Personalised Cancer Medicine 

The Good: 

Also called Precision Medicine. These are treatments that target a genetic mutation or a unique molecular target of a patient’s cancer. They are often less toxic, better tolerated and most importantly, more effective improving response, cure and/or survival rates. They allow treatment escalation or de-escalation depending on the aggressiveness of the original cancer. In other words, precision medicine means: “giving the right drug to the right patient at the right time”. 
 
In Breast Cancer, examples of personalised cancer medicine in curative and palliative settings include: 
Endocrine blockade such as Zoladex, Tamoxifen, Letrozole, Anastrozole, Exemestane and Fulvestrant (ESR mutants) target the main cancer feeding pathway of Oestrogen Receptor Positive Breast Cancers and are critically important in preventing breast cancer recurrence. They are also the core 1st line treatment of these cancers in the metastatic setting in combination with CDK4/6 inhibitors (described here next). 
CDK4/6 Inhibitors such as Palbociclib, Ribociclib and Abemaciclib block key signalling pathways in Oestrogen Receptor Positive Breast Cancer and are 1st line and second line treatments of choice in combination with endocrine blockade (as above). Abemaciclib is the only CDK4/6 inhibitor currently licenced in the adjuvant (preventative) setting. 
PIK3CA inhibitors such as Alpelisib can be used in up to 40% of patients with metastatic oestrogen receptor positive breast cancer after progression on CDK4/6 inhibitors, when a PIK3 mutation is identified on the cancer. 
Herceptin (traztuzumab), Pertuzumab, Neratinib, Tucatinib, T-DM1 (Kadcyla) and Trastuzumab Deruxtecan (Enhertu) are examples of anti-Her2 therapy, which block and kill Her2 Positive expressing Breast Cancer cells. These are core treatments in both the curative and non-curative treatment of these cancers. 
Atezolizumab and Pembrolizumab are called check point inhibitors and help the patient’s own immune system recognise and kill cancer. These drugs (also called immunotherapy) in combination with chemotherapy are the current best treatment for Triple Negative Breast Cancers in both the curative and non-curative settings. 
Olaparib and Talazoparib are examples of PARP inhibitors, which can selectively kill cancer cells harbouring BRCA1, BCRA2 and PALB2 mutations in both triple negative breast cancers and oestrogen receptor positive cancers (if they are BRCA carriers). They can be used in both curative and non-curative settings. 
Anti Trop2 therapy such as Sacituzumab Govitecan, uses antibody drug conjugates (ADCs) to target overexpressed target markers/receptors in triple negative breast cancer cells allowing direct and bi-standard killing of cancer cells. 
Genetic Profiling: such as OncotypeDx and Prosigma look at a specific combination of genes to assess the risk of recurrence of an already resected oestrogen receptor positive breast cancer. This score then dictates whether the patient would benefit from chemotherapy or not, to prevent that cancer from coming back. 

The Bad: 

Apart from most endocrine blockers, personalised cancer medicines are expensive. Patients often remain on these treatments for either years, until disease progression or unacceptable toxicity and therefore the price tag is very significant. In the UK for instance, patients do not pay for any anti-cancer treatment, personalised or not, but there is clearly a disparity in countries where health systems are not funded by central governments. Insurance companies will cover all personalised medicines once licenced and approved by local health authorities, but if patients are meant to be on treatment for a significant amount of time, the insurance company may only be able to pay to a pre-specified amount/total. The personalised treatment may be wonderful, but if we can’t afford it, it’s sadly good for nothing. 
The price of the genetic or molecular test trying to identify a potential target is the first expense and vary enormously. 
Multiclonality / tumour heterogenicity: No all cancer cells within the same patient are identical. Therefore, by exquisitely targeting certain (perhaps dominant) clones, there is always the risk of tumour escape and biased selection by the personalised treatment, where the non-target cancer cells survive and ultimately become dominant. 
Get in touch with Dr Hugo to learn more.