Agents of change

In 2005, Ellen Chen, then 63, was handed some unusually bad news. Not only did she have breast cancer, she had it in both breasts. Incidents of bilateral breast cancer in Hong Kong occur in less than 5 per cent of sufferers. Furthermore, both tumours tested positive for high levels of a protein called human epidermal growth factor receptor 2, or HER2, which meant that the cancer was fast-growing, more aggressive and spread through the body more quickly. A gene mutation within the cancer cells had resulted in an excess of HER2, which requires additional treatment. This type of gene mutation is not hereditary and occurs in about 20 per cent of breast cancer patients. As a former nurse, Chen had a wide network of friends in the medical community. Although she had both tumours successfully removed at a private hospital, a friend of hers recommended that she see Dr Kwan Wing-hong, who was working at a government hospital at the time, for follow-up treatment. Kwan treated Chen with chemotherapy, radiation therapy to both breasts and a targeted HER2 therapy called Herceptin. Chen was given Herceptin once every three weeks for a year, and recovered uneventfully. One year after she completed her treatment, Chen noticed that she had trouble signing her name: she could not control her right hand properly. Worried, she went back to Kwan. Kwan noted the clumsiness in her right hand and ordered a magnetic resonance imaging (MRI) scan of her brain. He discovered a tiny lesion in her right parietal lobe within the motor cortex, the area responsible for motor control for the right side of the body. It explained the difficulties she experienced in using her hand. Chen was referred to a neurosurgeon, but given the strategic location of the tumour, he was reluctant to operate on her. Instead, a highly precise form of radiation called stereotactic radiosurgery (SRS) was used to target and kill the cancer cells in her brain. By October 2007, Chen was cancer-free and back in full control of her hand. But this reprieve didn't last. Two years later, her hand control problems - and cancer - had returned. Given that she had received radiation only two years ago, the neurosurgeon could not risk damaging her surrounding brain tissue with another dose. Instead, he used surgery to remove the tumour. Tests confirmed that the brain tumour had metastasised from the breast cancer and was also HER2 positive. Chen was placed on another round of Herceptin with chemotherapy, but this time, her condition continued to deteriorate. Slowly, she had increasing difficulty in eating and muscle control. Doctors eventually gave her up as a terminal case, and she was moved to a hospice to await the end. The prognosis was so dire that Chen's family had even prepared a burial plot for her. But her son and daughter were unwilling to give up on their beloved mother without a fight. They heard that Chen's original doctor, Kwan, was now director of the Hong Kong Sanatorium & Hospital's Department of Radiotherapy. They pleaded with him to take her case. When Kwan saw Chen, she was in bad shape - unable to eat, speak or respond to questions. She also had weakness in her right arm and occasional convulsions. An MRI scan showed that the tumour had returned in her left frontal cortex, but thankfully the rest of Chen's body was clear of cancer. Still, given her advanced age of 70, Kwan did not hold out too much hope. Chemotherapy was not an option because of her poor general condition, and there were few other choices left. Nevertheless, as Chen's family was willing to try anything, Kwan opted for an unconventional route. Herceptin was not the only targeted HER2 therapy. There was another called Tykerb. Herceptin attaches itself to the HER2 receptors on the surface of the cancer cells and keeps out the growth stimulating agents. Tykerb has smaller molecules that penetrate the cancer cells and block the HER2 receptors from within the cells, thereby preventing growth agents from reaching the nucleus of the cell. Often one targeted therapy or other is used. But Kwan now tried using both. Perhaps this strategy could completely block the signals from the growth agents. The tactic paid off handsomely. One month after starting therapy, Chen's CA15-3 cancer marker fell significantly. An MRI scan showed that the cancer had shrunk from 3cm to half its original size. Starved of growth stimulants, the cancer was now dying. Another month later, Chen's feeding tube was removed and she could start eating normally. Two weeks later, she was able to speak and to regain muscle control in her right arm. After three months of treatment, Chen's cancer marker fell further to normal levels. At the end of six months, Chen was up and about, and enjoying weekly jaunts to dim sum restaurants with her family. Thanks to her children's love and stubborn grip on hope, and to the brilliant treatment strategy of her doctor, Chen was able claw her way back from the grave.