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Mammotome (Vacuum-assisted Breast Biopsy System) is a device for needle biopsy of the breast which is useful for the biopsy of non-palpable lesions. Although Mammotome biopsy is performed on mammography or ultrasound guided, mammography -guided (stereotactic) Mammotome is more important because it is almost only devise for the biopsy of non-palpable microcalcifications. We performed 1000 cases of stereotactic Mammotome biopsy between February 2000 and February 2005 in Cancer Institute Hospital, 31% of the cases were diagnosed as cancer, among these cases 83% were noninvasive carcinoma and 17% were invasive. Of the cases which Mammotome revealed noninvasive carcinoma 17% were found to have invasive lesions after the operation. Mammotome is useful device for the diagnosis of early breast cancer.

In Japan, 41% of surgeries for breast cancer were breast conserving treatment (BCT) in 2000. The indications for BCT in the guidelines of the Japanese Breast Cancer Society (1999) are as follows: (1) tumor size is 3 cm or less, (2) image diagnosis indicates no sign of extensive intraductal spread, (3) cases with multiple tumor are excluded, (4) radiation therapy is possible, (5) the patient wants to receive BCT. The pathological negative margin is favorable in BCT; however, we estimate based on our study that only about 30% of all breast cancers can be completely resected by partial mastectomy. To extend the indications for BCT, the roles of postoperative radiotherapy, endocrine therapy and preoperative chemotherapy will be important. Patients with ipsilateral breast tumor recurrence (IBTR) have increased risk of distant metastases, and the presence of IBTR is an important predictive factor for distant metastases. When we discuss the indications and limits of BCT, we have to take the rate of IBTR into careful consideration.

One hundred thirteen patients with metastatic brain tumor from breast cancer who were treated with external irradiation between 1989 and 1997 at Cancer Institute Hospital were studied. The patients were all histopathologically proven to have invasive ductal carcinoma (scirrhous type 54 cases, papillotubular type 18, solid-tubular type 41). The patients were evaluated for efficacy and histopathological subtypes. The time interval between the diagnosis of breast cancer and brain metastases was 53.6 months for the scirrhous type, 75.0 months for the papillotubular type, and 35.5 months for the solid-tubular type. The time interval between the diagnosis of initial distant metastases and brain metastases was 14.3 months for the scirrhous type, 22.5 months for the papillotubular type, and 12.5 months for the solid-tubular type. Efficacy rates (CR + PR) for external irradiation of the brain metastases were 40.0% for the scirrhous type, 66.7% for the papillotubular type, and 36.6% for the solid-tubular type. The papillotubular type had a favorable efficacy rate compared with the other two types. Median survival time (MST) from the start of treatment for brain metastases and one-year survival rate were 5 months and 11.1% for the scirrhous type, 7 months and 41.5% for the papillotubular type, and 4 months and 28.3% for the solid-tubular type, respectively. No statistically significant difference between survival rates was observed among the histopathological types. Univariate analysis showed performance status, number of metastatic tumors, and existence of extracranial metastases without bony metastasis to be significantly related to prognosis. Multivariate analysis showed only extracranial metastases without bony metastases to be related to prognosis.

The DNA ploidy pattern from fresh frozen specimens and survival rate was investigated in 91 primary breast cancers. Diploid patterns were found in 32 (35.2%) and aneuploid patterns in 59 (64.8%). The 5-year overall survival rate was significantly lower in aneuploid cases (76.3%) than diploid cases (93.8%) (p = 0.042), while there was no significant difference in disease-free survival between the two groups. there were negative nodes, no significant differences in 5-year overall or disease-free survival between patients with diploidy and aneuploidy. In contrast, when there were positive nodes, the 5-year overall and disease-free survival rates in patients with aneuploidy were 60.6% and 48.5%, which were significantly lower (p = 0.048 and p = 0.030) than the corresponding percentages of 92.3% and 84.6%, in those with diploidy. When the ploidy pattern was compared with other factors, a very close correlation was found between the ploidy pattern and histological grading (p < 0.0001). The ploidy pattern determined by flow cytometric DNA analysis may reflect the grade of malignancy of the breast cancer.

We call intraductal lesions of the breast, for example, intraductal papilloma, duct papillomatosis and noninvasive ductal carcinoma, "papillary lesions". Borderline lesions, if such exist in the breast, are included among papillary lesions. So accuracy of histopathological diagnosis is very important for research of precancerous lesion. To clarify the present conditions and problems of histopathological diagnosis of papillary lesion of the breast, fifty consecutive papillary lesions out of consultation cases were diagnosed using three categories, benign, borderline and malignant, by five pathologists. The rate of agreement of all diagnoses by five pathologists was only 20%. The borderline incidence was widely distributed from 0% to 46%. These results revealed that histopathological differential diagnosis between benign and malignant of papillary lesion was very difficult. This difficulty seems to be caused by various histological features and different criteria of histological atypia from other organs of papillary lesion of the breast.

In the Cancer Institute Hospital, two kinds of breast conservation have been adopted. Q + Ax is applied for cancers at the upper--outer quadrant and LUART is applied for those at other quadrants. The method, clinical matters, pathological findings and results are discussed together with the LUART of the national BCT group study funded by the Japanese Ministry of Welfare.

Pathological investigations for intramammary spread of breast cancer of 205 partially resected specimens were performed by making continuous section every 5 mm width of the whole specimen. The materials were 167 quadrantectomized and 38 lumpectomized specimens. The results showed that the margin of 15.6% of quadrantectomized and 28.9% of lumpectomized specimens were positive for cancer, main causes of which were intraductal spread of cancer occupying 65% of positive margin in quadrantectomy and 91% in lumpectomy, multiple cancer, interstitial spread of cancer and so on. Multiple cancers were found in eleven (6.6%) quadrantectomized and in one (2.6%) lumpectomized specimens. Second cancers were 11 noninvasive ductal and 3 invasive cancers, including two triple cancers. Fifteen cases of quadrantectomy and 4 of lumpectomy were changed to be mastectomized because of positive margin or nodal involvements. Radiotherapy was performed for 33 cases. The median 31 months follow-up results of 186 partially mastectomized breast in 184 patients were as follows; one local recurrence in lumpectomy, two new cancers in residual breast, two distant metastases and one death for other cause of death. Quadrantectomy plus axillary dissection without radiotherapy assured of pathological complete resection was safe enough at the present.

Breast cancer among Japanese females is characterized by its relatively low incidence and better prognosis than among Caucasian females. The annual mortality due to breast cancer among Japanese is about one-fifth that among Caucasians. Comparison of case distribution by histological type indicates that the ratio of well-differentiated carcinoma is slightly higher among Japanese, while the ratio of poorly differentiated carcinoma is slightly higher among Caucasian females. It is noteworthy that the incidence of in situ and invasive lobular carcinoma among Japanese is much lower than among Caucasian females. The age distribution shows that breast cancer is more frequent among middle-aged females in Japan, but more common among aged females in the West. Breast cancer among Japanese females shows a better prognosis than among Caucasian females as a whole, and even with equal tumor size and lymph node metastasis. It seems that postmenopausal breast cancer among Caucasian has a worse prognosis than the premenopausal one, although no remarkable difference in prognosis is found between premenopausal and postmenopausal patients in Japan. This suggests that the menopausal status is a critical factor for prognosis among Caucasians, but not among Japanese. As mentioned above, the morbidity and mortality rates of breast cancer among Japanese females are very low, but recently, both morbidity and mortality rates in Japan have been steeply increasing. For example, the mortality rate of breast cancer in Japan almost doubled during the past 20 years. Moreover, biological behavior of breast cancer among Japanese females has been recently changing. And time-trend data clearly indicate that breast cancer in Japan in future will be much more like that in the west, and nowadays it is westernized.

From breast cancer cases that were mastectomized between 1970 and 1987 at the Cancer Institute Hospital, 43 breast cancers during phases of pregnancy and lactation (pregnancy 11 cases, lactation 32 cases) have been analyzed. Taking the patient's age and the calendar-year at the time of diagnosis into account, we collected 43 cases as controls and compared the result. It was found that breast cancers during pregnancy and lactation metastasized to the lymph nodes at the same frequency as in the control cases, in lymph node-positive cases and in tumors of the same size the metastases involved more lymph nodes than in the control cases. Further, the survival rate of breast cancers during pregnancy and lactation was poorer in the lymph node-positive cases than in the controls. Therefore, we have concluded that pregnancy and lactation promote the progress of a metastatic cancer.

Prognostic factors of 229 patients with node negative breast cancer were analysed using Cox's proportional hazard regression model. From 11 pathological factors, four factors nuclear grade, pectoral invasion, fat infiltration and tumor size were selected under condition of p less than 0.05. When the three factors (moderate or poorly differentiated nuclear grade, marked fatty infiltration and tumor size 2 cm) were provided as poor prognostic factors, node negative breast cancer was successfully classified from the number of the poor prognostic factors: namely, the recurrence rate of subgroups with the number of 0,1,2,3 was 2%, 7%, 21%, 39%, respectively.

Breast cancer among Japanese females was characterized by a relatively low incidence and good prognosis. But recently its morbidity is increasing and its biological behavior is changing. The chronological changes and prospective features of breast cancer among Japanese females are follows: 1. Increase of morbidity and mortality 2. Increase of the ratio of poorly differentiated carcinoma and decrease of well differentiated carcinoma 3. Increase of the incidence of lobular carcinoma 4. Increase of the case of the aged females Above items show that breast cancer among Japanese females is becoming westernizing. The case-control study on "breast cancer occurrence and obesity" shows that an obesity of the aged is a significant high risk factor for breast cancer occurrence. There fore, it would be effective that the prevention of overweight at the postmenopausal women to reduce the breast cancer occurrence. The chronological rise of overall 10-year survival rate of operated breast cancer is caused by increasing the ratio of early stage cases. Suggesting an importance of regular self-examination of the breast. Furthermore, it is important to establish an adjuvant therapy without causing side effect for curatively operated cases. Concerning the cancer of the uterus among Japanese females, the chronological occurrence rate of endometrial cancer is increasing, while the death rate of cervical cancer is decreasing.

The influence of family history, irradiation and anti-cancer drug (Mitomycin C) on the occurrence of multiple primary neoplasms was analysed using the person-year method in 1359 Japanese breast carcinoma patients. There were 111 multiple primary neoplasms, including bilateral breast cancer, in 109 patients; the incidence rate was 0.0072 per person-year. The incidence rate in patients with a family history of cancer was 1.29 times higher than in those without. In the bilateral breast cancer group there was about a 3 times higher frequency of family history of breast cancer. Irradiation therapy raised the occurrence of multiple primary neoplasms 1.28 fold, and Mitomycin C (40 mg) had no effect on the occurrence of neoplasms during a 10-year observation period.

We examined the distribution and frequency of metastasis in 135 breast carcinoma cases autopsied between 1946 and 1981 at the Cancer Institute, Tokyo, and studied the relationship between the results and various factors such as histological type, patient age, therapy and clinical course. Breast carcinoma metastasizes more widely and more frequently than other malignant tumors; there is a high rate of metastasis to the bone, adrenals, opposite breast, and thyroid. Medullary tubular carcinoma metastasizes more highly than other histological types. The frequency of metastasis is higher in the younger age group and in patients irradiated to the primary sites. There is little correlation between the frequency of metastasis and total duration.

The characteristics of histological classification of breast cancer by Stewart F.W., WHO and Japan Mammary Cancer Society (published in 1971 and revised in 1984) are discussed. The classification of JMCS is fundamentally the same as WHO classification with a subclassification of invasive ductal carcinoma. Invasive ductal carcinoma has three subgroups; papillotubular, solid-tubular and scirrhous carcinoma. In these three subgroups, papillotubular carcinoma shows mainly ductal spread, well histologic differentiation, the lowest lymph node metastasis and the best prognosis. Scirrhous carcinoma shows diffuse stromal infiltration, poor histologic differentiation, the highest metastasis and the worst prognosis. Solid-tubular carcinoma with expansive stromal invasion shows intermediate biological behavior. Thus, the JMCS classification contains in itself not only histologic type but also the mode of spread, grade of histologic differentiation, ratio of lymph node metastasis and prognosis.

To study the effect of pre-operative biopsy for breast cancer on the 10-year-survival rate, 1123 cases with single cancer radically operated at the Cancer Institute Hospital between Jan. 1960 and Dec. 1969 were analyzed. The survival rate in 292 biopsied and non-biopsied patients with cancers less than 2 cm in diameter and no lymph node metastasis was not significantly different. There was no difference between incisional- and excisional-biopsied patients. However, the survival rates tended to decrease as the interval between biopsy and radical surgery increased. We conclude that pre-operative biopsy does not worsen the prognosis in patients with breast cancer. Early detection and treatment are of great importance.

A 74-year-old female with a left breast mass was admitted to the Cancer Institute Hospital and underwent mastectomy. Upon study of a frozen section, a diagnosis of breast carcinoma was made. Histopathological examination revealed a non-invasive tumor whose slightly eosinophilic rich cytoplasm was positive for PAS and Alcian-green staining and argyrophilic staining. The tumor showed medullary arrangement, partly with glandular and rosette-like structures. Electron microscopically, many dense core granules (170 +/- 30 nm in diameter) were diffusely distributed in almost all the tumor cytoplasm, they were thought to be neurosecretory granules. A diagnosis of mucocarcinoid of the breast was made. The patient experienced no dyshormonal disorder during the course of the disease and is alive and well without recurrence.

Endometrial carcinoma is found more frequently in obese subjects. In this study, we evaluated the comparative risks of endometrial cancer relative to obesity indices calculated using the Brocas coefficient. From 1979 to 1983, we treated 185 patients with endometrial cancer at the Cancer Institute Hospital, Tokyo. Compared to nonobese subjects, those who exhibited an obesity index of 1.2 or more were found to have a relative risk value of 2.0 or more times that of normal subjects across all age groups. Based on these findings, it is suggested that a practical and effective preventive measure against endometrial cancer is to avoid becoming obese.

Pure adenoma of the breast was seen in a 34-year-old Japanese woman. On examination, there was a firm, movable, nontender mass, 2.0 cm in diameter, in the upper outer quadrant of the left breast. The xeromammographic and macroscopical diagnosis was fibroadenoma. Histological examination, however, identified pure tubular adenoma of the breast. This was reported herein because of its extreme rarity.

Four cases of so-called carcinosarcoma of the breast were studied histopathologically. The patients were females aged 44, 37, 44 and 77 who were admitted to the Cancer Institute Hospital for breast tumors. Histologically, the tumors showed proliferation of sarcomatous cells with relatively small amounts of papillotubular carcinoma or scirrhous carcinoma. There were transitions between the sarcomatous portion and carcinoma. Two cases showed squamous metaplasia merging into the sarcomatous component, whereas the other 2 showed transition from adenocarcinoma to sarcomatous element. Lymph nodal metastases in 2 cases were papillotubular carcinoma. One patient died of lung and brain metastases, and autopsy revealed only sarcomatous element.

A case of mastopathy with cartilagenous and osseous metaplasia is reported. The patient is a 57-year-old Japanese woman complaining of a tumor measuring around 1.2 cm in diameter near the nipple of the left breast. The xeromammographic diagnosis was adenosis with calcification. Histological examination identified an intracystic tumor composed of papilloma and adenosis with cartilagenous and osseous metaplasia. This is the first Japanese case of its kind.

We analyzed the association of obesity with case distribution and prognosis of breast cancer. We obtained the following results by using 1,587 breast cancer cases mastectomized between 1965 and 1974 at the Cancer Institute Hospital, Tokyo. 1) Non-invasive ductal carcinoma was prominent in non-obese patients. 2) The ratio of obese group was increasing as the patients became older. 3) Obese patients had bigger size of tumor and more advanced lymph node metastasis than non-obese patients. 4) In premenopausal patients but not in postmenopausal ones, obese group showed poorer 5-year survival rate than non-obese group (p less than 0.01), and it was true even after equalizing the tumor size and lymph node metastasis.

Using 436 cases of infiltrating ductal carcinoma less than 2.0 cm in diameter mastectomized at the Cancer Institute Hospital, Tokyo, during 9 years from 1965 to 1973, association of mastopathy with breast cancer were analysed. Out of 436 cases, 128 (29.4%) were associated with mastopathy, and the association of mastopathy varied according to histologic type of breast cancer. The highest incidence was observed in carcinoma of papillotubular prototype and the lowest in carcinoma of medullary tubular prototype. Pure scirrhous carcinoma came between them. No correlationship was recognized between the grade of scirrhous stromal infiltration and incidence of mastopathy.

To evaluate the accuracy in diagnosing breast lesions by frozen sections, 657 consecutive diagnostic biopsies seen during 1982 were reviewed. Of 559 lesions considered benign at frozen sections, 558 were also benign in paraffin sections, the remaining one being a papillary carcinoma (i.e. 1/559 or 0.2% false negative). All 78 cases diagnosed as malignant in frozen sections were also malignant in paraffin sections (i.e. 0% false positive). Of the 20 doubtful cases, in frozen sections, 15 showed a papillary lesions; 7 of them were malignant in paraffin sections and the rest 13 benign. It is concluded that the frozen sections are usefull in the diagnoses of mammary disorders except for those cases with papillary tumors.

A clinicopathological study was performed on characteristics of mammary mucinous carcinoma and its 3 pathological subgroups: "gelatinous type"--with predominant mucin component, "epithelial type"--with predominant epithelial component, and "combined type"--with a small part of infiltrating ductal carcinoma and mucinous pattern. Among 4,653 primary breast cancers mastectomized at the C.I.H. between 1946 and 1981, 160 or 3.4% was mucinous carcinoma. They were divided into 106 gelatinous type, 20 epithelial type and 34 combined type. 10-year survival rate of mucinous carcinoma (75.3%) was better than whole breast cancer (65.6%). And it was 90.7%, 82.4% and 67.6% in gelatinous, epithelial and combined type, respectively.

Early cancer of the breast includes those categories of the so-called early breast cancer (TNM Stage I), minimal breast cancer, noninvasive breast cancer and T0 breast cancer. In the breast, it seems extremely rare that the lesion is genuine border-line of malignancy. A papillary or lobular lesion is usually worrisome in differential diagnosis, either benign or malignant. Sclerosing adenosis is most likely to be overdiagnosed as malignant. Tubular carcinoma, low papillary carcinoma and clinging carcinoma are most likely to be underdiagnosed as benign. To avoid overdiagnosis and/or underdiagnosis of malignancy, it is essential to learn exactly every histologic feature of various lesions.

Cases of early invasive mucinous carcinoma of the breast have been reviewed. Microscopically, a typical lesion exhibits leakage of cancerous mucus into the stromal tissue from an intraductal carcinomatous component which were shown to be mucus-producing and to be lower papillary projection. Among 5,360 primary breast cancers that had been mastectomized at the C.I.H., 11 or 0.21% were determined as being "early" cases. All of these cases exhibited "pure type" mucinous carcinomas which were found to be highly mucus. The average age of these patients was 41 years (range: 34-51 yrs.), and no cases showed a nodal involvement. During an average follow-up of 8 years, no recurrent case were found. Thus, we have found that these "early" cases revealed an early invasion of a mucinous carcinoma that is highly mucus-producing but without an invasive ductal carcinomatous pattern.

The effect of previous abortions, both induced and spontaneous, on the prognosis of breast cancer patients was analysed, applying the hazard regression model of 1190 radically mastectomized Japanese women. The 10-year disease-free survival rate of 800 patients without abortion, 312 with one or two abortions and 78 with 3 or more abortions was 64.8%, 69.8% and 77.3%, respectively. Previous abortions had a significantly favourable effect on the prognosis when the effects of 8 other co-variants were taken into account (p = 0.008). Histologic findings on resected materials showed that patients with previous abortions had a higher incidence of well-differentiated breast cancer (25%) than those without abortions (19%) (p = 0.026). The former group had significantly less metastasis to visceral organs (11.8%) than the latter (17.5%) (p = 0.011) when the first recurrence site was investigated.

A rare case of squamous cell carcinoma of the breast is presented. A 50 year-old female patient suffered from a painful tumor of the right breast 8 years prior to death. The histology of the resected mammary tumour revealed squamous cell carcinoma with an adenocarcinomatous feature in the minority. Malignancy developed in the left lung 5 years after the surgery and formed a huge mass including the pectoral muscle and esophagus. At autopsy, metastases were found in the pericardial sac and liver. Histologically, a prominent well-differentiated squamous cell carcinoma element was identified in the lung, whereas an adenocarcinomatous figure was predominant in the other sites.