1, c.18G>T, p.(=)). This case documenting activity of olaparib monotherapy in germline/somatic BRCA1/2 wild-type MBC illustrates that the clinical potential of PARP inhibition in MBC extends beyond currently approved indications to additional patients whose tumors have (epi)genetic changes affecting homologous recombination repair.

scholarly journals AGO Recommendations for the Diagnosis and Treatment of Patients with Locally Advanced and Metastatic Breast Cancer: Update 2021

Breast Care ◽  
2021 ◽  
pp. 1-8
Author(s):  
Marc Thill ◽  
Michael Friedrich ◽  
Cornelia Kolberg-Liedtke ◽  
Ute-Susann Albert ◽  
Maggie Banys-Paluchowski ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Diagnosis And Treatment

scholarly journals Olaparib in hormone receptor-positive, HER2-negative metastatic breast cancer with a somatic BRCA2 mutation

2021 ◽  
Vol 13 ◽  
pp. 175883592110069
Author(s):  
Lee S. Schwartzberg ◽  
Lesli A. Kiedrowski
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Clinical Response ◽  
Hormone Receptor ◽  
Brca2 Mutation ◽  
Locally Advanced ◽  
Susceptibility Gene ◽  
Metastatic Breast ◽  
Breast Cancer Susceptibility Gene ◽  
Hormone Receptor Positive

The oral poly(adenosine diphosphate-ribose) polymerase inhibitor olaparib is approved for the treatment of patients with human epidermal growth factor 2-negative (HER2−) metastatic breast cancer (mBC) and a germline breast cancer susceptibility gene (BRCA) mutation who have been treated with chemotherapy. This case report describes a 63-year-old postmenopausal woman with somatic BRCA2-mutated mBC who responded to olaparib treatment following multiple prior lines of therapy. The patient presented in January 2012 with locally advanced, hormone receptor-positive (HR+), HER2− BC which, despite initial response to neoadjuvant chemotherapy, recurred as bone disease in February 2014, and subsequently skin (June 2016) and liver (October 2016) metastases. A comprehensive 592-gene next-generation sequencing panel (Caris Life Sciences), performed on a skin biopsy, detected a pathogenic frameshift mutation in BRCA2 (H3154fs, c.9460delC), which was not identified in a 28-gene hereditary cancer germline analysis (Myriad Genetics, Inc.), and was therefore considered to be a somatic mutation. In January 2017, cell-free DNA (cfDNA) analysis (Guardant Health, Inc.) confirmed the BRCA2 H3154fs mutation in plasma. After several lines of chemotherapy and endocrine therapy, deriving clinical benefit from eribulin and capecitabine, the disease progressed by October 2017, and olaparib (300 mg orally twice daily) was initiated in January 2018. By April 2018, the liver lesions had shrunk by 80% and a >90% response in multiple skin lesions was noted. Clinical response was maintained for 8 months, followed by progression in the skin in September 2018. Biopsy of recurrent lesions revealed a novel BRCA2 mutation, E3152del (c.9455_9457delAGG), predicted to restore the open reading frame and presumably the mechanism of resistance to olaparib. Further likely resistance mutations were noted in subsequent cfDNA analyses. This case demonstrated a clinical response with olaparib as a later-line therapy for HR+, HER2− mBC with a somatic BRCA2 mutation.

scholarly journals 121P Impact of HER2 low (H2L) expression on prognosis in luminal locally advanced or metastatic breast cancer (BC): A retrospective study

2021 ◽  
Vol 32 ◽  
pp. S73
Author(s):  
C. Saavedra Serrano ◽  
B. Pérez Mies ◽  
M. Gion Cortes ◽  
A. Cortes Salgado ◽  
M. Fernández Abad ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Retrospective Study ◽  
Locally Advanced ◽  
Metastatic Breast
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