REVIEW ONCOLOGY

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

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)

Cryotherapy and radiofrequency ablation for renal cell carcinoma

Summary

Thermal ablation is being increasingly used for the treatment of clinical stage T1a renal cell carcinoma. However, it is not uncommon to hear mixed messages regarding this issue. Hence, it is necessary for every urologist to understand the basics of thermal ablation and its clinical outcome based on the latest literature to help guide their patients through treatment options. Patient selection criteria are also analysed. Among thermal ablation techniques, cryotherapy and radiofrequency are the most commonly performed ablative procedures. The superiority of one technique over the other is difficult to demonstrate in the absence of a randomised controlled trial. Local recurrence seems more likely after radiofrequency ablation than after cryotherapy, with the latter achieving better local control. When compared to partial nephrectomy, higher local recurrence rates are described with the thermal ablation techniques. However, the small difference at five year follow-up and the better tolerability profile of thermal ablation procedures in elderly and/or comorbid patients explain the rationale for their use in selected cases. Follow-up is mandatory in these patients to diagnose recurrence or persistence of the disease, to monitor renal function and to detect complications. Of note, redo-techniques and surgical approach, though challenging, remain possible salvage procedures after primary failure.

(BELG J MED ONCOL 2016;10(3):85–91)

Highlights in oncology 2015

Summary

This article is based on the 2016 clinical cancer advances article, published by the American Society of Clinical Oncology, and reviews the most important advances made in the different fields of oncology that are most likely to impact daily clinical practice.¹

(BELG J MED ONCOL 2016;10(2):49–57)

Early triple negative breast cancer in clinical practice

Summary

Up to 20% of breast cancers lack receptors for estradiol, progesterone and human epidermal growth factor receptor 2, triple negative breast cancer. Negativity for these receptors is not completely nor consistently defined. ImmunoHistoChemical/In Situ Hybridisation determined triple negative breast cancer is strong but incomplete compared to the molecular intrinsic basal like subtypes one and two, but also includes non-basal like subtypes. Most triple negative breast cancers are of the histological IDC-NOS type. Triple negative breast cancer in general has unfavourable clinical and prognostic characteristics and is most frequently diagnosed in young women and women with (germline) mutations in BRCA1. Therefore, triple negativity may be an indication for genetic testing of germline BRCA mutations. Lymphocytic infiltration of triple negative breast cancer correlates with a less detrimental prognosis. Triple negative breast cancers often lack mammographic micro calcifications.

Regardless of type of primary surgical treatment, patients with triple negative breast cancer are more at risk for local/regional recurrence than other types. But there is no reason for local/regional treatment or indications for (neo) adjuvant systemic therapy beyond accepted guidelines for breast cancer in general. The mainstay of (neo) adjuvant medical treatment of early triple negative breast cancer is combination (sequential) chemotherapy with anthracyclines and taxanes. Alternatives are pegylated liposomal doxorubicin or classical cyclophosphamide, methotrexate 5-fluorouracil. In triple negative breast cancer with BRCAness, platinums may replace taxanes in neoadjuvant treatment to optimise the pathologic complete response rate. Several targeted therapies proved to be effective in metastatic triple negative breast cancer, but to date there are no such validated treatments for early disease. Besides targeted therapies, immune modulatory strategies for well characterised immunogenic triple negative tumours (i.e. with different grades of lymphocytic infiltration) are promising.

(BELG J MED ONCOL 2016;10(1):7–14)

Systemic treatment for basal cell carcinoma of the skin

(BELG J MED ONCOL 2015;9(7):265–71)

Clinical application of targeted next generation sequencing for lung cancer patients

Summary

The successes of targeted agents in patients with molecularly defined tumours and improvements in genomic technology have generated enthusiasm for incorporating genomic profiling into clinical cancer practice and molecular testing has now become a standard of care for lung cancer. International guidelines recommend testing for EGFR mutations and ALK gene rearrangement to guide patient selection for therapy. However, different potentially targetable oncogenes, such as KRAS, PIK3CA, BRAF, ERBB2 or MET, for which agents are being evaluated, have been proposed as valuable for managing patients with lung cancer. Recently, the development of next generation sequencing has enabled simultaneous detection of many clinically relevant mutations in different genes in a single test. In this study, we have evaluated the clinical utility of targeted next generation sequencing, using a 22 genes panel, for patients with lung cancer on 234 samples, including cytology, biopsies and surgical resections, from two different institutions tested in routine daily practice since validation and accreditation of the method (BELAC ISO15189). On the 234 samples tested, only one case could not be sequenced due to an insufficient quantity of available tissue. Among the 233 cases tested, 223 (95.7%) samples were sequenced successfully. The median turnaround time between reception of the sample in the laboratory and report release was one week. The most frequent mutations were found in TP53 (42.1%) and KRAS (35.9%). Of successfully sequenced cases, 137 potentially actionable mutations were identified in 130 patients (58.3%), including 80 KRAS mutations, 26 EGFR mutations, fourteen BRAF mutations, eight PIK3CA mutations, three PTEN mutations, two ERBB2 insertions, two NRAS mutations and two MAP2K1 mutations. Overall, next generation sequencing can be applied in daily practice even for small samples, such as lung biopsies or cell blocks. Moreover, it provides clinically relevant information for lung cancer patients.

(BELG J MED ONCOL 2015;9(7):272–78)

Targeted therapy for the treatment of head and neck squamous cell carcinomas: hopes and pitfalls

Targeted therapy is a promising strategy for the treatment of head and neck squamous cell carcinoma and other cancers, which has been developed as a result of breakthroughs in molecular characterisation of carcinogenesis. It is thought to offer a higher therapeutic index and, therefore, to be associated with less toxicity than cytotoxic drugs. Unfortunately this kind of therapy also has weaknesses; in particular the long-term response rate is disappointing. This review will not only focus on the benefits of EGFR targeted agents in head and neck squamous cell carcinoma, but will also summarise its weaknesses.

(BELG J MED ONCOL 2015;9(5):175–78)