scholarly journals A Novel Adverse Event Associated with Olaparib Therapy in a Patient with Metastatic Breast Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
Megan Wheelden ◽  
Leah Cream ◽  
Jeffrey Sivik ◽  
Mark Robson
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Erythema Nodosum ◽  
Brca Mutation ◽  
Therapy Monitoring ◽  
Brca2 Mutation ◽  
Advanced Ovarian Cancer ◽  
Metastatic Breast ◽  
Brca Mutations ◽  
Initiation Of Therapy

Olaparib was first FDA approved for use in women with advanced ovarian cancer and germline BRCA mutations. Based on the results of subsequent research, the use of this drug has been expanded to patients with metastatic breast cancer with germline BRCA mutation. With the use of a relatively new medication and a larger patient population eligible for therapy, monitoring for novel adverse events associated with therapy is important. This case represents a patient with metastatic breast cancer and germline BRCA2 mutation who developed erythema nodosum after initiation of therapy with olaparib capsules. Her characteristic rash appeared shortly after starting olaparib and recurred after restarting olaparib an additional two times. She was treated with short courses of prednisone therapy with or without holding olaparib with resolution of her rash. The patient was later restarted on olaparib capsules 200 mg twice daily, and she more recently has been maintained on olaparib tablets 300 mg twice daily. On both regimens, the patient experienced only attenuated episodes of erythema nodosum that have not required cessation of therapy or steroid therapy.

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.

BRCA-associated breast cancer in young women.

1998 ◽  
Vol 16 (5) ◽  
pp. 1642-1649 ◽  
Author(s):  
M Robson ◽  
T Gilewski ◽  
B Haas ◽  
D Levin ◽  
P Borgen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brca Mutation ◽  
Brca2 Mutation ◽  
Prognostic Significance ◽  
Event Free Survival ◽  
Relapse Free Survival ◽  
Brca Mutations ◽  
Free Survival ◽  
Clinical Records ◽  
Incident Cases

PURPOSE To delineate the clinical characteristics and outcomes of breast cancer that arises in the setting of a germline BRCA mutation and to compare BRCA-associated breast cancers (BABC) with those that arise in women without mutations. PATIENTS AND METHODS We reviewed the clinical records of 91 Ashkenazi Jewish women ascertained during studies of the genetics of early-onset breast cancer. All women underwent testing for the BRCA1 mutations 185delAG and 5382insC. After the discovery of BRCA2, 79 women were also tested for the BRCA2 mutation 6174delT. RESULTS Mutations were identified in 30 women (33%). BABC were less likely to present with stage I disease than cases in women without mutations (27% v 46%), more likely to have axillary nodal involvement (54% v46%), and more likely to have extensive axillary involvement (25% v 17%). These differences were not statistically significant. BABC were significantly more likely to be histologic grade III (100% v 59%, P=.04) and to be estrogen receptor-negative (70% v 34%, P=.04). In the entire cohort, there were no significant differences between BABC and non-BRCA-associated cancers in 5-year relapse-free survival (65% v 69%, P=not significant [NS]), 5-year event-free survival (57% v 68%, P=NS), or 5-year overall survival. However, among cases diagnosed within 2 years of study entry, there was a trend toward shorter event-free survival in BRCA heterozygotes, but not relapse-free survival. Women with germline BRCA mutations were significantly more likely to develop contralateral breast cancer at 5 years (31% v 4%, P=.0007). CONCLUSION BABC present with adverse clinical and histopathologic features when compared with cases not associated with BRCA mutations. However, the prognosis of BABC appears to be similar to that of nonassociated cancer. Further studies of incident cases are necessary to define the independent prognostic significance of germline BRCA mutations.

scholarly journals Circulating Tumor Cells in Metastatic Breast Cancer: Clinical Applications and Future Possibilities

2020 ◽  
Vol 10 (9) ◽  
pp. 3311
Author(s):  
Maggie Banys-Paluchowski ◽  
Florian Reinhardt ◽  
Tanja Fehm
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Therapy Monitoring ◽  
Metastatic Breast ◽  
Study Groups ◽  
Clinical Applications ◽  
Response To Treatment ◽  
Cellsearch System

Circulating tumor cells (CTCs) have gained importance as an emerging biomarker in solid tumors in the last two decades. Several detection assays have been introduced by various study groups, with EpCAM-based CellSearch system being the most widely used and standardized technique. In breast cancer, detection of CTCs correlates with clinical outcome in early and metastatic settings. CTC persistence beyond first cycle of palliative chemotherapy indicates poor response to treatment in metastatic situation. Beyond prognostication and therapy monitoring, CTC counts can guide treatment decisions in hormone receptor positive HER2-negative metastatic breast cancer. Furthermore, CTC-based therapy interventions are currently under investigation in clinical trials. In this review, we focus on the current state of knowledge and possible clinical applications of CTC diagnostics in patients with metastatic breast cancer.

Metastatic breast cancer detection and therapy monitoring using folate-targeting flow cytometry.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 23-23
Author(s):  
B. Hong ◽  
M. Mace ◽  
R. Crowder ◽  
T. Coleman ◽  
W. He ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Flow Cytometry ◽  
Metastatic Breast Cancer ◽  
Hormone Therapy ◽  
Internal Control ◽  
Folate Receptor ◽  
Therapy Monitoring ◽  
Metastatic Breast ◽  
Normal Sample ◽  
Mesenchymal Transition

23 Background: Circulating tumor cell (CTC) has emerged as a valuable surrogate tumor marker for cancer diagnosis, prognosis, therapy personalization, and drug discovery. To identify CTCs, EpCAM and/or cytokeratin have been commonly used; however, their expression may diminish for subgroups of breast cancers or during epithelial-mesenchymal transition. A unique approach by targeting folate receptor (FR) on CTCs overcomes the limitation. Cancer cells overexpress FR with high affinity (KD=0.1 nM) to internalize high levels of folate for rapid growth. FR is also found upregulated in most cancers, while at very low levels in normal tissues. Methods: A flow cytometry based in-vitro CTC assay kit (OncoIVDx) was developed by IV Diagnostics Inc to specifically enumerate CTCs which overexpress FRs. 20 mL of 9 metastatic breast cancer (MBC) patients' peripheral blood was collected using CellSave tube before and after the treatment in midst of therapy. CTCs were tagged by fluorescently labeled folate conjugate, while leukocytes were counterstained by anti-CD45. To absolutely count the rare CTCs, a fluorescent bead was added serving internal control. Results: Table. Conclusions: No obvious shift in dot plots was found for patients' leucocytes compared to those in normal sample. Tumor size, histologic grade, nodal involvement and lymphovascular invasion (LVI) did not display a significant association with CTC presence, although more positive nodes with identified LVI might indicate an unfavorable increase in CTC counts. CTC presence was found associated with serum marker CA27.29. A score of 30 and less correlated with CTC response to the treatment. Chemotherapy alone or in combination with hormone therapy did not correlate with the change in CTC counts after treatment, except for hormone therapy alone. Unfavorable progression of cancers could be predicated for the patients with approximately 25 and more CTCs. We would like to thank NIH/NCI for SBIR phase I grant (1R43CA13789301A1). [Table: see text]

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