Know it, to control it
Biomarkers for Cancer Management
The definition of a biomarker given by National Cancer Institute, USA is: “A biological molecule found in blood, other body fluids or tissues that is a sign of a normal or abnormal process or of a condition or disease. A biomarker may be used to see how well the body responds to a treatment for a disease or condition, also called molecular marker and signature molecule’’.
Let us understand what does a biomarker mean? A biomarker is a biological substance found in the body which can either be identified in the body fluids viz. blood, urine, sputum or tissue after biopsy. It can be a particular disease or a type of cancer. A biomarker can be used:
a) To help diagnose cancer (Diagnostic)
b) To forecast how aggressive the type of cancer is (Prognostic)
c) Risk determination
e) Differential diagnosis
f) To predict and monitor the response to treatment (Predictive)
Cancer Specific biomarkers/Tumour markers
A biomarker may be picked up in the primary biopsy, lymph node, distant metastases, in blood circulation as a genetic material (RNA, DNA molecule) or as a whole cell.
The American Society of Clinical Oncology (ASCO) established the guidelines for use of biomarkers for colon and breast cancer in 1996. Following criteria must be met for a biomarker to have a clinical use:
a) The use is well defined
b) There is a difference in the outcomes to warrant a use
c) The estimated benefit must be accurately defined
The most commonly used biomarkers are for carcinoma breast and colon cancer, however their use for other sites is also emerging.
- Breast Cancer: Breast cancer is a model on which the biomarkers have been extensively studied. The earliest to be identified were oestrogen and progesterone receptors that are normally found in normal ovaries, breast, uterus and a lot of other organs. The patients that have breast cancers expressing oestrogen/progesterone receptors tend to have less aggressive cancers. There are guidelines to test all breast tumours for oestrogen/progesterone (ER/PR) receptors after biopsy as there are specific receptor blocker medicines available that can prevent the recurrence of this cancer.
Over the last twenty years a lot of medicines have been tested, refined and made clinically available after the failure of first line of receptor blockers. The earliest drug was Tamoxifen and it is estimated that this medicine alone is responsible for saving at least 30% of the women having breast cancer. It works best for the pre-menopausal women along with the removal of ovarian function (castration). It is heart and bone friendly and is well tolerated. Other biomarkers identified for breast cancer are HER2neu, UPA and PAI-1 multiparameter gene expression analysis proliferation markers (Ki-67, cyclin D, cyclin E, p27, p21 etc.), p53, CA 15-3 and CA 27.29 and many others. The only clinically relevant biomarker is HER2neu and a medicine by the name of transtuzumab which can be given in women with HER2neu positive women.
Patients whose cancers do not express oestrogen/progesterone and have a recurrence or relapse after the first treatment should undergo a biopsy again at the time of recurrence as sometimes the tissue may become receptor positive. This treatment is also called hormone treatment for metastatic breast cancer. In old age women, >70 years, with locally advanced breast cancers and ER/PR positive disease, the doctors prescribe the appropriate receptor blocker to downstage the cancer before surgery.
- Colorectal Cancer: Colorectal cancer has also been extensively studied and CEA or carcinoembrynic antigen is a serum (blood) test that may be asked for, in proven cancer patients. It cannot be used for screening. It can be ordered before operation and is of assistance in planning treatment. If the test is positive pre-operatively then it can be used for follow-up as well as planning further treatment after surgery. It should be done every three months post-operatively for 3 years after surgery/chemotherapy to detect a recurrence. Another biomarker recently made available in the clinic is KRAS mutation. The cancers that test positive for this mutation in metastatic colorectal disease, should not receive certain medicines (anti-EGFR or epidermal growth factor receptor blocker).
- Prostate cancer: There is enough evidence that prostate cancer is dependent upon its growth on the male hormone testosterone and it expresses a biomarker by the name of PSA or prostate specific antigen. PSA along with DRE or digital rectal examination have been used for last thirty years in the western world as a screening, treatment decision making and follow up tools. A simple test, it is advisable in men with family history of prostate cancer and every 2 years for men over the age of 50 years. Testosterone blockers/ or pituitary gland function modifying drugs are available to treat hormone response cancers. This treatment can be given upfront in advanced cancers/metastatic cancer along with radiation for locally advanced pelvis confined cancer or after surgical relapse. The blood test, if positive needs to be verified with a prostatic biopsy to define the aggressive nature of the disease, stage and correct treatment. After the treatment serum PSA or its rate of change (velocity) can help doctors decide whether to continue or discontinue treatment.
- Head and neck cancers: In the recent years a lot of work has been done on expression of epidermal growth factor receptor (EGFR) for the squamous cell cancers from head and neck region. If the tumour expresses this receptor then a direct blocker of this expression can be considered in patients who relapse after surgery and/or radiation. Some of the tumours in non-smokers/non-alcoholic patients have shown expression of human papilloma virus (HPV). The tumours in the tonsil and base of tongue commonly fall in this category and respond well to treatment with radiation alone. Studies have been done to show that in patients with head and neck cancers, expressing EGFR, the cure rates are better when radiation treatment is combined with EGFR blocker drug.
- Chronic Myeloid Leukaemia: Another biomarker is the Philadelphia chromosome that is expressed in a large percentage of patients presenting with chronic myeloid leukaemia. The patients with chronic myeloid leukaemia, a type of blood cancer respond very well to treatment with an oral medicine that acts and reverses the cancer mutation in this chromosome.