Masaru Izuo

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.

Oral high-dose medroxyprogesterone acetate (MAP) in treatment of advanced breast cancer. A preliminary report of clinical and experimental studies.

SummaryMedroxyprogesterone acetate (MAP) in the treatment of advanced breast cancer has been regarded as a minor agent according to the previous reports when used at low doses (<500 mg/day). High doses of more than 500 mg which have come into use since 1973 give a response rate of over 40%, but sometimes cause gluteal abcess or induration because of daily intramuscular injections.In order to administer easily and to avoid the side effect, we have attempted to use oral administration in a daily dose of 1200mg (400 mg × 3). Of those 20 patients treated with oral high-dose MAP, 1 showed complete response, 6 showed partial response, 7 no change, and 6 progressive disease. As for site of lesion, 4 out of 6 (67%) in skin and 4 out of 16 (25%) in bone responded. Neither severe side effects nor abnormal laboratory data were seen.Then, we examined the blood levels of MAP in vivo by RIA in 9 patients. The blood level of MAP reached 39–250 ng/ml in 3 days and was maintained at least over 50 ng/ml for 1 or 2 months of continuous administration. Subsequently, we examined the effects of MAP on binding to ER in vitro. The inhibition of binding of estradiol-17β to ER was about 60% at 10−5 M MAP. The blood level of 50 ng/ml in vivo corresponds to about 1.3 × 10−5 M.

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.

Effects of medroxyprogesterone acetate therapy on advanced or recurrent breast cancer and its influences on blood coagulation and the fibrinolytic system

The effects of medroxyprogesterone acetate (MPA) therapy on advanced or recurrent breast cancer and its influence on blood coagulation and the fibrinolytic system were compared among three different therapy regimens consisting of cyclophosphamide, adriamycin, and 5-fluorouracil (CAF) + MPA and CAF or MPA alone. A clinical response was observed in 42.9% (9/21) of the patients for CAF + MPA, 36.4% (8/22) for CAF and 23.8% (5/21) for MPA alone. No marked thrombosis or its prodromal condition was observed in any group. The effects on the test values for blood coagulation and the fibrinolytic system did not significantly change in the CAF group. However, both AT-III and protein C significantly increased above the normal ranges in the CAF + MPA and MPA groups. Increases in factor X, plasminogen, and α2-plasmin inhibitor/plasmin complex (PIC) and decreases in fibrinogen, tissue plasminogen activator, and D-dimer, were all observed in the MPA and CAF + MPA groups, especially in the MPA group, although these changes remained within the normal ranges. The data indicated that MPA has various influences on blood coagulation and the fibrinolytic system, but these changes did not suggest activation of the blood coagulation system.

Medical history: Seishu hanaoka and his success in breast cancer surgery under general anesthesia two hundred years ago

In 1804, Seishu Hanaoka performed the first successful surgical treatment of breast cancer under general anesthesia in the world. It preceeded by 38 years C W Long’s trial of ether anesthesia in 1842. In this paper, Hanaoka’s biography and his contributions to surgery and anesthesiology in those days, and also his advanced ideas about medicine and sanitation are presented.Hanaoka had made many efforts to develop the optimal prescriptionof the anesthetic“Tsusensan (or Mafutsu-To)”for almost 20 years. Finally, he succeeded in using it clinically for breast cancer surgery, on October 13,1804.Hanaoka performed operations for breast cancer in a total of 156 cases, and also for many other kinds of surgical procedures. He also eagerly contrived and modified many surgical instruments. In spite of such a busy daily schedule, he eagerly trained and educated many students, using his own philosophy for medical management. Details of his background and some discussion from a present-day viewpoints are included.

The Effect of Mass Screening for Breast Cancer: Results of a Multivariate Analysis

To evaluate the life‐prolonging effect of mass screening for breast cancer, we compared the risk of death for the patients detected by mass screening with that for the patients diagnosed in out‐patient clinics, after adjusting for other relevant factors simultaneously by using the Cox regression model. A multivariate analysis using the Cox regression model in which clinical staging of disease was taken as one of the independent variables, showed that the risk of death for patients detected by mass screening was smaller by 0.765 times than that for patients found in out‐patient clinics although the reduction was not statistically significant. This small reduction might be partly due to the effect of mass screening through early detection even within the same stage, and partly due to length bias, lead time bias and self‐selection bias. When clinical staging of disease was removed from the independent variables, the risk of death for patients detected by mass screening was reduced from 0.765 times to 0.677 times that for patients diagnosed in out‐patient clinics, which was statistically significant (P < 0.01). For asymptomatic patients detected by mass screening, such a reduction of the risk of death was from 0.789 times to 0.555 times that for patients found in out‐patient clinics (P < 0.05). These results suggest that mass screening for breast cancer may contribute to the reduction of the risk of death, although the effect of biases inherent in periodic screening was not removed completely in the present analysis.

Right hepatic lobectomy for primary lymphoma: A case report and literature review

Primary lymphoma of the liver is an extremely rare entity; only eight cases have been reported in the literature. We treated a 34-year-old man with primary hepatic lymphoma by right hepatic lobectomy, including right hemicolectomy and nephrectomy. The histological diagnosis was a small cell diffuse histiocytic lymphoma. Details of this case plus that of others in the literature are described in this report.

A phase III trial of oral high‐dose medroxyprogesterone acetate (MPA) versus mepitiostane in advanced postmenopausal breast cancer

A randomized controlled trial was performed to compare the therapeutic results of oral high‐dose medroxyprogesterone acetate (HD‐MPA) versus mepitiostane (MS) in the treatment of postmenopausal breast cancer. MPA was given at three doses of 400 mg orally daily to 47 patients and produced objective responses in 19 cases (40.4%). An objective response was seen in 14 of the 40 control patients given MS at two doses of 10 mg orally daily (35.0%). Among patients with bone metastases, 6 of 19 (31.6%) for HD‐MPA and 2 of 13 (15.4%) for MS showed objective responses. The other merits of HD‐MPA suggested in the study were improvement in performance status, increase in appetite, and myeloprotective effect.

Outcome of breast-conserving therapy in the Tokyo women’s medical university breast cancer society experience

BackgroundThe results of BCT in Japanese women have not been fully evaluated. The Tokyo Women’s Medical University Breast Cancer Society initiated BCT protocols in 1987. Here, we present a retrospective analysis of BCT outcomes and identify prognostic factors.MethodsThe study population comprised 348 patients (353 breasts) with UICC clinical stage 0, I or II breast cancer, for whom wide excision (n = 294), quadrantectomy (n = 56) and tumorectomy (n = 3) were performed. The final pathological margin states were positive in 102 breasts (cancer cells remained within 5 mm of the surgical margin). The whole breast was irradiated to a total dose with 44 Gy/20 fractions or 46 Gy/23 fractions in the patients with negative surgical margins. The patients with positive or close margins received 48.4 Gy/22 fractions or 50 Gy/25 fractions irradiation to the whole breast. All but 2 patients received a radiation boost to the tumor bed and all tumor beds were irradiated to more than 53 Gy. Adjuvant therapy was administered in 240 cases. The median follow-up time was 4.3 years.ResultsThe 5-year overall, cause-specific and disease-free survival rates were 95.8%, 97.3% and 92.5%, respectively. Recurrence was observed in 29 patients including 11 patients with loco-regional recurrence. Local recurrence was observed in 6 patients, 5 of whom were premenopausal. The 5-year local control and loco-regional control rates were 98.9% and 96.6%, respectively. T status (T1 to T2) was the only significant prognostic factor for disease-free survival. No severe morbidity has been observed. Cosmetic results were excellent or good in 73% of patients.ConclusionOur BCT protocols provide a high rate of local control and good cosmetic outcome. Pathologic margin status was not a major prognostic factor for local recurrence. Long term follow-up is required to reach a definite conclusion on optimal BCT protocols.

Changing practices in the surgical treatment of breast cancer in Japan: A nationwide survey by the Japanese Breast Cancer Society

A nationwide survey in Japan of the patients with primary breast cancer from 1989 to 1991 revealed marked changes in the surgical treatment of the disease. During this period, there was a significant trend toward fewer instances of radical and extended radical mastectomies, and an increase in modified radical mastectomies and breast-conserving surgery. The percentage of breast-conserving surgery for the early-stage disease increased from 6.8% to 12.7%. Among the types of operations for breast-conserving surgery, quadrantectomy was used for 51.5% of the cases, while either a partial mastectomy or a subcutaneous mastectomy was used for 18.2% and 18.9%, respectively; a lumpectomy was performed in 10.9% of the cases. As for the proportion of patients receiving radiation therapy after breast-conserving surgery, 77% of those undergoing lumpectomy received radiation in contrast to only 43% of the patients undergoing quadrantectomy. According to the data from 1991, we also found that breast-conserving surgery was performed more often in larger cities and urban areas in Japan. As a result, we found that substantial changes in the treatment of localized breast cancer had taken place from 1989 to 1991. Regarding the details of breast-conserving surgery, however, some variation still remains in spite of the publication of numerous clinical trials.