We know that breast cancer is divided now in hormone receptor positive, hormone receptor negative and HER2 receptor positive or negative and those tumours that are HER2 receptor positive usually have a bad prognosis. But we have changed their prognosis by adding anti-HER2 therapy which is trastuzumab mainly and we also have the pertuzumab, we have the TDM-1, we have the neratinib and we have a new compound called tucatinib. Now, the small tumours with HER2 positivity are also with a worse prognosis than other tumours. Usually once we do surgery on patients with HER2 positive receptor disease we give them adjuvant chemotherapy plus anti-HER2 therapy to prevent recurrence and improve survival.

We have several trials, the HER2 trial, NSABP B-31, North American N9831 and the BCIRG trials that classic four important trials, significant improvement, decrease of recurrence of 50%, decrease of mortality by 30%. Now, we tend to apply this also on small tumours with lymph node negative, however, this is a very aggressive treatment for those small tumours so we think that small tumours can be treated with a regimen called the APT regimen, adjuvant paclitaxel trastuzumab. It’s de-escalating chemotherapy, that’s all they need. We give them paclitaxel weekly 80mg/kg times twelve and we give them trastuzumab for six [...] a total of twelve months.

Now, there is also a new study that’s called the PERSEPHONE study that has shown that six months of trastuzumab is not inferior to twelve months of trastuzumab and this is applicable in smaller tumours. So I think that when we have a tumour less than 3cm, less than 2cm, we can do the APT regimen, node negative attention. We can do the APT regimen. Now, for smaller tumours less than 1cm and less than 0.5cm there is a debate about this. We agree, most experts agree, that 0.5-1.0cm tumours we give them adjuvant chemotherapy but this APT regimen is good. For really smaller tumours it is okay to do six months only of trastuzumab, this is an expert opinion and it is backed by the trial. So those are important advances of de-escalating treatment, chemotherapy and even sometimes you can de-escalate anti-HER2 therapy for those very small tumours and we have a lot of those very small tumours nowadays. Because of the campaigns of screening and early detection lots of breast cancers are now being discovered very small so this aspect of treatment is really very important.

Did the PERSEPHONE trial also cover these small tumours?

Yes, there were small. The PERSPEPHONE trial did not address those particularly but it did show that it was not inferior, six months not inferior to twelve months – different from other drugs that have not really shown that. So, yes, we can use it definitely for the very small trial. If we have a patient with a tumour that is large, a tumour that has oestrogen/progesterone receptors negative, then we do not de-escalate therapy. Usually for such a patient we may even escalate therapy by adding pertuzumab to trastuzumab in the adjuvant setting and also according to the APHINITY trial. If we have oestrogen receptor positivity and advanced tumours we may even consider, and it is approved in the US, adding neratinib at the end of trastuzumab adjuvant therapy as well.

What are the differences in toxicity between the APT regimen and the previous regimen?

You avoid the use of anthracyclines. The full regimen is AC followed by T, for instance, Adriamycin cyclophosphamide followed by paclitaxel or Taxotere. So you avoid the complications of anthracyclines and cyclophosphamide and that’s a very important aspect of the treatment. We have patients who do develop complications.

Also you’re even using Taxotere, cyclophosphamide, Herceptin, the TCH regimen. Again this is not a regimen without toxicity. So whenever we can achieve good results with a less intensive regimen, it’s better tolerated by the patient and it is also less toxic and it is also less costly as well.

This is important in most countries because the costs of those drugs is very high .So industrialised nations are suffering from costs and also low and middle income countries have a big problem with that. So when we de-escalate therapy we give shorter courses of treatment, definitely it should be recommended for low and middle income countries as well.

Is this something you have seen starting to be introduced in Lebanon?

I do see this. I work with the Breast Health Global Initiative and we do recommend, we have basic levels of you have to have treatment that is available. If a Ministry of Health in a country with limited resources or hospital have $100,000, for instance, instead of using it for four patients with the treatment they can use it for eight patients. Or instead of using it for ten they use it for twenty. So the health authorities at the end, they’re the ones who may decide this is how we are going to allocate the money. So we say we want to do the best we can with the resources that we have while improving our resources. As physicians, scientifically we try to find the best treatment for the patient with the least toxicity. This is why those regimens are important and this is why it is important when we have a small tumour, lymph node negative, to think what is best for the patient with the least toxicity.