MINDACT: 70-gene signature test as guidance for breast cancer treatment

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Published: 1 Oct 2020
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Josephine Lopes Cardozo - Netherlands Cancer Institute, Amsterdam, The Netherlands

Josephine Lopez Cardozo speaks to ecancer about screen-detected breast cancers and how they have a different tumour biology and better prognosis compared to interval breast cancers, the results from this paper were presented at EBCC-12.

She initially explains the purpose of the MINDACT randomised phase III trial and how it was used to detect tumour biology of the screened patients. She then highlights the role 70-gene signature plays in detection and prognosis for certain women with breast cancer.

Cardozo further explains what screen-detected and interval cancers are and tells how the overall survival in both these groups varies in comparison to each other. She concludes with speaking of the key results from this trial and how they can impact future breast cancer treatment and prognosis.

The purpose of the MINDACT trial was to combine standard clinical pathological characteristics and the 70-gene signature to better identify which patients benefit from chemotherapy. The main group of interest in MINDACT were patients who had a high risk according to standard clinical pathological characteristics but a low risk according to the 70-gene signature. These patients were then randomised to receive chemotherapy or not to evaluate if chemotherapy could be safely omitted in these patients. The long-term results of this trial will actually be discussed at EBCC as well.

What role does the 70-gene signature play in detection and prognosis for certain women with breast cancer?

The 70-gene prognosis signature looks at the tumour biology of breast cancers and identifies patients as being at low or high risk of developing distant metastasis and thus whether they have a good or poor prognosis. Clinicians use the 70-gene signature to help guide decisions for adjuvant systemic treatment for breast cancer patients and that’s mostly used in patients with a high risk based on clinical pathological criteria. It can be used to decide whether or not to give chemotherapy to these patients.

What was the difference in overall survival between women with screen detected cancers and interval cancers?

I will first explain a little bit more about the difference between screen detected and interval cancers. So, in our study we distinguished between screen detected cancers which are breast cancers that are found by mammographic screening in the national screening programme and, on the other side, interval cancers which are breast cancers that are found in the time between two screening rounds. We looked at tumour biology according to the 70-gene signature of these cancers and evaluated the time until patients developed distant metastasis or died from breast cancer, which is abbreviated as DMFI.

So the primary endpoint of this study was distant metastasis free interval because this focusses more on important breast cancer related events. For this endpoint the difference at eight years was 5.4% between screen detected and interval cancers but the difference in overall survival, the absolute difference at eight years, was 4.1%.

What were the key results obtained from this trial?

As I said before, we looked at tumour biology according to the 70-gene signature between and correlated that with survival for screen detected and interval cancers. We looked at the time until patients developed distant metastasis or died from breast cancer. To start with we found that screen detected cancers more often had a low or ultra-low risk tumour biology compared to interval cancers and we also found that the screen detected cancers had excellent distant metastasis free interval rates, regardless of their tumour biology.

In the interval cancers, on the other hand, we found a significant difference in distant metastasis free interval between patients with a low risk tumour biology and patients with a high risk tumour biology. An interesting group to look at are those cancers with a high risk tumour biology because we found that patients with high risk interval cancers have an 8.6% lower DMFI rate compared to high risk screen detected cancers. This shows that the way these high risk cancers are detected is a very important prognostic factor.

How will these results impact future breast cancer treatment and prognosis?

This research provides insights in the difference in tumour biology between screen detected and interval cancers and knowledge of the tumour biology provides further prognostic information but the method of detection remains a very important prognostic factor in itself. So we think that combining the prognostic information provided by the 70-gene signature and the method of detection can help to choose the best treatment for breast cancer patients. In this way clinicians can further personalise treatments for individual patients.