Personalised cancer treatment

Medical oncologist, Dr Devan Moodley, talks us through the development of cancer treatment, how the size of the cancer doesn’t always matter, and the advancement he envisions in the future.

Cancer therapies have evolved significantly in the last decade. In the past, we would have performed radical surgery on almost all patients, no matter what the disease stage was, and then we learnt that it may not make a huge impact on the outcome, to cut the cancer out of the breast, if the cancer had spread to other organs.

With this insight came a new concept in the management of breast cancer – that of giving some kind of treatment prior to the surgery. This so-called ‘changing in the order of therapies’ started producing better results, in a portion of patients, with the outcome that today we preferentially give treatments before surgery in large breast cancers and in instances where the axillary lymph nodes have cancer in them at diagnosis.

As our understanding of cancer behaviour became more sophisticated, we worked out that size does not always matter. Sometimes small cancers can be more dangerous than their larger siblings and therefore size alone did not form the basis for making decisions on treatment after surgery. This adjuvant therapy then became a much more directed and personal approach.

Today, in patients where we’re not sure whether chemotherapy in indicated or not, from standard diagnostic parameters, we use specialised gene profiling tests. These tests are able to accurately quantify a patient’s risk for relapse, and are also able to tell us – with a high degree of certainty – whether the use of adjuvant chemotherapy is of benefit or not.

This is, however, not utilised in patients in whom the indication for adjuvant chemotherapy is defined as clear-cut with the existing well-researched indications.

Many of these gene signatures are becoming available today and with the passage of time and availability, I am sure this will become common place in most breast cancers with early stage disease. I see the field expanding, in future, to also include testing in patients with triple-negative breast cancers – an indication which is not presently validated for this type of testing.

We would also look at more factors in patients’ histology and make decisions on future curative therapies by rates of divisions of cancer cells and proliferation indices. With these new profilers, a whole new way to look at breast cancer has emerged – the molecular classification.

This characterisation of breast cancer divides this disease into four major clusters: the HER2 group, the luminal group, the normal group and the basal group. This classification divides breast cancer into these clusters by virtue of their intrinsic gene expression. It is not possible to perform gene testing on all patients with breast cancer, as this would add a huge financial burden to the management of this common disease, so instead we use clues from the biopsy, and classify patients into one of these groups using factors like oestrogen and progesterone receptor status, HER2 status, tumour grade and Ki-67 proliferation index.

These parameters are used to help classify patients into molecular subgroups which then directs impending therapeutic strategies. The luminal A group tends to be primarily managed by hormonal manipulation, whereas the luminal B group uses chemotherapy initially, then patients’ responses tend to be maintained with hormonal therapies. The HER2 group uses targeted therapies which have revolutionised outcomes in this field. This group, which used to carry the most dismal prognosis, now has the best outcomes with respect to long-term survival. The basal group contains with its grouping the triple-negative type breast cancer. This group is presently managed by chemotherapy alone, as there are no discernible targets with which to treat these patients.

One principle still holds and will always – the more information we collect and the more research we participate in, the better we will become at appropriately managing this epidemic we know as breast cancer.

Written by Dr Devan Moodley.