P. Neven MD, PhD

Molecular test algorithms for breast tumours

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)

P.09 Tamoxifen metabolism and breast cancer efficacy in the neo-adjuvant or metastatic setting – a prospective multicenter trial

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)

Adjuvant endocrine therapy in pre- and perimenopausal women with breast cancer: practice guidelines

Summary

Oestrogen receptor positive early invasive breast cancer is a common disease in pre- and perimenopausal women. Adjuvant endocrine therapy is an essential part of its treatment. Until recently, premenopausal patients were uniformly treated with tamoxifen during five years. Given the recent publication of large clinical trials showing a benefit for other treatment regimens, the BSMO Breast Cancer Task Force met on the 6th of March, 2015, to propose common guidelines for adjuvant endocrine therapy for premenopausal patients. The members agreed that low-risk patients should be treated with five to ten years of tamoxifen, while the highest-risk patients should be treated with exemestane or tamoxifen plus ovarian function suppression. Special attention should be given to patients less than 35 years at diagnosis: in this subgroup, exemestane plus ovarian function suppression is preferred to tamoxifen plus ovarian function suppression.

(BELG J MED ONCOL 2016;10(3):92–96)

How to sequence systemic therapies and radiotherapy in early breast cancer?

Breast cancer is the most common malignancy in women in the Western world. Over the last decades, the use of postoperative systemic therapies (chemotherapy, hormonal therapy, trastuzumab) and radiotherapy led to significant survival benefits for patients with early breast cancer. Although these modalities have been extensively studied and used, a major question is how these systemic therapies are optimally sequenced with radiotherapy in the adjuvant setting. This article reviews available data on how to combine systemic therapies with radiotherapy in women with early stage breast cancer, and provides recommendations that unfortunately do not reach level I evidence due to insufficient quality of available clinical data.

BELG J MED ONCOL 2014;8(3):72–80

Transforming growth factor β: friend or foe in disguise?

TGF-β is a major regulator and driver of many biological processes, but its main function is inhibition of cell cycle progression and apoptosis, thus establishing a tumour-protective effect in early stages of malignant transformation. However, mutational alterations can occur at different levels of the TGF-β signaling cascade. These mutations, combined with the significant influence of the tumour microenvironment on this cascade, can cause a functional shift of TGF-β from being a tumour suppressor to becoming a tumour promoter in more advanced cancers. In most tumours this will ultimately contribute to the formation of metastatic laesions. In the clinical setting of breast cancer, TGF-β plays a significant role in the acquisition of endocrine resistance. Thus, therapeutic intervention of TGF-β signaling might deliver significant benefits in the treatment of cancer. (BELG J MED ONCOL 2012;6:188–193)

The changing role of the axillary dissection in the treatment of breast cancer

The aim of this article is to highlight the recent changes in the surgical approach of the axilla in breast cancer patients. Axillary staging is dominated by the sentinel lymph node (SLN) biopsy, which is now widely practiced in clinically node negative patients. Most authors believe a SLN biopsy may even be performed in patients with a large or multifocal tumour, before neo-adjuvant systemic therapy, during pregnancy, after prior excisional biopsy and after prior mantle field radiotherapy of the breast. Intra-operative assessment of the SLN is recommended as it can identify half of all positive lymph nodes. It is generally accepted that it is safe to omit an axillary lymph node dissection (ALND) in patients with a negative SLN or with only isolated tumour cells (<0.2 mm) in the SLN. Moreover, in a subset of patients with a micro-/macrometastasis in the SLN it might not be necessary to perform a completion of ALND. We suggest to accept the option of omitting completion of ALND in frail patients with a positive sentinel lymph node on final pathology OR in these patients with, on final pathology, one or two positive SLNs AND a grade I or II tumour smaller than 4 cm AND adjuvant radiotherapy on the whole breast or chest wall. In conclusion, an increasingly tailored surgical approach is guiding the management of the axilla for women with early breast cancer. (BELG J MED ONCOL 2012;6:87–95)