The incidence of breast cancer in parts of Asia is rising steeply and catching up with rates in the western world, Dr Louis Chow, Medical Director of the Comprehensive Centre for Breast Diseases, UNIMED Institute, Hong Kong told oncologists attending the recent 1st Asian Breast Cancer Conference in New Delhi, India, held February 9th and10th. The incidence is still low in comparison with western countries where there are 70 or more cases per 100,000 population in Europe, North America and Australia, but new cases in Asia are rising substantially by around 60 per cent in some parts and in Hong Kong and Shanghai have almost doubled over the space of 10 years. “The rise is particularly affecting younger women between 30 and 40 and some clinicians are even reporting cases among women in their early 20s,” he reported.
Breast cancer in the west has been linked to obesity, smoking, alcohol consumption, diets high in saturated fat, use of hormone replacement therapy, early onset of menarche and late menopause. The rise observed in Asia is in part attributed to the trend for young Asian women to adopt western lifestyles, he believes. “They are following stressful careers, eating high-cholesterol foods rather than their usual tofu and vegetable diet, using oral contraceptive pills and smoking,” he noted.
Unlike the West where women typically present after age 50 with early stage disease, breast cancer in Asian women occurs at a younger age and is usually presented and diagnosed at a later stage of development, he noted. More patients present with locally-advanced Stage III disease in Asian countries than in the West. And whilst in Europe and the US, breast cancer mortality is declining, in some areas, notably China, it is rising despite a lower incidence of more aggressive cancers expressing the HER2/neu gene. This contrast in mortality could be attributed to availability of better facilities for screening, diagnosis and adjuvant therapy in the West allowing cancers to be more successfully treated at earlier stages, he suggested. “Financial inducements for doctors to encourage screening are lacking in Asia.”
Clinical trials are less frequently conducted among Asian women and this needed to change, he said. Clinical experience is variable but also differs from experience with Western women in other ways. Typical responses to chemotherapy may differ. For example, docetaxel is associated with little of the toxicity seen in the West, he added. Investigators and clinical practitioners also have to bear in mind that a large percentage of Asian patients will be taking Chinese herbal remedies with a potential for drug-drug interactions and other side effects.
Case study
Treatment of late-stage breast cancers where metastasis to other sites has already occurred is challenging, he said. In one recent case, a 63-year-old patient, with controlled high blood pressure, who had previously undergone mastectomy at the age of 38 presented with a recurrence of breast cancer in her remaining breast. Her cancer was HER2/neu and oestrogen receptor-positive and was treated with the aromatase inhibitor exemestane. However, she was subsequently found to have developed lung metastases. She was treated with the chemotherapy gemcitabine until the onset of the common side effect of hand-foot syndrome forced a switch to capecitabine. Side effects continued to worsen so she was given further chemotherapy. Initially this controlled symptoms but she went on to develop a pleural effusion and severe shortness of breath after growth of a secondary tumour in the lung obstructed the main right bronchus.
At this point she began treatment with the targeted therapy sunitinib (Sutent) and saw a dramatic improvement, he reported. Shortness of breath was relieved and within a week she no longer required oxygen therapy. Her pleural effusion stabilised, cancer markers dropped and the tumour on the bronchus, seen on X ray, disappeared. Unfortunately, a return of hand-foot syndrome necessitated an interruption of sunitinib therapy whereupon shortness of breath returned and within three days the tumour on the right bronchus was visible again on X ray. Sunitinib was restarted and once again shortness of breath improved markedly as the tumour receded. A sudden loss of consciousness, however, necessitated the patient being rushed to intensive care where a CT scan showed she had suffered a cerebral haemorrhage. “At this time, her blood pressure was well controlled and the haemorrhage was thought to have resulted from a burst aneurysm,” said Dr Chow. Had this not occurred, the good response her secondary tumour had shown to sunitinib suggested her disease had ceased deteriorating and her quality of life would have improved. The case suggests sunitinib may have an important role in metastatic breast cancer, he concluded.
About sunitinib
Sunitinib is an oral tyrosine kinase inhibitor that targets tyrosine kinases, as well as all known vascular endothelial growth factors, platelet-derived growth factors and other targets associated with poor prognosis. It shrinks tumours by interfering with their blood supply as well as directly suppressing tumour growth. The drug is already approved for metastatic renal cancer, where it has become a treatment of choice, and for gastrointestinal stromal tumours that do not respond to imatinib. It is now being studied in advanced breast cancer, non-small cell lung cancer and colorectal cancer. In advanced breast cancer it is in four phase III trials studying its effects when used as first-line therapy in combination with either paclitaxel or docetaxel and is being compared to the existing targeted therapy bevacizumab. In patients who have failed to respond to prior chemotherapy, it is being investigated either alone or in combination with capecitabine.
Speaking at the same meeting, Professor John Crown of St Vincent’s University Hospital, Dublin, said sunitinib has shown proof of concept in preclinical models of advanced breast cancer and has demonstrated activity as a single agent in clinical studies. In a phase II clinical study of heavily pre-treated metastatic breast cancer patients, single-agent sunitinib therapy showed an 11 per cent partial response rate. In another study of 22 patients who had failed adjuvant therapy with anthracycline-containing drugs, sunitinib combined at a dose of 37.5mg/day with docetaxel (75mg/m2 every three weeks), showed synergistic activity achieving a 72 per cent partial response rate in 18 evaluable patients treated over 159 cycles.
The powerful anti-angiogenic effect of a simple small tablet like sunitinib and its impact on breast cancer is generating excitement among oncologists, said Professor Crown. “For doctors of my age in oncology, this really is the most extraordinary and exciting time. When I think back to how I treated cancer in my early career, trying to beat it to death with cytotoxic drugs, it seems like a bygone age of ignorance. We had no real idea of how those treatments worked” he recalled. “Thankfully I have lived long enough to see the development of molecular therapies come to fruition and move into the main frame. The phase III trials will help us quantify sunitinib’s clinical benefit in breast cancer,” he commented. Trials are currently still recruiting patients. Further information can be obtained at www.suntrials.com.
Written by – Olwen Glynn Owen
o.glynnowen@btinternet.com