Articles

Genomics of metastatic breast cancer

BJMO - 2022, issue 1, february 2022

T. Geukens MD, M. De Schepper MD, F. Richard PhD, M. Maetens PhD, K. Van Baelen MD, S. Leduc MSc, E. Isnaldi MD, PhD, H.L. Nguyen MSc, I. Bachir MD, E. Vanden Berghe MSc, W. Van Den Bogaert MD, K. Punie MD, P. Neven MD, PhD, H. Wildiers MD, PhD, G. Floris MD, PhD, C. Desmedt PhD

SUMMARY

The purpose of this review is to highlight the recent knowledge gathered on the genomics of metastatic breast cancer (BC), together with the clinical implications. Through large sequencing efforts, the genomic profile of BC is increasingly being deciphered, with a limited number of those findings having resulted in genomicmatched treatment options. The pace at which new discoveries are made is highest in the early setting, where large samples can easily be accessed through leftover tissue of resection specimens, and smaller diagnostic biopsies are also available. In the metastatic setting however, residual tissue from clinically indicated biopsies or resections are scarce. Some efforts have been undertaken through (inter)national, institutional, clinical trial- or patient-driven initiatives. They have highlighted important differences between the genomic landscape of metastatic versus primary tumour tissues. Especially in hormone receptor positive HER2 negative (HR+/HER2-) disease, driver mutations continue to accumulate after dissemination, most of them in the ESR1 or ERBB2 genes, or in genes involved in transcription regulation, MAPK- or PI3K-signaling pathways. Importantly, the genomic landscape is not homogeneous even within one patient, and significant heterogeneity is seen on an intra-patient, inter-lesion and intra-lesion level. This poses clinical challenges, with different subclones possibly harbouring differential sensitivity to systemic treatments and single biopsies not accurately reflecting the full molecular profile. Finally, through liquid biopsies, a more complete and less invasive insight into the tumour’s characteristic could theoretically be retrieved. However, it is unclear how well these profiles correlate with the actual diversity of the different lesions. Importantly, rapid autopsy programs have been shown to enhance research on the genomics of metastatic BC, and one such program was recently launched at UZ/KU Leuven.

(BELG J MED ONCOL 2022;16(1):18–28)

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Algorithms for molecular testing in solid tumours

BJMO - volume 13, issue 7, november 2019

Ir A. Hébrant PhD, M. Lammens MD, PhD, C. Van den Broecke MD, N. D’Haene MD, PhD, J. Van den Oord MD, PhD, A. Vanderstichele MD, PhD, A. Dendooven MD, PhD, P. Neven MD, PhD, K. Punie MD, G. Floris MD, PhD, J. Van der Meulen MD, HA. Poirel MD, PhD, C. Dooms MD, PhD, S. Rottey MD, PhD, T. Boterberg MD, PhD, L. Brochez MD, PhD, M.C. Burlacu MD, G. Costante MD, D. Creytens MD, PhD, P. De Paepe MD, PhD, R. De Pauwn MD, B. Decallonne MD, PhD, F. Dedeurwaerdere MD, H. Denys MD, PhD, L. Ferdinande MD, PhD, R. Forsyth MD, PhD, M. Garmyn MD, PhD, T. Gevaert MD, PhD, J. De Grève MD, PhD, E. Govaerts MD, E. Hauben MD, PhD, J. Kerger MD, O. Kholmanskikh Van Criekingen MD, PhD, V. Kruse MD, PhD, Y. Lalami MD, L. Lapeire MD, PhD, P. Lefesvre MD, PhD, J.P. Machiels MD, PhD, B. Maes MD, PhD, G. Martens MD, PhD, M. Remmelink MD, PhD, I. Salmon MD, PhD, R. Sciot MD, PhD, S. Tejpar MD, PhD, K. Van de Vijver MD, PhD, L. Van de Voorde MD, I. Van den Berghe MD, A. Van den Bruel MD, K. Vandecasteele MD, PhD, L. Vanwalleghem MD, K. Vermaelen MD, PhD, R. Salgado MD, PhD, E. Wauters MD, PhD, B. Weynand MD, PhD, E. Van Valckenborgh PhD, G. Raicevic PhD, M. Van den Bulcke PhD, P. Pauwels MD, PhD

SUMMARY

In order to advise the Federal Government on the reimbursement of molecular tests related to Personalised Medicine in Oncology, the Commission of Personalised Medicine (ComPerMed), represented by Belgian experts, has developed a methodology to classify molecular testing in oncology. The different molecular tests per cancer type are represented in algorithms and are annotated with a test level reflecting their relevance based on current guidelines, drug approvals and clinical data. The molecular tests are documented with recent literature, guidelines and a brief technical description. This methodology was applied on different solid tumours for which molecular testing is a clear clinical need.

(BELG J MED ONCOL 2019;13(7):286–95)

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Molecular test algorithms for breast tumours

BJMO - volume 13, issue 2, march 2019

Ir A. Hébrant PhD, K. Punie MD, F.P. Duhoux MD, PhD, C. Colpaert MD, PhD, G. Floris MD, PhD, K. Lambein MD, PhD, P. Neven MD, PhD, M. Berlière MD, PhD, R. Salgado MD, PhD, M. Chintinne MD, PhD, K. Dahan MD, PhD, S. Dedeurwaerdere MD, J. De Grève MD, PhD, A. de Leener MD, PhD, H. Denys MD, PhD, R. de Putter MD, L. Desmyter PhD, M. Baldewijns MD, PhD, D. Feret MD, C. Fontaine MD, C. Galant MD, P. Hilbert PhD, J. Janssens MD, PhD, D. Larsimont MD, PhD, P. Lefesvre MD, PhD, T. Sticca PhD, M-D. Tkint de Roodenbeke MD, G. Van Den Eynden MD, PhD, I. Vanden Bempt PhD, C. Van den Broecke MD, I. Vandernoot MD, C. Sotiriou MD, PhD, J. van Dorpe MD, PhD, H.A. Poirel MD, PhD, E. Van Valckenborgh PhD, G. Raicevic PhD, M. Van den Bulcke PhD, P. Aftimos MD

SUMMARY

In order to advise the Federal Government on all matters related to personalised medicine in oncology, including the reimbursement of molecular tests, the Commission of Personalized Medicine (ComPerMed) has applied, for the breast tumours, the same methodology as previously applied for the digestive tumours. Meaning, the different molecular tests, represented in the shape of algorithms, are annotated with test levels — which aim to reflect their relevance based on current available data and to define the reimbursement — and are documented with recent literature, guidelines and a brief technical description.

(BELG J MED ONCOL 2019;13(2):40–45)

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State of the art: gene expression profiles in early breast cancer

BJMO - volume 10, issue 4, july 2016

K. Van Asten MSc, P. Neven MD, PhD, G. Floris MD, PhD, R. Salgado MD, PhD, C. Sotiriou MD, PhD, H. Wildiers MD, PhD

Summary

Gene expression profiles provide strong prognostic information and can predict breast cancer outcome mainly in women with lymph node-negative, oestrogen receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. They are primarily designed to enable a more precise assessment on whether or not a patient needs adjuvant chemotherapy. However, the optimal use in clinical practice is still not established. The first set of data published from the TAILORx study and the results from the MINDACT study provide strong evidence for the clinical utility of gene expression profiles. Full disclosure of the results of prospective studies such as MINDACT and TAILORx on this topic is awaited in order to define their exact place in clinical decision-making. However, in several countries, these tests are already used in daily clinical practice, and are reimbursed. In addition, the use of gene expression profiles as a potential ancillary tool for treatment decisions is supported in several international treatment guidelines. Multiple studies have shown that there is a change in treatment decision based on gene expression profiles. In addition, different assays may provide different risk stratification at short-, middle- and long-term, so thoughtful use of these tests is recommended. Patients should be well informed about the benefits, risks, costs and uncertainties associated with these tests. Clinicians should also be educated on these matters. Furthermore, as gene expression profiles are expensive and not reimbursed in many countries, these tests are not accessible to all breast cancer patients. Patients’ preferences are important when making risk assessments and treatment decisions in those cases where there is doubt on the benefit of giving adjuvant chemotherapy. Taken together, gene expression profiles provide information that may be complementary to that provided by standard clinicopathological assessment in guiding decision of therapy in the adjuvant setting. These assays represent a step forward towards personalised medicine. We strongly propose to allow reimbursement of gene expression profiles in Belgium, but pragmatic and clear criteria for reimbursement should be developed with all stakeholders to avoid overconsumption.

(BELG J MED ONCOL 2016;10(4):114–122)

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