Tsunehiro Ishida

Clinicopathologic Characteristics and Prognosis of Breast Cancer Patients Associated with Pregnancy and Lactation: Analysis of Case-Control Study in Japan

Clinicopathologic characteristics and prognosis of breast cancer patients associated with pregnancy and lactation were clarified by means of a case‐control study of matched non‐pregnant and non‐lactating patients with breast cancer. From 18 institutions in Japan, a total of 192 subjects with breast cancer diagnosed during pregnancy (72 cases) and lactation (120 cases) were collected between 1970 and 1988, accounting for 0.76% of all breast cancer patients. The duration of symptoms was longer and tumor size was larger in the study subjects. Although the disease‐free interval was longer than that in the control patients, the survival time was shorter. There was no characteristic difference in histologic type. Vascular invasion and lymph node metastasis were found more frequently in the subjects. The positive rates of estrogen receptor and progesterone receptor were lower in the subjects. The 5‐ and 10‐year survival rates of the study patients were 65% and 55%, respectively, and these survivals were significantly lower than those of the control (P < 0.001). The survival rates were poorer in the subjects, in accordance with stage and lymph node metastasis. The results suggest that most of the patients with breast cancer diagnosed during pregnancy and lactation are in a more advanced stage because of a delay in detection and diagnosis, and hence have unfavorable prognosis. Therefore, it is important to diagnose and treat early for improvement of prognosis in patients with breast cancer during pregnancy and lactation.

A case-control study of breast cancer among Japanese women: with special reference to family history and reproductive and dietary factors.

SummaryTo study the effects of family history and reproductive, anthropometric, and dietary factors on the risk of breast cancer among low risk populations, we conducted a hospital-based case-control study involving 908 patients with breast cancer and their matched controls, in Japan. A positive family history of breast cancer significantly increased the risk of breast cancer (odds ratio = 1.52, 95% confidence interval: 1.14–2.03). The risk further increased with increasing number of family members affected. Obesity, single marital status, fewer births, a late childbirth, and less consumption of green-yellow vegetables and dairy products were also associated with an increased risk of breast cancer. These associations were independent in multivariate analyses. There was no increase in risk associated with consumption of high fat foods. When analyzed by menopausal status, the association with family history of breast cancer, especially in the first degree of relatives, was more evident for premenopausal breast cancer. The associations with obesity and lower consumption of dairy products were more pronounced for postmenopausal breast cancer, while those with lower parity and single marital status were stronger for premenopausal breast cancer.

Tumor growth rate and prognosis of breast cancer mainly detected by mass screening.

To investigate the relationship between the tumor growth rate of the primary breast cancer and its prognosis, records for 122 breast cancer patients in 9 hospitals in Japan were retrospectively reviewed. These records contained at least two measurements of the same tumor mass in the breast. So the growth rate was estimated from these measurements taken at different points in time. The doubling time of the breast tumors showed an approximately log‐normal distribution. The geometric mean of doubling times for all cases was 174 days. The solid‐tubular histologic type of carcinoma had the shortest geometric mean of doubling time (126 days), the scirrhous carcinoma had the second shortest one (205 days), and the papillotubular carcinoma had the longest one (252 days). The patients with shorter doubling time of tumor tended to have a poorer prognosis. The Cox multiple regression analysis showed that the tumor growth rate was related significantly with survival, after adjusting for other covariates such as clinical stage, lymph node metastasis, age of patient, histological type, and year of treatment.

Mass Screening for Breast Cancer: Comparison of the Clinical Stages and Prognosis of Breast Cancer Detected by Mass Screening and in Out-patient Clinics

To establish the criteria for assessing the life‐prolonging effect of mass screening for breast cancer, clinical stage and prognosis of breast cancer detected by mass screening in 11 regions of Japan were compared with those for matched patients in out‐patient clinics. A total of 728 patients detected by mass screening and 1,450 found in the out‐patient clinics were reviewed. The stage of the disease was Tis or I in 40.9% of the patients detected by mass screening, and 28.7% of those found in the out‐patient clinics. In contrast, stage III was found in 9.3% and 14.6%, respectively, indicating that early stages were significantly more common in the patients detected by mass screening. The overall survival curve for the patients detected by mass screening was compared with that for those found in the out‐patient clinics. The 5‐year survival rate was significantly higher in the patients detected by mass screening (91.7% vs. 85.6%; P<0.01), while the 10‐year survival rate was slightly higher in the same group of patients, but the difference from the other group was not significant (80.5% vs. 78.1%). Women who had conducted breast self‐examination (BSE) showed a higher survival rate than those who had not conducted BSE.

N-ras mutation of thyroid tumor with special reference to the follicular type

Using the method of polymerase chain reaction‐single strand conformation polymorphism, the point mutations of the ras oncogenes in a total of 33 thyroid tissues, including 12 follicular adenomas, 6 follicular carcinomas, 11 papillary carcinomas, and 4 undifferentiated carcinomas, were examined. The frequency of the mutation was 3% (1/33) in codon 12,13 of Ki‐ras and 18% (6/33) in codon 61 of N‐ras, including 17% (2/12) in follicular adenoma, 50% (3/6) in follicular carcinoma, 0% (0/11) in papillary carcinoma and 25% (114) in undifferentiated carcinoma. In follicular adenoma, positivity was observed in microfollicular or trabecular subtypes. Furthermore, the mutation of ras was examined in histologically different parts, coexisting in the same tumor in a total of four cases. Both the undifferentiated carcinoma and coexisting follicular adenoma, and both the microfollicular adenoma and trabecular nodule growing in the tumor, had the same N‐ras (61) mutation. Direct sequencing analysis showed that all mutations were CAA (Gln) to CGA (Arg) transition of codon 61, except for CAA to AAA transversion in one case of follicular carcinoma. A similar genetic abnormality of N‐ras genes at codon 61 between follicular adenoma and follicular carcinoma suggests that the mutation of N‐ras at codon 61 might play a part in oncogenesis in follicular tumors.

Preparation and clinical evaluation of technetium-99m dimercaptosuccinic acid for tumour scintigraphy.

We describe a simple method of pentavalent technetium-99m dimercaptosuccinic acid [99mTc(V)-DMSA] preparation for the imaging of medullary carcinoma of the thyroid using commercially available kits. 99mTc(V)-DMSA is available at high pH (approximately 7.5) by adding NaHCO3 solution in the presence of a small amout of reducing agent (SnCl2). On the other hand, trivalent 99mTc-DMSA [99m-Tc(III)-DMSA] can be obtained at low pH (below 3) in the presence of an excess amount of reducing agent. In the clinical evaluation of a patient with a medullary carcinoma of the thyroid, only 99mTc(V)-DMSA revealed an area of intense accumulation.

Immunohistochemical Study on the Expression of c-erbB-2 Oncoprotein in Breast Cancer

Expression of the c-erbB-2 oncogene protein was investigated by immunohistochemistry in 110 paraffin-embedded blocks of primary breast cancer. 25 (22.7%) of 110 tumors were stained positively with c-erbB-2 protein antibody. There was no correlation between c-erbB-2 immunostaining and age at diagnosis, menopausal status, hormone receptor status, tumor size, or clinical stage. The tumors with an extensive intraductal component showed a higher incidence of the c-erbB-2 expression than those without. A significantly shorter overall survival was obtained in patients with the expression of c-erbB-2 protein than in patients without. Staining of c-erbB-2 protein is an effective prognostic indicator in patients with breast cancer.

The efficacy of technetium-99m-MIBI scan and intraoperative methylene blue staining for the localization of abnormal parathyroid glands.

The efficacy of the technetium-99m-2-methoxy-isobutylisonitrile (Tc-MIBI) scan and intraoperative methylene blue staining was analyzed in a consecutive series of 15 patients with primary hyperparathyroidism who underwent neck surgical exploration. A total of 17 abnormal parathyroid glands were removed, 7 of which were confirmed histologically as adenomas and 10 as hyperplasias. The Tc-MIBI scan and the thallium-201-technetium-99m subtraction (TI/Tc) scan preoperatively localized 11 (69%) of 16, and 6 (40%) of 15 abnormal parathyroid glands, respectively. The Tc-MIBI scan correctly localized two ectopic abnormal parathyroid glands which were not localized by the Tl/Tc scan or ultrasonography (US). However, it also demonstrated falsepositive accumulations caused by thyroid diseases in two patients. There were 4 abnormal parathyroid glands not detected by the preoperative imaging techniques, whereas all 17 abnormal parathyroid glands were stained with methylene blue, the infusion of which caused no adverse effects or toxicity. In conclusion, Tc-MIBI scanning and intraoperative methylene blue staining are effective techniques for the localization of abnormal parathyroid glands in patients with primary hyperparathyroidism.

The Effect of Breast Self‐examination on Early Detection and Survival

To investigate the effect of breast self‐examination (BSE), we compared the stages, survival, and the risk of death for 355 patients with breast cancer detected by BSE with those for 1,327 patients with breast cancer detected by chance. The early stages of the disease were found to be more common among the symptomatic breast cancer patients detected by BSE than those by chance. The 5‐year overall survival rate was 94.4% for the symptomatic patients detected by BSE, and was significantly higher by 8.7% than that (85.7%) for patients detected by chance (P< 0.001). The 10‐year survival rate was 81.6% for patients detected by BSE, and 76.6% for cases detected by chance (the difference was not significant). The overall difference between the two survival curves was statistically significant by the Iogrank test (P<0.01). A multivariate analysis using the Cox proportional hazards model showed that the risk of death for patients detected by BSE was smaller by 0.570 times than that for patients detected by chance, which was statistically significant (P< 0.05). The effect of biases inherent to BSE in the survival analysis cannot be controlled completely even after conducting multivariate analysis. These results suggest that BSE may contribute to the reduction of the risk of death through early detection of breast cancer. However, further examination should be conducted by other methods to obtain conclusive evidence.

Endobronchial metastasis of breast cancer 5 years after breast-conserving therapy.

Abstract A 42-year-old woman, who had received right breast-conserving therapy 5 years previously, was admitted with hemoptysis. Chest X-rays showed a tumor shadow in the left pulmonary hilus with partial atelectasis in the left lower lobe. Bronchofiberscopic examination showed a polypoid tumor arising from the endobronchial wall, with bleeding and a white surface coat. Although, microscopically, the tumor resembled the breast cancer resected previously, as we could not rule out primary lung carcinoma, and as the tumor seemed to be localized, thoracotomy was performed. During posterolateral thoracotomy, however, pleural metastatic nodules were found; therefore, only sampling of these nodules and the administration of 50 mg of cisplatin (CDDP) into the thoracic cavity were performed. From a comparison of the histopathological features of the original tumor and the intrathoracic tumor, and from the hormone receptor positivity of the pleural metastasis, we diagnosed the intrathoracic tumor as being highly suspicious of metastasis from breast cancer. The measurement of hormone receptor was informative for the diagnosis of and for selecting a therapeutic strategy for the metastatic breast cancer.