An orchestrated attack on cancer

A leading European oncologist advocates the use of biological weapons to keep breast cancer from returning.

breast cancer ribbon 88 (photo credit: )
breast cancer ribbon 88
(photo credit: )
Belgian oncology Prof. Martine Piccart, an accomplished pianist who has performed to raise money for cancer research, chose medicine as a career over music. But today, as head of an international research consortium aimed at integrating breast cancer treatment, Piccart is actually a skilled conductor. Many resources, says the scientist in an interview with The Jerusalem Post, are wasted because they are not coordinated. Since funding is limited, she adds, smaller studies should be examined so they do not go over familiar territory. Since cancer has struck her own mother and other relatives and friends, she takes a personal interest. Each year, around half a million women are diagnosed with breast cancer, a disease that accounts for almost 20% of all deaths in women. One in nine women will get it at some time in their lives. Piccart, a leading oncologist at the Free University in Brussels and head of the internal medicine department and chemotherapy unit of her city's Jules Bordet Institute, was in Israel recently to receive additional recognition for her achievements. She was one of seven scientists to share the Jacqueline Seroussi Memorial Foundation's $900,000 prize for 2005. The non-profit foundation, through the auspices of Tel Aviv University, has since 2002 aimed to reward outstanding individuals devoted to fighting breast cancer. Piccart was honored for her work on gene expression that makes it possible to predict the progression of breast cancer and patients' chances for recovery. The daughter of a gynecologist father who saw patients at home, Piccart decided to study medicine when she was only eight. She recalls that when she was about to start a medical fellowship in New York, a friend's mother died of ovarian cancer. Her own mother survived two bouts of breast cancer two decades ago, giving Piccart a relatively high risk of the same disease, and she and her husband, German-born orthopedic surgeon Dr. Michael Gebhart, have three daughters. A few years ago, at an international breast cancer conference, Piccart - an all-round talent - gave an impressive medical lecture. Then she walked across to the piano and performed a couple of movements from a Smetana trio, accompanied by two of her daughters while the youngest turned the pages. "The audience was first taken aback and later spellbound," a member of the audience reported. "After the applause, Piccart returned to the podium and coolly mediated a discussion. One delegate muttered: 'Now she'll probably go home and cook a six-course meal for them all…' " The author or co-author of 200 publications in peer-reviewed journals, Piccart has also contributed to more than 20 books on cancer, and is on the editorial board of several journals. She founded her international research consortium, acronymed BIG (for Breast International Group), in 1996. It has brought together 35 groups involved in breast cancer research, with clinical trials encompassing over 60,000 women. She also plays an active role in new drug development, both as a researcher and as a clinical expert for registration. Last year, she established a sister consortium called TRANSBIG, aimed at research for "translating" the findings of basic research into bedside care. Piccart says she will spend her prize money coordinating breast cancer research through her consortia. Transbig, says Piccart, has been working on the first phase of an ambitious clinical trial called MINDACT. This trial will determine whether microarray - a new technology that can analyze the genetic make-up of individual breast tumors - is better than conventional methods in assessing whether women should receive additional (adjuvant) treatment after surgery, such as chemotherapy or hormonal treatment. The use of conventional methods makes it impossible to accurately determine which women are most at risk of having their breast cancer come back, so as many as a fifth get more and longer treatment than they need. This, she says, is very expensive, and since chemotherapy and other treatments are unpleasant and toxic, patients may suffer from serious long-term side effects. The validation and standardization phase of the MINDACT trial, supported in part by the Breast Cancer Research Foundation and the European Commission, has now been able to confirm that a 70-gene tumor "signature" identified by Dutch scientists and based on the microarray technology is indeed better than methods currently used to decide who is at high or low risk of the disease coming back. Now MINDACT will study several thousand women to identify those who would benefit most from drug treatment after breast surgery. The most talked-about breast cancer drug these days is Herceptin, a biotherapeutic "monoclonal antibody" - rather than a toxic chemotherapy drug. Made by Roche Pharmaceuticals and costing some NIS 150,000 per year per patient, it specifically blocks the HER2 (human epidermal growth factor 2) receptor on the surface of breast cancer cells, and thus halts the constantly "on" stimulus to cell division. In 25% to 30% of patients with metastatic breast cancer, the HER2 protein is overexpressed in the cancer cells, usually due to the "amplification" of the HER2 gene. Cancer cells with this characteristic respond less well than other tumor cells to conventional chemotherapy and hormonal therapy. Herceptin does not cure breast cancer, but in many patients with metastatic breast cancer, it prevents cancer's escalation, thus extending survival time. Most recently, it has been found to keep breast cancer at bay in about half of women taking it after their initial tumor was removed by surgery and/or radiotherapy or chemotherapy. The only significant side effect is that it can weaken the heart, but this occurs only in about 4% of women. IN JANUARY 2000, the Health Ministry and the government approved the inclusion of Herceptin in the basket of health services for women who have metastatic cancer; experts estimated that it would be needed by over 400 women. Since then, the drug has not been provided by the health funds (as part of the basket) for the prevention of a recurrence in suitable (HER2) women, but the Israel Cancer Association has launched a campaign to get the government to finance Herceptin for relevant women even before the 2005 state budget and health basket are decided. A NIS 35 million private fund recently established by philanthropist Sami Ofer and his family will try to supply Herceptin to many of the 600 women a year who are now deemed suitable for therapy to reduce the risk of a recurrence. To try to save the lives of their wives, mothers, sisters and daughters, many families have been forced to sell off cars and homes to buy the drug. The Ofer fund is negotiating with drug companies and importers to receive Herceptin at a reduced price so that it can be given to more women who need and can benefit from it. Maccabi Health Services, Israel's second-largest health insurer, recently announced that with the Ofer Foundation, it would jointly finance Herceptin therapy for Maccabi members who have been successfully treated for breast cancer and want to prevent its recurrence. But this is certainly no solution for women who are members of the three other health funds, which do not offer Herceptin in such cases. Piccart notes that she faces the same problems in her native country. "In Belgium, it also takes a long time to get reimbursement for new cancer drugs. I went to the health ministry to try to explain that it has a big impact on high-risk women and demanded that something be done. We hope Herceptin, which would cost 15 million euro a year and benefit 1,000 HER2 women, will be paid for by government even before it is approved for inclusion in our medication basket." A just-released Herceptin study pairing it with chemotherapy in patients suffering from early-stage breast cancer has found this combination significantly increases disease-free survival time in HER2 women. The large international study was carried out by the the Breast Cancer International Research Group (BCIRG) and presented to the San Antonio Breast Cancer Symposium in Texas. "The chemotherapy combinations we tested with Herceptin proved to be superior to the best available standard therapy," said the principal investigator. "This further illustrates the promise of targeted therapies, and moves us closer to our goal of minimizing the toxicity of therapy while maximizing efficacy." "Breast cancer is really a team effort; Israel, whose breast cancer researchers have a very good name abroad, is involved too," concludes Piccart, "and our international efforts are aimed at showing people that good collaboration can advance it."