Japanese Journal of Clinical Oncology

Figure 1. The Twelfth International Symposium of the Foundation for Promotion of Cancer Research, Tokyo, 1999.

SESSION 3: SCREENING PROGRAM

A screening program is crucial for the early detection of breast cancer and two speakers presented their recent data in this session. Laszlo Talbar (Falun Central Hospital, Sweden), gave a talk with the title `Control of breast cancer through early detection: the natural history of breast cancer. What we have learned from screening'. He showed a significant reduction in breast cancer mortality achieved through mammographic screening in a Swedish trial. This was due to a significant decrease in the incidence of advanced-stage breast cancer. Noriaki Ohuchi presented a paper `Perspective of mammographic screening of breast cancer in Japan'. He reported a Japanese case-control study of clinical breast examination which had failed to show its effectiveness as a screening method and stressed the importance of mammography. He described a current Japanese trial to evaluate mammographic screening and discussed a new direction in the organization of screening delivery.

SESSION 4: FAMILIAL BREAST CANCER AND GENE COUNSELING

In this session, recent progress in BRCA1 and BRCA2 studies were reported. Piri L. Welcsh (University of Washington, USA) presented a paper entitled `Genetic analysis of breast and ovarian cancer', in which she mentioned genomic-scale expression technologies and suggested that BRCA1 target genes may be novel genes involved in either inherited or sporadic breast or ovarian cancer. Takashi Fukutomi (NCC, Japan) gave a paper entitled `BRCA1 and BRCA2 germline mutations in Japanese breast cancer families'. They examined germline mutations in Japanese breast cancer families and found that only 30% of the families had a mutation in one of the two genes, which was definitely low compared with those observed in Caucasian families. This suggested a different role of these genes in breast carcinogenesis between Japanese and Caucasian women.

SESSION 5: PATHOLOGY

This session had two speakers. D. Craig Allen (Graduate University of Utah, USA) presented `Molecular pathology of human premalignant breast disease' and Hitoshi Tsuda presented `A chromosomal rearrangement der(16)t(1;16)/der(1;16) in breast cancer - histopathological and diagnostic implications'. The term `molecular pathology' sounds unique, but it has begun to occupy an important area even in routine pathology. Allen mentioned that recent molecular studies using loss of heterozygosity have found clonal allelic imbalance at more than 100 genetic loci collectively involving nearly all chromosomes, suggesting that the evolution of premalignant breast lesions is very complex and involves a large number of activated oncogenes and mutated suppressor genes, most of which are still unknown. Tsuda reported that der(16)t(1;16)/der(1;16) was detected in 77% of low-grade papillary carcinomas but not detected in papillomas. This rearrangement was detected in 33% of common breast cancers and correlated with better patient prognosis.

SESSION 6: PROGNOSTIC FACTORS

No cancer other than breast cancer has been shown to have so many prognostic factors. Two speakers contributed to this session: C. Kent Osborne, who presented `Prognostic and predictive markers in breast cancer' and Shinzaburo Noguchi, who presented `Detection of breast cancer micrometastases in bone marrow by keratin 19 mRNA RT-PCR'. As reported by Osborne, it seems possible to predict the outcome of each breast cancer patient by the combined use of various markers including genetic ones such as HER-2. New microarray technology to assess multiple gene alterations in each patient is awaited. Noguchi reported that K19RT-PCR assay was more sensitive than immunocytological methods in the detection of bone marrow micrometastases from breast cancer and suggested that the former could serve as a significant and independent risk factor for relapse.

SESSION 7: IMAGING DIAGNOSTICS AND SENTINEL NODE BIOPSY

Four papers were presented in this session, namely `Diagnostic value of contrast-enhanced computed tomography for diagnosing the intraductal component and small invasive foci of breast cancer' by Sadako Akashi-Tanaka (NCC, Tokyo), `Sentinel node evaluation for breast cancer' by David Krag (University of Vermont, USA), `Japanese experience of sentinel node biopsy in 600 patients' by Masakuni Noguchi (Kanazawa University, Kanazawa) and `Problems in sentinel node biopsy' by Tadashi Ikeda (Keio University, Tokyo). Akashi-Tanaka reported experience of contrast-enhanced helical CT in diagnosing intraductal components and small invasive foci of breast cancer. A high sensitivity as compared with conventional ultrasound or mammography was shown. Sentinel node biopsy is currently a hot subject in breast cancer surgery to achieve a minimally invasive lymphadenectomy. Technical aspects together with retrospective clinical data were discussed and the ongoing NCI-sponsored randomized trial which will recruite 4000 patients was presented.

SESSION 8: SURGERY AND POST-SURGICAL FOLLOW-UP

Three breast surgeons contributed to this session. Fujio Kasumi (Cancer Institute Hospital, Tokyo) presented `Safe breast conservation without radiotherapy sustained by serial pathological examination of resected specimens'. He demonstrated by showing their experience of 1073 cases of breast conservative surgery that unnecessary post-operative irradiation could be avoided by examining the resected specimens serially. A problem with this method is that such meticulous pathological examination is possible only in selected institutions. Norman Wolmark of NSABP reported on `The addition of tamoxifen to lumpectomy and radiotherapy in the treatment of ducal carcinoma in situ (DCIS): preliminary results of NSABP Protocol B-24'. He concluded that radiotherapy following lumpectomy for DCIS significantly reduced the subsequent incidence of invasive and non-invasive ipsilateral breast tumor recurrence and the addition of further reduces the cumulative 5 year incidence of subsequent breast cancer-related events.

SESSION 9: CHEMOTHERAPY TAILORED FOR INDIVIDUAL PATIENTS AND HIGH DOSE CHEMOTHERAPY

In his presentation entitled `Construction of a prognostic index for patients with metastatic breast cancer', Toru Watanabe (NCC, Tokyo) showed highly variable survival in patients with metastatic breast cancer. He proposed a prognostic index with which metastatic breast cancer patients could be categorized into three risk groups and the treatment might be individualized in each patient. Alan Coates (University of Sydney, Australia) presented `Metastatic breast cancer: survival and quality of life'. Although continuous efforts have been made to improve the treatment efficacy, the progress is modest and cure is rarely achieved in patients with metastatic breast cancer. He emphasized the importance of maintaining or improving the quality of life (QOL) of breast cancer patients who receive systemic therapy. William Peters (Carmanos Cancer Institute, USA) presented `High-dose chemotherapy and autologous bone marrow support for primary breast cancer'. Phase II trials suggested the survival advantage of high-dose chemotherapy in patients with breast cancer not only in a post-operative adjuvant setting but also in metastatic disease. Prospective randomized trials will give answers to the questions of the efficacy of high-dose chemotherapy in breast cancer. Yutaka Tokuda (Tokay University, Kanagawa) presented, in his paper entitled `High-dose chemotherapy with autologous hematopoietic stem cell support in Japan', the 3-year progression-free survival rate of 14% of metastatic breast cancer patients who had shown a complete response (CR) or partial response (PR) to induction therapy and were treated with high-dose chemotherapy with autologous stem cell support. He suggested the necessity for developing more efficacious induction regimens to achieve higher CR rates.

SESSION 10: HORMONE RECEPTOR FUNCTION AND ENDOCRINE THERAPY

Suzanne A. W. Fuqua (University of Texas at San Antonio, USA) presented `Molecular mechanisms of estrogen receptor action'. She reported recent data on the nuclear receptor co-regulator in transcriptional activation of estrogenic effects on breast cancer. She focused on the mechanisms for acquired resistance to tamoxifen, which is most frequently prescribed for breast cancer, and also described the mechanism of the pure anti-estrogen faslodex. Shigeaki Kato (University of Tokyo, Tokyo) presented `Cross-talk of estrogen receptor function with growth factors'. He reported that MAP kinase activated by growth factors modulates the estrogen receptor molecule and modifies its function. This may be a novel cross-talk between estrogenic stimulation and the growth factor signaling pathway.

SESSION 11: BONE METASTASIS

This session dealt with bone metastasis as an issue of both basic and clinical importance. Isamu Adachi (NCC, Tokyo) presented `Possibilities and limitations of medical therapy for bone metastases'. The incidence of bone metastases as the initial recurrence site is 30% and it reaches 70% during the clinical course of metastatic breast cancer patients. Etsuro Ogata (Cancer Institute Hospital, Tokyo) presented `Newer modalities in diagnosis, treatment and monitoring of bone metastasis'. Modulation of the function of osteoclasts and osteoblasts at the site of bone metastasis is the focus of effective treatment of this complication.

SESSION 12: NEW TREATMENTS BASED ON BIOLOGY

In this session, five papers on recent progress in the treatment of breast cancer were presented. Daniel F. Hayes (Lombardi Cancer Center, USA) presented `HER-2 as a predictive factor'. HER-2 over-expression or amplification is a significant prognostic factor in breast cancer. In addition, recent clinical investigatons demonstrated that it was a positive predictive factor for anthracycline-containing chemotherapeutic regimens and a negative predictive factor for endocrine therapy. I. Craig Henderson (University of California at San Francisco, USA) presented `Application of STEALTH technology in oncology'. Adriamycin encapsulated in liposomes with polyethylene glycol (PEG) on the outer surface remains longer in circulation and has reduced cardiac toxicity. This technique may also prove to be a powerful tool for the delivery of gene therapy, small molecules and monoclonal antibody. `Herceptin and other therapies based on biology' was presented by Richard M. Elledge (University of Texas at San Antonio, USA). Herceptin, a humanized monoclonal mouse antibody against HER2/neu protein overexpression, is a novel modality of breast cancer treatment and is now clinically useful for treating breast cancer patients. Masakazu Toi (Tokyo Metropolitan Komagome Hospital, Tokyo) presented `Novel strategy of adjuvant therapy based on inhibition of angiogenesis'. He suggested that high levels of thymidine phosphorylase and low levels of vascular endothelial growth factor characterize patients with node-positive breast cancer treated with adjuvant CMF who had the highest likelihood of a favorable outcome. Ken Yamaguchi (NCC, Tokyo) presented `Chemopreventive and anti-tumor effects of a synthetic progestational steroid, dienogest, in experimental mammary carcinoma models'. Based on a well designed in vivo model system, it was suggested that dienogest can be a potential candidate as an agent for hemoprevention and also endocrine therapy for breast cancer.

SESSION 13: SUMMARY OF THE SYMPOSIUM

Kent Osborne (University of Texas at San Antonio) comprehensively summarized the symposium. During the past 30 years, various therapeutic and diagnostic agents have been developed and brought into breast cancer clinics. Owing to these developments, what was unknown or thought to be impossible has now become well known and possible. Continuing effort in both basic and clinical investigation into the 21st century has cardinal importance. Throughout this symposium, several issues in breast cancer have become clear, mainly on the basis of mutual understanding of the Japanese delegates and guests from the overseas. The symposium was very useful and productive.

Acknowledgements

The organizing committee greatly appreciates the contribution of all the speakers and participants of this international symposium and their contribution to its ultimate success. This symposium was supported by the Japan Keirin Association and the Foundation for Promotion of Cancer Research to promote the program of the Second Term Comprehensive 10-year Strategy for Cancer Control by the Ministry of Health and Welfare, Japan.

Received June 11, 1999; accepted June 14, 1999
For reprints and all correspondence: Toru Watanabe, Department of Medical Oncology, National Cancer Center Hospital, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan

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