Over the past 20 years our knowledge of the molecular biology of tumours has increased significantly. This has led to the discovery and development of a number of biological or molecular markers, which have allowed us, in practice, to confirm their role in many different tumours. All of these biomarkers can be conditionally divided into two large groups – prognostic or predictive markers.
Prognostic markers are indicators, which allow us to evaluate the potential course and outcome of the disease including, for example, the risk of recurrence after a course of standard therapy and life expectancy (years lived with the disease). Today, many prognostic markers are available, which can differ for a variety of tumours. The presence or lack of these markers and their larger or smaller expression can help us to determine a treatment strategy, but they can’t guarantee a successful result. Many prognostic markers can be detected at Latvian laboratories.
Testing positive for the BRCA1 mutation usually indicates a less-favourable prognosis for untreated breast cancer patients. Similarly, an elevated level of CEA, or the carcinoembryonic antigen, in pre-op colon cancer patients can also indicate a less-favourable prognosis. And patients with metastatic cancer, who have an elevated level of CTC, or circulating tumour cells, can also expect a worse prognosis. For example, intestinal cancer patients with a result of CTC ≥ 3/7.5ml of peripheral blood will most likely have a shorter interval of time without progression (the time between the first diagnosis and the first metastasis) and a shorter life expectancy. A result of CTC ≥ 5/7.5ml of peripheral blood in breast and cancer patients can similarly indicate a shorter interval of time without progression and a shorter life expectancy. On the other hand, K-ras mutations suggest a less-favourable prognosis for patients with non-small cell lung cancer. Oncotype DX, or the 21 gene mutation test, is used to predict the possibility of recurrence after 10 years in patients with ER+ and N0 breast tumours. A high concentration of VEGF, or vascular endothelial growth factor receptors, is often associated with a less-favourable prognosis for patients with clear cell renal tumours. The ER, PR and HER2 markers discussed in a previous blogpost can also be listed among these prognostic markers.
Predictive markers allow us to evaluate whether or not a treatment method will be effective or potentially toxic. Naturally, this information could help us to avoid ineffective, toxic and expensive therapies in favour of something better.
Testing positive for BRCA1 is often associated with higher success rates for chemotherapy in breast cancer patients. On the other hand, patients with GIST (gastrointestinal stromal tumours) and the C-KIT mutation often respond well to imatinib and sunitinib, even though a large number eventually develop a resistance to these drugs. The EGFR1 mutation in patients with non-small cell lung cancer can often respond well to gefitinib or erlotinib, while patients with intestinal tumours often fare better with panitumumab. However, the K-ras gene mutation often indicates that drugs such as cetuximab and panitumumab will be ineffective with these patients and should not be prescribed. HER2/neu expression (+++) usually means that patients with both early stage and metastatic breast cancer will respond well to trastuzumab, while a high PR level often means that treatment with tamoxifen will be the most successful course of therapy.
By studying these indicators, it’s possible to, more or less, select the patients with the highest risk of a recurrence and to predict how the patient will react to therapy. Although oncology is a field of medicine that still follows a classical medical protocol, where specific therapies (there may be several types of therapies) are used in particular situations, today we often hear the words personalised, precision or targeted therapy. In other words, treatment is prescribed to a patient on an individual basis depending on the characteristics of his tumour. However, this is not nearly as simple or definitive as it may sound. Unfortunately, even with a nuanced, personalised approach, no one has been completely cured of cancer. But let’s not be so judgemental, because many patients could be saved from unnecessary and even toxic treatments with this approach. A person and their cancer are such unique worlds, which are also constantly changing, so finding an ideal treatment method is a difficult task. I’ve read documents to patients who have requested sophisticated genetic analyses to hopefully find, with the help of BigData, the most appropriate drug for their tumour’s unique genetic profile. It turns out that the patient had already used some of the potentially beneficial drugs suggested by the data, but the disease continued to progress. What now? This is the reason why I’m usually quite cautious about these genetic tests and why I always try to discuss all of the potential scenarios. It should also be mentioned that the personalised approach is only possible with some tumours and, sadly, for now, only for a limited period of time.