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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Clinical outcome and prognostic factors in oligometastatic breast cancer

BJMO - 2019, issue 2, february 2019

T. Geukens MD

Background

Metastatic breast cancer is generally regarded as incurable. A subset of these patients presents with oligometastasic. We wanted to describe patient, disease and treatment characteristics of this subgroup and identify their long-term outcome and prognostic factors.

Methods

We retrospectively selected patients diagnosed with synchronous metastatic breast cancer in our institution over the past 15 years who underwent resection of the primary tumour. Exclusion criteria were non-radical breast surgery, number of metastatic lesions >5 and number of organs involved >3. Kaplan-Meier method was used for progression-free survival (PFS) and overall survival (OS) analysis. Univariate and multivariate analysis were performed with Cox proportional hazards model. A p-value <0.05 was considered statistically significant.

Results

Sixty-five patients were included in the study. After a median follow-up of 77 months, PFS-rate was 46% and OS-rate was 63%. In univariate analysis, PFSwas significantly longerfor patients who underwent additional local treatment for metastases (n = 40/65; treatment modalities including radiotherapy, surgery and/or radiofrequency ablation) (hazard ratio (HR) 0.32, p = 0.001), endocrine receptor positive breast cancer (HR 0.44, p = 0.047) and invasive ductal carcinoma compared to other histological subtypes (HR 0.32, p = 0.016). A trend towards better PFS was additionally seen in premenopausal patients, HER2-positive tumours and patients selected for local therapy for metastases after neoadjuvant chemotherapy or endocrine treatment. Only local treatment for metastases correlated significantly with better OS (HR 0.25, p = 0.002). After correction for endocrine receptor positivity in multivariate analysis, local treatment for metastases remained a significant predictor of PFS (HR 0.33, p = 0,002) and OS (HR 0.26, p = 0.002).

Conclusion

Our data suggest that a significant proportion of highly selected oligometastatic breast cancer patients experience long term remission. In the oligometastatic population who underwent surgery of the primary tumour with curative intent, local therapy for metastases is an independent predictor of better PFS and OS. Ongoing and future efforts will better delineate the optimal patient population where significant benefit of this approach can be achieved, while avoiding morbidity of multimodality treatment in patients who will not encounter long-term disease control.

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Depression as an early manifestation of pancreatic cancer

BJMO - volume 11, issue 5, september 2017

T. Geukens MD, J. Verheezen MD

SUMMARY

Ever since the early 1930’s, an association between pancreatic cancer and depression has been noticed. The prevalence of depression is higher in patients with pancreatic cancer than it is in patients with other abdominal neoplasms, and psychiatric symptoms often precede somatic symptoms. Despite further research on this co-occurrence, the true mechanism of interaction is still not clear. Knowing what it is that forms the biological link between depression and the pancreatic tumour, could be of great importance to the future diagnostic and therapeutic workup of these patients.

Different theories are proposed. Plausible are the depression being induced through cytokines more specifically IL-6, alterations in the tryptophan-kynurenine, glutamate and serotonin pathways, and antibodies disturbing brain functioning directly or through serotonin. Depression causing cancer is also possible, but to date of unknown importance in pancreatic cancer. All this information brought together makes depressive symptoms of diagnostic importance in pancreatic cancer. The insights pave the way for the development of targeted therapies, hopefully to be implemented in clinical practice in the future.

(BELG J MED ONCOL 2017;11(5):212–217)

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