Authors: Dr PN Mainwaring MBBS(Syd) MD (Lond) FRACP
Institution: iCON Cancer Care, Australia
The hope after the sequencing of the human genome was that by defining disease in terms of its molecular make up novel therapeutics could be developed to treat, prevent and screen for diseases. Cancer is the leading paradigm of this approach with over 100 anti-cancer agents approved by the FDA, but not all of which are cost-effective. Arguably breast cancer was the first disease that was targeted by alterations in its molecular make up (ER biology), initially by adrenalectomy, but in the 1970s by tamoxifen, 1980s aromatase inhibitors and more recently the CDK 4/6 inhibitors, which are now being used in the curative setting.
In the metastatic breast cancer (MBC) setting, it can be strongly argued that all cancers should undergo molecular screening for breast specific aberrations such as ESR1 mutations, PIK3CA/PTEN/AKT aberrations, somatic and germline aberrations in the homologous recombination deficiency genes, e.g. BRCA1/2, as well as the updated implications of protein HER2, ER, PgR and PD-L1 expression.
As metastatic disease progresses, further clonal heterogeneity is also important for second line and beyond therapies as MBC will acquire one or more of these common aberrations, as well as currently undruggable targets such as TP53 for which numerous clinical trials are underway as well as finally rare agnostic targets, MSI, HER2mu, NTRK which are also druggable. Naturally, each of these different pathways starts from the initial molecular sub type and hence we now have algorithms for first second and third line therapies for each of these.
I will share some of the challenges of building the infrastructure from a laboratory, hardware as well as software point of view in order to deliver ISO15189 accredited molecular pathology reports bringing first world medicine rapidly and at an affordable cost to Bangladeshi breast cancer patients in 2025.