Does chemo make cancer worse?

The most exciting science headlines of the week were undoubtedly based on an exciting new study published in Science Translational Medicine showing that chemotherapy can promote breast cancer metastasis. Media coverage on the subject has varied from highly sensationalist to more sensible – and for once, the panic-striken ALL CAPITALS approach doesn’t seem like it’s out of place. After all, breast cancer is one of the most prevalent forms of cancer and the idea that while trying to make it better we are actually making it WORSE is undoubtedly terrifying for everyone. For once, most of the articles online do not grossly misrepresent of just flat out lie about the contents of the study. However, the truth is much less scary than it sounds.

Neoadjuvant chemotherapy is the first line of defense against breast cancer – it is the first treatment prescribed to patients who are diagnosed with the disease. Usually, the strategy is to use neoadjuvant therapy to shrink the tumor before surgery, when the bulk of the cancer is cut off. Cancer cells are different from every other cell type in the body because they are dividing very quickly and, crucially uncontrollably. Chemotherapy targets cells that are dividing, which kills a lot of the tumor cells and shrinks the size of the cancer, as well as accidentally harm other cells in the body that also divide quickly – such as cells in the hair follicles, which is why chemo patients often lose their hair. However, the main tumor body is not necessarily the most dangerous aspect of cancer. 90% of patients that pass away from cancer do so because the cancer has spread throughout the body to other organs and tissues. For example, breast cancer cells can get into the bloodstream and get transported to the bones, to the lungs and to the liver (for more on this process, look up my post series). This process in known as metastasis and is unquestionably the most dangerous side of cancer. Unfortunately, in many cases after the cancer is removed and the patient undergoes more chemotherapy there will be signs that some cancer cells have escaped the surgery and have started growing elsewhere. It might take a long time – even decades is some cases, but metastasis is sadly a very common occurrence.

The authors of this study use an interesting and relatively novel marker of metastasis which is called tumor microenvironment of metastasis – TMEM for short. Each TMEM site is a spot where cancer cells are likely to make a transition between the tissue they are from and the bloodstream – which acts as a very effective transportation system to carry cancer cells throughout the body. Ingeniously, in this particular piece of research scientists use three molecules that are known to be very highly present at TMEM sites. Therefore, counting the number of spots where these molecules are highly expressed is a by-proxy way of measuring how many opportunities breast cancer cells have to make that fatal move out of the breast tissue and into the bloodstream. The study also shows that neoadjuvant chemotherapy increases the number of TMEM sites – which means there is an increased risk for cancer cells to metastasize. Given these data it is unsurprising that in the mice that are used as a model in this study the use of chemotherapy leads to an increased amount of metastasis.

However, there are two very important things to keep into consideration. First of all, in a huge number of patients, surgery and neoadjuvant therapy (including chemotherapy as well as hormone and radiation therapy) can be successful in eradicating all cancer cells – or at least clear enough that the immune system is able to deal with the rest. The fact that cancer cells have more “open doors” leading to the rest of the body does not mean that enough survive to make it through and invade other tissues. Secondly, the while this study presents with a terrifying problem it also comes with a solution. The authors find that using a drug known as rebastinib, which blocks one of the markers of TMEM sites, is very successful in preventing this most dangerous side effect of neoadjuvant therapy. Therefore, this study is a fantastic opportunity to update the way cancer patients are treated – for instance by using this anti-metastatic drug in patients who have particularly extensive tumors, very aggressive forms of breast cancer or tumors that are around a large number of blood vessels and are therefore at a higher risk of spreading.

The bottom line is that while in a small number of cases neoadjuvant chemotherapy has the potential to do more harm than good, studies such as these are unlocking the secrets to provide even better care for high-risk patients, maintaining all the positive benefits of using chemotherapy while preventing cancer cells from escaping and generating even more disease.