Implementation of Precision Oncology for Patients with Metastatic Breast Cancer in an Interdisciplinary MTB Setting

The advent of molecular diagnostics and the rising number of targeted therapies have facilitated development of precision oncology for cancer patients. In order to demonstrate its impact for patients with metastatic breast cancer (mBC), we initiated a Molecular Tumor Board (MTB) to provide treatment recommendations for mBC patients who had disease progression under standard treatment. NGS (next generation sequencing) was carried out using the Oncomine multi-gene panel testing system (Ion Torrent). The MTB reviewed molecular diagnostics’ results, relevant tumor characteristics, patient’s course of disease and made personalized treatment and/or diagnostic recommendations for each patient. From May 2017 to December 2019, 100 mBC patients were discussed by the local MTB. A total 72% of the mBC tumors had at least one molecular alteration (median 2 per case, range: 1 to 6). The most frequent genetic changes were found in the following genes: PIK3CA (19%) and TP53 (17%). The MTB rated 53% of these alterations as actionable and treatment recommendations were made accordingly for 49 (49%) patients. Sixteen patients (16%) underwent the suggested therapy. Nine out of sixteen patients (56%; 9% of all) experienced a clinical benefit with a progression-free survival ratio ≥ 1.3. Personalized targeted therapy recommendations resulting from MTB case discussions could provide substantial benefits for patients with mBC and should be implemented for all suitable patients.

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CATCH: A Prospective Precision Oncology Trial in Metastatic Breast Cancer

JCO Precision Oncology ◽

10.1200/po.20.00248 ◽

2021 ◽

pp. 676-686

Author(s):

Mario Hlevnjak ◽

Markus Schulze ◽

Shaymaa Elgaafary ◽

Carlo Fremd ◽

Laura Michel ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Clinical Management ◽

Metastatic Breast ◽

Previous Treatment ◽

Progression Free Survival ◽

Tumor Board ◽

Precision Oncology ◽

Whole Genome ◽

Free Survival

PURPOSE CATCH (Comprehensive Assessment of clinical feaTures and biomarkers to identify patients with advanced or metastatic breast Cancer for marker driven trials in Humans) is a prospective precision oncology program that uses genomics and transcriptomics to guide therapeutic decisions in the clinical management of metastatic breast cancer. Herein, we report our single-center experience and results on the basis of the first 200 enrolled patients of an ongoing trial. METHODS From June 2017 to March 2019, 200 patients who had either primary metastatic or progressive disease, with any number of previous treatment lines and at least one metastatic site accessible to biopsy, were enrolled. DNA and RNA from tumor tissue and corresponding blood-derived nontumor DNA were profiled using whole-genome and transcriptome sequencing. Identified actionable alterations were brought into clinical context in a multidisciplinary molecular tumor board (MTB) with the aim of prioritizing personalized treatment recommendations. RESULTS Among the first 200 enrolled patients, 128 (64%) were discussed in the MTB, of which 64 (50%) were subsequently treated according to MTB recommendation. Of 53 evaluable patients, 21 (40%) achieved either stable disease (n = 13, 25%) or partial response (n = 8, 15%). Furthermore, 16 (30%) of those patients showed improvement in progression-free survival of at least 30% while on MTB-recommended treatment compared with the progression-free survival of the previous treatment line. CONCLUSION The initial phase of this study demonstrates that precision oncology on the basis of whole-genome and RNA sequencing is feasible when applied in the clinical management of patients with metastatic breast cancer and provides clinical benefit to a substantial proportion of patients.

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Prospective testing of circulating tumour DNA in metastatic breast cancer facilitates clinical trial enrollment and precision oncology

Annals of Oncology ◽

10.1093/annonc/mdz239.016 ◽

2019 ◽

Vol 30 ◽

pp. v30 ◽

Cited By ~ 1

Author(s):

A.Z. Bujak ◽

C.-F. Weng ◽

M.-J. Silva ◽

M. Yeung ◽

L. Lo ◽

...

Keyword(s):

Breast Cancer ◽

Clinical Trial ◽

Metastatic Breast Cancer ◽

Metastatic Breast ◽

Precision Oncology ◽

Clinical Trial Enrollment ◽

Circulating Tumour Dna

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Circulating tumour DNA in metastatic breast cancer to guide clinical trial enrolment and precision oncology: A cohort study

PLoS Medicine ◽

10.1371/journal.pmed.1003363 ◽

2020 ◽

Vol 17 (10) ◽

pp. e1003363

Author(s):

Andjelija Zivanovic Bujak ◽

Chen-Fang Weng ◽

Maria João Silva ◽

Miriam Yeung ◽

Louisa Lo ◽

...

Keyword(s):

Breast Cancer ◽

Clinical Trial ◽

Cohort Study ◽

Metastatic Breast Cancer ◽

Metastatic Breast ◽

Precision Oncology ◽

Circulating Tumour Dna

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Ribociclib for the treatment of hormone-positive HER2-negative breast cancer

Medical Council ◽

10.21518/2079-701x-2019-10-72-80 ◽

2019 ◽

pp. 72-80

Author(s):

I. P. Ganshina ◽

D. A. Filonenko ◽

O. O. Gordeeva ◽

E. V. Lubennikova ◽

I. V. Kolyadina ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Molecular Diagnostics ◽

Metastatic Breast ◽

Topical Issue ◽

High Efficacy ◽

First Line ◽

Mortality Pattern ◽

First Line Therapy ◽

Line Therapy

Breast cancer steadily holds leading market positions in the malignancy morbidity and mortality pattern. The treatment of metastatic breast cancer remains an extremely topical issue, when its aim is not only to prolong the patient’s life, but also to preserve its quality. Due to advances in molecular diagnostics, it has become possible to use several new classes of drugs in recent times. CDK4/6 inhibitors that demonstrate high efficacy in the first-line therapy for luminal metastatic breast cancer is one of these groups. This review presents data from recent registration studies and a description of observations from our own clinical experience.

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Next-Generation Sequencing-Directed Therapy in Patients with Metastatic Breast Cancer in Routine Clinical Practice

Cancers ◽

10.3390/cancers13184564 ◽

2021 ◽

Vol 13 (18) ◽

pp. 4564

Author(s):

Simona Bruzas ◽

Sherko Kuemmel ◽

Hakima Harrach ◽

Elisabeth Breit ◽

Beyhan Ataseven ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Clinical Practice ◽

Next Generation Sequencing ◽

Standard Therapy ◽

Metastatic Breast ◽

Genetic Alterations ◽

Tumor Board ◽

Next Generation ◽

Generation Sequencing

Next-generation sequencing (NGS) followed by matched therapy has opened up new therapeutic options to patients with metastatic breast cancer (mBC). Here we report our experience with this approach in everyday clinical practice. This retrospective study included 95 patients with mBC who were genotyped with the FoundationOne® (CDx) assay in a commercial molecular pathology laboratory. Genetic alterations were identified in all tumor specimens, and 83 patients (87.4%) had a median of 2 (range, 1–6) potentially actionable alterations. A multidisciplinary tumor board recommended genomically guided therapy to 63 patients, 30 of whom received such treatment. Everolimus (n = 15) and anti-human epidermal growth factor receptor 2 (HER2) therapy (n = 6) were most frequently administered. The ratio of progression-free survival (PFS) under NGS-based therapy to PFS under the last line of standard therapy prior to NGS was >1.3 in 13 (43.3%) patients, indicative of a clinical benefit to NGS-directed therapy. One-year overall survival rates were 22.7% (95% CI, 6.5–44.4) in 65 patients allocated to the standard therapy versus 62.9% (95% CI, 41.6–78.2) in 30 patients receiving the matched therapy. In conclusion, NGS-matched treatment improved the clinical outcomes in a subgroup of mBC patients.

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Liver Metastasectomy for Metastatic Breast Cancer Patients: A Single Institution Retrospective Analysis

Journal of Personalized Medicine ◽

10.3390/jpm11030187 ◽

2021 ◽

Vol 11 (3) ◽

pp. 187

Author(s):

Armando Orlandi ◽

Letizia Pontolillo ◽

Caterina Mele ◽

Mariangela Pasqualoni ◽

Sergio Pannunzio ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Retrospective Analysis ◽

Therapeutic Option ◽

Univariate Analysis ◽

Metastatic Breast ◽

Tumor Board ◽

Breast Cancer Patients ◽

Negative Resection Margin

The liver represents the first metastatic site in 5–12% of metastatic breast cancer (MBC) cases. In absence of reliable evidence, liver metastasectomy (LM) could represent a possible therapeutic option for selected MBC patients (patients) in clinical practice. A retrospective analysis including MBC patients who had undergone an LM after a multidisciplinary Tumor Board discussion at the Hepatobiliary Surgery Unit of Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS in Rome, between January 1994 and December 2019 was conducted. The primary endpoint was overall survival (OS) after a MBC-LM; the secondary endpoint was the disease-free interval (DFI) after surgery. Forty-nine MBC patients underwent LM, but clinical data were only available for 22 patients. After a median follow-up of 71 months, median OS and DFI were 67 months (95% CI 45–103) and 15 months (95% CI 11–46), respectively. At univariate analysis, the presence of a negative resection margin (R0) was the only factor that statistically significantly influenced OS (78 months versus 16 months; HR 0.083, p < 0.0001) and DFI (16 months versus 5 months; HR 0.17, p = 0.0058). A LM for MBC might represent a therapeutic option for selected patients. The radical nature of the surgical procedure performed in a high-flow center and after a multidisciplinary discussion appears essential for this therapeutic option.

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Characterizing advanced breast cancer heterogeneity and treatment resistance through serial biopsies and comprehensive analytics

npj Precision Oncology ◽

10.1038/s41698-021-00165-4 ◽

2021 ◽

Vol 5 (1) ◽

Author(s):

Allen Li ◽

Jamie M. Keck ◽

Swapnil Parmar ◽

Janice Patterson ◽

Marilyne Labrie ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Metastatic Breast ◽

Molecular Heterogeneity ◽

Precision Oncology ◽

Cancer Management ◽

Metastatic Lesions ◽

Mixed Response ◽

Clinical Scenarios ◽

Tumor Boards

AbstractMolecular heterogeneity in metastatic breast cancer presents multiple clinical challenges in accurately characterizing and treating the disease. Current diagnostic approaches offer limited ability to assess heterogeneity that exists among multiple metastatic lesions throughout the treatment course. We developed a precision oncology platform that combines serial biopsies, multi-omic analysis, longitudinal patient monitoring, and molecular tumor boards, with the goal of improving cancer management through enhanced understanding of the entire cancer ecosystem within each patient. We describe this integrative approach using comprehensive analytics generated from serial-biopsied lesions in a metastatic breast cancer patient. The serial biopsies identified remarkable heterogeneity among metastatic lesions that presented clinically as discordance in receptor status and genomic alterations with mixed treatment response. Based on our study, we highlight clinical scenarios, such as rapid progression or mixed response, that indicate consideration for repeat biopsies to evaluate intermetastatic heterogeneity (IMH), with the objective of refining targeted therapy. We present a framework for understanding the clinical significance of heterogeneity in breast cancer between metastatic lesions utilizing multi-omic analyses of serial biopsies and its implication for effective personalized treatment.

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