Breast and Medical Oncology Division

Introduction
During the last several years, significant deve-lopment in the field of medico-pharmacotherapy in the field of medical oncology has been made. Among them, Herceptin is the most outstanding compound. Herceptin, a monoclonal antibody against HER2 protein, a machinery involving in the regulation of breast cancer cell growth was introduced into oncology clinics last year in Japan. Our group played the leading role in the clinical development of the agent. It was in 1995 when the first phase I trial protocol design was filed to the IRB of this institute. The dominant opinion among the committee member was very discouraging. But the next five years passed with accumulating evidence that the novel compound really worked. Following the successes of Herceptin, a lot of molecular target agents has been developed. Reflecting the facts that medical treatment of solid tumors are becoming more complicated and sophisticated, specialized skill and knowledge are needed to provide the most appropriate oncological care for the patients. During the past several years, we have intentionally restructured the identity of our group to fulfill the need of the patients and changing the name of our division. The most suitable heading that represents our activity at the present time is the breast and Medical Oncology Division. As a major field of medical oncology, we have been keeping the leadership in breast cancer research and treatment. In addition to the main, we extended our activities to cover ovarian cancer, uterine cancers and cancers of unknown origin. Another goal for our group is to introduce and establish evidence-based medical oncology in daily clinical practice. In this annual report, achievement of the Breast and Medical Oncology Division is comprehensively reviewed in sub-heading of Daily Clinical Activity, Clinical Research and Education and Training.

Routine Activities　
60-90 patients a day visit the outpatient clinic and more than 80% of oncology patients are given chemotherapy on the outpatient base. Even highly myelosuppressive chemotherapeutic regimens such as AT (adriamycin plus taxotere) can be administered without severe complications in the outpatient clinic. The outpatient chemotherapy has become possible owing to good collaboration with oncologists, nurses and pharmacists. Based on the result of our primary chemotherapy program of breast cancer, cure-oriented chemotherapy which produces pathological complete response in 10% of the patient become one of the routine care of stage II, III breast cancer patients. In addition to breast cancer, ovarian and uterine cancer patients are successfully treated with chemotherapy in the outpatient clinics.
Our group takes care of 45-55 inpatients in 11A, 13A, 13B, 15A, 16A and 18F wards. In order to share the most up-to-date medical problems of each patient, we have Morning Briefing every day. All staff and resident physicians attend the meeting. Newly admitted patients and patients with problems are quickly reviewed and relevant evidence-based discussion may follow. In addition to daily rounds, three group rounds and a ground round are scheduled every week. We have a multidisciplinary case conference once a week. Medical, surgical, radiation oncologists, diagnostic radiologists gather to find out the best treatment plan for individual patients.
Another goal of our group is to establish treatment plan based on as high level of evidence as possible. Using the computer terminal of the MIRACLE system, on-line information such as UpToDate, Clinical Evidence or Pubmed are readily available from the ward through Internet. Both staff and resident oncologists in our group always refer to the most current clinical evidence for providing the most efficacious medical and oncological care for each patient.

Research Activities
Our main objectives in the research of breast oncology is to prove that surgical manipulation can be avoided to achieve cure. We emphasize the need to introduce a concept of Primary Treatment Complex for breast cancer. In this concept, cytotoxic chemotherapy, biological therapy (including traditional hormonal agents and Herceptin), surgery and radiation therapy are equally important and at least one of the modalities are employed to achieve cure of the disease based of the prognostic and predictive factors of the individual patients. In the context of this new approach, primary chemotherapy with doxorubicin and docetaxel was developed and now is used as a routine. The next program is to test the efficacy of Herceptin as a part of primary pharmacotherapy.
Accrual of patients for NSAS (National Surgical Adjuvant Study) BC 02 trial for node negative breast cancer patients closed at the end of March 2001. Among the 732 patients enrolled from 45 participating institutions, 152 were from our group. The results regarding survival will be available at the end of the year 2007. It took about two years to establish a new clinical trial group, C-Spore-BC (Compre-hensive Support Project for Oncological Research of Breast Cancer). As the first C-Spore-BC trial, the protocol of NSASBC 02 study, where chemotherapy including taxanes for node positive breast cancer patients are to be compared, has been approved by the NCC-IRB. The system, the structure, the design and the conduct of the trial is entirely independent from pharmaceutical companies and the entire structure of the trial group is quite new.
For metastatic breast cancer (MBC) patients, our goal is to individualize treatment according to prognostic and predictive factors. We have established criteria for categorization of MBC patients according to response to the first line anthracycline containing regimens and examined response to the second line docetaxel. As a JCOG multi-institutional trial, a randomized study of the first line chemotherapy comparing AC (adriamycin and cyclophosphamide) and docetaxel in metastatic breast cancer patients (JCOG 9802) is ongoing. In the field of gynecological cancer, multi-institutional trials of chemotherapy are actively conducted. For the front-line chemotherapy against ovarian cancer, a combination chemotherapy of paclitaxel, doxorubicin and cisplatin has been tested. Weekly dose-dense chemotherapy of carbo-platin and paclitaxel as a new approach of salvage chemotherapy for ovarian cancer demonstrated a good response and palliative effect. In addition to these academic leading trials, our group is actively involved in company sponsored IND (Investigational New Drug) trials. We will continue our efforts to effectively use the clinically relevant evidence in order to provide the highest level of oncological care and to actively generate high quality evidence through vigorous involvement in clinical researches.

T. WATANABE

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