Cancer is a terrible disease, however, advancements in ‘personalized medicine’ have greatly improved the outcomes that you can now expect. Over the course of the next six blog posts I will focus on the top 6 solid cancers that are diagnosed worldwide:
- Breast cancer
- Gastric cancer
- Malignant melanoma (melanoma)
- Non-small-cell lung cancer (NSCLC)
- Ovarian cancer
- Colorectal cancer
In Focus: Breast Cancer (#1 of 6)
- There are 1,850,010 incidents of breast cancer per year
- Breast Cancer accounts for almost 34% of all cancers
- Key genes include HER2 and BRCA
So where does personalized medicine come in? Normally, a diagnostic laboratory tests on primary breast tumor tissue are used to establish Hormone Receptor (HR) and HER2 status, thereby providing valuable information about how an individual breast tumor is likely to progress and offering targets for treatment (more about these a little later on). HER2 status is routinely used as a biomarker to identify patients likely to benefit from HER2-targeted therapies. Immunohistochemistry (IHC) or fluorescence in-situ hybridization (FISH) diagnostic techniques are used to determine the status of a patient (see figure below).
The figure above illustrates a typical HER2-testing decision tree. A pathologist scores patient tumor samples on the left hand side as 0, 1+, 2+ or 3+ depending on the severity of the staining. 0 being the absence of HER2 whilst 3+ being the ‘most.
Samples scored 2+ using the IHC technique are considered neither clearly positive nor negative (or under expressed) and should be retested with FISH or CISH. Note: that this step is important because up to 30% of retested samples are positive for HER2. Treatment guidelines are available here.
Screening is a major factor that has affected breast cancer incidence since widespread screening was introduced in the 1980s. Incidence initially increased because screening identified previously undetected cancers at an earlier stage of disease, resulting in an increase in the proportion of stage I and II breast cancer cases. In recent years, the incidence rate has declined in many countries attributed mainly to the reduced use of Hormone Replacement Therapy (HRT) through best practice.
So what can be done in breast cancer? HER2 testing provides a great target for pharmaceutical to develop drugs to combat cancer, and develop they have! Other mutations (such as BRCA) do exist, although none have actionable therapeutics (see below). Four different HER2 statuses do exist:
- HR-positive/HER2-negative: estrogen- and/or progesterone-receptor-positive and no HER2 amplification
- HR-positive/HER2-positive: estrogen- and/or progesterone-receptor-positive with HER2 amplification
- HER2+ subtype: estrogen- and progesterone-receptor-negative with HER2 amplification
- HR-negative/HER2-negative: estrogen- and progesterone-receptor-negative and no HER2 amplification
|Type||Mode of action|
|Monoclonal antibodies||Selectively bind to receptors, causing some receptors to be internalized into the cell, thereby reducing the signal for cell growth.|
|Tyrosine kinase inhibitors||Inhibit receptor autophosphorylation and activation by binding to the ATP-binding pocket of the HER protein kinase domains.|
Overall market share of therapies amongst the 6 solid tumor cancers:
Looking at Breast Cancer in particular, current recommended therapies include:
And when we combine both Trastuzumab and Pertuzumab therapies, it’s quick to see that they reflect just over 50% of the world’s spending on cancer drugs – no small amount at all! For pharmaceutical companies and diagnostic labs. At a cost of US$70,000 for a full course of treatment breast cancer is a critical one to get right.
This is further reflected in the overall market share of biomarkers amongst the 6 solid tumor cancers (bellow):
With two FDA-approved commercial kits available on the market for HER2 IHC; Dako HercepTest and Ventana Pathway. HER2 and EGFR, when combined, dominate the personalized medicine and genetic testing landscape. Although I’ve only touched the surface of how breast cancer fits into the landscape of personalized medicine, the complexity of the market and testing shows the difficulties the industry faces.
Next week, gastric cancer.