1979 INTERDISCIPLINARY PROGRAM AND COORDINATION AREA ADMINISTRATIVE REPORT

INTERDISCIPLINARY PROGRAM AND COORDINATION AREA

Program Coordinators:

Dr. Robert W. Miller, U.S.A.
Dr. Haruo Sugano, Japan

ADMINISTRATIVE REPORT

Activities in this area during the past year focused on analysis of radiation related breast cancer, especially in the atomic-bomb survivors of Hiroshima and Nagasaki.

A. Seminars

1) A planning meeting for a “US-Japan Cooperative Pathology Study of Radiation Related Breast Cancer” was held at the Department of Pathology, Vanderbilt University, Nashville Tenn., U.S.A. on July 16 to 20, 1979. The meeting was organized by Dr. Donald E. Henson, National Cancer Institute (NCI) and Dr. Shoji Tokuoka, Department of Pathology, Hiroshima University.

2) A pathological review meeting and a summation meeting on “US-Japan Cooperative Pathology Study of Radiation Related Breast Cancer” was held at Radiation Effect Research Foundation (RERF, formerly ABCC) at Nagasaki and at Hiroshima on November 26 to December 4, 1979. The meeting was organized by Dr. Shoji Tokuoka, Hiroshima University and Dr. Donald E. Henson, NCI. Both Coordinators, Dr. Robert W. Miller and Dr. Haruo Sugano participated in the summation meeting.

The purpose of this study is to determine if there are differences between breast cancer arising spontaneously in Japanese and American women and breast cancer developing in women exposed to radiation especially from the atomic bomb; and to determine, if data permit, the approximate minimal level of radiation required to induce breast cancer.
Results obtained:
At the planning meeting, the following was concluded.
(a) Breast cancer cases subject to be investigated are as many as 331. All of these have been registered in the Life Span Study Sample at RERF and are available for histological study. All exposed cases, composing approximately half of all cases, are expected to have estimated available of their radiation doses at the time of atomic bomb exposure (ATB).
(b) As a “pilot study”, the breast tissue of autopsied nonbreast cancer cases, as many as 50, known to be irradiated with doses of 100+ rad ATB are to be investigated to detect potential premalignant histological lesions and/or chronic radiation effects on the normal tissues.
(c) As to the histological classification of breast cancer, one classification was adopted for this study, based on those proposed by WHO and the Japan Mammary Cancer Society.
(d) Data obtained through the histological work are to be analyzed by bi-national representatives to complete the final report. Following the planning meeting, a histological workshop on the basis of newly adopted histological standards of breast cancer as described above was at the same location by all participants.
The pathological review meeting was held at Nagasaki and Hiroshima. The collected cases to be investigated were as follows:
(a) Breast cancer in atomic bomb survivors 150 cases
(b) Breast cancer in non-exposed controls 150 cases
(c) Breast lesions in autopsied non-breast cancer patients, whose exposures were known 50 cases to be 100+ rad.
(d) US radiation-related breast cancer, if any
The following was concluded at a summation meeting held in Hiroshima:
(a) The group confirmed that the number of breast cancer cases of atomic-bomb survivors is 149 and of non-exposed age-matched control is 153, totaling 302.
(b) It also confirmed that these 302 cases include those previously collected by McGregor et al. in 1971 and by Tokunaga et al. in 1978, and consist of all breast cancers known to have developed during the period of 1950 through 1978 among exposed and non-exposed females registered in the Life Span Study Sample at RERF.
(c) All participants agreed that subsequent analytical study of data accumulated through the histological study on these 302 cases is expected to be made by members of the bi-national participants, Dr. D. E. Henson and Dr. M. Tokunaga.
(d) Through the analytical work, the following should be elucidated:
(1) the relationship between radiation dose and breast cancer development and the minimal dose required for breast cancer development; (2) The relationship between breast cancer development and age ATB; (3) morphological characteristics of breast cancer in atomic-bomb survivors; (4) prognostic evaluation of breast cancer in atomic-bomb survivors; and (5) changes in the breast tissue attributable to ionizing radiation-as revealed by the “Pilot Study” As to potential radiation-related breast cancer cases in the United States it was reported by one of the US participants at the summation meeting that histological materials were not readily available from breast cancer among people who were treated with either repeated fluoroscopies of the chest or with x-ray irradiation for acute post-partum mastitis.

Preliminary Conclusions:
All cases were classified according to a combined WHO-Japan Mammary Cancer Society classification. The combined classification scheme was adopted so that results could be compared with international studies using the WHO format and with other studies conducted in Japan.
Based on a preliminary analysis, no significant difference was found in the distribution of histological types between the irradiated and non-irradiated groups. In fact, the distribution did not differ from the expected distribution of breast cancer in Japan as determined by other pathologists. Fundamentally, the distribution was not changed by considering the age ATB, age of diagnosis, interval from age ATB to diagnosis, and amount of irradiation. The peak age of diagnosis was the same in both groups. On the basis of this study, it was concluded that radiogenic breast cancer does not differ histologically from spontaneously occurring breast cancer in Japanese women, and no histologic features were found that distinguish radiogenic from spontaneous breast cancer. It should be emphasized, however, that further data analysis is being made.
The pilot study revealed no residual atypical or epithelial proliferative lesions in either lobules or duct However, there was fibroelastotic degeneration of the stroma and atrophy of adipose tissue, changes that are associated with irradiation, but also found in other conditions such as severe malnutrition.

B. Exchange of Scientists

The name of each visiting scientist is followed by his address the dates of his visit, the names and addresses of all host scientists, and a brief description of techniques studies.

1) Dr. Jacob Furth, Columbia University Presbyterian Medical Center Division of Health Sciences
	Dates:	May 21-28, 1979
	Host:	Dr. Kenjiro Yokoro, Professor of Pathology, Hiroshima University, Hiroshima

2) Dr. Robert Yonemoto, Department of General and Oncologic Surgery City of Hope National Medical Center, Duarte California
	Dates:	May 31-July 7, 1979
	Host:	Dr. Seigo Fukuma, Chiba Cancer Center, Chiba 280 Dr. Haruo Sugano, Cancer Institute, Tokyo 170 Dr. Keijiro Kuno, Surgical Department, Cancer Institute Hospital, Tokyo 170 Dr. Masaru Izuo, Surgical Department, Gunma University Hospital, Maebashi 371 Dr. Yuichi Yamamura, Department of Internal Medicine Osaka University Hospital, Osaka 553 Dr. Keishi Matsumoto, Institute for Cancer Research, Osaka University, Osaka 553 Dr. Hideki Koyama, Department of Surgery, The Center for Adult Diseases, Osaka 537 Dr. Takao Hattori, Department of Surgery, Hiroshima University Hospital, Hiroshima 734 Dr. Hiroshi Kobayashi, Cancer Institute, Hokkaido University Sapporo 060 Dr. Susumu Kishimoto, Department of Internal Medicine Kumamoto University Hospital, Kanamoto 860 Dr. Takeshi Hirayama, Epidemiology Division, National Cancer Center Research Institute, Tokyo 104 Dr. Toshio Wagai, Medical Ultrasonics Research Center Juntendo University Hospital, Tokyo 113 Dr. Akio Matsuzawa, The Institute of Medical Science The University of Tokyo, Tokyo 168

Dr. Yonemoto visited various laboratories that were working in the field of breast cancer and immunology, since his major interest was in the field of immunology of breast cancer. He obtained and exchanged knowledge on the following subjects from the Japanese scientists.
(1) Unique features of breast cancer in Japanese women, (2) immunotherapy, BCG cell wall skeleton, (3) newer diagnostic tools, and (4) animal models relevant to human breast cancer.
3) Dr. Donald E. Henson
4) Dr. William Hartman
5) Dr. Robert V. P. Hutter

6) Dr. Masayoshi Tokunaga, Department of Pathology, Kagoshima University Medical School, Kagoshima 890, Japan
	Dates:	January 15-May 4, 1980
	Host:	Dr. Donald E. Henson, Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, Md. 20205, U.S.A. Dr. William H. Hartmann, Department of Pathology, Vanderbilt University, Nashville, Tenn. 37232 U.S.A. Dr. Robert V. P. Hutter, Department of Pathology, St. Barnabas Medical Center, New Jersey 07039, U.S.A.

Dr. Tokunaga has been working with Dr. Donald E. Henson on a collaborative study of radiation related breast cancer at the NCI, NIH, Bethesda, Md. In addition, he has made a short visit to Dr. Hartmann’s laboratory, and Dr. Hutter’s laboratory for reviewing American breast cancer cases, including preoperatively irradiated cancer cases.

C. Exchange of Materials

A program for review of histopathological material on breast cancer in atomic bomb survivors has been developed by both Japanese and American groups. Dr. Tokunaga carrying histopathological slides visited Dr. Henson, NCI to make a collaborative study and to prepare a final report.