Breast cancer is the most common type of cancer among women worldwide. Research over the past few decades has unlocked many mysteries of this disease, leading to the creation of better detection tests and drugs for patients.
The disease is classified into different types based on the expression of certain proteins, like hormone receptors. More than half of all breast cancer patients have tumours that express these receptors. Traditionally, patients were treated with surgery, radiation, endocrine drugs (which specifically target the receptor) and chemotherapy. Although chemotherapy has revolutionised breast cancer treatment, it is associated with significant side-effects, such as nausea, vomiting, hair loss and fatigue. In the long term, it can also result in heart failure or leukaemia.
The choice of chemotherapy depends on a delicate balance between benefit and risk. However, not all patients will benefit from chemotherapy. Sometimes, some patients are unnecessarily given chemotherapy even when there is no potential benefit.
A study recently published in the New England Journal of Medicine (NEJM) offers a ray of hope in this regard. In the study, researchers have identified patients who will benefit most from chemotherapy based on the Oncotype Dx test. Oncotype Dx (genomic health) is the most widely used assay to determine the chances of a cancer recurring after treatment in a particular type of breast cancer (hormone receptor positive, Her2 negative, axillary node negative). It is also used to predict which patients will benefit from chemotherapy based on the expression of a panel of 21 genes in a tumour.
The assay predicts prognosis in terms of a recurrence score calculated between 0 and 100, staggered thus:
- 0-10 – Low risk of recurrence, benefit less from chemotherapy and therefore only receive endocrine therapy
- Over 26 – High-risk group with high chances of cancer coming back; such patients benefit from both chemotherapy and endocrine therapy
- 11-25 – Unfortunately, patients with scores within this range have not had a choice in treatment options as clinicians have not been able to ascertain the risk. As a result, these patients are often over-treated with chemotherapy and have to tolerate its side-effects even when they might not benefit from it.
The study published in the New England Journal of Medicine concerned the largest-ever clinical trial involving breast cancer – the Trail-Assigning Individualised Options for Treatment Rx (TAILORx), spanning six countries and 1,000 cancer centers; it prospectively followed 10,273 hormone receptor positive, Her2 negative and axillary node negative patients for nine years. Based on their Oncotype Dx recurrence scores, the patients at low risk (0-10) were given endocrine therapy alone and those with high risk (above 26) were given both endocrine therapy and chemotherapy. The patients who had an uncertain midrange score were then randomised and given either of the treatment regimens.
The researchers observed that after five years, the chances of survival were similar among patients receiving endocrine therapy alone or both endocrine therapy and chemotherapy. This is a landmark observation because it shows that 70% of the women who belong to the early stage of the most common breast cancer can be spared from the economic, emotional and physical burden of chemotherapy.
This is the first ever clinical trial on the methodology for tailor-made, or personalised, medicine and this study is bound to have a big impact on the way breast cancer is treated. Although breast cancer is a growing concern in India, it is doubtful the Oncotype Dx test will be used to benefit breast cancer patients in the country. The test alone costs around $3,400 (Rs 2.3 lakh). In addition, the breast cancer specimen has to be sent to laboratories in the US. In a country like India, where the bulk of the population belongs to middle or lower income groups, this is a prohibitory amount rendering the test inaccessible for millions of women. Another concern is that the test is useful only for early-stage breast cancer of a particular subtype. However, in India, women often visit the doctor with advanced-stage breast cancer.
These are legitimate concerns left to be addressed by the government as well as healthcare professionals to allow Indian patients to benefit from this study, and allow early-stage breast cancer patients (hormone receptor positive, Her2 negative, axillary node negative) with a medium range risk score in Oncotype Dx to safely avoid chemotherapy and its associated costs.
Radhika Nair is a Ramanujan Faculty Fellow at the Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram.
This article was originally published by India Science Wire.