Sources, Effects and Risks of Ionizing Radiation

The pattern of growth of human breast cancer is important theoretically and clinically. Speer et al. (Cancer Res., 44: 4124–4130, 1984) have recently proposed that all individual tumors initially grow with identical Gompertzian parameters, but subsequently develop kinetic heterogeneity by a random time-dependent process. This concept has elicited interest because it fits clinical data for the survival of untreated patients, for the progression of shadows on serial paired mammograms, and for time-to-relapse following mastectomy. The success of these curve-fits is compelling, and the model has been applied to clinical trials. However, the assumption of uniform nascent growth is not supported by theory or data, and individual cancers have not been shown to follow the complex growth curves predicted by the Speer model. As an alternative, if kinetic heterogeneity is understood to be an intrinsic property of neoplasia, the same three historical data sets are fit well by an unadorned Gompertzian model which is parsimonious and has many other intuitive and empirical advantages. The two models differ significantly in such clinical projections as the estimated duration of silent growth prior to diagnosis and the anticipated optimal chemotherapy schedule postsurgery.

https://cancerres.aacrjournals.org/content/canres/48/24_Part_1/7067.full.pdf

A Gompertzian Model of Human Breast Cancer Growth

Hereditary breast and ovarian cancer syndromes can be caused by loss-of-function germline mutations in one of two tumour-suppressor genes, BRCA1 and BRCA2 (ref 1) Each gene product interacts with recombination/DNA repair proteins in pathways that participate in preserving intact chromosome structure However, it is unclear to what extent such functions specifically suppress breast and ovarian cancer Here we analyse what is known of BRCA gene function and highlight some unanswered questions in the field

/pdf/in-search-of-the-tumour-suppressor-functions-of-brca1-and-2dvhtof11f.pdf

In search of the tumour-suppressor functions of BRCA1 and BRCA2

Oxidative stress and cell cycle checkpoint function

Ascertainment of breast cancer incidence among the cohort of the RERF Life Span Study extended sample identified 574 breast cancers among 564 cases diagnosed during 1950-1980 of which 412 cancers were reviewed microscopically. There were no dose-dependent differences with respect to diagnostic certainty or histological type. As in previous studies, the dose response appeared to be roughly linear and did not differ between the two cities. The most remarkable new finding was the emergence of a radiation-related excess among women under 10 years of age at exposure. The risk of radiogenic breast cancer appears to decrease with increasing age at exposure, whether expressed in relative or absolute terms. These results suggest that exposure of female breast tissue to ionizing radiation at any time during the first four decades of life, even during the premature stage, can cause breast cancer later in life, and that the length of time that tumor promoters such as endogenous hormones operate following exposure has an important influence on the development of radiation-induced breast cancer. An unresolved question is whether breast cancer risk is increased by radiation exposure at ages older than 40.

Incidence of female breast cancer among atomic bomb survivors, Hiroshima and Nagasaki, 1950-1980.

For 1950-74, 360 cases of malignant breast tumors were identified among the 63,000 females of the Radiation Effects Research Foundation's (Hiroshima and Nagasaki) Extended Life-Span Study sample of survivors of the 1945 atomic bombings of Hiroshima and Nagasaki; 288 of these females were residing in one of these two cities at the time of bombing (ATB). Two-thirds of all cases were classified as breast cancers on the basis of microscopic review of slides, and 108 cases received an estimated breast tissue dose of at least 10 rads. The number of cases of radiogenic breast cancer could be well estimated by a linear function of radiation dose for tissue doses below 200 rads. Excess risk estimates, based on this function, for women 10-19, 20-29, 30-39, and 50 years old or older ATB were 7.3, 4.2, 2.6, and 4.7 cases per million women per year per rad, respectively. Women irradiated in their forties showed no dose effect. Among all women who received at least 10 rads, those irradiated before age 20 years will have experienced the highest rates of breast cancer throughout their lifetimes. Separate excess risk estimates for Hiroshima and Nagasaki did not differ significantly, which indicates that for radiogenic breast cancer the effects of neutrons (emitted only in the Hiroshima explosion) and gamma radiation were about equal. Radiation did not reduce the latency period for the development of breast cancer, which was at least 10 years. The distribution of histologic types of cancers did not vary significantly with radiation dose. The data suggested that irradiation prior to menarche conferred a greater risk than irradiation after menarche.

Malignant breast tumors among atomic bomb survivors, Hiroshima and Nagasaki, 1950-74.

This report details our experience in 34 patients with primary bronchogenic carcinoma who underwent broncho-plastic lobectomy between 1969 and 1981. Twenty-four had squamous cell carcinoma, 6 had adenocarcinonia, 2 large-cell carcinoma, 1 small-cell carcinoma, and 1 combined type. Twelve patients had no lymph node involvement, while 10 had hilar node metastasis and 12 had mediastinal node metastasis. 
Sleeve lobectomy was accomplished in 19 patients and wedge lobectomy in the remaining 15. Bronchoplasty was performed for direct tumorous invasion in 26 patients, whereas in 8 patients this procedure was done when metastatic cancer had involved the main bronchus. 
There were 3 operative deaths (8.8%). One was ascribed to tension pneumothorax, one to postoperative bleeding, and the other to myocardial infarction. One patient developed a bronchopleural fistula and died 44 days after completion pneumonectomy. Another died of massive hemorrhage from a bronchopulmonary artery fistula in the fourth postoperative month. Bronchial stenosis was observed in 4 patients: 3 granulation formation and 1 local recurrence. 
The 5-year survival rate was 17%, which was higher than that of pneumonectomy. Early postoperative pulmonary function studies revealed good function of the reconstructed lung. 
Bronchoplasty for bronchogenic carcinoma is an effective procedure for preserving pulmonary parenchyma and controlling the disease.

Yasukuni Tsuji

Papers

Malignant breast tumors among atomic bomb survivors, Hiroshima and Nagasaki, 1950-74.

Bronchoplasty for bronchogenic carcinoma.

Primary tumors of the small bowel

The clinical consideration on the surgical treatment for early gastric cancer

Spontaneous rupture of the primary liver cancer